Aug 2026· International Journal of Biological Macromolecules· pp.
154131
· 0 citations· 36 references
Medicine
TL;DR
Results highlight the critical interplay between macromolecular composition, 3D microenvironment, and cell response, demonstrating that GelMA+TA systems represent a promising preliminary platform for the development of tunable bioactive scaffolds for wound-related applications.
Abstract
Although 3D cell bioprinting has emerged as a powerful strategy for engineering biomimetic skin substitutes and wound-related materials, the development of bioinks that simultaneously provide structural integrity, cytocompatibility, and bioactivity remains challenging. In this work, gelatin methacryloyl (GelMA)-based hydrogels incorporating tannic acid (TA) were developed and processed via digital light processing to fabricate 3D scaffolds as prototype platforms for skin-related applications. The incorporation of TA significantly enhanced hydrogel stability, mechanical stiffness, and antibacterial activity, while maintaining high water content and improving print fidelity. Structural characterization by SEM and micro-CT revealed that TA promoted the formation of a more compact and homogeneous porous network, consistent with increased storage modulus, improved compressive strength and delayed degradation under physiological conditions. Rheological analysis confirmed that GelMA+TA systems exhibit enhanced viscoelastic stability and resistance to deformation. Sustained TA release over 25 days endowed the scaffolds with antibacterial activity against E. coli and S. aureus. Importantly, 3D bioprinting and encapsulation studies demonstrated cell-type-dependent biological responses. Human skin fibroblasts exhibited robust long-term viability and proliferation within pure GelMA scaffolds, while TA-containing hydrogels promoted early cell-material interactions and fibronectin deposition but were associated with reduced long-term fibroblast proliferation, suggesting a dose- and exposure-dependent effect of TA. In contrast, Vero cells, used as a model epithelial cell line, showed improved viability and morphology under encapsulation conditions in GelMA+TA scaffolds. These results highlight the critical interplay between macromolecular composition, 3D microenvironment, and cell response, demonstrating that GelMA+TA systems represent a promising preliminary platform for the development of tunable bioactive scaffolds for wound-related applications.
Collagen is widely used in bone tissue engineering due to its biocompatibility; however, its poor mechanical properties, limited print fidelity restrict its use in extrusion-based bioprinting. Collagen methacrylate (ColMA) improves structural stability via photopolymerization but remains prone to enzymatic degradation. In this study, methacrylated silk fibroin (SFMA) and montmorillonite clay (MMT) were incorporated into ColMA-based systems to enhance mechanical performance and mimic aspects of the bone extracellular matrix. Successful methacrylation of ColMA and SFMA was confirmed by 1H NMR and TNBS assay, while FTIR analysis indicated interactions between the polymeric network and the clay phase. Rheological characterization, before and after UV exposure, revealed increased viscosity and a transition to predominantly elastic behavior after photopolymerization, indicating effective network formation. Extrusion-based 3D printing of SFMA/ColMA +3.0% MMT enabled the fabrication of porous grid structures with good shape fidelity, followed by rapid curing under UV light (365 nm, 40 s). These results demonstrate that montmorillonite-reinforced ColMA/SFMA systems are promising hydrogel-based inks for bone scaffold applications.
B. S. L. Antunes, Flavia Pedrini, Daniel Komatsu et al.· International Journal of Bio...· 0 citations
3D bioprinting enables the layer-by-layer fabrication of living tissue constructs and supports patient-specific customization. This technology holds strong promises for regenerative medicine and drug discovery. However, its broader translation remains limited by material variability, safety considerations, cost constraints and regulatory requirements. This study investigates the use of safe, affordable and regulatory-compliant pharmaceutical polymers as biomaterials for 3D bioprinting. It specifically focuses on hydrogels formulated from Starch 1500®, maltodextrin and sodium alginate. The objective is to assess their potential applications in skin tissue engineering and oral drug delivery through semisolid extrusion-based 3D bioprinting techniques. Ionic crosslinking of the hydrogel was confirmed by FTIR analysis. The hydrogel exhibited a viscosity of 1.56 × 106 mPa·s, supporting semisolid extrusion bioprinting and excellent printability under ambient conditions. It enabled the fabrication of multilayer scaffolds with uniform filaments, well-defined square pore geometry and good shape fidelity. Rheological analysis showed shear-thinning behavior under applied stress, 87% thixotropic recovery and predominantly solid-like behavior at rest. Cast films showed a tensile strength of 33.9 MPa with limited extensibility, whereas lyophilized scaffolds exhibited high porosity and an average pore size of 39.2 μm. The 3D-printed scaffolds swollen upto 72% within 24 h and showed the onset of degradation after 2 weeks. Biological evaluation confirmed non-cytotoxicity, with more than 70% cell viability in skin-relevant L929 and HaCaT cells and good hemocompatibility, indicated by 5.0% hemolysis. Confocal microscopy further showed cell growth on the crosslinked hydrogel, supporting their potential for skin tissue engineering. Glimepiride-loaded bioinks were successfully formulated into chewable tablets for drug delivery, which exhibited acceptable physical properties. The tablets demonstrated excellent content uniformity (100.4%), while dissolution results showed sustained-release profiles over a time period of four hours. Our research indicates that pharmaceutical-grade polymer-based hydrogels are promising candidates for skin tissue engineering and drug delivery through 3D bioprinting. The findings of this study underscore the potential of these formulations to advance bioprinting technologies and related applications.
H. K. Bankhede, Maheswari Sivaravi, A. P. Raiturker et al.· Journal of Biological Engine...· 0 citations
Stable hydrogel formation with favorable porous architecture, swelling behavior, thermal stability, and homogeneous distribution of nanovesicles was well established and exhibited excellent biocompatibility, hemocompatibility, and enhanced cell-material interactions.
Rizos Evangelos Bikiaris, Ioanna Koumentakou, A. Niti et al.· ACS Applied Bio Materials· 0 citations
The escalating global demand for sustainable protein sources has accelerated research into cultivated meat. A critical requirement for large-scale production is developing edible, three-dimensional (3D) scaffolds that support cell growth and muscular tissue formation. This study developed and evaluated a biocompatible, cost-effective 3D scaffold for cultivated meat applications. Here, a novel methylcellulose/gelatin composite scaffold (4MC2G) was engineered via freeze-drying, demonstrating significant improvements over pure methylcellulose for myogenesis. Gelatin (G) incorporation significantly enhanced the physicochemical and biological performance of the scaffold. Mechanically, the 4MC2G scaffold exhibited a substantial increase in elastic modulus and displayed desirable nonlinear hyperelastic behavior. Microstructural analysis using SEM revealed that G incorporation refined the pore architecture (43.59 ± 14.21 μm) and created a more heterogeneous surface morphology. The cumulative release profile showed an initial burst release of G (~60.91 ± 0.81%) during the first 6 h, followed by a stabilized release rate. AFM confirmed that G incorporation enhanced the nanotopography and stiffness of both dry and hydrated scaffolds, which are critical for mechanotransduction. Additionally, the 4MC2G scaffold significantly promoted C2C12 myoblast adhesion, proliferation, and differentiation compared to its pure MC counterpart. Robust myogenic differentiation was confirmed by myotube formation, the upregulation of myosin heavy chain (MHC) and myogenin (MYOG), and the downregulation of paired box 7 (PAX7) mRNA expression. Finally, porcine muscle stem cell (PMSC) validation confirmed attachment, myotube formation, and MHC expression, establishing 4MC2G as a promising biocompatible and edible platform. These findings provide a valuable strategy for designing macromolecular composites for sustainable food production.
Pongphol Prattapong, Wasina Watcharanapapan, Thunyarat Pongtharangkul et al.· International Journal of Bio...· 0 citations
Tissue engineering scaffolds (TESs) play a crucial role in regenerative medicine by providing structural support for cell adhesion, proliferation, differentiation, and tissue formation. However, developing TESs that simultaneously meet the requirements of biocompatibility, mechanical robustness, structural controllability, and cost-effective manufacturing remains a significant challenge. In this study, fully bio-based TESs were fabricated using polylactic acid (PLA) reinforced with cellulose nanofibers (CNFs) via a green and scalable microcellular injection molding process. The incorporation of CNFs derived from renewable biomass, significantly enhanced the rheological property, crystallinity, and foaming behavior of PLA. Compared with the PLA foams fabricated by regular foam injection molding (RFIM), the pore size of the PLA/CNF foam fabricated by mold-opening foam injection molding (MOFIM) was decreased by 96.5%, with the pore density increased by 7 orders of magnitude. The tensile toughness and impact strength were improved by up to 276.5% and 40.0%, reaching 6.4 MJ/m3 and 2.1 kJ/m2, respectively. Thanks to the improved scaffold architecture and introduced hydroxyl groups, the PLA/CNF foam enabled outstanding cell viability and proliferation, as evidenced by abundant live cells, uniform distribution, and minimal cell death. This work provides a sustainable and scalable strategy for developing high-performance TESs with tunable pore structures for biomedical applications.
Hydrogels combining the biochemical complexity of the native extracellular matrix (ECM) with the tunable properties of protein-based biomaterials are promising for neural tissue engineering. In this study, decellularized spinal cord meninges (dSCM) were combined with water-soluble hydrophilic silk fibroin (hSF) and enzymatically crosslinked using a horseradish peroxidase/H2O2 system to develop composite hydrogels. A detergent-free, sonication-assisted decellularization method effectively removed cellular components while preserving matrix integrity, reducing residual double-stranded DNA to below 50 ng mg-1 dry weight and retaining key ECM constituents, including collagen and glycosaminoglycans. Hydrogels prepared at different dSCM:hSF ratios showed composition-dependent structural and mechanical behavior, with the 1:0.5 and 1:1 formulations exhibiting the most favorable compressive stiffness and viscoelastic performance. Structural, thermal, and morphological analyses further indicated that hSF incorporation improved matrix stability and contributed to more controlled swelling and degradation behavior. Biological evaluation showed that the 1:0.5 formulation promoted neovascularization in the chorioallantoic membrane assay without evident adverse inflammatory response. In addition, SH-SY5Y cells maintained high viability and showed increased expression of the neuronal-associated markers β-III tubulin and MAP2 over time. Overall, these findings suggest that dSCM:hSF hydrogels provide a promising platform for neural tissue engineering.
Tugce Kurt, Burak Derkuş, Y. E. Arslan· ACS Biomaterials Science & E...· 0 citations
