Bioengineering

19 pages, 1477 KB

Open AccessEditor’s ChoiceArticle

Circular Approach to Biomanufacturing: Enhancing Therapeutic Protein Production Using Chum Salmon Head Peptone

by Svini Dileepa Marasinghe, Minthari Sakethanika Bandara, Somyong Lee, Young Hwa Kim, Su-Jin Lee, Dong Soo Hwang, Youngdeuk Lee, Eunyoung Jo, Tae-Yang Eom, Gun-Hoo Park and Chulhong Oh

Bioengineering 2026, 13(4), 409; https://doi.org/10.3390/bioengineering13040409 - 31 Mar 2026

Viewed by 438

Abstract

Fish waste disposal poses significant environmental and economic challenges, limiting sustainability in the marine food industry. Hence, sustainable valorization strategies are needed to enhance resource recovery while minimizing waste. As an approach, this study aimed to evaluate the potential of converting chum salmon [...] Read more.

Fish waste disposal poses significant environmental and economic challenges, limiting sustainability in the marine food industry. Hence, sustainable valorization strategies are needed to enhance resource recovery while minimizing waste. As an approach, this study aimed to evaluate the potential of converting chum salmon (Oncorhynchus keta) head (CSH) waste into a high-value peptone for microbiological applications. Various proteolytic enzymes were screened for CSH hydrolysis, among which Protamex achieved the highest hydrolysis and recovery rates. The resulting chum salmon head peptone (CSHP) exhibited favorable characteristics, including a low average molecular mass (557 Da) and a high amino nitrogen content (4.9%), outperforming commercial animal (AP) and vegetable (VP) peptones. To assess its biotechnological potential, CSHP was evaluated as a nitrogen source for recombinant protein production and supported higher expression of human superoxide dismutase (hSOD) and human growth hormone (hGH) in Escherichia coli BL21(DE3), compared with AP, VP, and Luria–Bertani (LB) media. Furthermore, life cycle assessment revealed a substantially lower carbon footprint for CSHP production than that of conventional peptone sources. These findings suggest that CSHP is a reliable and sustainable alternative to traditional peptones, offering both therapeutic and industrial applications while contributing to marine waste reduction and circular bioeconomy strategies. Full article

(This article belongs to the Section Biochemical Engineering)

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14 pages, 1785 KB

Open AccessEditor’s ChoiceArticle

An Anaerobic Trickle-Bed Reactor Filled with Siporax™ as a Novel Approach for Biomethanation of Hydrogen and Carbon Dioxide

by Gert Hofstede, Arjan Kloekhorst, Janneke Krooneman, Kemal Koç, Kor Zwart, Folkert Faber, Jan-Peter Nap and Gert-Jan Euverink

Bioengineering 2026, 13(4), 382; https://doi.org/10.3390/bioengineering13040382 - 26 Mar 2026

Viewed by 703

Abstract

To broaden the application of biomethanation for energy storage and renewable integration, this study investigates the performance of a trickle-bed reactor (TBR) for hydrogen (H₂) utilisation in biogas upgrading, using both pure Carbon dioxide (CO₂) and biogas-derived CO₂ [...] Read more.

To broaden the application of biomethanation for energy storage and renewable integration, this study investigates the performance of a trickle-bed reactor (TBR) for hydrogen (H₂) utilisation in biogas upgrading, using both pure Carbon dioxide (CO₂) and biogas-derived CO₂ as substrates for methane (CH₄) production. Renewable sources such as wind and solar are inherently variable, increasing the need for scalable storage solutions. Converting surplus electricity into H₂ and CH₄ via biological methanation offers an efficient and safer alternative to direct H₂ storage. By reducing CO₂ produced by biogas plants, methanogenic archaea produce CH₄, enabling H₂ valorisation and enhanced biogas yields. This study demonstrates that TBR technology can achieve CH₄ formation rates up to 15 L-CH₄/L-reactor/day under optimised conditions. Siporax carrier material supported dense biofilm formation and effective gas–liquid mass transfer, facilitating high conversion efficiency. The system showed operational robustness, with rapid recovery after prolonged idle periods and stable production rates of 10–12 L-CH₄/L/day. Wastewater was used as a realistic medium to assess reactor performance under complex, variable conditions. Reactor design focused primarily on enhancing gas–liquid mass transfer and supporting sustained microbial activity through adequate nutrient supply, ensuring sufficient buffer capacity to maintain pH stability. These results demonstrate the potential of TBR-based systems for high-rate, stable biomethanation and highlight their applicability in future energy infrastructures for integrating H₂ through decentralised biogas upgrading. Full article

(This article belongs to the Special Issue Anaerobic Biotechnologies for Energy and Resource Recovery from Waste)

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24 pages, 1315 KB

Open AccessEditor’s ChoiceArticle

Algal and Cyanobacteria Cell Walls as Biosorbents for Phenolic Compounds: Comparative Performance and Sustainability Assessment of Limnospira platensis

by Lorenzo Mollo, Alessandra Norici, Linda Raffaelli and Alessia Amato

Bioengineering 2026, 13(4), 373; https://doi.org/10.3390/bioengineering13040373 - 24 Mar 2026

Viewed by 573

Abstract

Adsorption is a method widely used to remove low-molecular-weight organics from wastewaters, and phenolic compounds from olive mill wastewater are a persistent class of bioactive pollutants of environmental concern. We screened eleven microalgal candidates at 0.10 g·L⁻¹ using batch kinetics fitted with [...] Read more.

Adsorption is a method widely used to remove low-molecular-weight organics from wastewaters, and phenolic compounds from olive mill wastewater are a persistent class of bioactive pollutants of environmental concern. We screened eleven microalgal candidates at 0.10 g·L⁻¹ using batch kinetics fitted with the Lagergren pseudo-first-order model to obtain rate constants (k) and fitted equilibrium capacities (q_e). Cyanobacteria, particularly Anabaena spp. and Limnospira platensis, exhibited the highest adsorptive potential in the screening; wall-less species (e.g., Dunaliella salina, Isochrysis galbana) showed negligible surface adsorption, indicating that the presence and type of cell wall highly influence biosorption. L. platensis was selected for detailed study because of its established industrial cultivation and valorisation potential. Equilibrium experiments with HCl-functionalized L. platensis at four biomass loadings (0.10–1.00 g·L⁻¹; initial phenolic mix 30 mg·L⁻¹) showed that increasing dose reduced equilibrium concentration (C_e) but decreased specific uptake from ≈77 mg·g⁻¹ to ≈18 mg·g⁻¹ while removal rose from ~26% to ~61%. Nonlinear isotherm fitting favoured the Freundlich model (1/n < 1), consistent with heterogeneous, multi-site adsorption. Targeted macromolecular extractions abolished phenol uptake, demonstrating that the intact protein–polysaccharide matrix is essential for binding. L. platensis route delivered higher single-cycle removal (≈61%) compared to the maize-derived activated carbon reference (≈49%) while also incurring a 1.3-fold lower GWP (approximately 3 kg CO₂-eq per treatment) than the activated carbon route (approximately 4 kg CO₂-eq per treatment) in our model. Overall, L. platensis represents a lower-impact alternative for natural phenols remediation, especially when integrated into valorisation pathways that recover algal co-products. Full article

(This article belongs to the Special Issue Microalgae Biotechnology and Microbiology: Prospects and Applications)

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19 pages, 2500 KB

Open AccessEditor’s ChoiceArticle

Comparison of 2D, 3D In Vitro, and Ex Vivo Platforms for Modeling the Rat Small Intestine

by Shani Elias-Kirma, Reece McCoy, Douglas van Niekerk, Verena Stoeger, Sophie Oldroyd, Emma Sumner, Achilleas Savva and Róisín M. Owens

Bioengineering 2026, 13(3), 349; https://doi.org/10.3390/bioengineering13030349 - 17 Mar 2026

Viewed by 605

Abstract

Physiologically relevant in vitro intestinal models are essential for studying key physiological processes, including barrier function, drug screening and gut-microbiota interactions. However, conventional 2D culture systems often fail to recapitulate structural and functional complexity. Here, we aimed to validate a 3D bioelectronic transmembrane [...] Read more.

Physiologically relevant in vitro intestinal models are essential for studying key physiological processes, including barrier function, drug screening and gut-microbiota interactions. However, conventional 2D culture systems often fail to recapitulate structural and functional complexity. Here, we aimed to validate a 3D bioelectronic transmembrane platform, previously used for monitoring human intestinal epithelium and vascular endothelium, for modeling the rat small intestinal barrier in vitro. The device integrates a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) scaffold supporting co-cultures of rat intestinal epithelial cells (IEC-6) and rat fibroblasts (208F), enabling real-time monitoring of barrier formation through electrical measurements using electrochemical impedance spectroscopy (EIS). Barrier formation was monitored over 21 days and exhibited a time-dependent increase in barrier resistance. The 3D platform was compared with traditional 2D insert-based cultures and ex vivo rat tissue using an Ethylene Glycol Tetraacetic Acid (EGTA)-induced calcium switch assay to evaluate barrier disruption and recovery. EGTA treatment and removal induced reversible barrier disruption in the 3D in vitro and ex vivo models, whereas 2D in vitro cultures showed limited recovery. These findings demonstrate that the 3D platform more faithfully recapitulates native tissue architecture and function, closely paralleling ex vivo responses. Our study highlights the importance of validating advanced 3D in vitro models and establishes this bioelectronic platform as a robust tool for drug screening, barrier studies, and preclinical gastrointestinal research. Full article

(This article belongs to the Special Issue Advanced Physical Techniques in Tissue Engineering and Regenerative Medicine)

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14 pages, 11989 KB

Open AccessEditor’s ChoiceArticle

Detecting Condylar Lift-Off with a Piezoelectric Smart Knee Replacement

by Brandon D. Hines, Ryan Willing and Steven R. Anton

Bioengineering 2026, 13(3), 346; https://doi.org/10.3390/bioengineering13030346 - 17 Mar 2026

Viewed by 420

Abstract

Smart knee replacement technology seeks to provide an in vivo method of tracking long-term postoperative joint loads with the goal of identifying clinically relevant phenomena linked to postoperative dissatisfaction in real time. This study evaluated the ability of a piezoelectric compartmental force and [...] Read more.

Smart knee replacement technology seeks to provide an in vivo method of tracking long-term postoperative joint loads with the goal of identifying clinically relevant phenomena linked to postoperative dissatisfaction in real time. This study evaluated the ability of a piezoelectric compartmental force and compartmental center of pressure sensing total knee replacement to sense condylar lift-off, which is a clinically relevant phenomenon commonly attributed to postoperative dissatisfaction. A commercially available total knee replacement was modified to include six piezoelectric transducers capable of measuring compartmental forces and tibiofemoral centers of pressure on the articular surface of the tibial bearing insert. The smart knee replacement was evaluated with a six-degree-of-freedom joint motion simulator applying a varus lift-off profile. The study demonstrated that the lift-off was evident in both the sensed joint loads and the localized tibiofemoral centers of pressure obtained from the piezoelectric sensing system. The results indicated that the piezoelectric smart knee replacement could be effective for detecting this clinically problematic mechanical issue. Full article

(This article belongs to the Special Issue Joint Biomechanics and Implant Design)

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20 pages, 2068 KB

Open AccessEditor’s ChoiceArticle

Establishment of a 3D Multicellular HCC Tumor Spheroid Model to Unravel Nrf2’s Influence on the Tumor Immune Microenvironment

by Nicole Böttcher, Philipp Krumm, Rosanna Huchzermeier, Lara Berschkeit, Johanna Vollmer, Julie Dick, Thomas Pufe and Athanassios Fragoulis

Bioengineering 2026, 13(3), 336; https://doi.org/10.3390/bioengineering13030336 - 13 Mar 2026

Viewed by 1582

Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death, yet adequate in vitro models mimicking the tumor immune microenvironment (TIME) are rare. Specifically, the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in modulating interactions between tumor cells [...] Read more.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death, yet adequate in vitro models mimicking the tumor immune microenvironment (TIME) are rare. Specifically, the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in modulating interactions between tumor cells and tumor-associated macrophages (TAMs) is not fully understood. We established a 3D multicellular tumor spheroid (MCT) model using murine N-HCC25 cells with CRISPR/Cas9-mediated knockouts of Nrf2 and its negative regulator Kelch-like ECH-associated protein 1 (Keap1), the latter mimicking constitutive activation. N-HCC25 cells were co-cultured with bone marrow-derived macrophages (BMDMs) isolated from wild-type and Nrf2-knockout C57BL/6J mice. We compared co-culture setups (conditioned media, transwell systems, direct contact) using RT-qPCR, flow cytometry, and invasion assays. 3D spheroid systems better preserved stemness than 2D cultures and revealed functional Nrf2-dependent effects such as increased Vegf-α secretion in Keap1-deficient spheroids. Among the different co-cultivation models, the most profound effects were observed in the MCT model. Macrophages successfully integrated into the spheroids and triggered invasive outgrowth, whereas MCTs containing Nrf2-deficient macrophages displayed markedly reduced tumor spheroid growth and lower programmed cell death ligand-1 expression. These findings demonstrate that Nrf2 signaling in macrophages fosters an immunosuppressive and pro-invasive microenvironment. The established MCT model provides a suitable platform to further unravel Nrf2-dependent mechanisms in the HCC TIME. Full article

(This article belongs to the Special Issue 3D Cell Culture Systems: Current Technologies and Applications)

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18 pages, 2193 KB

Open AccessEditor’s ChoiceArticle

Impact of Ball-Milling and Thermal Hydrolysis on Physicochemical Properties and Anaerobic Digestion Kinetics of Mixed Slaughterhouse and Agricultural Wastes

by Sang Heon Lee, Oh Hyun Gweon, Hye Sun Lee, Byoung Seung Jeon, Youngwook Go, Chang Sook Jin, Youngseob Yu, Byoung-In Sang and Jin Hyung Lee

Bioengineering 2026, 13(3), 326; https://doi.org/10.3390/bioengineering13030326 - 11 Mar 2026

Viewed by 517

Abstract

Slaughterhouse by-products are promising feedstocks for anaerobic digestion due to their high lipid and protein content. However, their complex structures often limit hydrolysis, and excessive pretreatment can induce inhibitory conditions. This study evaluates the effects of ball-milling (BM), ball-milling with water (BM + [...] Read more.

Slaughterhouse by-products are promising feedstocks for anaerobic digestion due to their high lipid and protein content. However, their complex structures often limit hydrolysis, and excessive pretreatment can induce inhibitory conditions. This study evaluates the effects of ball-milling (BM), ball-milling with water (BM + water), and combined thermal hydrolysis and ball-milling (THP + BM) on the digestion performance of a mixed substrate of slaughterhouse and agricultural wastes. The results demonstrate that all BM-based pretreatments significantly improved digestion kinetics, reducing the lag phase by 26–66% and shortening the T₅₀ values by approximately 40% compared to the untreated substrate. While no statistically significant differences were observed in the ultimate methane yield, the onset of methanogenesis was markedly accelerated in the BM and BM + water treatments. In contrast, despite achieving superior solubilization, the THP + BM treatment failed to provide proportional kinetic enhancements. This was attributed to a severe initial metabolic imbalance—characterized by a pH drop below the inhibitory threshold (6.33)—which induced physiological stress and delayed the functional recovery of methanogens. These findings indicate that while ball-milling effectively facilitates digestion initiation by enhancing physical accessibility, the intensity of combined thermal-mechanical processes must be strategically optimized. For high-strength organic biomass, managing pretreatment severity is crucial to prevent initial acid stress and maximize process efficiency. Full article

(This article belongs to the Special Issue Anaerobic Digestion Advances in Biomass and Waste Treatment)

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21 pages, 3598 KB

Open AccessEditor’s ChoiceArticle

Breeding Chlorophyll-Deficient Mutants of Chlorella vulgaris to Enhance Consumer Acceptance

by Malene Lihme Olsen, Daniel Poveda-Huertes, Duygu Ozcelik, Emil Gundersen, Jens Frederik Bang Thøfner, Maryna Kobylynska, Stefania Marcotti, Roland A. Fleck, Damien McGrouther, Johan Andersen-Ranberg, Charlotte Jacobsen and Poul Erik Jensen

Bioengineering 2026, 13(3), 318; https://doi.org/10.3390/bioengineering13030318 - 10 Mar 2026

Viewed by 904

Abstract

The use of microalgae as a food source is limited by consumers’ dislike of their organoleptic traits, primarily the intense green color and bitter taste associated with high chlorophyll content. The eukaryotic microalgae Chlorella vulgaris can grow under heterotrophic conditions, providing the opportunity [...] Read more.

The use of microalgae as a food source is limited by consumers’ dislike of their organoleptic traits, primarily the intense green color and bitter taste associated with high chlorophyll content. The eukaryotic microalgae Chlorella vulgaris can grow under heterotrophic conditions, providing the opportunity to cultivate chlorophyll-less strains. In this work we applied random mutagenesis for breeding chlorophyll-deficient C. vulgaris strains. Wild-type strain was UVC-radiated, and 12 colonies with changed pigmentation were selected. Based on phenotypic stability two mutants, M6 and M11, were selected for characterization of growth, pigment and biomass accumulation. Cultivation under photo-, mixo- and heterotrophic conditions revealed distinct phenotypes for the two mutants. M6 remained chlorophyll-deficient in all cultivation conditions tested, while chlorophyll was observed in M11 when grown under light. Under heterotrophic and mixotrophic growth conditions, both mutants were chlorophyll-deficient while biomass productivity, protein content, and amino acid composition remained similar to wild type. Characterization of the cellular ultrastructure of the wild type and mutants using cryo Focused Ion-Beam Scanning Electron Microscopy revealed that functional chloroplasts and thylakoid membranes were absent in the mutants. Our work demonstrates how a simple approach using UV mutagenesis and visual screening can provide novel strains of C. vulgaris with traits for improved consumer acceptance, without compromising the use of the algae biomass as a protein-rich food source. Full article

(This article belongs to the Special Issue Blue Economy: Innovative Strategies for Valorising Micro- and Macroalgae)

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12 pages, 443 KB

Open AccessEditor’s ChoiceArticle

A Predictive Bioengineering Model of Dental Implant Instability in Systemic Bone Disorders: A Periotest-Based Analysis

by Liliana Sachelarie, Ramona Feier, Corina-Laura Ștefănescu, Mircea Grigorian, Rodica-Maria Murineanu, Zaharia Agripina and Loredana Liliana Hurjui

Bioengineering 2026, 13(3), 297; https://doi.org/10.3390/bioengineering13030297 - 3 Mar 2026

Viewed by 595

Abstract

(1) Background: Dental implant instability represents a dynamic biomechanical process influenced by functional loading, peri-implant bone stiffness, and systemic conditions affecting bone metabolism. In patients with systemic bone disorders, altered material properties and impaired remodeling may reduce effective implant–bone interface stiffness, potentially increasing [...] Read more.

(1) Background: Dental implant instability represents a dynamic biomechanical process influenced by functional loading, peri-implant bone stiffness, and systemic conditions affecting bone metabolism. In patients with systemic bone disorders, altered material properties and impaired remodeling may reduce effective implant–bone interface stiffness, potentially increasing micromotion beyond what is detectable by conventional clinical indicators. The aim of this study was to develop and evaluate a predictive bioengineering model of implant instability based on Periotest-derived dynamic measurements. (2) Methods: A retrospective analysis was performed on 79 dental implants placed in patients with and without systemic bone disorders. Implant micromotion was quantified using Periotest values (PTVs). Linear and logistic regression analyses were applied to model the relationship between systemic bone status, implant location, and biomechanical instability (defined as PTV > +2.0). A load–stiffness–micromotion framework was used to provide mechanical interpretation of the findings. (3) Results: Implants placed in patients with systemic bone disorders exhibited significantly higher Periotest values compared to controls (+2.1 ± 1.3 vs. −0.4 ± 1.1; mean difference 2.5 PTV units, 95% CI 1.97–3.04; p < 0.001). High-risk biomechanical instability (PTV > +2.0) was observed in 46% of implants in the systemic group compared to 9% in controls. Multivariable logistic regression demonstrated that systemic bone disorders were independently associated with a 2.6-fold increase in the odds of high-risk instability after adjustment for implant location. The observed instability pattern was consistent with reduced effective peri-implant stiffness in systemically compromised bone. (4) Conclusions: Dental implant instability in systemically compromised patients can be interpreted as a load–stiffness imbalance at the implant–bone interface. The proposed predictive bioengineering framework links dynamic Periotest measurements with mechanical modeling and systemic bone status, enabling quantitative risk stratification beyond static stability assessments. Full article

(This article belongs to the Special Issue Mechanobiology in Biomedical Engineering—2nd Edition)

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35 pages, 10613 KB

Open AccessEditor’s ChoiceSystematic Review

Current Trends in Artificial Intelligence for Recognizing Work Postures to Prevent Work-Related Musculoskeletal Disorders: Systematic Review and Meta-Analysis by Occupational Activity

by Philippe Gorce and Julien Jacquier-Bret

Bioengineering 2026, 13(3), 298; https://doi.org/10.3390/bioengineering13030298 - 3 Mar 2026

Viewed by 1254

Abstract

The use of artificial intelligence (AI) to recognize postures is a promising approach for the prevention of work-related musculoskeletal disorders (WMSDs). The aim was to conduct a systematic review with meta-analysis to assess the performance of work posture recognition systems during occupational activity. [...] Read more.

The use of artificial intelligence (AI) to recognize postures is a promising approach for the prevention of work-related musculoskeletal disorders (WMSDs). The aim was to conduct a systematic review with meta-analysis to assess the performance of work posture recognition systems during occupational activity. The results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Google Scholar, IEEE Xplore, PubMed/MedLine, and ScienceDirect databases were screened without date restrictions. Two authors independently selected articles and extracted data. Studies were included if they presented a performance analysis of an AI deep learning (DL) or machine learning (ML) method that assessed the WMSD risk associated with working postures. Only peer-reviewed studies written in English including accuracy, precision, specificity, sensitivity, or F1-score values were included. The risk of bias was assessed using the Prediction Model Study Risk of Bias Assessment Tool. Of the 157 unique records, 58 studies were selected. The five performance parameters were investigated and averaged for seven occupational activities, eight posture categories, and the AI methods (ML vs. DL). Statistical analyses showed that DL methods produced better results. The reported systems detected sitting and standing postures with high accuracy. The solutions proposed in Manufacturing and Construction were the most numerous and the most effective on average. The major limitation lies in the wide variety of methods used. This analysis is a valuable source of information for designing new detection systems that are effective, ergonomic, easy to use, and acceptable so that humans remain at the center of the production process as defined by Industry 5.0. Full article

(This article belongs to the Special Issue New Trends in Biomechanical Modeling in Musculoskeletal Disorders and Diseases)

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45 pages, 8058 KB

Open AccessEditor’s ChoiceReview

Bioengineered 3D Human Trabecular Meshwork Models for Outflow Physiology and Glaucoma Research

by Andrea Valarezo, Pujhitha Ramesh, Rong Du, Rohit Sharma, Evan Davis, Susan T. Sharfstein, John Danias, Yiqin Du and Yubing Xie

Bioengineering 2026, 13(3), 291; https://doi.org/10.3390/bioengineering13030291 - 28 Feb 2026

Viewed by 1125

Abstract

Primary open angle glaucoma (POAG) is one of the leading causes of irreversible blindness and is associated with dysfunction of the trabecular meshwork (TM), a three-dimensional (3D) structure that regulates aqueous humor outflow and, consequently, intraocular pressure (IOP). IOP is the only modifiable [...] Read more.

Primary open angle glaucoma (POAG) is one of the leading causes of irreversible blindness and is associated with dysfunction of the trabecular meshwork (TM), a three-dimensional (3D) structure that regulates aqueous humor outflow and, consequently, intraocular pressure (IOP). IOP is the only modifiable factor for glaucoma. Outflow facility is the inverse of aqueous humor outflow resistance caused by the presence of the TM and adjacent tissues, and reflects the TM’s central role in IOP control, representing the most physiologically relevant measure of human trabecular meshwork (HTM) function. Therefore, development of ex vivo systems to study outflow facility and IOP regulation is critical for advancing glaucoma research. We present a comprehensive review of bioengineering approaches to generation of 3D HTM models using synthetic, natural, and hybrid hydrogels, micro- and nanofabricated synthetic substrates or porous scaffolds, and microfluidic devices. These 3D HTM systems have been designed to capture key features such as topography, stiffness, and fluid flow in the conventional outflow pathway. In particular, we highlight HTM models that recapitulate IOP regulation and allow measurement of outflow facility, which directly reflect pressure-dependent outflow resistance in dynamic HTM physiology and glaucoma pathophysiology. By integrating these bioengineering approaches with emerging stem cell technologies, this review offers an evidence-based landscape overview and framework for designing next-generation 3D human-relevant TM models for outflow physiological studies and IOP-modulating drug discovery. Full article

(This article belongs to the Special Issue Bioengineering and the Eye—3rd Edition)

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18 pages, 1379 KB

Open AccessEditor’s ChoiceReview

Bioresorbable Vascular Stents: How Neutrophil Extracellular Traps Influence Biocompatibility, Degradation Kinetics, and Device Performance

by Rasit Dinc and Nurittin Ardic

Bioengineering 2026, 13(3), 278; https://doi.org/10.3390/bioengineering13030278 - 27 Feb 2026

Cited by 1 | Viewed by 775

Abstract

Bioresorbable scaffolds (BRS; also referred to as bioresorbable vascular scaffolds, BVS) represent a promising approach in interventional cardiology, offering theoretical advantages such as temporary mechanical support followed by complete resorption. However, clinical experience has revealed challenges, including late-stage scaffold thrombosis and heterogeneous scaffold [...] Read more.

Bioresorbable scaffolds (BRS; also referred to as bioresorbable vascular scaffolds, BVS) represent a promising approach in interventional cardiology, offering theoretical advantages such as temporary mechanical support followed by complete resorption. However, clinical experience has revealed challenges, including late-stage scaffold thrombosis and heterogeneous scaffold discontinuity during degradation, prompting investigation into host immune responses. Neutrophil extracellular traps (NETs), which are network-like structures composed of decondensed chromatin decorated with antimicrobial proteins, have emerged as critical mediators of vascular inflammation and thrombosis. This review explores the intersection between NET biology and BRS performance, investigating how NETosis affects biocompatibility, degradation kinetics, and device-related complications. We discuss the molecular mechanisms that trigger neutrophil activation and NET formation in scaffold materials, the effect of NET components on polymeric and metallic scaffold degradation, and emerging biomarkers to monitor NET-mediated complications. We also evaluate therapeutic strategies targeting NET pathways, including DNase-based therapies, peptidylarginine deiminase 4 (PAD4) inhibitors, and anti-inflammatory coatings that can optimize next-generation BRS outcomes. Understanding the immunological environment surrounding bioresorbable vascular devices is crucial for developing scaffolds that deliver predictable degradation while minimizing adverse inflammatory responses. Full article

(This article belongs to the Section Biomedical Engineering and Biomaterials)

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17 pages, 870 KB

Open AccessEditor’s ChoiceArticle

Control of Joint Reaction Forces During Single-Joint Strengthening Exercises via Adaptive Electromechanical Technologies: An Analytical Biomechanical Framework

by Andrea Biscarini

Bioengineering 2026, 13(3), 270; https://doi.org/10.3390/bioengineering13030270 - 26 Feb 2026

Viewed by 777

Abstract

Background: Modern electromechanical technologies can be integrated into strength training machines to regulate the magnitude, direction, and point of application of resistance during exercise, either through preprogrammed settings or adaptively in response to real-time kinematic data. However, this potential remains largely unexplored. [...] Read more.

Background: Modern electromechanical technologies can be integrated into strength training machines to regulate the magnitude, direction, and point of application of resistance during exercise, either through preprogrammed settings or adaptively in response to real-time kinematic data. However, this potential remains largely unexplored. The objective of this study was to investigate how these new-generation devices may be managed to enable precise control of the mechanical load applied to specific joint structures during strengthening exercises. Methods: A foundational framework of biomechanical equations was developed to establish the functional relationships between joint reaction forces and key variables, including kinematic parameters (joint angle, angular velocity, and angular acceleration) and resistance characteristics (magnitude, direction, and point of application). The analysis focused on analytically determined single-joint exercises, which are commonly employed in early-stage rehabilitation and athletic conditioning programs. Results: Application of the model to single-joint knee extension exercises demonstrated that the anterior cruciate ligament (ACL)-loading shear tibiofemoral force can be entirely eliminated throughout the full range of knee motion, without increasing either the tibiofemoral compressive force or the posterior cruciate ligament (PCL)-loading shear component, while preserving the desired peak and profile of the resistance torque. Conclusion: The proposed analytical framework enables a comprehensive understanding of how to regulate resistance parameters through advanced electromechanical technologies to minimize joint stress during single-joint strengthening exercises. Precise control of joint reaction forces during exercise is critical for the design of therapeutic and safety-enhanced training protocols. Full article

(This article belongs to the Special Issue Biomechanics of Physical Exercise)

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13 pages, 1472 KB

Open AccessEditor’s ChoiceArticle

Preliminary Effects of Hyperbaric Oxygen Therapy on Hair Follicle Characteristics in Healthy Subjects

by Hee Young Lee, Ji Yong Lee, Seung Chan Kim and Yoonsuk Lee

Bioengineering 2026, 13(2), 240; https://doi.org/10.3390/bioengineering13020240 - 19 Feb 2026

Viewed by 1098

Abstract

Background: Hyperbaric oxygen therapy (HBOT) has regenerative effects in various tissues, but its impact on hair follicles is unclear. This preliminary study evaluated HBOT-induced changes in hair and scalp characteristics in healthy adults. Methods: Nine healthy volunteers completed 50 HBOT sessions [...] Read more.

Background: Hyperbaric oxygen therapy (HBOT) has regenerative effects in various tissues, but its impact on hair follicles is unclear. This preliminary study evaluated HBOT-induced changes in hair and scalp characteristics in healthy adults. Methods: Nine healthy volunteers completed 50 HBOT sessions over three months (2.0 ATA, 100% oxygen, 90 min per session). Objective assessments included follicle density, hairs per follicle, hair volume, and shaft thickness using the Becon phototrichogram system. Subjective evaluations were conducted via a 7-point Likert questionnaire on scalp appearance, hair density, thickness, growth, and shedding. Pre- and post-treatment data were compared using paired statistical tests. Results: Positive trends were observed in follicle density (61.3→66.8 counts/cm²), hairs per follicle (1.24→1.33), and hair volume (24.9→27.7%), though not statistically significant. Hair shaft thickness decreased significantly (0.18→0.10 mm, p = 0.011), consistent with early anagen-phase regrowth. Subjective assessments showed significant improvements across all domains (p < 0.05). Scalp imaging visually supported these findings. Conclusions: HBOT may enhance hair follicle activation and scalp health in healthy adults. These preliminary findings justify further controlled studies to explore HBOT as a non-pharmacological approach to hair regeneration. Full article

(This article belongs to the Special Issue Advanced Physical Techniques in Tissue Engineering and Regenerative Medicine)

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20 pages, 3322 KB

Open AccessEditor’s ChoiceArticle

Parametric Finite Element Evaluation of Load Redistribution Under Progressive Lumbar Disc Degeneration

by Oleg Ardatov, Sofia Rita Fernandes, Artūras Kilikevičius and Vidmantas Alekna

Bioengineering 2026, 13(2), 234; https://doi.org/10.3390/bioengineering13020234 - 17 Feb 2026

Cited by 1 | Viewed by 838

Abstract

This study presents a finite element (FE) investigation of intervertebral disc (IVD) degeneration in the human lumbar spine (L1–L3 segment). The model, based on CT-derived geometry and isotropic hyperelastic representation of disc tissues, incorporates controlled simplifications, detailed in the limitations section. Degenerative changes [...] Read more.

This study presents a finite element (FE) investigation of intervertebral disc (IVD) degeneration in the human lumbar spine (L1–L3 segment). The model, based on CT-derived geometry and isotropic hyperelastic representation of disc tissues, incorporates controlled simplifications, detailed in the limitations section. Degenerative changes were parametrically simulated across healthy, mild, moderate, and severe stages by reducing disc height (up to 60%), nucleus pulposus volume (up to 70%), and adjusting tissue stiffness to reflect dehydration and fibrosis. Displacement-controlled compressive loading was applied to assess von Mises stress distributions, reaction forces, and load transfer mechanisms. Results indicate significant load redistribution: annulus fibrosus stresses increased by up to 175% in severe degeneration, while nucleus pulposus stresses decreased by ~70%, indicating a diminished compressive load-bearing contribution of the nucleus. Model predictions were validated against cadaveric and in vivo data, confirming trends in intradiscal pressure (IDP) reductions (40–70%) and stress elevations. The parametric framework elucidates interactions between geometric and material changes, providing clinicians with insights into degeneration progression and guiding biomedical engineers in implant design and interventions. Full article

(This article belongs to the Special Issue Spine Biomechanics)

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19 pages, 6361 KB

Open AccessEditor’s ChoiceArticle

Increased Cervical Disc Height and Decreased Neck Pain and Disability Following Improvement in Cervical Lordosis and Posture Using Chiropractic BioPhysics

by Evan A. Katz, Seana B. Katz, Sophie F. Katz, Curtis A. Fedorchuk, Cole G. Fedorchuk and Douglas F. Lightstone

Bioengineering 2026, 13(2), 229; https://doi.org/10.3390/bioengineering13020229 - 15 Feb 2026

Viewed by 2565

Abstract

Background/Objectives: Cervical degenerative disc disease (DDD) is associated with decreased disc height, spinal arthrosis, decreased spinal stability, neck pain (NP), and increased years living with disability and global disease burden. Methods: A total of 64 patients (19 males, 45 females) between 23 and [...] Read more.

Background/Objectives: Cervical degenerative disc disease (DDD) is associated with decreased disc height, spinal arthrosis, decreased spinal stability, neck pain (NP), and increased years living with disability and global disease burden. Methods: A total of 64 patients (19 males, 45 females) between 23 and 77 years (mean age of 49.05 ± 3.34 years) presented to a private practice with NP and disability. Pre-treatment radiographs revealed decreased cervical curvature (ARA C2–C7) measuring −6.18 ± 3.06° (ideal is −42.0°), anterior head translation (Tz C2–C7) measuring 22.03 ± 2.39 mm (ideal is 0 mm), anterior cervical disc height (ADH C2–C7) measuring 3.68 ± 0.20 mm, and posterior cervical disc height (PDH C2–C7) measuring 3.21 ± 0.15 mm. Pre-treatment NP numeric rating scale (NRS) scored 6.66 ± 0.27, and neck disability index (NDI) scored 40.28 ± 1.42%, indicating moderate disability due to NP. Patients were treated using Chiropractic BioPhysics^® (CBP^®) Mirror Image^® spinal rehabilitation for mean values of 37.80 ± 2.44 treatment visits over 19.48 ± 3.89 weeks at a frequency of 2.89 ± 0.45 treatment visits per week. Results: Post-treatment radiographs revealed improvements in ARA C2–C7 to −19.95 ± 3.05°, Tz C2–C7 to 12.11 ± 2.34 mm, ADH C2-C7 to 5.19 ± 0.21 mm, and PDH C2-C7 to 4.36 ± 0.16 mm. Post-treatment patient-reported outcomes showed improvements in NP NRS to 1.52 ± 0.26 and NDI to 12.66 ± 0.96, indicating minimal NP and disability. Conclusions: CBP^® helps improve sagittal cervical spinal alignment and posture, which may help improve cervical disc height and NP and disability in adult patients with cervical DDD. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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33 pages, 2135 KB

Open AccessEditor’s ChoiceReview

The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing

by Hannah Shelby, Sarah Bergren, Julian Wier, Edward M. Schwarz and Jay R. Lieberman

Bioengineering 2026, 13(2), 223; https://doi.org/10.3390/bioengineering13020223 - 14 Feb 2026

Cited by 1 | Viewed by 740

Abstract

Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may [...] Read more.

Fracture nonunion or delayed union remains a significant clinical problem that burdens both the patient and the healthcare system. Defined as failure for bone to unite 9 months post injury or 3 months with no progression toward union, the pathology of nonunion may require multiple surgical interventions with associated morbidity. Increasing evidence has highlighted that nonunion is a multifaceted problem, not only a result of mechanical failure, but also a product of persistent dysregulation of the osteoimmune microenvironment manifested as impaired osteogenesis and bone healing. While current approaches focus on enhanced fixation and various bone grafting strategies, these treatments often fail to coordinate healing with osteoimmune regulation. This review summarizes the emerging biologic and bioengineering approaches that target osteoimmunology to enhance fracture repair. Scaffold systems, including metals, bioceramics, hydrogels, and micro/nanoparticle formulations, are being increasingly engineered to provide structural support while directing macrophage polarization and stimulating osteogenic signaling. We also review cell-based therapies and gene-modified constructs that are being developed to introduce osteoimmunology cues that halt chronic inflammation and promote an osteogenic microenvironment. Full article

(This article belongs to the Special Issue Application of Bioengineering to Orthopedics)

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17 pages, 4590 KB

Open AccessEditor’s ChoiceArticle

Beyond Decellularization: Remnant Mitochondrial DNA Can Act as Hidden Damage-Associated Molecular Pattern

by Elena V. A. van Hengel, Kuan Liu, Henk P. Roest, Jorke Willemse, Kimberley Ober-Vliegen, Selina M. W. Teurlings, Jeroen de Jonge, Monique M. A. Verstegen and Luc J. W. van der Laan

Bioengineering 2026, 13(2), 193; https://doi.org/10.3390/bioengineering13020193 - 9 Feb 2026

Viewed by 825

Abstract

Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) [...] Read more.

Tissue decellularization aims to obtain bioscaffolds for regenerative applications by removing all cellular components while preserving the extracellular matrix (ECM) architecture. Although decellularization removes the majority of linear nuclear DNA (nDNA), residual amounts remain detectable. However, the fate of circular mitochondrial DNA (mtDNA) after decellularization has not yet been reported. Cell death or injury can cause the release of mtDNA, which is resistant to breakdown by exonucleases. Extracellular mtDNA acts as a damage-associated molecular pattern (DAMP) that can trigger immune responses. The aim of this study is to assess the presence of residual mtDNA in the liver, bile duct, and vascular scaffolds after decellularization and whether this causes inflammatory responses in macrophages. Decellularized tissues showed a marked reduction in total DNA content well below the threshold of 50 ng/mg tissue. However, in liver and vascular scaffolds, a relative increase in the mtDNA:nDNA ratio was detected in the remnant DNA fraction. Residual mtDNA in bioscaffolds acted as DAMPs causing macrophage activation, as shown by increased cell proliferation and cytokine production. Strategies to further reduce remnant mtDNA were tested. We found that treatment with the endonuclease enzyme HpaII was effective in degrading residual mtDNA. Importantly, mtDNA removal resulted in a significantly reduced macrophage activation. In conclusion, our study shows that mtDNA is relatively resistant to the decellularization procedure and can act as a DAMP in bioscaffolds. This underscores the importance of removing mtDNA from decellularized bioscaffolds to improve the immunocompatibility for biomedical applications. Full article

(This article belongs to the Special Issue Extracellular Matrix Biomaterial for Tissue Engineering and Regenerative Medicine, 2nd Edition)

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13 pages, 2395 KB

Open AccessEditor’s ChoiceArticle

Engineering the Future of Heart Failure Therapeutics: Integrating 3D Printing, Silicone Molding, and Translational Development for Implantable Cardiac Devices

by Carleigh Eagle, Aarti Desai, Michael Franklin, Robert Pooley, Elizabeth Johnson, Shawn Robinson, Mark Lopez and Rohan Goswami

Bioengineering 2026, 13(2), 192; https://doi.org/10.3390/bioengineering13020192 - 8 Feb 2026

Viewed by 748

Abstract

Three-dimensional (3D) anatomic modeling derived from high-resolution medical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has been increasingly adopted in preclinical testing and device development. This white paper describes a cardiac-specific workflow that integrates 3D printing and silicone molding [...] Read more.

Three-dimensional (3D) anatomic modeling derived from high-resolution medical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has been increasingly adopted in preclinical testing and device development. This white paper describes a cardiac-specific workflow that integrates 3D printing and silicone molding for support device development and procedural simulation. Patient-derived computed tomography angiography data were segmented using FDA-cleared medical modeling software to isolate the left ventricular anatomy and were further processed in computer-aided design (CAD) to ensure accurate physiological wall thickness and structural fidelity. Material jetting 3D printing was performed on a Stratasys J750 using material distributions designed to mimic the mechanical properties of myocardium, thereby approximating myocardial compliance. In parallel, stereolithography apparatus molds were designed from the left ventricle CAD model to cast transparent, pliable left ventricular models in Sorta-Clear™ 18 silicone. The 3D-printed models preserved intricate morphological detail and were suitable for mechanical manipulation and device deployment studies, whereas silicone models offered tunable mechanical properties, transparency for visualization, and durability for repeated use. Together, these complementary modalities provided rapid manufacturing capability and application-relevant physical representation. Case-specific parameters, strengths, and limitations of both models in enhancing patient care and device testing are highlighted, with relevance to heart failure applications. Current knowledge gaps, workflow and integration challenges, and future opportunities are identified, positioning this work as a reference framework for continued innovation in anatomic modeling. Within the collaborative framework of Mayo Clinic’s Anatomic Modeling Unit and Simulation Center, this integrated modeling workflow demonstrates the value of multidisciplinary collaboration between engineers and clinicians. Clinically, these patient-specific left ventricular models may enable pre-procedural device sizing and positioning and may support simulation of mechanical circulatory support (MCS) deployment while identifying possible anatomic constraints prior to intervention. This workflow has direct applicability in advanced heart failure patients undergoing MCS support, such as the Impella axillary MCS device or the durable LVAD, with potential to reduce procedural uncertainty while reducing complications and improving peri-procedural outcomes. Additionally, these models also serve as high-accuracy educational tools, enabling trainees and multidisciplinary care teams to visualize and possibly rehearse procedural steps while gaining hands-on experience in a risk-free environment. Full article

(This article belongs to the Special Issue Advancements in Biocompatible Materials for Implantable Medical Devices)

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25 pages, 515 KB

Open AccessEditor’s ChoiceArticle

Engineering Elite Swimming Start Performance: Key Kinetic and Kinematic Variables with Reference Values

by Dennis-Peter Born, Lina Nussbaumer, Markus Buck, Jesús J. Ruiz-Navarro and Michael Romann

Bioengineering 2026, 13(2), 180; https://doi.org/10.3390/bioengineering13020180 - 3 Feb 2026

Viewed by 1200

Abstract

To provide deeper insights into the complex and multidimensional nature of swimming start performance, the present study aimed to determine its key performance indicators (KPIs) and provide percentile-based reference values for elite junior and adult swimmers. Hence, routine performance analysis data of Swiss [...] Read more.

To provide deeper insights into the complex and multidimensional nature of swimming start performance, the present study aimed to determine its key performance indicators (KPIs) and provide percentile-based reference values for elite junior and adult swimmers. Hence, routine performance analysis data of Swiss junior and senior national team members were analyzed, including multiple European champions, World champions, Olympic medalists and a World record holder (n = 136, age: 18.3 ± 3.6 [13–32] years, World Aquatics swimming points: 761 ± 73 [609–1061]). All kinetic and kinematic variables measured by the instrumented starting block were analyzed, and variables with pairwise correlation > 0.80 were clustered using principal component analysis with orthogonal Varimax rotation, retaining components with Eigenvalue > 1.0 and factor loadings > 0.6. The highest loaded variables of each component were used as independent variables, alongside the variables with low co-variance, to determine KPIs with multiple linear regression analysis. As such, peak and average power (p ≤ 0.05), front horizontal and total vertical peak forces (p ≤ 0.04), timing of peak power and rear horizontal forces (p ≤ 0.02), resultant grab forces and their timing (p ≤ 0.05), center-of-gravity height at take-off (p = 0.03), take-off horizontal and vertical velocity (p = 0.02), resultant entry velocity (p = 0.01), entry time (p < 0.01), distance before the first kick (p < 0.01), maximal swimming depth (p = 0.02) and distance before breaking through the water surface (p < 0.01) showed a significant effect on the dependent variables (15 m start time). In conclusion, swimmers should maximize power and force production peaking earlier and grab forces peaking later during the block phase. They should increase take-off and entry velocities, distance before the first undulating kick, maximal swimming depth and underwater distance. Full article

(This article belongs to the Special Issue Biomechanics of Physical Exercise)

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23 pages, 16175 KB

Open AccessEditor’s ChoiceArticle

The Effects of Ovine-Derived Reinforced Tissue Matrix Surrounding Silicone-Based Implants in a Rat Prepectoral Reconstruction Model

by Sai L. Pinni, Cameron Martin, Nicholas Fadell, Xiaochao Xia, Evan Marsh, Lauren Schellhardt, Xiaowei Li, Matthew D. Wood and Justin M. Sacks

Bioengineering 2026, 13(2), 150; https://doi.org/10.3390/bioengineering13020150 - 28 Jan 2026

Viewed by 773

Abstract

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, [...] Read more.

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape and qualitatively demonstrated a shell with an inner solid gel-like structure. Fabricated implants had smooth surfaces, as well as tunable features including implant stiffness (storage modulus). From initial studies in our rat model, placement of bilateral prepectoral implants allowed assessment of both muscle- and skin-facing capsules and were well-tolerated for at least 12 weeks. Comparison of the foreign body response between RTM-covered and uncovered (control) implants in this model revealed that the capsule thickness did not differ between groups at the 12-week endpoint. However, RTM reduced contractile fibroblasts (alpha-smooth muscle actin) and macrophages (Iba1) compared to the control. Our findings suggested that RTM may improve capsule quality by attenuating cells involved in fibrosis, even when total capsule thickness remains unchanged. However, these changes to cells involved in fibrosis were only observed at this early endpoint and may not predict long-term clinical outcomes. Full article

(This article belongs to the Section Biomedical Engineering and Biomaterials)

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12 pages, 782 KB

Open AccessEditor’s ChoiceArticle

Development of an Immersive Virtual Reality-Based Nursing Program Involving Patients with Respiratory Infections

by Eun-Joo Ji, Sang Sik Lee and Eun-Kyung Lee

Bioengineering 2026, 13(1), 98; https://doi.org/10.3390/bioengineering13010098 - 15 Jan 2026

Viewed by 802

Abstract

This study aimed to develop an immersive virtual reality (VR) program and conduct preliminary evaluation of its feasibility and learner perception for enhancing nursing students’ clinical practicum education. The VR program was designed using the ADDIE model (analysis, design, development, implementation, and evaluation) [...] Read more.

This study aimed to develop an immersive virtual reality (VR) program and conduct preliminary evaluation of its feasibility and learner perception for enhancing nursing students’ clinical practicum education. The VR program was designed using the ADDIE model (analysis, design, development, implementation, and evaluation) and implemented on the UNITY 3D platform. Expert evaluation was conducted through a VR application, and its effectiveness was further assessed among 25 fourth-year nursing students in terms of immersion, presence, and satisfaction. The expert evaluation yielded a mean score of 6.54 out of 7, indicating acceptable content validity. Among learners, evaluation demonstrated immersion at 42.28 ± 2.37 out of 50 (95% CI: 41.30–43.26), presence at 81.36 ± 7.32 out of 95 (95% CI: 78.34–84.38), and satisfaction at 13.48 ± 1.26 out of 15 (95% CI: 12.96–14.00). Overall, the developed VR program demonstrated acceptable expert validity and positive learner perceptions. These preliminary findings suggest feasibility as a supplementary practicum. However, the single-group design without control comparison and reliance on self-reported measures preclude conclusions about educational effectiveness. Full article

(This article belongs to the Section Biosignal Processing)

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16 pages, 1629 KB

Open AccessEditor’s ChoiceReview

Gut Microbiota and Dopamine: Producers, Consumers, Enzymatic Mechanisms, and In Vivo Insights

by Giovanni Albani, Vasuki Ranjani Chellamuthu, Lea Morlacchi, Federica Zirone, Maryam Youssefi, Marica Giardini, Yin-Xia Chao, Eng-King Tan and Salvatore Albani

Bioengineering 2026, 13(1), 55; https://doi.org/10.3390/bioengineering13010055 - 31 Dec 2025

Cited by 1 | Viewed by 2762

Abstract

The human gut microbiota plays a key role in neurochemical communication, especially through the gut–brain axis. There is growing evidence that the gut microbiota influences dopamine metabolism through both production and consumption mechanisms. Two key bacterial enzymes are central to this process: tyrosine [...] Read more.

The human gut microbiota plays a key role in neurochemical communication, especially through the gut–brain axis. There is growing evidence that the gut microbiota influences dopamine metabolism through both production and consumption mechanisms. Two key bacterial enzymes are central to this process: tyrosine decarboxylase (TDC), which primarily catalyzes the decarboxylation of tyrosine to tyramine but can also act on L-DOPA to produce dopamine in certain bacterial strains, and aromatic L-amino acid decarboxylase (AADC), which can convert precursors such as L-DOPA, tryptophan, or 5-hydroxytryptophan into bioactive amines including dopamine, tryptamine, and serotonin. Identifying the bacterial families corresponding to TDC and AADC enzymes opens new avenues for clinical intervention, particularly in neuropsychiatric and neurodegenerative disorders, such as Parkinson’s disease. Moreover, elucidating strain-specific microbial contribution and host-microbe interactions may enable personalized therapeutic strategies, such as selective microbial enzyme inhibitors or tailored probiotics, to optimize dopamine metabolism. Emerging technologies, including biosensors and organ-on-chip platforms, offer new tools to monitor and manipulate microbial dopamine activity. This article explores the bacterial taxa capable of producing or consuming dopamine, focusing on the enzymatic mechanisms involved and the methodologies available for studying these processes in vivo. Full article

(This article belongs to the Section Biochemical Engineering)

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19 pages, 3773 KB

Open AccessEditor’s ChoiceArticle

Engineering Resilience: How Irradiation Strategies Influence 3D-Bioprinted Adipose Stem Cells

by Nicki Amiri, Rafael Schmid, Stefan Schrüfer, Zan Lamberger, Philipp Stahlhut, Gregor Lang, Yvonne Kulicke, Andreas Arkudas, Raymund E. Horch and Wibke Müller-Seubert

Bioengineering 2026, 13(1), 25; https://doi.org/10.3390/bioengineering13010025 - 26 Dec 2025

Viewed by 1779

Abstract

Background: Reconstructive defect coverage after irradiation remains a challenge in reconstructive surgery, as ionizing radiation leads to tissue ischemia and fibrosis. Therefore, the application of adipose-derived stem cells (ASCs) might be a therapeutic strategy for improving flap survival. Nevertheless, the influence of irradiation [...] Read more.

Background: Reconstructive defect coverage after irradiation remains a challenge in reconstructive surgery, as ionizing radiation leads to tissue ischemia and fibrosis. Therefore, the application of adipose-derived stem cells (ASCs) might be a therapeutic strategy for improving flap survival. Nevertheless, the influence of irradiation on ASCs remains unclear. This study examines the effect of irradiation on 3D-printed ASCs. Methods: ASCs were 3D-cultured. The constructs were irradiated with 2 Gy and 5 Gy; one group treated with 0 Gy served as the non-irradiated control group. Cell viability was measured via a WST-8 assay, a live/dead assay and fluorescence microscopy 24 h, 48 h and 72 h after irradiation. Furthermore, qPCR analysis was performed to detect the expression of HIF-1α, p53 and IL-6 at the same timepoints. Results: Cell survival was high after 24 h. Expression of HIF1α after 24 h was 1.5 times significantly higher in the 2 Gy group compared with the 0 Gy group. The expression of other genes was not significantly affected by irradiation. Measurement of the metabolic activity and survival of the ASCs did not show differences between the different groups at all timepoints. Conclusions: 3D-cultured adipose-derived stem cells maintain high viability after moderate irradiation, suggesting radioresistance. Full article

(This article belongs to the Special Issue Advanced 3D Cell Culture Technologies and Formats, 2nd Edition)

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15 pages, 3698 KB

Open AccessEditor’s ChoiceArticle

Discovering the Effects of Superior-Surface Vocal Fold Lesions via Fluid–Structure Interaction Analysis

by Manoela Neves, Anitha Niyingenera, Norah Delaney and Rana Zakerzadeh

Bioengineering 2025, 12(12), 1360; https://doi.org/10.3390/bioengineering12121360 - 13 Dec 2025

Viewed by 950

Abstract

This study examines the impact of vocal fold (VF) lesions located on the superior surface on glottal airflow dynamics and tissue oscillatory behaviors using biomechanical simulations of a two-layered realistic VF model. It is hypothesized that morphological changes in the VFs due to [...] Read more.

This study examines the impact of vocal fold (VF) lesions located on the superior surface on glottal airflow dynamics and tissue oscillatory behaviors using biomechanical simulations of a two-layered realistic VF model. It is hypothesized that morphological changes in the VFs due to the presence of a lesion cause changes in tissue elasticity and rheological properties, contributing to dysphonia. Previous research has lacked the integration of lesions in computational simulations of anatomically accurate larynx-VF models to explore their effects on phonation and contribution to voice disorders. Addressing the current gap in literature, this paper considers a computational model of a two-layered VF structure incorporating a lesion that represents a hemorrhagic polyp. A three-dimensional, subject-specific, multilayered geometry of VFs is constructed based on STL files derived from a human larynx CT scan, and a fluid–structure interaction (FSI) methodology is employed to simulate the coupling of glottal airflow and VF tissue dynamics. To evaluate the effects of the lesion’s presence, two FSI models, one with a lesion embedded in the cover layer and one without, are simulated and compared. Analysis of airflow dynamics and tissue vibrational patterns between these two models is used to determine the impact of the lesion on the biomechanical characteristics of phonation. The polyp is found to slightly increase airflow resistance through the glottis and disrupt vibratory symmetry by decreasing the vibration frequency of the affected fold, leading to weaker and less rhythmic oscillations. The results also indicate that the lesion increases tissue stress in the affected fold, which agrees with clinical observations. While quantitative ranges depend on lesion size and tissue properties, these consistent and physically meaningful trends highlight the biomechanical mechanisms by which lesions influence phonation. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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21 pages, 10700 KB

Open AccessEditor’s ChoiceArticle

A 3D ColMA-Based Tenogenic Microenvironment Unveils the Behavior of Tendon Stem/Progenitor Cells (TSPCs) from Tendinopathic Surgical Explants

by Giacomo Cortella, Erwin Pavel Lamparelli, Joseph Lovecchio, Emanuele Giordano, Nicola Maffulli and Giovanna Della Porta

Bioengineering 2025, 12(12), 1337; https://doi.org/10.3390/bioengineering12121337 - 8 Dec 2025

Cited by 2 | Viewed by 2222

Abstract

Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it [...] Read more.

Tendon injuries present significant clinical challenges due to limited intrinsic healing and complex pathological mechanisms. Here, we developed a novel 3D bioprinted methacrylated type I collagen (ColMA) scaffold integrated with Growth Differentiation Factor-5 (GDF-5)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and dynamically cultured it under perfusion to establish a tenogenic microenvironment in vitro. Pathological human Tendon Stem/Progenitor Cells (hTSPCs) derived from tendinopathic surgical explants were encapsulated to investigate their impaired extracellular matrix (ECM) deposition and associated pro-inflammatory signaling. GDF-5-loaded nanoparticles (average diameter 140 ± 40 nm) were fabricated via microfluidic-assisted nanoprecipitation and homogeneously incorporated within the ColMA synthetic ECM to enable sustained growth factor release. Continuous perfusion culture (1 mL/min) ensured efficient mass transfer and supported cell viability above 70% over 21 days. Pathological hTSPCs exhibited impaired ECM remodeling, characterized by the absence of type I collagen and a 2.56-fold increase in type III collagen at day 7, indicative of a fibrotic-like phenotype. Western blot densitometry demonstrated a 5.31-fold elevation in secreted tenomodulin at day 14, while ECM analysis verified a type III to type I collagen ratio of 4.5. In addition, a markedly pro-inflammatory cytokine profile was observed, with elevated secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) from day 7 onward, consistent with the chronic inflammatory status of cells derived from pathological tendon tissues. This modular 3D platform represents a robust in vitro model for mechanistic studies and the advancement of personalized regenerative strategies targeting chronic tendon disorders. Full article

(This article belongs to the Special Issue Biofabrication Technologies: Novel Tools for More Effective Personalized Medicine and Regenerative Therapies)

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22 pages, 6021 KB

Open AccessEditor’s ChoiceArticle

Deep Temporal Clustering of Pathological Gait Recovery Patterns in Post-Stroke Patients Using Joint-Angle Trajectories: A Longitudinal Study

by Jinwoo Kim, Teh-Hao Teng, Yun-Hee Kim, Seung-Jong Kim and Mun-Taek Choi

Bioengineering 2025, 12(12), 1314; https://doi.org/10.3390/bioengineering12121314 - 30 Nov 2025

Viewed by 1116

Abstract

This study aims to analyze long-term gait recovery patterns in sub-acute post-stroke hemiplegic patients by applying end-to-end deep learning (DL)-based clustering to sagittal joint-angle trajectories throughout the gait cycle. To address the data scarcity issue in long-term follow-up patient gait trajectory datasets, two [...] Read more.

This study aims to analyze long-term gait recovery patterns in sub-acute post-stroke hemiplegic patients by applying end-to-end deep learning (DL)-based clustering to sagittal joint-angle trajectories throughout the gait cycle. To address the data scarcity issue in long-term follow-up patient gait trajectory datasets, two time-series data augmentation methods, TimeVAE and Diffusion-TS, were employed to generate high-fidelity synthetic joint-angle trajectories. The augmented dataset were subsequently analyzed using a Deep Temporal Clustering (DTC) model, which effectively captured individualized longitudinal recovery patterns by jointly learning temporal representations and cluster assignments. Based on the clustering evaluation criteria, the model identified six clusters as the optimal grouping. These clusters were statistically well represented by distinct kinematic characteristics. This study represents the first attempt to analyze longitudinal gait recovery patterns in post-stroke patients using a deep clustering model. While exploratory in nature, it provides a conceptual basis for future longitudinal research in stroke rehabilitation. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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16 pages, 3513 KB

Open AccessEditor’s ChoiceReview

Tinkering with Blood: Optimizing the Coagulation System for Therapeutic Purposes

by Eduardo Anitua and Sabino Padilla

Bioengineering 2025, 12(12), 1301; https://doi.org/10.3390/bioengineering12121301 - 26 Nov 2025

Viewed by 1035

Abstract

Blood is a multitask, fluid tissue that is considered as an endless goldmine for regenerative therapies. This connective tissue carries myriad multidomain proteins as the workhorse of biological functions integrated in complex molecular networks. Among them, the coagulation system stands out, with platelets [...] Read more.

Blood is a multitask, fluid tissue that is considered as an endless goldmine for regenerative therapies. This connective tissue carries myriad multidomain proteins as the workhorse of biological functions integrated in complex molecular networks. Among them, the coagulation system stands out, with platelets and plasma coagulation proteins playing multiple roles in clotting, defense and tissue repair, the latter of which is the final byproduct process stemming from the hemostatic–inflammatory, cell-reprogramming and inflammation resolution after a tissue injury. By mimicking coagulation and hemostasis but lacking inflammatory properties, platelet-rich plasma (PRP) is emerging as an innovative autologous therapy operating as a local delivery system of growth factors. Processing of the patient blood to manufacture PRP encompasses blood anticoagulation; blood deconstruction through centrifugation and fractionation; and activation of plasma, endowing the applied product with anti-inflammatory, trophic, antifibrotic and antialgic properties in a context-dependent manner. However, the field of PRPs faces controversies due to the heterogeneity of their biological compositions and modalities of application. Moreover, there are some drawbacks derived from patient age and some other conditions, all impinging negatively on PRP clinical outcomes. Standardization of the manufacturing process, elaboration of guidelines of application and use of allogenic PRPs are emerging as possible solutions to surmount these pitfalls. Full article

(This article belongs to the Special Issue Advances in Biomolecular Engineering for Regenerative Therapeutics)

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20 pages, 2950 KB

Open AccessEditor’s ChoiceArticle

The Role of MER Processing Pipelines for STN Functional Identification During DBS Surgery: A Feature-Based Machine Learning Approach

by Vincenzo Levi, Stefania Coelli, Chiara Gorlini, Federica Forzanini, Sara Rinaldo, Nico Golfrè Andreasi, Luigi Romito, Roberto Eleopra and Anna Maria Bianchi

Bioengineering 2025, 12(12), 1300; https://doi.org/10.3390/bioengineering12121300 - 26 Nov 2025

Cited by 1 | Viewed by 867

Abstract

Microelectrode recording (MER) is commonly used to validate preoperative targeting during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s Disease (PD). Although machine learning (ML) has been used to improve STN localization using MER data, the impact of preprocessing steps on [...] Read more.

Microelectrode recording (MER) is commonly used to validate preoperative targeting during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s Disease (PD). Although machine learning (ML) has been used to improve STN localization using MER data, the impact of preprocessing steps on the accuracy of classifiers has received little attention. We evaluated 24 distinct preprocessing pipelines combining four artifact removal strategies, three outlier handling methods, and optional feature normalization. The effect of each data processing procedure’s component of interest was evaluated in function of the performance obtained using three ML models. Artifact rejection methods (i.e., unsupervised variance-based algorithm (COV) and background noise estimation (BCK)), combined with optimized outlier management (i.e., statistical outlier identification per hemisphere (ORH)) consistently improved classification performance. In contrast, applying hemisphere-specific feature normalization prior to classification led to performance degradation across all metrics. SHAP (SHapley Additive exPlanations) analysis, performed to determine feature importance across pipelines, revealed stable agreement with regard to influential features across diverse preprocessing configurations. In conclusion, optimal artifact rejection and outlier treatment are essential in preprocessing MER for STN identification in DBS, whereas preliminary feature normalization strategies may impair model performance. Overall, the best classification performance was obtained by applying the Random Forest model to the dataset treated using COV artifact rejection and ORH outlier management (accuracy = 0.945). SHAP-based interpretability offers valuable guidance for refining ML pipelines. These insights can inform robust protocol development for MER-guided DBS targeting. Full article

(This article belongs to the Special Issue AI and Data Analysis in Neurological Disease Management)

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10 pages, 1210 KB

Open AccessEditor’s ChoiceReview

Agentic AI and Large Language Models in Radiology: Opportunities and Hallucination Challenges

by Sara Salehi, Yashbir Singh, Kelly K. Horst, Quincy A. Hathaway and Bradley J. Erickson

Bioengineering 2025, 12(12), 1303; https://doi.org/10.3390/bioengineering12121303 - 26 Nov 2025

Cited by 4 | Viewed by 3896

Abstract

The field of radiology is experiencing rapid adoption of large language models (LLMs), yet their tendency to generate hallucinations (plausible but incorrect information) remains a significant barrier to trust. This comprehensive review evaluates emerging agentic artificial intelligence (AI) approaches, including multi-agent role-based systems, [...] Read more.

The field of radiology is experiencing rapid adoption of large language models (LLMs), yet their tendency to generate hallucinations (plausible but incorrect information) remains a significant barrier to trust. This comprehensive review evaluates emerging agentic artificial intelligence (AI) approaches, including multi-agent role-based systems, retrieval-augmented generation (RAG), and uncertainty quantification, to assess their potential for reducing hallucinations in radiology workflows. Evidence from 2024 to 2025 demonstrates that agentic AI can improve diagnostic accuracy and reduce error rates, though these methods remain computationally demanding and lack comprehensive clinical validation. Multi-agent frameworks enable cross-validation through role-based specialization and systematic workflow orchestration, while RAG strategies enhance accuracy by grounding responses in verified medical literature. Within multi-agent systems, uncertainty quantification enables agents to communicate confidence levels to one another, allowing them to appropriately weigh each other’s contributions during collaborative analysis. While multi-agent frameworks and RAG strategies show significant promise, practical deployment will require careful integration with human oversight, robust evaluation metrics tailored to medical imaging tasks, and regulatory adaptation to ensure safe clinical use in diverse patient populations and imaging modalities. Full article

(This article belongs to the Special Issue Machine Learning-Driven Innovations in Biomedical Signal and Image Processing)

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19 pages, 7348 KB

Open AccessEditor’s ChoiceArticle

A Novel Approach to Pattern Dermal Papilla Spheroids in Dermal–Epidermal Composites Using Non-Adherent Microwell Arrays

by E. Cate Wisdom, Donald C. Aduba, Jr., Owen Lewis, Sandhya Xavier, Ernest O. N. Phillips, Kristin H. Gilchrist, Ira M. Herman, Vincent B. Ho, Thomas N. Darling and George J. Klarmann

Bioengineering 2025, 12(12), 1281; https://doi.org/10.3390/bioengineering12121281 - 21 Nov 2025

Viewed by 1372

Abstract

Bioengineered dermal–epidermal composites (DECs) have demonstrated promise initiating skin regeneration and hair follicle neogenesis after injury. DECs in our work comprise a collagen matrix embedded with human dermal papilla cells (HDPCs) overlaid with human keratinocytes. HDPCs, as three-dimensional spheroids, enhance hair follicle formation, [...] Read more.

Bioengineered dermal–epidermal composites (DECs) have demonstrated promise initiating skin regeneration and hair follicle neogenesis after injury. DECs in our work comprise a collagen matrix embedded with human dermal papilla cells (HDPCs) overlaid with human keratinocytes. HDPCs, as three-dimensional spheroids, enhance hair follicle formation, working in tandem with keratinocytes. Herein, 3D printed stamped PDMS microwell arrays were used as a strategy for spatially patterning dermal papilla spheroids in the dermal components of the DEC. DECs were transferred to cell culture media for 5 days followed by air–liquid interface culture for 2 days. Spheroid diameter, cell viability, and qPCR gene expression analyses were conducted. DECs were surgically grafted on immunocompromised mice, and healing was followed for 10 weeks. HDPCs cultured in the microwell arrays formed patterned viable spheroids and successfully transferred to the collagen dermal matrix. RNA analysis using qPCR showed upregulation of key HDPC markers (VCAN and BMP6) in DC microwell patterned HDPC spheroids compared to monolayers. This work represents a novel 3D printing strategy optimizing designing patterned HDPC spheroids in the extracellular matrix to regenerate functional human skin instead of scar tissue after injury. Full article

(This article belongs to the Special Issue Advances and Innovations in Wound Repair and Regeneration)

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18 pages, 616 KB

Open AccessEditor’s ChoiceArticle

Does Resistance Indicate Malposition? A Standardized Comparison of Pedicle Screw Placement

by Sascha Kurz, Benjamin Fischer, Janine Schultze, Florian Metzner, Toni Wendler, Christoph-Eckhard Heyde and Stefan Schleifenbaum

Bioengineering 2025, 12(11), 1254; https://doi.org/10.3390/bioengineering12111254 - 16 Nov 2025

Cited by 1 | Viewed by 903

Abstract

Pedicle screw malpositioning remains a frequent complication, with reported rates from 2% to 15%, often leading to revision surgeries. Analyzing mechanical resistance and torque encountered during screw insertion has been implicated as a promising approach for real-time detection. Five fresh-frozen human thoracolumbar spine [...] Read more.

Pedicle screw malpositioning remains a frequent complication, with reported rates from 2% to 15%, often leading to revision surgeries. Analyzing mechanical resistance and torque encountered during screw insertion has been implicated as a promising approach for real-time detection. Five fresh-frozen human thoracolumbar spine specimens were utilized in this study. Using 3D-printed templates, correct trajectories were systematically compared against four defined malpositions (medial, lateral, superior, superolateral), with offsets ranging from 2.0 mm to 3.5 mm. Drilling, tapping, and insertion phases were conducted at a constant speed and defined feed force. Contrary to the anticipated behavior, malpositioned trajectories showed no statistically significant difference in peak torque compared to correct trajectories across all phases (e.g., tapping

p = 0.944

,

r = 0.01

; insertion

p = 0.693

,

r = 0.05

). Regional stratification between thoracic and lumbar spine also failed to yield significant differences. The only statistically significant difference was observed between the correct trajectory and the superolateral malposition during drilling (

p = 0.038

). Under the tested standardized conditions, torque-based mechanical resistance during pedicle screw placement is generally not a reliable and consistent real-time indicator of malposition. Full article

(This article belongs to the Special Issue Spine Biomechanics)

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32 pages, 31629 KB

Open AccessEditor’s ChoiceArticle

Aspects Concerning Parallel Robots Used in Rehabilitation

by Adrian Todor, Daniel Vasile Banyai, Cornel Brisan and Adriana Daniela Banyai

Bioengineering 2025, 12(11), 1224; https://doi.org/10.3390/bioengineering12111224 - 9 Nov 2025

Cited by 1 | Viewed by 869

Abstract

This study presents a comprehensive simulation-based comparative analysis of four parallel robotic mechanisms, each developed to assist patient recovery through adaptive movement control and feedback, particularly for upper and lower limb therapy. Kinematic and dynamic models were developed and implemented in Matlab-Simulink, integrating [...] Read more.

This study presents a comprehensive simulation-based comparative analysis of four parallel robotic mechanisms, each developed to assist patient recovery through adaptive movement control and feedback, particularly for upper and lower limb therapy. Kinematic and dynamic models were developed and implemented in Matlab-Simulink, integrating force control via conventional regulators and real-time interaction with simulated patient-applied forces. The structural differences between spherical, rotational, and universal joints in each kinematic chain variant were evaluated. To systematically determine the most suitable design, a detailed Analytic Hierarchy Process was applied considering performance, precision, stability, and actuator effort. The study emphasizes the advantages of parallel robots in rehabilitation due to their precision, rigidity, and compact design, highlighting the potential of parallel robotic systems in customized and adaptive physical therapy interventions. These insights contribute to the optimal design selection of clinical motor therapy robots. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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27 pages, 3246 KB

Open AccessEditor’s ChoiceReview

Biochar for Soil Amendment: Applications, Benefits, and Environmental Impacts

by Ujjwal Pokharel, Gururaj Neelgund, Ram L. Ray, Venkatesh Balan and Sandeep Kumar

Bioengineering 2025, 12(11), 1137; https://doi.org/10.3390/bioengineering12111137 - 22 Oct 2025

Cited by 8 | Viewed by 8003

Abstract

The excessive use of chemical fertilizers results in environmental issues, including loss of soil fertility, eutrophication, increased soil acidity, alterations in soil characteristics, and disrupted plant–microbe symbiosis. Here, we synthesize recent studies available from up to 2025, focusing on engineered biochar and its [...] Read more.

The excessive use of chemical fertilizers results in environmental issues, including loss of soil fertility, eutrophication, increased soil acidity, alterations in soil characteristics, and disrupted plant–microbe symbiosis. Here, we synthesize recent studies available from up to 2025, focusing on engineered biochar and its application in addressing issues of soil nutrient imbalance, soil pollution from inorganic and organic pollutants, soil acidification, salinity, and greenhouse gas emissions from fields. Application of engineered biochar enhanced the removal of Cr (VI), Cd²⁺, Ni²⁺, Zn²⁺, Hg²⁺, and Eu³⁺ by 85%, 73%, 57.2%, 12.7%, 99.3%, and 99.2%, respectively, while Cu²⁺ and V⁵⁺ removal increased by 4 and 39.9 times. Adsorption capacities for Sb⁵⁺, Tl⁺, and F⁻ were 237.53, 1123, and 83.05 mg g⁻¹, respectively, and the optimal proportion of polycyclic aromatic hydrocarbon (PAH) removal was 57%. Herbicides such as imazapyr were reduced by 23% and 78%. Low-temperature pyrolyzed biochar showed high cation exchange capacity (CEC) resulting from improved surface functional groups. Although biochar application led to a yield increase of 43.3%, the biochar–compost mix enhanced it by 155%. The analysis demonstrates the need for future studies on the cost-effectiveness of biochar post-processing, large-scale biochar aging studies, re-application impact, and studies on biochar–compost or biochar–fertilizer mix productivity. Full article

(This article belongs to the Section Biochemical Engineering)

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17 pages, 1190 KB

Open AccessEditor’s ChoiceArticle

The Effects of Neuromuscular Training on Electromyography, Lower Extremity Kinematics, and Ground Reaction Force During an Unanticipated Side-Cut on Recreational Female Hockey Players

by Tom Johnston, Stephanie Valentin, Susan J. Brown and Konstantinos Kaliarntas

Bioengineering 2025, 12(10), 1101; https://doi.org/10.3390/bioengineering12101101 - 13 Oct 2025

Viewed by 2023

Abstract

During an unpredictable side-cut, this study examined how a sport-specific neuromuscular training program (NMTP) influenced electromyography responses in the lower limb posterior muscles, leg movement angles, maximum vertical ground reaction force (vGRF), and the rate of force development of vGRF. Thirty-eight adult female [...] Read more.

During an unpredictable side-cut, this study examined how a sport-specific neuromuscular training program (NMTP) influenced electromyography responses in the lower limb posterior muscles, leg movement angles, maximum vertical ground reaction force (vGRF), and the rate of force development of vGRF. Thirty-eight adult female recreational hockey players were randomly allocated into an intervention group (INT) or a control group (CON). Before beginning training or matches, the INT carried out the NMTP three times per week for eight weeks, whereas the CON performed their routine warm-up. A 45° sidecut (dominant leg only) was performed at baseline and after eight-weeks and recorded with a motion capture system. The effect of group and time, and their interaction, was investigated using a mixed-design ANOVA. After landing, the participants in the INT had greater activation of their gastrocnemius lateralis, gastrocnemius medialis, and gluteus maximus muscles than those in the CON. INT participants showed significantly lower amounts of maximum knee abduction and knee excursion, while there was an increase in these variables for the CON. At week eight, the vGRF RFD decreased for the INT but increased for the CON. Although non-significant, the overall muscle activity showed an increasing trend for the INT when it came to supervised NMTP for eight weeks compared to the effect seen in the CON. This activity caused greater alterations in the motion and forces of the lower body for the INT than the CON. Full article

(This article belongs to the Special Issue Dynamic Insights: Unveiling the Biomechanics of Sport Through Motion Analysis)

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31 pages, 1305 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence in Cardiac Electrophysiology: A Clinically Oriented Review with Engineering Primers

by Giovanni Canino, Assunta Di Costanzo, Nadia Salerno, Isabella Leo, Mario Cannataro, Pietro Hiram Guzzi, Pierangelo Veltri, Sabato Sorrentino, Salvatore De Rosa and Daniele Torella

Bioengineering 2025, 12(10), 1102; https://doi.org/10.3390/bioengineering12101102 - 13 Oct 2025

Cited by 6 | Viewed by 6412

Abstract

Artificial intelligence (AI) is transforming cardiac electrophysiology across the entire care pathway, from arrhythmia detection on 12-lead electrocardiograms (ECGs) and wearables to the guidance of catheter ablation procedures, through to outcome prediction and therapeutic personalization. End-to-end deep learning (DL) models have achieved cardiologist-level [...] Read more.

Artificial intelligence (AI) is transforming cardiac electrophysiology across the entire care pathway, from arrhythmia detection on 12-lead electrocardiograms (ECGs) and wearables to the guidance of catheter ablation procedures, through to outcome prediction and therapeutic personalization. End-to-end deep learning (DL) models have achieved cardiologist-level performance in rhythm classification and prognostic estimation on standard ECGs, with a reported arrhythmia classification accuracy of ≥95% and an atrial fibrillation detection sensitivity/specificity of ≥96%. The application of AI to wearable devices enables population-scale screening and digital triage pathways. In the electrophysiology (EP) laboratory, AI standardizes the interpretation of intracardiac electrograms (EGMs) and supports target selection, and machine learning (ML)-guided strategies have improved ablation outcomes. In patients with cardiac implantable electronic devices (CIEDs), remote monitoring feeds multiparametric models capable of anticipating heart-failure decompensation and arrhythmic risk. This review outlines the principal modeling paradigms of supervised learning (regression models, support vector machines, neural networks, and random forests) and unsupervised learning (clustering, dimensionality reduction, association rule learning) and examines emerging technologies in electrophysiology (digital twins, physics-informed neural networks, DL for imaging, graph neural networks, and on-device AI). However, major challenges remain for clinical translation, including an external validation rate below 30% and workflow integration below 20%, which represent core obstacles to real-world adoption. A joint clinical engineering roadmap is essential to translate prototypes into reliable, bedside tools. Full article

(This article belongs to the Special Issue Mathematical Models for Medical Diagnosis and Testing)

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12 pages, 1349 KB

Open AccessEditor’s ChoiceArticle

Effect of the Ankle–Foot Orthosis Dorsiflexion Angle on Gait Kinematics in Individuals with Hemiparetic Stroke

by Hiroshi Hosokawa, Fumiaki Tamiya, Ren Fujii, Ryu Ishimoto, Masahiko Mukaino and Yohei Otaka

Bioengineering 2025, 12(10), 1091; https://doi.org/10.3390/bioengineering12101091 - 10 Oct 2025

Viewed by 2810

Abstract

Ankle-foot orthoses (AFOs) are widely used to improve gait; nonetheless, it remains unclear how specific settings, particularly the dorsiflexion angle, affect gait kinematics in individuals with stroke. This study investigated the effect of different AFO dorsiflexion angles on gait kinematics in ambulatory adults [...] Read more.

Ankle-foot orthoses (AFOs) are widely used to improve gait; nonetheless, it remains unclear how specific settings, particularly the dorsiflexion angle, affect gait kinematics in individuals with stroke. This study investigated the effect of different AFO dorsiflexion angles on gait kinematics in ambulatory adults with hemiparesis. Twenty-six individuals with post-stroke hemiparesis walked on a treadmill while wearing the same type of AFO at four ankle dorsiflexion angles: 0°, 5°, 10°, and 15°. Temporal-spatial variables, joint angles, and toe clearance and its components were quantified using three-dimensional analysis. The double-stance time before the paretic swing shortened significantly with increasing dorsiflexion angle, whereas the mean stride time and length did not significantly change. During the swing phase, increased AFO dorsiflexion was associated with reduced maximal knee flexion, in addition to its direct effect on ankle angles. The absolute toe clearance height was unaffected by the AFO settings; however, the contribution of ankle dorsiflexion to limb shortening increased stepwise from 0° to 15°, and the hip elevation and compensatory movement ratio declined. In conclusion, increasing the AFO dorsiflexion angle significantly altered gait kinematics, with distal ankle mechanics replacing inefficient hip compensation and reducing double-stance time. Full article

(This article belongs to the Section Biomechanics and Sports Medicine)

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17 pages, 1144 KB

Open AccessEditor’s ChoiceArticle

Modelling of Escherichia coli Batch and Fed-Batch Processes in Semi-Defined Yeast Extract Media

by Fabian Schröder-Kleeberg, Markus Zoellkau, Markus Glaser, Christian Bosch, Markus Brunner, Mariano Nicolas Cruz Bournazou and Peter Neubauer

Bioengineering 2025, 12(10), 1081; https://doi.org/10.3390/bioengineering12101081 - 4 Oct 2025

Viewed by 2305

Abstract

Model-based approaches provide increasingly advanced opportunities for optimizing and accelerating bioprocess development. However, to accurately capture the complexity of biotechnological processes, continuous refinement of suitable models remains essential. A crucial gap in this field has been the lack of suitable model for describing [...] Read more.

Model-based approaches provide increasingly advanced opportunities for optimizing and accelerating bioprocess development. However, to accurately capture the complexity of biotechnological processes, continuous refinement of suitable models remains essential. A crucial gap in this field has been the lack of suitable model for describing Escherichia coli growth in cultivation media containing yeast extract, while accounting for key bioprocess parameters such as biomass, substrate, acetate, and oxygen. To address this, a published mechanistic macro-kinetic model for E. coli was extended with a set of mathematical equations that describe key aspects of the uptake of yeast extract. The underlying macro-kinetic approach is based on the utilization of amino acids in E. coli, where growth is primarily influenced by two distinct classes of amino acids. Using fed-batch cultivation data from an E. coli K-12 strain supplemented with yeast extract, it was demonstrated that the proposed model extensions were essential for accurately representing the bioprocess. This approach was further validated through fitting the model on cultivation data from five different yeast extracts sourced from various manufacturers. Additionally, the model enabled reliable predictions of growth dynamics across a range of yeast extract concentrations up to 20 g L⁻¹. Further differentiation of the data into batch and fed-batch revealed that for less complex datasets, such as those obtained from a batch phase, a simplified model can be sufficient. Due to its modular structure, the developed model provides the necessary flexibility to serve as a tool for the development, optimization, and control of E. coli cultivations with and without yeast extract. Full article

(This article belongs to the Section Biochemical Engineering)

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20 pages, 1488 KB

Open AccessEditor’s ChoiceArticle

Attention-Fusion-Based Two-Stream Vision Transformer for Heart Sound Classification

by Kalpeshkumar Ranipa, Wei-Ping Zhu and M. N. S. Swamy

Bioengineering 2025, 12(10), 1033; https://doi.org/10.3390/bioengineering12101033 - 26 Sep 2025

Cited by 3 | Viewed by 1292

Abstract

Vision Transformers (ViTs), inspired by their success in natural language processing, have recently gained attention for heart sound classification (HSC). However, most of the existing studies on HSC rely on single-stream architectures, overlooking the advantages of multi-resolution features. While multi-stream architectures employing early [...] Read more.

Vision Transformers (ViTs), inspired by their success in natural language processing, have recently gained attention for heart sound classification (HSC). However, most of the existing studies on HSC rely on single-stream architectures, overlooking the advantages of multi-resolution features. While multi-stream architectures employing early or late fusion strategies have been proposed, they often fall short of effectively capturing cross-modal feature interactions. Additionally, conventional fusion methods, such as concatenation, averaging, or max pooling, frequently result in information loss. To address these limitations, this paper presents a novel attention fusion-based two-stream Vision Transformer (AFTViT) architecture for HSC that leverages two-dimensional mel-cepstral domain features. The proposed method employs a ViT-based encoder to capture long-range dependencies and diverse contextual information at multiple scales. A novel attention block is then used to integrate cross-context features at the feature level, enhancing the overall feature representation. Experiments conducted on the PhysioNet2016 and PhysioNet2022 datasets demonstrate that the AFTViT outperforms state-of-the-art CNN-based methods in terms of accuracy. These results highlight the potential of the AFTViT framework for early diagnosis of cardiovascular diseases, offering a valuable tool for cardiologists and researchers in developing advanced HSC techniques. Full article

(This article belongs to the Section Biosignal Processing)

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21 pages, 1795 KB

Open AccessEditor’s ChoiceReview

Nanoparticle-Based Delivery Systems for Synergistic Therapy in Lung Cancers

by Zicheng Deng, Ali Al Siraj, Isabella Lowry, Ellen Ruan, Rohan Patel, Wen Gao, Tanya V. Kalin and Vladimir V. Kalinichenko

Bioengineering 2025, 12(9), 968; https://doi.org/10.3390/bioengineering12090968 - 9 Sep 2025

Cited by 7 | Viewed by 3298

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, with conventional treatments often limited by systemic toxicity, different tumor sensitivity to the drugs, and the emergence of multidrug resistance. To address these challenges, nanoparticle-based delivery systems have emerged as an innovative strategy, [...] Read more.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with conventional treatments often limited by systemic toxicity, different tumor sensitivity to the drugs, and the emergence of multidrug resistance. To address these challenges, nanoparticle-based delivery systems have emerged as an innovative strategy, enabling the simultaneous transport of multiple agents, including chemotherapeutic drugs and expression vectors, to enhance treatment efficacy and overcome tumor resistance. This review explores various nanocarrier platforms, such as liposomes, solid lipid nanoparticles, polymeric micelles, and inorganic nanoparticles, specifically designed for lung cancer therapy. Synergistic effects and physicochemical properties of therapeutic agents must be carefully considered in the design of nanoparticle-based co-delivery systems for lung cancer therapy. We highlight the applications of these nanoparticle systems in drug–drug, gene–gene, and drug–gene co-delivery approaches. By addressing the limitations of traditional therapies, nanoparticle-based systems offer a promising avenue to improve outcomes in patients with lung cancers. Full article

(This article belongs to the Section Nanobiotechnology and Biofabrication)

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52 pages, 44108 KB

Open AccessEditor’s ChoiceArticle

Experimental Validation of Time-Explicit Ultrasound Propagation Models with Sound Diffusivity or Viscous Attenuation in Biological Tissues Using COMSOL Multiphysics

by Nuno A. T. C. Fernandes, Shivam Sharma, Ana Arieira, Betina Hinckel, Filipe Silva, Ana Leal and Óscar Carvalho

Bioengineering 2025, 12(9), 946; https://doi.org/10.3390/bioengineering12090946 - 31 Aug 2025

Cited by 8 | Viewed by 4542

Abstract

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear [...] Read more.

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear acoustic wave simulations, in which the equations are directly solved in the time domain using an explicit solver. This approach captures the full transient waveform without relying on frequency-domain simplifications, offering a more realistic representation of ultrasound propagation in heterogeneous media. The study estimates both sound diffusivity and viscous damping parameters (dynamic and bulk viscosity) for a broad range of ex vivo tissues (skin, adipose tissue, skeletal muscle, trabecular/cortical bone, liver, myocardium, kidney, tendon, ligament, cartilage, and gray/white brain matter). Four regression models (power law, linear, exponential, logarithmic) were applied to characterize their frequency dependence between 0.5 and 5 MHz. Results show that attenuation is more strongly driven by bulk viscosity than dynamic viscosity, particularly in fluid-rich tissues such as liver and myocardium, where compressional damping dominates. The power-law model consistently provided the best fit for all attenuation metrics, revealing a scale-invariant frequency relationship. Tissues such as cartilage and brain showed weaker viscous responses, suggesting the need for alternative modeling approaches. These findings not only advance fundamental understanding of attenuation mechanisms but also provide validated parameters and modeling strategies to improve predictive accuracy in therapeutic ultrasound planning and the design of non-invasive, tissue-specific acoustic devices. Full article

(This article belongs to the Special Issue Recent Advances in the Application of Mathematical and Computational Models in Biomedical Science and Engineering (2nd Edition))

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36 pages, 4960 KB

Open AccessEditor’s ChoiceSystematic Review

The Effects of Rehabilitation Programs Incorporating Breathing Interventions on Chronic Neck Pain Among Patients with Forward Head Posture: A Systematic Review and Meta-Analysis

by Seri Park, Kihyun Kim and Minbong Kang

Bioengineering 2025, 12(9), 947; https://doi.org/10.3390/bioengineering12090947 - 31 Aug 2025

Cited by 1 | Viewed by 7066

Abstract

The effectiveness of breathing interventions on postural alignment, pain reduction, and functional improvement in patients with forward head posture (FHP) and chronic neck pain remains uncertain. Previously conducted randomized controlled trials (RCTs) that involved breathing interventions were identified through searches of the PubMed, [...] Read more.

The effectiveness of breathing interventions on postural alignment, pain reduction, and functional improvement in patients with forward head posture (FHP) and chronic neck pain remains uncertain. Previously conducted randomized controlled trials (RCTs) that involved breathing interventions were identified through searches of the PubMed, Cochrane Library, Web of Science, and Scopus databases. Studies were included if they applied diaphragmatic breathing, breathing muscle training, or feedback breathing exercises for at least 2 weeks to chronic neck pain (duration ≥ 3 months) and/or forward head posture. The craniovertebral angle (CVA), the visual analog scale (VAS), and the neck disability index (NDI) were the primary outcome measures. The results showed that breathing interventions had a moderate effect size in terms of improving the CVA. Limited effects were observed for pain reduction, and improvements in neck disability approached statistical significance. However, despite these positive findings, the overall evidence was rated as ‘very low certainty’ in the GRADE assessment, primarily due to high heterogeneity among studies, limited sample sizes, and the potential for unit-of-analysis errors in diagnosis-based subgroup analyses. Consequently, their overall effectiveness in chronic neck pain was limited. Future research is needed to explore a multidisciplinary approach to neck pain using standardized protocols and larger samples. Full article

(This article belongs to the Special Issue Physical Therapy and Rehabilitation)

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14 pages, 752 KB

Open AccessEditor’s ChoiceArticle

High-Precision Multi-Axis Robotic Printing: Optimized Workflow for Complex Tissue Creation

by Erfan Shojaei Barjuei, Joonhwan Shin, Keekyoung Kim and Jihyun Lee

Bioengineering 2025, 12(9), 949; https://doi.org/10.3390/bioengineering12090949 - 31 Aug 2025

Cited by 2 | Viewed by 1968

Abstract

Three-dimensional bioprinting holds great promise for tissue engineering, but struggles with fabricating complex curved geometries such as vascular networks. Though precise, traditional Cartesian bioprinters are constrained by linear layer-by-layer deposition along fixed axes, resulting in limitations such as the stair-step effect. Multi-axis robotic [...] Read more.

Three-dimensional bioprinting holds great promise for tissue engineering, but struggles with fabricating complex curved geometries such as vascular networks. Though precise, traditional Cartesian bioprinters are constrained by linear layer-by-layer deposition along fixed axes, resulting in limitations such as the stair-step effect. Multi-axis robotic bioprinting addresses these challenges by allowing dynamic nozzle orientation and motion along curvilinear paths, enabling conformal printing on anatomically relevant surfaces. Although robotic arms offer lower mechanical precision than CNC stages, accuracy can be enhanced through methods such as vision-based toolpath correction. This study presents a modular multi-axis robotic embedded bioprinting platform that integrates a six-degrees-of-freedom robotic arm, a pneumatic extrusion system, and a viscoplastic support bath. A streamlined workflow combines CAD modeling, CAM slicing, robotic simulation, and automated execution for efficient fabrication. Two case studies validate the system’s ability to print freeform surfaces and vascular-inspired tubular constructs with high fidelity. The results highlight the platform’s versatility and potential for complex tissue fabrication and future in situ bioprinting applications. Full article

(This article belongs to the Special Issue Insights in Tissue Engineering: Novel Developments, Current Challenges, and Future Perspectives)

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16 pages, 1173 KB

Open AccessEditor’s ChoiceReview

by Ezra T. Yoseph, Rukayat Taiwo, Ali Kiapour, Gavin Touponse, Elie Massaad, Marinos Theologitis, Janet Y. Wu, Theresa Williamson and Corinna C. Zygourakis

Bioengineering 2025, 12(8), 858; https://doi.org/10.3390/bioengineering12080858 - 10 Aug 2025

Cited by 6 | Viewed by 8308

Abstract

Pregnancy induces substantial anatomical, hormonal, and biomechanical changes in the spine and pelvis to accommodate fetal growth and maintain postural adaptation. This narrative review synthesizes peer-reviewed evidence regarding pregnancy-related spinal biomechanics, with a particular focus on low back pain, spinopelvic alignment, sacroiliac joint [...] Read more.

Pregnancy induces substantial anatomical, hormonal, and biomechanical changes in the spine and pelvis to accommodate fetal growth and maintain postural adaptation. This narrative review synthesizes peer-reviewed evidence regarding pregnancy-related spinal biomechanics, with a particular focus on low back pain, spinopelvic alignment, sacroiliac joint dysfunction, and potential contributions to degenerative spinal conditions. A systematic search of PubMed, Embase, and Google Scholar was conducted using Boolean operators and relevant terms, yielding 1050 unique records, with 53 peer-reviewed articles ultimately cited. The review reveals that increased lumbar lordosis, ligamentous laxity, altered gait mechanics, and muscular deconditioning elevate mechanical load on the lumbar spine, predisposing up to 56% of pregnant individuals to low back pain. These changes are often associated with sacroiliac joint laxity, anterior pelvic tilt, and multiparity. Long-term risks may include degenerative disc disease and spondylolisthesis. Conservative interventions such as pelvic floor muscle training, prenatal exercise, and surface topography monitoring offer symptom relief and support early rehabilitation, although standardized protocols and longitudinal outcome data remain limited. Pregnancy-related spinal changes are multifactorial and clinically relevant; an interdisciplinary approach involving spinal biomechanics, physical therapy, and obstetric care is critical for optimizing maternal musculoskeletal health. Full article

(This article belongs to the Special Issue Spine Biomechanics)

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13 pages, 2210 KB

Open AccessEditor’s ChoiceArticle

The Use of Therapeutic Peptides in Combination with Full-Thickness Skin Columns to Improve Healing of Excisional Wounds

by Anders H. Carlsson, Ira M. Herman, Sean Christy, David Larson, Rodney K. Chan, Thomas N. Darling and Kristo Nuutila

Bioengineering 2025, 12(8), 856; https://doi.org/10.3390/bioengineering12080856 - 9 Aug 2025

Cited by 2 | Viewed by 2083

Abstract

Split-thickness skin grafting (STSG) is the standard of care for skin replacement therapy. While STSG is a well-established technique, it has several limitations at both the donor and recipient sites. Full-thickness skin column (FTSC) grafting is an alternative approach that involves the orthogonal [...] Read more.

Split-thickness skin grafting (STSG) is the standard of care for skin replacement therapy. While STSG is a well-established technique, it has several limitations at both the donor and recipient sites. Full-thickness skin column (FTSC) grafting is an alternative approach that involves the orthogonal harvesting of small skin columns containing the epidermis, dermis, and associated skin appendages. Peptides have been shown to promote wound repair through various reparative and regenerative mechanisms. In this study, we aimed to evaluate the extent to which FTSCs and the matrix-derived peptide TSN6, individually or in combination, influenced the rate and quality of healing, as assessed by metrics such as epithelialization, epithelial thickness, and the presence of adnexal structures. TSN6 peptide and its scrambled form was synthetized in a laboratory and mixed with a carboxymethylcellulose (CMC) hydrogel. Up to 16 standardized full-thickness excisional wounds (∅ 5 cm) were created on the dorsum of two anesthetized pigs. FTSC biopsies (∅ 1.5 mm) were harvested from donor sites located on the rump of the pig at a ratio of up to eight 1.5 mm-diameter skin columns/1 cm². Subsequently, the wounds were randomized to receive either (1) FTSC + TSN6, (2) FTSC + scrambled peptide, (3) FTSC alone, and (4) blank CMC hydrogel. Healing was monitored for 14 or 28 days. After euthanasia, the wounds were excised and processed for histology. Additionally, non-invasive imaging systems were utilized to assess wound healing. By day 14, wounds treated with FTSC or FTSC + TSN6 were significantly more re-epithelialized compared to those treated with blank CMC hydrogel. By day 28, all FTSC-transplanted wounds were fully re-epithelialized. Notably, wounds treated with FTSC + TSN6 exhibited improved healing quality, characterized by a thicker neo-epidermis and increased rete ridges at day 28 post-transplantation. All FTSC-transplanted wounds healed better than the untransplanted controls. The TSN6 peptide further improved healing quality when applied in combination with FTSCs, particularly by enhancing epidermal maturation. Full article

(This article belongs to the Special Issue Advanced Techniques and Applications in Burn Reconstruction: A Bioengineering Perspective)

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12 pages, 1338 KB

Open AccessEditor’s ChoiceReview

Most Custom Oral Appliances for Obstructive Sleep Apnea Do Not Meet the Definition of Custom

by Leonard A. Liptak, Erin Mosca, Edward Sall, Shouresh Charkhandeh, Sung Kim and John E. Remmers

Bioengineering 2025, 12(8), 798; https://doi.org/10.3390/bioengineering12080798 - 25 Jul 2025

Cited by 1 | Viewed by 4306

Abstract

Obstructive sleep apnea is a highly prevalent respiratory disease linked to increased morbidity and mortality, a reduced quality of life, and increased economic costs if not treated. Oral appliances are an emerging treatment option for obstructive sleep apnea. This review concluded that many [...] Read more.

Obstructive sleep apnea is a highly prevalent respiratory disease linked to increased morbidity and mortality, a reduced quality of life, and increased economic costs if not treated. Oral appliances are an emerging treatment option for obstructive sleep apnea. This review concluded that many oral appliances marketed as “custom” include modifications and prefabricated items, and therefore do not meet the definition of “custom” oral appliances. This misclassification could hinder the accurate characterization, evaluation, and appropriate prescription of oral appliances. To better inform the clinical utilization of custom oral appliances and to more closely align sleep medicine with the benefits of personalized medicine, we propose that the custom oral appliance classification be further refined into semi-custom and precision-custom categories. Full article

(This article belongs to the Section Biomedical Engineering and Biomaterials)

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18 pages, 2593 KB

Open AccessEditor’s ChoiceArticle

Accuracy of Drill Sleeve Housing in 3D-Printed and Milled Implant Surgical Guides: A 3D Analysis Considering Machine Type, Layer Thickness, Sleeve Position, and Steam Sterilization

by Anna Seidel, Kai Zerrahn, Manfred Wichmann and Ragai Edward Matta

Bioengineering 2025, 12(8), 799; https://doi.org/10.3390/bioengineering12080799 - 25 Jul 2025

Cited by 2 | Viewed by 1847

Abstract

Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning [...] Read more.

Successful dental implant therapy relies on accurate planning and placement, e.g., through static, computer-aided implant surgery using CAD/CAM-fabricated surgical guides. This study examined production methods’ influence on surgical guide sleeve housing geometry. A model with two edentulous spaces was digitized using intraoral scanning and CBCT, and two virtually positioned implants were planned. Ten guides per group were produced using milling (MCX5), DLP printing (ASIGA and SHERA), and SLA printing (FORM), printing with 50 µm and 100 µm layers each. Each guide (n = 70) was then digitized using an industrial scanner before and after sterilization. Superimposition of the actual guide data with the reference data allowed for evaluation of deviations at the drill sleeve housing along the x-, y-, z-, and dxyz-axes. Descriptive and statistical evaluation was performed (significance level: p ≤ 0.0125). Significant differences existed among the production methods: Milling and SLA showed higher deviations than the DLP group (p < 0.001). Milled guides post-sterilization showed the highest deviations (0.352 ± 0.08 mm), while one DLP printer at 50 μm layer thickness showed lowest deviations (0.091 ± 0.04 mm). The layer thickness was insignificant, whereas sterilization increased deviation (p < 0.001). DLP produced the most precise implant surgical guides. All 3D printers were suitable for fabricating clinically acceptable surgical guides. Full article

(This article belongs to the Special Issue Advances in Additive Manufacturing Technologies in the Clinical, Pharmaceutical and Biomedical Sectors)

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11 pages, 584 KB

Open AccessEditor’s ChoiceSystematic Review

Artificial Intelligence for Non-Invasive Prediction of Molecular Signatures in Spinal Metastases: A Systematic Review

by Vivek Sanker, Sai Sanikommu, Alexander Thaller, Zhikai Li, Philip Heesen, Srinath Hariharan, Emil O. R. Nordin, Maria Jose Cavagnaro, John Ratliff and Atman Desai

Bioengineering 2025, 12(8), 791; https://doi.org/10.3390/bioengineering12080791 - 23 Jul 2025

Cited by 2 | Viewed by 1244

Abstract

Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: [...] Read more.

Background: Spinal metastases (SMs) are associated with poor prognosis and significant morbidity. We hypothesize that artificial intelligence (AI) models can enhance the identification and clinical utility of genetic and molecular signatures associated with SMs, improving diagnostic accuracy and enabling personalized treatment strategies. Methods: A systematic review of five databases was conducted to identify studies that used AI to predict genetic alterations and SMs outcomes. Accuracy, area under the receiver operating curve (AUC), and sensitivity were used for comparison. Data analysis was performed in R. Results: Eleven studies met the inclusion criteria, covering three different primary tumor origins, comprising a total of 2211 patients with an average of 201 ± 90 patients (range: 76–359 patients) per study. EGFR, Ki-67, and HER-2 were studied in ten (90.9%), two (18.1%), and one (9.1%) study, respectively. The weighted average AUC is 0.849 (95% CI: 0.835–0.863) and 0.791 (95% CI: 0.738–0.844) for internal and external validation of the established models, respectively. Conclusions: AI, through radiomics and machine learning, shows strong potential in predicting molecular markers in SMs. Our study demonstrates that AI can predict molecular markers in SMs with high accuracy. Full article

(This article belongs to the Section Biosignal Processing)

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19 pages, 259 KB

Open AccessEditor’s ChoiceArticle

Understanding the Impact of Assistive Technology on Users’ Lives in England: A Capability Approach

by Rebecca Joskow, Dilisha Patel, Anna Landre, Kate Mattick, Catherine Holloway, Jamie Danemayer and Victoria Austin

Bioengineering 2025, 12(7), 750; https://doi.org/10.3390/bioengineering12070750 - 9 Jul 2025

Cited by 6 | Viewed by 3393

Abstract

This study presents an analysis of England’s 2023 national assessment of assistive technology (AT) access and use, with a particular focus on the qualitative impact of AT as described by users. It aims to address limitations in conventional AT impact assessments, which often [...] Read more.

This study presents an analysis of England’s 2023 national assessment of assistive technology (AT) access and use, with a particular focus on the qualitative impact of AT as described by users. It aims to address limitations in conventional AT impact assessments, which often prioritize clinical outcomes or user satisfaction, by offering a deeper account of how impact is experienced in everyday life. Drawing on data from a nationally representative survey of 7000 disabled adults and children, as well as six focus group discussions and 28 semi-structured interviews with stakeholders across the WHO 5Ps framework (People, Providers, Personnel, Policy, and Products), the study applies Amartya Sen and Martha Nussbaum’s Capability Approach to explore these experiences. Using inductive thematic analysis, we identify three main domains of user-reported impact: Functions and Activities (e.g., mobility, communication, vision, leisure, daily routines, and cognitive support), Outcomes (e.g., autonomy, quality of life, safety, social participation, wellbeing, and work and learning), and Lived Experience (e.g., access barriers, essentiality, identity and emotional connection, peace of mind, and sense of control and confidence). These findings offer a more user-centered understanding of AT impact and can inform the development of future measurement tools, research design, and government-led interventions to improve AT provision. Full article

(This article belongs to the Special Issue Measuring Outcomes and Impact Related to Assistive Technology and Accessibility for Disability)

11 pages, 2829 KB

Open AccessEditor’s ChoiceArticle

Biomimetic Full-Thickness Artificial Skin Using Stromal Vascular Fraction Cells and Autologous Keratinocytes in a Single Scaffold for Wound Healing

by Jung Huh, Seong-Ho Jeong, Eun-Sang Dhong, Seung-Kyu Han and Kyung-Chul Moon

Bioengineering 2025, 12(7), 736; https://doi.org/10.3390/bioengineering12070736 - 5 Jul 2025

Viewed by 1747

Abstract

We developed biomimetic full-thickness artificial skin using stromal vascular fraction (SVF) cells and autologous keratinocytes for the dermal and epidermal layers of skin, respectively. Full-thickness artificial skin scaffolds were fabricated using 4% porcine collagen and/or elastin in a low-temperature three-dimensional printer. Two types [...] Read more.

We developed biomimetic full-thickness artificial skin using stromal vascular fraction (SVF) cells and autologous keratinocytes for the dermal and epidermal layers of skin, respectively. Full-thickness artificial skin scaffolds were fabricated using 4% porcine collagen and/or elastin in a low-temperature three-dimensional printer. Two types of scaffolds with collagen-to-elastin ratios of 100:0 and 100:4 were printed and compared. The scaffolds were analyzed for collagenase degradation, tensile strength, and structural features using scanning electron microscopy. By 24 h, the collagen-only scaffolds showed gradual degradation, and the collagen-elastin scaffolds retained the highest structural integrity but were not degraded. In the tensile strength tests, the collagen-only scaffolds exhibited a tensile strength of 2.2 N, while the collagen-elastin scaffolds showed a tensile strength of 4.2 N. Cell viability tests for keratinocytes displayed an initial viability of 89.32 ± 3.01% on day 1, which gradually increased to 97.22 ± 4.99% by day 7. Similarly, SVF cells exhibited a viability of 93.68 ± 1.82% on day 1, which slightly improved to 97.12 ± 1.64% on day 7. This study presents a novel strategy for full-thickness artificial skin development, combining SVF and keratinocytes with an optimized single collagen scaffold and a gradient pore-density structure. Full article

(This article belongs to the Special Issue Advances and Innovations in Wound Repair and Regeneration)

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