Search Results (508)

Background and Objectives: Hypocalcemia due to hypoparathyroidism (HypoPTH) is the most common complication following thyroid surgery, typically resulting from iatrogenic removal, tissue damage, or compromised vascularization of the parathyroid glands. Patients with persistent HypoPTH are at risk for long-term complications such as osteoporosis, cardiac dysfunction, and renal impairment. Lifelong regulation of calcium levels is therefore essential to prevent morbidity and mortality associated with these complications. In this study, we aimed to evaluate the functional engraftment efficacy of 3D bioprinted human parathyroid tissue constructs in a xenograft model in vivo. Materials and Methods: Primary cells obtained from freshly excised human parathyroid tissue specimens were isolated and 3D bioprinted using alginate-based bioink. The bioprinted tissue constructs were implanted into CD1 athymic mice. Histopathological evaluation of the grafted constructs was performed at different time points. In addition, surface calcium-sensing receptor (CaSR) expression was assessed by immunofluorescence as an indicator of functional parathyroid tissue engraftment. Results: The presence of CaSR on parathyroid cells within the 3D-printed scaffolds confirmed the persistence of functional parathyroid cells following implantation. In tissue samples obtained during the first, second, and third weeks after implantation, CaSR positivity was consistently observed in the parathyroid cells. However, at the three-month follow-up, the pores within the scaffolds were found to be filled with calcified material and replaced by fibrotic tissue. At this stage, the absence of parathyroid hormone (PTH) expression indicated a loss of functional activity in the grafted biomaterial. Conclusions: Human primary parathyroid cells were successfully isolated, and a functional, hormone-active parathyroid tissue substitute was developed ex vivo using 3D-bioprinted hydrogel scaffolds combined with autologous cells. Although short-term functional engraftment was achieved, long-term graft viability and hormonal activity were limited due to scaffold degradation and fibrosis. These findings indicate the necessity for further improvement in scaffold biocompatibility to enhance the therapeutic potential of 3D-bioprinted parathyroid tissue constructs for in vivo applications. Full article

In this work, we report the synthesis and evaluation of a bioink based on marine collagen, chitosan, and silica-doped hydroxyapatite (HA–SiO₂) for extrusion-based 3D bioprinting. FTIR spectroscopy confirmed amide (I–III) and phosphate/siloxane signals, TGA showed initial dehydration and degradation stages compatible with the process’s thermal handling, and SEM revealed an interconnected porous microstructure. Rheologically, the ink exhibited elastic dominance (G′ > G″) within the linear range and pseudoplastic, shear-thinning behavior—consistent with pneumatic extrusion. Process evaluation on a BIO X printer (14 G nozzle, low print speeds, moderate pressure, cartridge at 37 °C to 45 °C, and a cooled build platform) enabled deposition of strands with local shape retention. However, filament continuity was limited and line width varied, indicating only preliminary printability and a narrow operating window. Overall, physicochemical, microstructural, and rheological evidence supports the formulation’s viability as a starting point for scaffold fabrication. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Extrusion-based 3D bioprinting enables the fabrication of complex tissue structures, yet achieving both high structural fidelity and cell viability remains challenging due to complex bioink rheology and parameter interplay. This review presents a quantitative framework linking hydrogel properties to printing outcomes. Key rheological features—shear-thinning, yield stress, reversible gel-sol transition, self-healing, and creep resistance—are examined for their roles in extrusion and shape retention. We also evaluate printing accuracy using metrics such as filament uniformity and multilayer stability. Advanced models, including Herschel-Bulkley and extrusion pressure models, correlate material parameters with flow dynamics and predict critical factors like wall shear stress. Finally, we propose an integrated assessment system combining material properties, process parameters, and structural fidelity to guide bioink design and printing optimization, advancing the field of hydrogel bioprinting. Full article

Decellularization removes immunogenic intracellular components of fish tissues while keeping the extracellular matrix (dECM) structure, mechanical integrity, and bioactivity. Fish-derived dECM retains native bioactive components, exhibiting high biocompatibility, low immunogenicity, and biodegradability, while supporting cell adhesion, proliferation, and tissue regeneration. Due to its abundance, minimal ethical concerns, and low zoonotic risks, fish wastes are emerging as sustainable sources of dECM, offering an eco-friendly alternative to mammalian biomaterials. This review highlights advances in decellularizing fish wastes such as skin, scales, bones, viscera, and swim bladders from species including tilapia, tuna, milkfish, carp, goldfish, and sturgeon. Physical, chemical, biological, and hybrid decellularization methods are assessed for cell removal, ECM preservation, and mechanical performance. Recent advances in polymer-dECM composites, crosslinking, and 3D bioprinting have significantly improved scaffold performance, making fish-derived dECM applicable for healing of wounds, regeneration of bone and cartilage, and repair of soft tissues. Despite its potential, challenges remain in optimizing perfusion rates, temperature variations, and tissue-specific protocols, as well as developing eco-friendly decellularization techniques using biodegradable reagents. Future perspectives include expanding decellularized fish tissue sources, innovating bio-inks for 3D bioprinting, and refining tissue-specific processing methods to maximize the potential of fish-derived dECM in regenerative medicine and tissue engineering. Full article

Autologous adipose tissue (AT) grafting is often compromised by insufficient early vascularization, leading to ischemia, fibrosis, and inconsistent long-term volume retention. Incorporating platelet-rich plasma (PRP) into AT bioinks offers a clinically accessible means to enhance vascular recruitment, but the in vivo impact of PRP dosage remains unclear. Here, we investigated how PRP concentration, uniformly integrated into a previously reported clinically relevant AT bioink, regulates vascular infiltration, tissue remodeling, and overall graft survival. High-dose PRP markedly improved graft performance, including an 8-fold increase in highly perfused regions, a 3.8-fold enhancement in adipocyte survival, a 1.67-fold reduction in fibrosis, and a 2.51-fold increase in collagen III deposition compared with PRP-free AT grafts. Histological analysis further demonstrated that PRP mitigates the adverse effects of poor perfusion, reducing regional disparities in survival and extracellular matrix (ECM) remodeling. High-dose PRP also maximized graft retention, preserving 103% of graft mass relative to 50.6% in native AT. Together, these results establish a clear in vivo dose–response relationship for PRP-enhanced AT grafts and highlight platelet concentration as a key design parameter for soft-tissue reconstruction. This work provides a translational framework for optimizing PRP-functionalized bioinks to improve clinical outcomes in reconstructive surgery. Full article

Three-dimensional bioprinting revolutionized tissue and organ replacement by enabling the precise deposition of living cells and biomaterials, making it ideal for biomedical applications. Natural polymers are commonly used as bioink for their biocompatibility and bioactivity. Among them, type I collagen, the most abundant protein of extracellular matrix, is commonly used as bioink. However, mammalian-derived collagens raise concerns related to zoonotic disease transmission, religious restrictions, and immunogenicity. Fish-derived collagen represents a safer and more sustainable alternative, although its rapid degradation and limited mechanical properties remain significant challenges. In this study, the printability of a novel fish collagen ink was assessed for micropatterned scaffolding by extrusion. In order to overcome material-related challenges, the effect of UV-induced crosslinking was investigated. Morphological, rheological, and physicochemical characterizations—including thermal behavior, degradation resistance, exposed chemical groups, and roughness—were performed before and after UV treatment. Results demonstrated that UV crosslinking significantly improved the structural integrity and stability of the printed scaffolds. These findings support the potential of UV-crosslinked fish collagen as biomaterial ink for regenerative medicine and tissue engineering applications. Full article

Extrusion-based bioprinting is widely used for fabricating cell-laden constructs; however, its success is highly dependent on the rheological and biological performance of the bioink. Natural polysaccharide gums have emerged as promising bioink components due to their biocompatibility and tunable properties. Among them, tragacanth gum (TG), a complex anionic heteropolysaccharide composed of tragacanthin and bassorin fractions, has gained increasing attention for extrusion bioprinting applications. TG exhibits pronounced shear-thinning behavior, high water uptake, and spontaneous gel-forming ability, which collectively enhance the printability, shape fidelity, and structural stability of bioinks. This review critically summarizes recent advances in TG-based hydrogels and bioinks, with emphasis on their molecular characteristics, rheological and physicochemical properties, and biological performance in extrusion bioprinting systems. The role of TG as a functional component in composite bioinks, particularly in improving mechanical integrity, extrusion consistency, and cytocompatibility, is discussed. Finally, current challenges and future research directions are highlighted to support the development and clinical translation of TG-based bioinks for tissue engineering applications. Full article

High-resolution biofabrication requires precise microscale deposition, yet drop-on-demand (DOD) inkjet bioprinting is constrained by a narrow printable viscosity window. Many biocompatible hydrogel precursors display high zero-shear viscosity and strong shear-thinning, so stable droplet ejection typically requires dilution or reformulation that can compromise the biochemical microenvironment. We present a transient shear-enabled jetting method that exploits intrinsic shear-thinning by using a high-frequency electromagnetic microvalve to deliver short, high-pressure pulses. The resulting localized shear dynamically lowers apparent viscosity in the nozzle region and promotes controlled nucleation, ligament formation, necking, and pinch-off. A coupled, rheology-informed modeling framework (axisymmetric transient CFD, valve dynamics, and electromagnetic FEM) links actuation parameters to droplet volume and stability and guides hardware optimization. Experiments with 2.5% (w/v) sodium alginate validate stable droplet generation and tunable droplet size via stroke length and driving conditions. These results define a practical process window for high-resolution droplet printing of high-viscosity shear-thinning hydrogel inks. Full article

This review synthetizes experimental evidence on collagen-related bioactivity and the biomaterial potential of plant species native to the Chihuahuan Desert, aiming to identify natural compounds that could enhance next-generation dermal bioinks for 3D bioprinting. A structured search across major databases included studies characterizing plant extracts or metabolites, with reported effects on collagen synthesis, fibroblast activity, inflammation, oxidative balance, or interactions with polymers commonly used in skin-engineering materials being developed. Evidence was organized thematically to reveal mechanistic patterns despite methodological heterogeneity. Several species, among them Larrea tridentata, Opuntia spp., Aloe spp., Matricaria chamomilla, Simmondsia chinensis, Prosopis glandulosa, and Artemisia ludoviciana, repeatedly demonstrated the presence of bioactive metabolites such as lignans, flavonoids, phenolic acids, terpenoids, and polysaccharides. These compounds support pathways central to extracellular matrix repair, including stimulation of fibroblast migration and collagen I/III expression, modulation of inflammatory cascades, antioxidant protection, and stabilization of ECM structures. Notably, several metabolites also influence viscoelastic and crosslinking behaviors, suggesting that they may enhance the printability, mechanical stability, and cell-supportive properties of collagen-, GelMA-, and hyaluronic acid-based bioinks. The review also reflects on the bioethical and sustainability considerations regarding endemic floral resources, highlighting the importance of responsible sourcing, conservation extraction practices, and alignment with international biodiversity and access to benefit/sharing frameworks. Taken together, these findings point to a promising, yet largely unexplored, opportunity: integrating regionally derived phytochemicals into bioinks to create biologically active, environmentally conscious, and clinically relevant materials capable of improving collagen remodeling and regenerative outcomes in 3D-printed skin. Full article

Three-dimensional (3D) culture systems that recapitulate the tumor microenvironment are essential for studying cancer cell behavior, drug response, and cell–matrix interactions. Here, we present a detailed protocol for generating 3D spheroid cultures from murine breast cancer cells using methacrylated gelatin (GelMA)-based bioink and a CELLINK BioX bioprinter. This method enables precise deposition of spheroid-laden GelMA droplets into low-attachment plates, facilitating high-throughput and reproducible 3D culture formation. The protocol includes steps for spheroid formation, GelMA preparation, bioprinting, and post-printing analysis using a customized CellProfiler pipeline. The analysis pipeline takes advantage of the functionality of CellProfiler and ImageJ software (version 2.14.0) packages to create a versatile and accessible analysis tool. This approach provides a robust and adaptable platform for in vitro cancer research, including studies of metastasis, drug resistance, cancer cell lipid metabolism, and TME-associated hypoxia. Full article

A major objective of this study is to investigate the incorporation of hydroxyapatite nanoparticles (nHA) in a biopolymeric matrix of alginate (Alg) and gelatin (Gel), with particular emphasis understanding how controlled variation in nHA concentration affects rheological, mechanical, printing, and biological performance. Although Alg–Gel blends and nHA-containing hydrogels have been previously explored, a systematic and quantitative correlation between nHA loading, viscoelastic recovery, yield behavior, filament fidelity, and cell viability under optimized bioprinting conditions has not been established. Here, we address this by preparing and evaluating six composite inks (0, 1, 2, 3, 4, and 5% w/v nHA). The parameters of interest included the printing accuracy, the rheological profile, including over 70% viscosity recovery after 10 s in almost all formulations, the elastic modulus, which was over 10 kPa, and the swelling degree. In addition, pre-osteoblastic cells were embedded in these formulations, subsequently bioprinted, and demonstrated viability over 70% after 7 days. The results advance our understanding on the effect of the chemical composition behind the modification of the properties of the composite materials and their applications for biofabrication. This work contributes quantitative insight into how compositional tuning influences the performance of alginate–gelatin–nHA bioinks for extrusion-based bioprinting applications. Full article

A biomimetic cartilage scaffold featuring a continuous hydroxyapatite (HA) concentration gradient and a spatially curved architecture was developed using a dual-channel mixing extrusion-based 3D printing approach. By dynamically regulating the feeding rates of two bioinks during printing, a continuous HA gradient decreasing from the bottom to the top of the scaffold was precisely achieved, mimicking the compositional transition from the calcified to the non-calcified cartilage region in native articular cartilage. The integration of gradient material deposition with synchronized multi-axis motion enabled accurate fabrication of curved geometries with high structural fidelity. The printed scaffolds exhibited stable swelling and degradation behavior and showed improved compressive performance compared with step-gradient counterparts. Rheological analysis confirmed that the bioinks possessed suitable shear-thinning and recovery properties, ensuring printability and shape stability during extrusion. In vitro evaluations demonstrated good cytocompatibility, supporting bone marrow mesenchymal stem cell (BMSC) adhesion and proliferation. Chondrogenic assessment based on scaffold extracts indicated that the incorporation of HA and its gradient distribution did not inhibit cartilage-related extracellular matrix synthesis, confirming the biosafety of the composite hydrogel system. Overall, this study presents a controllable and versatile fabrication strategy for constructing curved, compositionally graded cartilage scaffolds, providing a promising platform for the development of biomimetic cartilage tissue engineering constructs. Full article

The increasing demand for sustainable and functional plant-based foods has driven interest in 3D food printing technologies, which require bioinks with tailored rheological and structural properties. This study investigated the effects of transglutaminase (TGase) on the structure–function relationships of plant protein bioinks from fava bean, mung bean, pea, and soybean. TNBS assays showed a dose-dependent increase in crosslinking (27.46–64.57%), with soybean and pea proteins exhibiting the highest reactivity (p < 0.05). ¹H-NMR confirmed protein-specific ε-(γ-glutamyl)lysine bond formation, and synchrotron FTIR revealed TGase-induced α-helix reduction and β-sheet enrichment, indicative of network formation across all proteins. SDS-PAGE analysis demonstrated TGase-mediated polymerization with high-molecular-weight aggregates, particularly pronounced in soybean, while SEM images revealed denser, more continuous protein networks compared to untreated samples. Rheological characterization showed enhanced viscoelasticity and shear-thinning behavior in all bioinks, supporting extrusion and post-printing stability. Textural analysis indicated improvements in hardness, springiness, cohesiveness, and chewiness across all proteins, with soybean and fava showing the most pronounced increases. These results demonstrate that TGase is a versatile tool for reinforcing plant protein networks, improving printability, structural integrity, and texture in 3D-printed foods, while highlighting protein-specific differences in response. Full article

Recent advances in biomaterials, immunomodulation, stem cell therapy, and biofabrication are reshaping maxillofacial surgery, shifting reconstruction paradigms toward biologically integrated and patient-specific tissue regeneration. This review provides a comprehensive synthesis of current and emerging strategies for bone and soft-tissue regeneration in the craniofacial region, with particular emphasis on bioactive ceramics, biodegradable polymers, hybrid composites, and stimuli-responsive smart materials. We further examine translational technologies such as extracellular vesicles, decellularized extracellular matrices, organoids, and 3D bioprinting, highlighting key challenges such as bioink standardization, perfusion limitations, and regulatory classification. Maxillofacial surgery is positioned for a paradigm shift toward personalized, biologically active, and clinically scalable regenerative solutions. Full article