Journal of Functional Biomaterials

12 pages, 1487 KiB

Open AccessArticle

Enhancing the Physical Properties of Calcium Silicate Cement Modified with Elastin-like Polypeptides and Bioactive Glass

by Jiyoung Kwon and Hyun-Jung Kim

J. Funct. Biomater. 2025, 16(5), 188; https://doi.org/10.3390/jfb16050188 - 19 May 2025

Abstract

Conventional calcium silicate cement (CSC) formulations often exhibit insufficient mechanical strength and low initial stability. This study aimed to develop an organic–inorganic hybrid biomaterial by incorporating an elastin-like polypeptide (ELP) (V125E8) and bioactive glass (BG) (63S) into CSC to improve its mechanical properties [...] Read more.

Conventional calcium silicate cement (CSC) formulations often exhibit insufficient mechanical strength and low initial stability. This study aimed to develop an organic–inorganic hybrid biomaterial by incorporating an elastin-like polypeptide (ELP) (V125E8) and bioactive glass (BG) (63S) into CSC to improve its mechanical properties and wash-out resistance during the initial setting. Experimental groups included ProRoot MTA (Dentsply Sirona, USA) as a control (0BG), inorganic hybrids containing BG (2% or 5%; 2BG, 5BG), and organic–inorganic hybrids combining BG (2% or 5%; 2BG-L, 5BG-L) with a 10 wt% ELP solution. The compressive strength, microhardness, and wash-out resistance of the specimens were evaluated. The organic–inorganic hybrid groups (2BG-L and 5BG-L) exhibited significantly higher compressive strength and microhardness than the control (0BG) and inorganic-only groups (2BG and 5BG). Additionally, the incorporation of ELP markedly improved wash-out resistance, minimizing material disintegration during the initial setting in aqueous environments. The organic–inorganic hybrid groups (2BG-L and 5BG-L) exhibited significantly higher compressive strength and microhardness than the control (0BG) and inorganic-only groups (2BG and 5BG). Additionally, the incorporation of ELP markedly improved wash-out resistance, minimizing material disintegration during the initial setting in aqueous environments. Full article

(This article belongs to the Special Issue Biomechanical Studies and Biomaterials in Dentistry)

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19 pages, 8938 KiB

Open AccessArticle

Stress–Strain State Investigation and Ultimate Load on Femoral Implants Based on S-Type Ti6Al4V Titanium Alloy

by Ivan Panfilov, Ilya Vilkovyskiy, Evgeniy Sadyrin, Sergei Aizikovich, Alexey N. Beskopylny and Besarion Meskhi

J. Funct. Biomater. 2025, 16(5), 187; https://doi.org/10.3390/jfb16050187 - 19 May 2025

Abstract

Hip replacement is a widespread surgical procedure that eliminates pain and restores motor functions of the pathologically altered hip joint. The issue lies in the lack of pre-operative strength calculations for implant shapes. So, they tend to break after surgery or damage the [...] Read more.

Hip replacement is a widespread surgical procedure that eliminates pain and restores motor functions of the pathologically altered hip joint. The issue lies in the lack of pre-operative strength calculations for implant shapes. So, they tend to break after surgery or damage the bone due to the complex stress–strain state. In the present paper, we studied the stress–strain state and ultimate load of S-type canine femoral implants based on titanium alloy Ti6Al4V using finite element analysis for static and cyclic loads. X-ray computed micro tomography data were used to construct the models. Re-engineering and restoration of the 3D geometry of the product were conducted. Strength analysis was performed in the finite element analysis software package Ansys Mechanical was used for various types of implant support. Locations with stress concentrators were identified, and ultimate loads on the implant were obtained. The influence of the rigidity of the support on the prosthesis stem was also studied. For the case of rigid support, the stress–strain state of the prosthesis was studied and the ultimate load was found to be 30.1 kg. Full article

(This article belongs to the Section Bone Biomaterials)

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17 pages, 5819 KiB

Open AccessArticle

Three-Axis Plate for Open Rigid Internal Fixation of Base Fracture of Mandibular Condyle

by Marcin Kozakiewicz

J. Funct. Biomater. 2025, 16(5), 186; https://doi.org/10.3390/jfb16050186 - 19 May 2025

Abstract

Metallic biomaterials are prevalent in medical applications. In the treatment of mandibular fractures, the use of metallic biomaterials makes it possible to recover the ability to bite and partially recover speech through preventing ankylosis of the temporomandibular joints, the formation of pseudoarthritic joints, [...] Read more.

Metallic biomaterials are prevalent in medical applications. In the treatment of mandibular fractures, the use of metallic biomaterials makes it possible to recover the ability to bite and partially recover speech through preventing ankylosis of the temporomandibular joints, the formation of pseudoarthritic joints, and the consolidation of reduced bones. This article presents the concept of a triaxial plate for osteosynthesis of basal fractures of the mandibular condyle, which are very common fractures in humans. Approximately half of patients with such fractures have wide (squat) condylar processes, which allows for the use of as many as three straight plates. However, installing three plates is quite troublesome, and the use of a single and transversely reinforced plate would facilitate treatment. This study proposes a plate with three reinforcements running along three divergent axes. The plate is fixed to the bone fragments with 11 screws. This concept for the treatment of basal fractures allows patients to quickly recover their primary system functions due to rigid fixation through the use of short (4 mm) screws, as there is no trauma to the medial pterygoid muscle and the mandible canal contents and no intermaxillary immobilization. Full article

(This article belongs to the Special Issue Advances in Oral and Maxillofacial Implants)

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25 pages, 1292 KiB

Open AccessReview

Nano/Micro-Enabled Modification and Innovation of Conventional Adjuvants for Next-Generation Vaccines

by Xingchi Liu, Xu Yang, Lu Tao, Xuanchen Li, Guoqiang Chen and Qi Liu

J. Funct. Biomater. 2025, 16(5), 185; https://doi.org/10.3390/jfb16050185 - 19 May 2025

Abstract

The global spread of infectious diseases has raised public awareness of vaccines, highlighting their essential role in protecting public health. Among the components of modern vaccines, adjuvants have received increasing attention for boosting immune responses and enhancing efficacy. Recent advancements in adjuvant research, [...] Read more.

The global spread of infectious diseases has raised public awareness of vaccines, highlighting their essential role in protecting public health. Among the components of modern vaccines, adjuvants have received increasing attention for boosting immune responses and enhancing efficacy. Recent advancements in adjuvant research, particularly nanodelivery systems, have paved the way for developing more effective and safer adjuvants. This review outlines the properties, progress, and mechanisms of FDA-approved conventional adjuvants, focusing on their contributions to and challenges in vaccine success. Despite these advancements, conventional adjuvants still face suboptimal immunomodulatory effects, potential side effects, and limitations in targeting specific immune pathways. Nanodelivery systems have emerged as a transformative approach in adjuvant design, offering unique advantages such as enhancing vaccine stability, enabling controlled antigen release, and inducing specific immune responses. By addressing these limitations, nanocarriers improve the safety and efficacy of conventional adjuvants and drive the development of next-generation adjuvants for complex diseases. This review also explores strategies for incorporating nanodelivery systems into adjuvant development, emphasizing its role in optimizing vaccine formulations. By summarizing current challenges and recent advances, this review aims to provide valuable insights guiding future efforts in designing innovative adjuvants that meet the evolving needs of global immunization programs. Full article

(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)

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29 pages, 3411 KiB

Open AccessReview

A Comprehensive Literature Review for Total Hip Arthroplasty (THA): Part 2—Material Selection Criteria and Methods

by Salvatore Garofalo, Chiara Morano, Luigi Bruno and Leonardo Pagnotta

J. Funct. Biomater. 2025, 16(5), 184; https://doi.org/10.3390/jfb16050184 - 18 May 2025

Viewed by 149

Abstract

Total Hip Arthroplasty (THA) is a widely used surgical procedure to restore mobility and reduce pain in patients with hip joint disorders. Implant success and longevity are influenced by the selection of appropriate materials. This study presents a comprehensive literature review based on [...] Read more.

Total Hip Arthroplasty (THA) is a widely used surgical procedure to restore mobility and reduce pain in patients with hip joint disorders. Implant success and longevity are influenced by the selection of appropriate materials. This study presents a comprehensive literature review based on structured searches in Scopus and Web of Science, focusing on material selection criteria and methods in THA. The inclusion criteria targeted original studies and reviews addressing material properties, selection techniques, and clinical performance. A bibliometric analysis and keyword co-occurrence network were used to highlight major research themes. The review examines traditional materials such as Metal-on-Polyethylene (MoP), as well as advanced options like ceramics, composites, and Functionally Graded Materials (FGMs). Key challenges discussed include aseptic loosening, wear resistance, and stress shielding. Selection methodologies such as Multi-Criteria Decision-Making (MCDM), Weighted Properties Methods (WPM), and computational tools like Ashby charts and CES Selector are analyzed. The findings from international arthroplasty registries show that more than half of implant failures are linked to material-related factors. This study therefore aims to guide material selection processes in THA by aligning clinical performance with biomechanical and biological requirements, supporting improved implant outcomes and long-term surgical success. Future developments should focus on patient-specific solutions and continuous innovation. Full article

(This article belongs to the Section Bone Biomaterials)

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12 pages, 984 KiB

Open AccessArticle

Surface Analysis of Lithium Disilicate Ceramics After Use of Charcoal-Containing Toothpastes

by Franciele Floriani, Bayaan Jabr, Silvia Rojas-Rueda, Rene Garcia-Contreras, Carlos A. Jurado and Abdulrahman Alshabib

J. Funct. Biomater. 2025, 16(5), 183; https://doi.org/10.3390/jfb16050183 - 15 May 2025

Viewed by 179

Abstract

Background: This study evaluated the effect of charcoal-containing toothpaste on the surface roughness of CAD/CAM lithium disilicate ceramic (e.max CAD) after simulated toothbrushing. Methods: Forty-eight e.max CAD ceramic specimens were divided into four groups (n = 12) and subjected to 18,000 brushing cycles [...] Read more.

Background: This study evaluated the effect of charcoal-containing toothpaste on the surface roughness of CAD/CAM lithium disilicate ceramic (e.max CAD) after simulated toothbrushing. Methods: Forty-eight e.max CAD ceramic specimens were divided into four groups (n = 12) and subjected to 18,000 brushing cycles using a toothbrushing simulator. The groups included Crest 3D White Charcoal, Colgate Optic White with Charcoal, Arm & Hammer Charcoal White, and a control group (conventional toothpaste). Surface roughness was measured with a profilometer before and after brushing, and scanning electron microscopy (SEM) was used for topographical analysis. Statistical analysis was performed using the Kruskal–Wallis test and post hoc comparisons. Results: Significant differences in surface roughness were found among the groups (p < 0.001). The mean roughness values were 540.70 ± 21.68 µm (Control), 294.88 ± 11.49 µm (Crest 3D White Charcoal), 1157.00 ± 52.85 µm (Colgate Optic White with Charcoal), and 593.37 ± 37.69 µm (Arm & Hammer Charcoal White). Post hoc analysis showed that Colgate Optic White with Charcoal had the highest roughness, which was significantly different from all other groups (p < 0.001). SEM analysis revealed severe surface degradation with Colgate Optic White with Charcoal, while Crest 3D White Charcoal caused minimal changes. Conclusions: Charcoal-containing toothpastes vary in abrasiveness, with Colgate Optic White with Charcoal causing the most significant surface roughness and damage to lithium disilicate ceramics. Full article

(This article belongs to the Special Issue Surface Analyses, Physicochemical and Mechanical Properties of Dental Biomaterials (2nd Edition))

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15 pages, 2411 KiB

Open AccessArticle

Versatile Polycaprolactone-Based Drug Delivery System with Enhanced Cytocompatibility and Antibacterial Activity

by Celine Guder, Anja Hofmann, Therese Schüler, Torsten Sterzenbach, Hans-Peter Wiesmann, Katrin Lorenz, Christian Hannig, Christian Reeps and Benjamin Kruppke

J. Funct. Biomater. 2025, 16(5), 182; https://doi.org/10.3390/jfb16050182 - 15 May 2025

Viewed by 160

Abstract

Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing [...] Read more.

Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing the dosage necessary. A biodegradable polyester polycaprolactone (PCL)-based DDS was thus produced, containing various clinically relevant drugs. It was shown that the incorporation of four distinct antibiotic classes (amoxicillin, doxycycline, metronidazole and rifampicin), with very high mass fractions ranging up to 20 wt%, was feasible within the PCL matrix. This DDS showed the capacity for effective and sustained release. The release kinetics over 14 days were proven, showing a significant decrease in cytotoxicity with smooth muscle cells as well as an antibacterial effect on (1) aerobic, (2) anaerobic, (3) Gram-positive and (4) Gram-negative pathogens in vitro. The DDS demonstrated a markedly diminished cytotoxic impact owing to sustained release in comparison to pure antibiotics, while simultaneously maintaining their antibacterial efficacy. In conclusion, DDSs are a more tolerable form of antibiotics administration due to the hydrophobic PCL matrix causing a slower diffusion-controlled release, proven as a release mechanism via the Peppa–Sahlin model. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Biotechnology: Applications in Dental Medicine—2nd Edition)

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13 pages, 5872 KiB

Open AccessArticle

In Vivo Cell Migration and Growth Within Electrospun Porous Nanofibrous Scaffolds with Different Pore Sizes in a Mouse Pouch Model

by David C. Markel, Therese Bou-Akl, Bin Wu, Pawla Pawlitz, Xiaowei Yu, Liang Chen, Tong Shi and Weiping Ren

J. Funct. Biomater. 2025, 16(5), 181; https://doi.org/10.3390/jfb16050181 - 14 May 2025

Viewed by 136

Abstract

Cellular infiltration into traditional electrospun nanofibers (NFs) is limited due to their dense structures. We were able to obtain polycaprolactone (PCL) NFs with variable and defined pore sizes and thicknesses by using a customized programmed NF collector that controls the moving speed during [...] Read more.

Cellular infiltration into traditional electrospun nanofibers (NFs) is limited due to their dense structures. We were able to obtain polycaprolactone (PCL) NFs with variable and defined pore sizes and thicknesses by using a customized programmed NF collector that controls the moving speed during electrospinning. NFs obtained by this method were tested in vitro and have shown better cell proliferation within the NFs with larger pore sizes. This study investigated in vivo host cell migration and neovascularization within implanted porous PCL NF discs using a mouse pouch model. Four types of PCL NFs were prepared and classified based on the electrospinning speed: NF-zero (static control), NF-low (0.085 mm/min), NF-mid (0.158 mm/min) and NF-high (0.232 mm/min) groups. With the increase in the speed, we observed an increase in the pore area; NF-zero (11.6 ± 6.2 μm²), NF-low (37.4 ± 28.6 μm²), NF-mid (67.6 ± 54.8 μm²), and NF-high (292.3 ± 286.5 μm²) groups. The NFs were implanted into air pouches of BALB/cJ mice. Mice without NFs served as control. Animals were sacrificed at 7 and 28 days after the implantation. Pouch tissues with implanted NFs were collected for histology (n = three per group and time point). The efficiency of the tissue penetration into PCL NF sheets was closely linked to the pore size and area. NFs with the highest pore area had more efficient tissue migration and new blood vessel formation compared to those with a smaller pore area. No newly formed blood vessels were observed in NF-zero sheets up to 28 days. We believe that a porous NF scaffold with a controllable pore size and thickness has great potential for tissue repair/regeneration and for other healthcare applications. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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16 pages, 1044 KiB

Open AccessArticle

Treatment of Medication-Related Osteonecrosis of the Jaw Without and With the Use of Advanced Platelet-Rich Fibrin: A Retrospective Clinical Study

by Paulina Adamska, Marcin Stasiak, Natalia Kobusińska, Michał Bartmański, Adam Zedler and Michał Studniarek

J. Funct. Biomater. 2025, 16(5), 180; https://doi.org/10.3390/jfb16050180 - 14 May 2025

Viewed by 96

Abstract

Background: Medication-related osteonecrosis of the jaw (MRONJ) is drug-induced bone destruction that is exposed for a minimum of 6 to 8 weeks in patients who have not received head and neck radiotherapy and who have not been diagnosed with facial bone metastases. MRONJ [...] Read more.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is drug-induced bone destruction that is exposed for a minimum of 6 to 8 weeks in patients who have not received head and neck radiotherapy and who have not been diagnosed with facial bone metastases. MRONJ treatment outcomes are unpredictable. Therefore, alternative treatment methods are being explored, such as blood-derived platelet-rich preparations enriched with growth factors, including advanced platelet-rich fibrin (A-PRF). The presence of growth factors may enhance healing and reduce post-procedure complications. There are no studies examining the effect of A-PRF on the healing of patients with MRONJ. The aim of this study was to retrospectively evaluate treatment outcomes of patients with MRONJ surgically treated without and with the use of A-PRF. Materials and methods: This retrospective study included 28 patients who suffered from osteomyelitis due to MRONJ and underwent surgical treatment between 2019 and 2024. The patients were divided into two groups: the first group received surgical treatment without A-PRF, and the second group received surgical treatment with the application of A-PRF. This study analyzed demographic and clinical data, as well as treatment outcomes. Results: The patients were aged from 43 to 82 years. The most common cause of MRONJ was the administration of zoledronic acid for oncological reasons (22 patients, 78.6%), given intravenously. In 20 patients (71.4%), the antiresorptive treatment lasted longer than three years. The obtained healing distribution was binomial (presence or absence of healing). Estimation of the probability of healing using the maximum likelihood method provided a result of approximately 64%. The probability of ten or more healed patients in the A-PRF group was 41%. A-PRF helps with a probability of 59%, and without A-PRF, it was lower. Concomitantly, the differences between the group with A-PRF and without A-PRF were not statistically significant. Conclusions: The patients with MRONJ should have regular check-ups with radiological examinations at least every six months to detect possible recurrence. Treatment for MRONJ is long and difficult. Treatment of non-advanced lesions, without additional risk factors (such as treatment with zoledronate intravenously for oncological purposes for 3 years), showed a better prognosis. Sometimes, in addition to surgery, it is necessary to consider alternative methods. A-PRF may enhance MRONJ healing. However, there is no evidence of a significant effect of A-PRF on the healing of MRONJ. Full article

(This article belongs to the Special Issue Functional Biomaterials for Regenerative Dentistry)

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38 pages, 7741 KiB

Open AccessReview

A Comprehensive Literature Review of Total Hip Arthroplasty (THA): Part 1—Biomaterials

by Chiara Morano, Salvatore Garofalo, Paolo Bertuccio, Agata Sposato, Irene Zappone and Leonardo Pagnotta

J. Funct. Biomater. 2025, 16(5), 179; https://doi.org/10.3390/jfb16050179 - 14 May 2025

Viewed by 174

Abstract

The rapid advancement of materials science has revolutionized total hip arthroplasty (THA), a critical orthopedic procedure aimed at restoring mobility and improving patient quality of life. This review investigates the evolution of biomaterials used in THA, analyzing their mechanical, biological, and chemical properties. [...] Read more.

The rapid advancement of materials science has revolutionized total hip arthroplasty (THA), a critical orthopedic procedure aimed at restoring mobility and improving patient quality of life. This review investigates the evolution of biomaterials used in THA, analyzing their mechanical, biological, and chemical properties. The study outlines the transition from early natural materials to modern metals, polymers, and ceramics, highlighting their benefits and limitations in clinical applications. Particular emphasis is placed on the development of advanced materials such as highly cross-linked polyethylene (HXLPE), zirconia-toughened alumina (ZTA), and tantalum alloys (Ta), which demonstrate enhanced biocompatibility, wear resistance, and longevity. By examining emerging trends, including bioactive coatings and nanotechnology, this paper aims to provide a comprehensive understanding of current challenges and future directions in material selection for hip prostheses, ultimately aiming to minimize annual revision rates and improve long-term outcomes. Full article

(This article belongs to the Section Bone Biomaterials)

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12 pages, 926 KiB

Open AccessArticle

Evaluation of Physicochemical and Mechanical Properties of a Modified Adhesive System by Resveratrol Incorporation

by Amanda Guedes Nogueira Matuda, Karen Cristina Kazue Yui, Nathália Moreira Gomes, Gabriela da Silva Chagas, Marcella Batista Rocha, Fernanda Labiapari Senefonte, Mariane Cintra Mailart and Cesar Rogério Pucci

J. Funct. Biomater. 2025, 16(5), 178; https://doi.org/10.3390/jfb16050178 - 14 May 2025

Viewed by 156

Abstract

This study aimed to evaluate the physicochemical and mechanical properties of a modified adhesive system containing resveratrol by assessing its microtensile bond strength (µTBS), degree of conversion (DC), mini-flexural strength (MFS), and antibacterial activity. The modified etch-and-rinse adhesive system was prepared by resveratrol [...] Read more.

This study aimed to evaluate the physicochemical and mechanical properties of a modified adhesive system containing resveratrol by assessing its microtensile bond strength (µTBS), degree of conversion (DC), mini-flexural strength (MFS), and antibacterial activity. The modified etch-and-rinse adhesive system was prepared by resveratrol (RES) incorporation in different concentrations: adhesive with 0.5% RES (RES0.5), adhesive with 1% RES (RES1), adhesive with 2% RES (RES2), and adhesive with no RES incorporation (RES0—control group). The µTBS test was conducted on 40 human molars with dentin exposure, which were etched, bonded with the adhesives (n = 10), and restored with resin composite. Fourier Transform Infrared Spectroscopy (FTIR) measured the DC for the MFS; ten adhesive sticks were made for each group. Antibacterial activity was assessed using colony-forming unit (CFU) counts. For µTBS, no difference between the groups was found (mean ± SD): RES0.5—42.93 ± 15.49^A; RES1—42.61 ± 13.97^A and RES2—39.43 ± 9.14^A; RES0—41.01 ± 2.64^A. The DC (% ± SD) of the experimental groups was similar: RES0.5—81.02 ± 1.95^A; RES1—76.02 ± 9.00^A; RES2—58.86 ± 15.94^A; RES0—77.75 ± 3.22^A. For MFS (mean ± SD): RES0.5—33.14 ± 13.83^A; RES1—31.1 ± 12.21^A; RES2—19.72 ± 5.43^B; RES0—29.72 ± 11.95^A. For CFU (mean ± SD): RES0.5—0.67 × 10⁷ ± 0.37^B; RES1—0.68 × 10⁷ ± 0.34^B; RES2—0.60 × 10⁷ ± 0.02^C; RES0—0.75 × 10⁷ ± 0.03^A. The incorporation of resveratrol into the adhesive system at low concentrations (0.5 and 1%) does not alter the bond strength of the adhesive interface, the degree of conversion, or the flexural strength. Additionally, both concentrations exhibited antibacterial properties by reducing the colony-forming units of S. mutans. Full article

(This article belongs to the Section Dental Biomaterials)

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18 pages, 8336 KiB

Open AccessArticle

Metformin-Enhanced Secretome from Periodontal Ligament Stem Cells Promotes Functional Recovery in an Inflamed Periodontal Model: In Vitro Study

by Han Na Suh, Ju Young Ji and Jung Sun Heo

J. Funct. Biomater. 2025, 16(5), 177; https://doi.org/10.3390/jfb16050177 - 13 May 2025

Viewed by 302

Abstract

Objective: Secretory factors, termed the secretome, in the conditioned medium (CM) from dental mesenchymal stem cells (MSCs) have shown anti-inflammatory, anti-apoptotic, and tissue regenerative potential. This cell-free product could be further developed by preconditioning cells with various biochemical agents, which lead to a [...] Read more.

Objective: Secretory factors, termed the secretome, in the conditioned medium (CM) from dental mesenchymal stem cells (MSCs) have shown anti-inflammatory, anti-apoptotic, and tissue regenerative potential. This cell-free product could be further developed by preconditioning cells with various biochemical agents, which lead to a change in secretome and CM profiles. Among the favorable candidates for CM production, metformin as an anti-diabetic medication is currently considered a potential agent for dental hard tissue and periodontal regeneration. Here, we aimed to assess the composition of CM from periodontal ligament stem cells (PDLSCs) grown in metformin-preconditioned media (Met-CM) compared to normal PDLSC-CM and assess the ability of Met-CM to recover the function of inflamed PDLSCs. Methods: Met-CM and normal CM were collected from PDLSCs grown with or without 50 µM metformin, respectively, under healthy culture conditions. Mass spectrometry and liquid chromatography–tandem mass spectrometry (LC–MS/MS) were performed to comparatively evaluate the proteomic profiles in PDLSC-CM versus Met-CM. We then treated the PDLSC cultures with lipopolysaccharide (LPS) from Porphyromonas gingivalis to induce inflammation and evaluated the osteogenic/cementogenic differentiation in the presence of Met-CM or normal PDLSC-CM by assessing alkaline phosphatase activity, intracellular calcium levels, and mRNA expression of osteogenic and cementogenic factors, including RUNX2, OCN, OSX, and CEMP-1. Subsequently, we performed RNA sequencing to identify transcriptomic changes in the treated cells. Results: We identified 202 differentially expressed proteins, 175 of which were significant, in Met-CM versus normal PDLSC-CM. Among the analyzed groups, the top three protein classes were protein-binding activity modulator, cytoskeletal protein, and extracellular matrix (ECM) protein. Treatment of PDLSCs with LPS significantly attenuated ALP activity, [Ca²⁺]_i, and the mRNA expression levels of RUNX2, OCN, OSX, and CEMP-1, whereas treatment with Met-CM alone markedly enhanced PDLSC differentiation activity compared with the control. Moreover, osteogenic/cementogenic differentiation of the LPS-treated PDLSCs was recovered through incubation in Met-CM. Transcriptomic analysis identified 511 and 3591 differentially expressed genes in the control versus Met-CM and LPS versus LPS + Met-CM groups, respectively. The enrichment of biological processes includes positive regulation of DNA-templated transcription and skeletal system morphogenesis in the control versus Met-CM comparison, as well as positive regulation of transcription from the RNA polymerase II promoter and negative regulation of the apoptotic process in the LPS versus LPS + Met-CM comparison. Molecular function analysis demonstrated the enrichment of protein-binding terms among the DEGs from each comparison. Conclusions: Metformin preconditioning enhanced the recovery effect of PDLSC-CM on LPS-induced inflamed PDLSCs. These findings suggest that metformin preconditioning could represent a practical formula for PDLSC-secretome, which may contribute to the development of future cell-free periodontal regenerative strategies. Full article

(This article belongs to the Special Issue Natural Biomaterials for Biomedical Applications)

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20 pages, 8364 KiB

Open AccessArticle

Animal Experimental Study on Delayed Implantation in a Severely Atrophic Alveolar Ridge Reconstructed Using a 3D-Printed Bioactive Glass Scaffold: A Pilot Study

by Lei Deng, Liya Ai, Runxu Li, Wusheng Xu, Lingling Zheng, Chao Wang and Haitao Huang

J. Funct. Biomater. 2025, 16(5), 176; https://doi.org/10.3390/jfb16050176 - 13 May 2025

Viewed by 223

Abstract

In this study, a scaffold was designed using 3-Matic software 12.0 (Materialise, Leuven, Belgium) and fabricated via Digital Light Processing (DLP) 3D printing technology, followed by a mechanical property evaluation. The scaffold was bilaterally implanted into mandibular bone defect models in four Beagle [...] Read more.

In this study, a scaffold was designed using 3-Matic software 12.0 (Materialise, Leuven, Belgium) and fabricated via Digital Light Processing (DLP) 3D printing technology, followed by a mechanical property evaluation. The scaffold was bilaterally implanted into mandibular bone defect models in four Beagle dogs to facilitate guided alveolar bone regeneration. After 12 weeks, samples were harvested from two dogs for radiographic and histopathological evaluations. In the remaining two dogs, two dental implants were placed into the scaffold sites. After an additional 12 weeks, samples were harvested for further radiographic and histopathological assessments. (1) Compression testing of the scaffold demonstrated a compressive strength of 24.77 ± 2.36 MPa. (2) Three of the implantation sites exhibited poor wound healing and exposure of the bone grafts early post-surgery (4 weeks), with an exposure rate of 37.5%. (3) Micro-CT imaging revealed a uniform distribution of newly formed bone within the scaffold, with an average bone height of 4.05 ± 0.55 mm and a bone volume fraction of 43.93 ± 4.68%. Histopathological analysis demonstrated the presence of vascularized tissue, non-calcified bone, and newly calcified bone within the scaffold. Additionally, newly formed calcified bone and vascularized tissue were observed at the interface between the implant and the scaffold. These findings suggest that DLP 3D-printed A-W bioactive glass scaffolds represent a promising approach for guided alveolar bone regeneration in dental implant applications. Full article

(This article belongs to the Section Dental Biomaterials)

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14 pages, 2882 KiB

Open AccessArticle

Wharton’s Jelly Bioscaffolds Improve Cardiac Repair with Bone Marrow Mononuclear Stem Cells in Rats

by Luize Kremer Gamba, Laiza Kremer Gamba, Camila da Costa, Aline Luri Takejima, Rossana Baggio Simeoni, Isabella Cristina Mendes Rossa, Anna Clara Faidiga Silva, Julia Letícia de Bortolo, Marcos Antônio Denk, Seigo Nagashima, Carlos de Almeida Barbosa, Paulo Cesar Lock Silveira, Júlio César Francisco and Luiz César Guarita-Souza

J. Funct. Biomater. 2025, 16(5), 175; https://doi.org/10.3390/jfb16050175 - 12 May 2025

Viewed by 166

Abstract

This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary [...] Read more.

This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary artery ligation was used. Treatments included an intramyocardial injection of 0.9% sodium chloride (control, n = 14), decellularized WJ (n = 12), bone marrow-derived mononuclear cells (BMMC) (n = 12), and bone marrow-derived mononuclear cells (BMMC) combined with WJ (n = 15). Echocardiography assessed the left ventricular function and ejection fraction over four weeks. Histological and immunohistochemical analyses with anti-factor VIII evaluated angiogenesis and collagen types I and III. The results showed no statistically significant effect on ventricular remodeling 30 days post-acute myocardial infarction (AMI). Moreover, the infarct area was significantly smaller in the BMMC + WJ group compared to the control group, suggesting a potential benefit in reducing myocardial scarring. BMMC + WJ therapy demonstrated potential for functional improvement and infarct size reduction 30 days post-infarction. Further studies are needed to confirm its therapeutic benefits. Full article

(This article belongs to the Collection Feature Papers in Biomaterials for Healthcare Applications)

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14 pages, 1812 KiB

Open AccessReview

AMP-IBP5: A Multifunctional Antimicrobial Peptide for Advanced Wound Healing and Inflammatory Skin Disorders

by Alafate Abudouwanli, Ge Peng, Mengyao Yang, Wanchen Zhao, Quan Sun, Shan Wang, Yi Tan, Arisa Ikeda, Hideoki Ogawa, Ko Okumura and François Niyonsaba

J. Funct. Biomater. 2025, 16(5), 174; https://doi.org/10.3390/jfb16050174 - 12 May 2025

Viewed by 247

Abstract

Wound healing is a complex, multiphase process crucial for restoring tissue integrity and functionality after injury. Among the emerging therapeutic approaches, antimicrobial peptides (AMPs) have shown substantial promise because of their dual role in microbial defense and cellular modulation. AMP-IBP5, a novel AMP [...] Read more.

Wound healing is a complex, multiphase process crucial for restoring tissue integrity and functionality after injury. Among the emerging therapeutic approaches, antimicrobial peptides (AMPs) have shown substantial promise because of their dual role in microbial defense and cellular modulation. AMP-IBP5, a novel AMP derived from insulin-like growth factor-binding protein 5, exhibits both antimicrobial and wound-healing properties, making it a promising therapeutic candidate. This peptide exhibits robust antimicrobial activity, augments keratinocyte proliferation, increases fibroblast migration, induces angiogenesis, and modulates the immune response. Mechanistically, AMP-IBP5 activates Mas-related G protein-coupled receptors and low-density lipoprotein receptor-related protein 1 (LRP1) in keratinocytes, stimulating IL-8 production and vascular endothelial growth factor expression to accelerate wound healing. This molecule also interacts with LRP1 in fibroblasts to increase cell migration and promote angiogenesis while mitigating inflammatory responses through targeted cytokine modulation. Preclinical studies have demonstrated its remarkable efficacy in promoting tissue repair in diabetic wounds and inflammatory skin conditions, including atopic dermatitis and psoriasis. This review delves into the broad therapeutic potential of AMP-IBP5 across dermatological applications, focusing on its intricate mechanisms of action, comparative advantages, and its path toward clinical and commercial application. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Their Potential Clinical Applications)

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17 pages, 547 KiB

Open AccessSystematic Review

Do Clear Aligners Release Toxic Chemicals?—A Systematic Review

by Mariana Ferreira, Hélder Costa, Nélio Veiga, Maria J. Correia, Ana T. P. C. Gomes and Pedro C. Lopes

J. Funct. Biomater. 2025, 16(5), 173; https://doi.org/10.3390/jfb16050173 - 10 May 2025

Viewed by 203

Abstract

Clear aligners are a modern orthodontic solution designed to address dental malocclusions discreetly and effectively. In terms of clinical side effects, the most reported issues among aligner users are mild irritation of the oral mucosa, localized inflammation, and hypersensitivity. The use of advanced [...] Read more.

Clear aligners are a modern orthodontic solution designed to address dental malocclusions discreetly and effectively. In terms of clinical side effects, the most reported issues among aligner users are mild irritation of the oral mucosa, localized inflammation, and hypersensitivity. The use of advanced polymer materials in clear aligners, such as polyurethane and PET-G, has gained widespread acceptance due to their mechanical properties, biocompatibility, and aesthetic appeal. However, concerns persist regarding their potential to release chemical compounds. Our goal is to understand the impact of clear aligner toxicity on the oral cavity of orthodontic patients. An extensive systematic search was conducted in the electronic databases PubMed, Scopus, and Cochrane to identify articles with relevant data. This systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines (PRISMA) to answer a question formulated according to the Population, Intervention, Comparison, and Outcomes. Four hundred and thirteen articles potentially relevant were identified and after applying PRISMA guidelines and inclusion/exclusion criteria, seven articles were included in this review. Our results suggest that clear aligners are generally safe, but concerns remain regarding the chemical leaching of thermoplastic materials, bacterial accumulation due to reduced saliva flow, and mild inflammatory responses. Our review emphasizes that although most materials are biocompatible, some exhibit moderate cytotoxicity, with the potential to impact these patients’ oral health, underscoring the need for continued research and improvements in material composition. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Biotechnology: Applications in Dental Medicine—2nd Edition)

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18 pages, 2565 KiB

Open AccessArticle

Six-Year Implants Follow-Up After Guided Bone Regeneration Using Autologous Tooth Graft: Innovative Biomaterial for Bone Regeneration Tooth Transformer^®

by Elio Minetti, Angelo Michele Inchingolo, Laura Ferrante, Grazia Marinelli, Francesco Inchingolo, Alessio Danilo Inchingolo, Andrea Palermo and Gianna Dipalma

J. Funct. Biomater. 2025, 16(5), 172; https://doi.org/10.3390/jfb16050172 - 9 May 2025

Viewed by 292

Abstract

Objectives: Recently, there has been great interest in teeth and their derivatives as suitable substrates for the treatment of alveolar bone defects. This retrospective study evaluates the clinical and radiographic outcomes of implants inserted in a site that underwent GBR procedure using a [...] Read more.

Objectives: Recently, there has been great interest in teeth and their derivatives as suitable substrates for the treatment of alveolar bone defects. This retrospective study evaluates the clinical and radiographic outcomes of implants inserted in a site that underwent GBR procedure using a tooth derivate material. Materials and methods: A total of 21 patients received a GBR using an autologous extracted tooth. Four months after the GBR techniques, the implants were inserted and were followed for an average of 5.28 + −1.10 years after loading. The X-ray was analyzed after a period of 63.36 + −13.2 months for a total follow-up period. Results: A total of 28 implants were inserted. All the implants were clinically functional after the follow-up period. The average bone loss from the X-ray images was 0.1208 + −0.1307. Conclusion: Within the limitations of this study, the use of a tooth as a graft using a tooth transformer device guarantees the production of bone and maintenance over time. Full article

(This article belongs to the Special Issue Application of Biomaterials and Techniques in Dental Surgical Treatment (2nd Edition))

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2 pages, 2188 KiB

Open AccessCorrection

Correction: Al Madhoun et al. Randomized Clinical Trial: Bone Bioactive Liquid Improves Implant Stability and Osseointegration. J. Funct. Biomater. 2024, 15, 293

by Ashraf Al Madhoun, Khaled Meshal, Neus Carrió, Eduard Ferrés-Amat, Elvira Ferrés-Amat, Miguel Barajas, Ana Leticia Jiménez-Escobar, Areej Said Al-Madhoun, Alaa Saber, Yazan Abou Alsamen, Carles Marti and Maher Atari

J. Funct. Biomater. 2025, 16(5), 171; https://doi.org/10.3390/jfb16050171 - 9 May 2025

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Abstract

Error in Figure and Figure Legend [...] Full article

(This article belongs to the Section Dental Biomaterials)

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17 pages, 23065 KiB

Open AccessArticle

The Influence of Ca on Mechanical Properties of the Mg–Ca–Zn–RE–Zr Alloy for Orthopedic Applications

by Mircea Cătălin Ivănescu, Corneliu Munteanu, Ramona Cimpoeșu, Bogdan Istrate, Fabian Cezar Lupu, Marcelin Benchea, Eusebiu Viorel Șindilar, Alexandru Vlasa, Ovidiu Stamatin and Georgeta Zegan

J. Funct. Biomater. 2025, 16(5), 170; https://doi.org/10.3390/jfb16050170 - 9 May 2025

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Abstract

Background: This study examined how the concentration of calcium (Ca) influences the microstructure, mechanical characteristics, and tribological attributes of Mg–Ca–Zn–RE–Zr alloys for orthopedic medicine. Materials and methods: Experimental alloys with 0.1 and 0.5 wt% Ca were prepared in a controlled atmosphere induction furnace. [...] Read more.

Background: This study examined how the concentration of calcium (Ca) influences the microstructure, mechanical characteristics, and tribological attributes of Mg–Ca–Zn–RE–Zr alloys for orthopedic medicine. Materials and methods: Experimental alloys with 0.1 and 0.5 wt% Ca were prepared in a controlled atmosphere induction furnace. The microstructure of the alloys was investigated by scanning electron microscopy, the chemical composition by X-ray fluorescence and energy-dispersive spectroscopy, the mechanical properties by indentation and scratching, and the corrosion resistance by linear and cyclic potentiometry. Results: The alloy with 0.1% Ca exhibited greater fluctuations in the coefficient of friction, while the sample with 0.5% Ca showed a higher susceptibility to cracking. Regarding corrosion resistance, both samples exhibited a generalized corrosion trend with similar corrosion currents. At lower Ca concentrations (0.1%), the refined microstructure of the alloys provided an elastic modulus closer to that of human bone, minimizing the risk of excessive local stress and promoting uniform load distribution at the bone-implant interface. Conclusion: The 0.5% Ca alloy offered superior tribological stability and better shock absorption, making it suitable for applications requiring long-term stability. The study highlighted the potential of both compositions based on the specific requirements of biodegradable orthopedic implants. Full article

(This article belongs to the Special Issue Advanced Biomaterials for Bone Tissue Engineering)

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18 pages, 1215 KiB

Open AccessArticle

Evaluation of the Genotoxicity and Cytotoxicity of Bioceramic Endodontic Sealers in HepG2 and V79 Cell Lines: An In Vitro Study Using the Comet and Micronucleus Assays

by Antonija Tadin, Marija Badrov, Danijela Juric Kacunic, Nada Galic, Matea Macan, Ivan Kovacic and Davor Zeljezic

J. Funct. Biomater. 2025, 16(5), 169; https://doi.org/10.3390/jfb16050169 - 9 May 2025

Viewed by 238

Abstract

Background: The primary objective of this study was to evaluate the cytotoxic and genotoxic effects of calcium silicate-based sealers (BioRoot RCS and MTA Fillapex) compared to an epoxy-based sealer (AH Plus). Materials and methods: The study was conducted in vitro with the cell [...] Read more.

Background: The primary objective of this study was to evaluate the cytotoxic and genotoxic effects of calcium silicate-based sealers (BioRoot RCS and MTA Fillapex) compared to an epoxy-based sealer (AH Plus). Materials and methods: The study was conducted in vitro with the cell lines HepG2 and V79 to evaluate cytotoxicity and genotoxicity using the comet and micronucleus assays. Eluates of the materials were tested at two different concentrations (3 cm²/mL and 0.5 cm²/mL) after an exposure time of 72 h. Data were analyzed using the Mann–Whitney and Kruskal–Wallis tests (p < 0.05). Results: At lower concentrations in both cell lines, MTA Fillapex showed no significant difference in the measured comet assay parameters compared to the negative control (p > 0.05). In addition, it showed significantly lower genotoxic effects compared to AH Plus for all comet assay parameters, concentrations, and cell lines (p ≤ 0.001). BioRoot RCS showed lower primary DNA damage (p ≤ 0.001) than AH Plus, only at higher concentrations and in the HepG2 cell line. Concerning the two tested bioceramic sealers, BioRoot RCS showed higher tail intensity values compared to MTA Fillapex (p < 0.05). In contrast to the results of the comet assay, BioRoot RCS significantly reduced the number of nuclear buds and nucleoplasmic bridges in the HepG2 cell line compared to MTA Fillapex, whereas reduction in the V79 cell line was only observed for nuclear buds (p < 0.05). Both materials increased the number of apoptotic cells compared to the negative control (p < 0.05). In comparison to AH Plus, BioRoot RCS and MTA Fillapex significantly reduced the number of cells with micronuclei and increased the number of cells with undamaged chromatin (p < 0.05). Conclusions: The findings suggest that MTA Fillapex and BioRoot RCS exhibit superior biocompatibility over AH Plus, as evidenced by their lower cytotoxic and genotoxic effects in vitro. These results support the use of calcium silicate-based sealers in clinical practice, highlighting the need for further studies to evaluate their performance in vivo and their implications for patient safety. Full article

(This article belongs to the Section Dental Biomaterials)

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27 pages, 5228 KiB

Open AccessReview

Analysis of Biomechanical Characteristics of Bone Tissues Using a Bayesian Neural Network: A Narrative Review

by Nail Beisekenov, Marzhan Sadenova, Bagdat Azamatov and Boris Syrnev

J. Funct. Biomater. 2025, 16(5), 168; https://doi.org/10.3390/jfb16050168 - 8 May 2025

Viewed by 303

Abstract

Background: Bone elasticity is one of the most important biomechanical parameters of the skeleton. It varies markedly with age, anatomical zone, bone type (cortical or trabecular) and bone marrow status. Methods: This review presents the result of a systematic review and analysis of [...] Read more.

Background: Bone elasticity is one of the most important biomechanical parameters of the skeleton. It varies markedly with age, anatomical zone, bone type (cortical or trabecular) and bone marrow status. Methods: This review presents the result of a systematic review and analysis of 495 experimental and analytical papers on the elastic properties of bone tissue. The bone characteristics of hip, shoulder, skull, vertebrae as a function of the factors of age (young and old), sex (male and female), presence/absence of bone marrow and different test methods are examined. The Bayesian neural network (BNN) was used to estimate the uncertainty in some skeletal parameters (age, sex, and body mass index) in predicting bone elastic modulus. Results: It was found that the modulus of elasticity of cortical bone in young people is in the range of 10–30 GPa (depending on the type of bone), and with increasing age, this slightly decreases to 10–25 GPa, while trabecular tissue varies from 0.2 to 5 GPa and reacts more acutely to osteoporosis. Bone marrow, according to several studies, is able to partially increase stiffness under impact loading, but its contribution is minimal under slow deformations. Conclusions: BNN confirmed high variability, supplementing the predictions with confidence intervals and allowed the formation of equations for the calculation of bone tissue elastic modulus for the subsequent selection of the recommended elastic modulus of the finished implant, taking into account the biomechanical characteristics of bone tissue depending on age (young and old), sex (men and women) and anatomical zones of the human skeleton. Full article

(This article belongs to the Special Issue Biomaterials in Bone Reconstruction)

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15 pages, 3256 KiB

Open AccessArticle

Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts In Vitro

by Nancy Avila-Martinez, Maren Pfirrmann, Madalena L. N. P. Gomes, Roman Krymchenko, Elly M. M. Versteeg, Marcel Vlig, Martijn Verdoes, Toin H. van Kuppevelt, Bouke K. H. L. Boekema and Willeke F. Daamen

J. Funct. Biomater. 2025, 16(5), 167; https://doi.org/10.3390/jfb16050167 - 8 May 2025

Viewed by 439

Abstract

In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound [...] Read more.

In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound healing, type I collagen scaffolds with and without HA were prepared and characterized. Their immune effect was tested using macrophages and their phenotypes were analyzed through cell surface markers and cytokine expression after 48 h. Since fibroblasts are the main cellular component in the dermis, adult, fetal and eschar-derived cells were cultured on scaffolds for 14 days and evaluated using histology, gene and protein expression analyses. Biochemical assays demonstrated that HA was successfully incorporated and evenly distributed throughout the scaffolds. Macrophages (M0) cultured on Col I+HA scaffolds exhibited a profile resembling the M2c-like phenotype (CD206^high, CD163^high and IL10^high). HA did not significantly affect gene expression in adult and fetal fibroblasts, but significantly reduced scarring-related genes, such as transforming growth factor beta 1 (TGFB1) and type X collagen alpha 1 chain (COL10A1), in myofibroblast-like eschar cells. These findings highlight the potential of incorporating HA into collagen-based skin substitutes to improve the wound healing response. Full article

(This article belongs to the Collection Feature Papers in Biomaterials for Tissue Engineering and Regenerative Medicine)

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33 pages, 10568 KiB

Open AccessReview

Emerging Trends in Microfluidic Biomaterials: From Functional Design to Applications

by Jiaqi Lin, Lijuan Cui, Xiaokun Shi and Shuping Wu

J. Funct. Biomater. 2025, 16(5), 166; https://doi.org/10.3390/jfb16050166 - 8 May 2025

Viewed by 514

Abstract

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses [...] Read more.

The rapid development of microfluidics has driven innovations in material engineering, particularly through its ability to precisely manipulate fluids and cells at microscopic scales. Microfluidic biomaterials, a cutting-edge interdisciplinary field integrating microfluidic technology with biomaterials science, are revolutionizing biomedical research. This review focuses on the functional design and fabrication of organ-on-a-chip (OoAC) platforms via 3D bioprinting, explores the applications of biomaterials in drug delivery, cell culture, and tissue engineering, and evaluates the potential of microfluidic systems in advancing personalized healthcare. We systematically analyze the evolution of microfluidic materials—from silicon and glass to polymers and paper—and highlight the advantages of 3D bioprinting over traditional fabrication methods. Currently, despite significant advances in microfluidics in medicine, challenges in scalability, stability, and clinical translation remain. The future of microfluidic biomaterials will depend on combining 3D bioprinting with dynamic functional design, developing hybrid strategies that combine traditional molds with bio-printed structures, and using artificial intelligence to monitor drug delivery or tissue response in real time. We believe that interdisciplinary collaborations between materials science, micromachining, and clinical medicine will accelerate the translation of organ-on-a-chip platforms into personalized therapies and high-throughput drug screening tools. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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19 pages, 6997 KiB

Open AccessArticle

Engineering Stepped Structures on Hydroxyapatite Surfaces: A Potential Strategy to Modulate Bone Marrow Mesenchymal Stem Adhesion, Spreading, and Proliferation

by Yongmei Wang, Fang Wang, Min Gong, Lidan Chen, Yun Wang, Pu Xu, Zhu Zeng, Zuquan Hu and Jin Chen

J. Funct. Biomater. 2025, 16(5), 165; https://doi.org/10.3390/jfb16050165 - 8 May 2025

Viewed by 274

Abstract

Constructing the surface structures of hydroxyapatite (HA) materials is a promising strategy for orchestrating the cell behaviors of bone marrow mesenchymal stem cells (BMSCs), beneficial for advancing BMSC-based tissue repair and regenerative therapies. The majority of previous strategies have focused on fabricating artificial [...] Read more.

Constructing the surface structures of hydroxyapatite (HA) materials is a promising strategy for orchestrating the cell behaviors of bone marrow mesenchymal stem cells (BMSCs), beneficial for advancing BMSC-based tissue repair and regenerative therapies. The majority of previous strategies have focused on fabricating artificial micro-/nano-scale geometric topographies or patterns on HA surfaces. Yet, constructing surface crystal defects has received insufficient attention and application, despite their importance as highlighted by theoretical calculations. This is largely due to the instability of crystal defects, which tend to be eliminated during crystallization. Here, given the fact that stepped structures are rich in stable crystal defects along their edges and kinks, we crafted HA dishes featuring stepped surfaces and utilized them to establish cell culture models of BMSCs. The outcomes revealed that the stepped structures markedly altered the physicochemical properties of HA surfaces and affected the cytoskeleton structures, spreading area, cell morphology, and focal adhesions of BMSCs in the cell culture model, resulting in inhibited cell adhesion. Given that YAP is a key mechanical sensitive factor, and its nuclear translocation is closely tied to cytoskeletal reorganization, the nuclear translocation efficiency of YAP has been investigated. The results showed that a changed cell adhesion could affect the nuclear translocation efficiency of YAP, which would be an important reason for the change in proliferation and differentiation ability of BMSCs. This work not only enhances the understanding of the responses of BMSCs to HA surface structures but also facilitates the design and optimization of HA materials. Moreover, our manufacturing method is facile and efficient, positioning it to potentially integrate with other processing techniques for the more effective and precise regulation of BMSCs. Full article

(This article belongs to the Section Bone Biomaterials)

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20 pages, 13885 KiB

Open AccessArticle

Biodegradable Double-Layer Hydrogels with Sequential Drug Release for Multi-Phase Collaborative Regulation in Scar-Free Wound Healing

by Xinyu Zhang, Qianhe Zu, Chunlin Deng, Xin Gao, Hongxu Liu, Yi Jin, Xinjian Yang and Enjun Wang

J. Funct. Biomater. 2025, 16(5), 164; https://doi.org/10.3390/jfb16050164 - 7 May 2025

Viewed by 245

Abstract

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This [...] Read more.

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article

(This article belongs to the Special Issue Biomaterials for Wound Healing and Tissue Repair)

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45 pages, 18946 KiB

Open AccessReview

Advancements in Musculoskeletal Tissue Engineering: The Role of Melt Electrowriting in 3D-Printed Scaffold Fabrication

by Kunal Ranat, Hong Phan, Suhaib Ellythy, Mitchell Kenter and Adil Akkouch

J. Funct. Biomater. 2025, 16(5), 163; https://doi.org/10.3390/jfb16050163 - 7 May 2025

Viewed by 203

Abstract

Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard [...] Read more.

Musculoskeletal tissue injuries of the bone, cartilage, ligaments, tendons, and skeletal muscles are among the most common injuries experienced in medicine and become increasingly problematic in cases of significant tissue damage, such as nonunion bone defects and volumetric muscle loss. Current gold standard treatment options for musculoskeletal injuries, although effective, have limited capability to fully restore native tissue structure and function. To overcome this challenge, three-dimensional (3D) printing techniques have emerged as promising therapeutic options for tissue regeneration. Melt electrowriting (MEW), a recently developed advanced 3D printing technique, has gained significant traction in the field of tissue regeneration because of its ability to fabricate complex customizable scaffolds via high-precision microfiber deposition. The tailorability at microscale levels offered by MEW allows for enhanced recapitulation of the tissue microenvironment. Here, we survey the recent contributions of MEW in advancing musculoskeletal tissue engineering. More specifically, we briefly discuss the principles and technical aspects of MEW, provide an overview of current printers on the market, review in-depth the latest biomedical applications in musculoskeletal tissue regeneration, and, lastly, examine the limitations of MEW and offer future perspectives. Full article

(This article belongs to the Special Issue Recent Advances in 3D Printing of Biomaterials)

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18 pages, 7605 KiB

Open AccessArticle

Modulating Osteoclast Activity and Immune Responses with Ultra-Low-Dose Silver Nanoparticle-Loaded TiO₂ Nanotubes for Osteoporotic Bone Regeneration

by Zhen Wang, Penghui Xiang, Zhe Xu, Meiqi Gu, Rui Zhang, Yifei Li, Fei Xin and Chengla Yi

J. Funct. Biomater. 2025, 16(5), 162; https://doi.org/10.3390/jfb16050162 - 4 May 2025

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Abstract

Introduction: Osteoporosis results from the dysregulation of osteoclast activation mechanisms. The subsequent inflammation in osteoporotic environments further hampers bone healing and impedes osseointegration. Therefore, developing treatments that can modulate osteoclast activity and regulate immune responses is essential for effectively treating osteoporotic bone defects. [...] Read more.

Introduction: Osteoporosis results from the dysregulation of osteoclast activation mechanisms. The subsequent inflammation in osteoporotic environments further hampers bone healing and impedes osseointegration. Therefore, developing treatments that can modulate osteoclast activity and regulate immune responses is essential for effectively treating osteoporotic bone defects. Methods: In this study, silver nanoparticle-decorated TiO₂ nanotubes (Ag@TiO₂-NTs) were synthesized through an electrochemical anodization technique for surface modification. The morphology and elemental composition of the Ag@TiO₂-NTs structures were characterized using scanning electron microscopy (SEM) and related methods. Subsequently, a series of in vitro and in vivo experiments were conducted to investigate the regenerative potential of Ag@TiO₂-NTs in osteoporotic bone defects. In vitro assays focused on evaluating cell viability and osteoclast function, while in vivo assessments employed osteoporotic rat models to monitor bone healing via histological examination and micro-computed tomography (micro-CT) imaging. Results: Our results demonstrated that Ag@TiO₂, through the controlled release of trace amounts of silver ions, significantly suppressed osteoclast activity and consequently alleviated bone resorption under osteoporotic conditions. In addition, Ag@TiO₂-NTs facilitated the polarization of macrophages toward the M2 phenotype. These biological effects were associated with the stimulation of autophagy, a fundamental mechanism involved in cellular repair. Moreover, the activation of autophagy contributed to the suppression of RANKL-induced NF-κB signaling, a pathway essential for the regulation of bone metabolism Conclusion: These results suggest that this surface modification strategy has the potential to be an ideal implant biomaterial for treating osteoporotic bone defects and a promising strategy for future implant surgeries. Full article

(This article belongs to the Special Issue Antibacterial Biomaterials for Medical Applications)

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39 pages, 8870 KiB

Open AccessReview

Bioglasses Versus Bioactive Calcium Phosphate Derivatives as Advanced Ceramics in Tissue Engineering: Comparative and Comprehensive Study, Current Trends, and Innovative Solutions

by Monika Furko

J. Funct. Biomater. 2025, 16(5), 161; https://doi.org/10.3390/jfb16050161 - 3 May 2025

Viewed by 349

Abstract

Tissue engineering represents a revolutionary approach to regenerating damaged bones and tissues. The most promising materials for this purpose are calcium phosphate-based bioactive ceramics (CaPs) and bioglasses, due to their excellent biocompatibility, osteoconductivity, and bioactivity. This review aims to provide a comprehensive and [...] Read more.

Tissue engineering represents a revolutionary approach to regenerating damaged bones and tissues. The most promising materials for this purpose are calcium phosphate-based bioactive ceramics (CaPs) and bioglasses, due to their excellent biocompatibility, osteoconductivity, and bioactivity. This review aims to provide a comprehensive and comparative analysis of different bioactive calcium phosphate derivatives and bioglasses, highlighting their roles and potential in both bone and soft tissue engineering as well as in drug delivery systems. We explore their applications as composites with natural and synthetic biopolymers, which can enhance their mechanical and bioactive properties. This review critically examines the advantages and limitations of each material, their preparation methods, biological efficacy, biodegradability, and practical applications. By summarizing recent research from scientific literature, this paper offers a detailed analysis of the current state of the art. The novelty of this work lies in its systematic comparison of bioactive ceramics and bioglasses, providing insights into their suitability for specific tissue engineering applications. The expected primary outcomes include a deeper understanding of how each material interacts with biological systems, their suitability for specific applications, and the implications for future research directions. Full article

(This article belongs to the Special Issue Advanced Bioglasses, Bioceramics and Their Composites: State of the Art and Applications)

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15 pages, 3084 KiB

Open AccessArticle

Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix

by Tanmay Kulkarni, Sreya Banik, Debabrata Mukhopadhyay, Hani Babiker and Santanu Bhattacharya

J. Funct. Biomater. 2025, 16(5), 160; https://doi.org/10.3390/jfb16050160 - 3 May 2025

Viewed by 232

Abstract

Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails [...] Read more.

Tumor-Treating Fields (TTFields), a novel therapeutic avenue, is approved for therapy in Glioblastoma multiforme, malignant pleural mesothelioma, and metastatic non-small cell lung cancer (NSCLC). In pancreatic ductal adenocarcinoma (PDAC), several clinical trials are underway to improve outcomes, yet a significant knowledge gap prevails involving the cell-extracellular matrix (ECM) crosstalk. Herein, we hypothesized that treatment with TTFields influence this crosstalk, which is reflected by the dynamic alteration in nanomechanical properties (NMPs) of cells and the ECM in a co-culture system. We employed an ECM gel comprising collagen, fibronectin, and laminin mixed in 100:1:1 stoichiometry to co-culture of Panc1 and AsPC1 individually. This ECM mixture mimics the in vivo tumor microenvironment closely when compared to the individual ECM components studied before. A comprehensive frequency-dependent study revealed the optimal TTFields frequency to be 150 kHz. We also observed that irrespective of the ECM’s presence, TTFields increase cell membrane stiffness and decrease deformation several-folds in both Panc1 and AsPC1 cells at both 48 h and 72 h. Although adhesion for AsPC1 decreased at 48 h, at 72 h it was observed to increase irrespective of ECM’s presence. Moreover, it significantly alters the NMPs of ECM gels when co-cultured with PDAC cell lines. However, AsPC1 cells were observed to be more detrimental to these changes. Lastly, we attribute the stiffness changes in Panc1 cells to the membrane F-actin reorganization in the presence of TTFields. This study paves a path to study complex PDAC TME as well as the effect of various chemotherapeutic agents on such TME with TTFields in the future. Full article

(This article belongs to the Section Biomaterials for Cancer Therapies)

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16 pages, 4209 KiB

Open AccessArticle

Squid Skin Decellularised Dermal Matrix for Enhancing Repair of Acute Cranial Injuries in Rabbit Model

by Lixin Liu, Yida Pang, Haoze Yang, Qiyi Zhou, JinHua Hou, Wenhui Wu and Jeevithan Elango

J. Funct. Biomater. 2025, 16(5), 159; https://doi.org/10.3390/jfb16050159 - 30 Apr 2025

Viewed by 392

Abstract

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating [...] Read more.

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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J. Funct. Biomater., Volume 16, Issue 5 (May 2025) – 40 articles

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