Search Results (733)

Bacterial cellulose (BC) is a highly pure biomaterial that can be produced from agro-industrial residues, making it a sustainable candidate for tissue engineering applications such as biocompatible hydrogel. However, pure BC is rigid and brittle, which limits its clinical handling. This study aimed to synthesise BC membranes from the non-photosynthetic bacterium Komagataeibacter nataicola (TISTR 975) using mature coconut water as the primary fermentation medium, and to improve its mechanical properties by forming an in situ composite hydrogel with polyhydroxyalkanoate (PHA). Sucrose concentration and cultivation period were systematically varied and analysed using response surface methodology (RSM), which identified the optimal condition as a 7-day cultivation at 50 g/L sucrose, yielding a highly uniform membrane with the best structural integrity. In situ fabrication of the BC/PHA composite, achieved by dispersing PHA powder in the culture medium during synthesis, markedly enhanced the material’s flexibility and water-holding capacity. The elongation at break increased from 22.9% for pure BC to 28.2% for the composite, with only a slight reduction in ultimate tensile strength. A cradle-to-gate life cycle assessment (LCA) showed that the BC/PHA membrane had a global warming potential approximately 3.2 times lower than that of bovine collagen membranes, while the incorporation of PHA introduced a negligible additional environmental burden. These findings indicate that the locally producible and biodegradable BC/PHA composite hydrogel offers a favourable balance between mechanical performance, water-holding capacity, and environmental sustainability, positioning it as a promising candidate for the future development of guided tissue regeneration (GTR) gel membranes in dentistry. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive loss of articular cartilage and an associated decline in its intrinsic mechanoelectrical signaling. Current osteoarthritis treatments relieve symptoms but fail to prevent cartilage degeneration or restore its native biophysical microenvironment. Here, we present an ultrasound-activated, mussel-inspired bio-adhesive hydrogel that addresses these challenges by recreating the cartilage’s piezoelectric cues in situ while achieving stable intra-articular retention under synovial conditions. The hydrogel, denoted SFHD-BT@PDA, consists of a silk fibroin (SF) matrix integrated with dopamine-functionalized hyaluronic acid (HADA) and embedded barium titanate nanoparticles coated with polydopamine (BT@PDA). This multi-level design imparts strong interfacial adhesion to wet cartilage (via catechol-mediated bonding to collagen) and piezoelectric sensitivity to external ultrasound. Under ultrasound stimulation, SFHD-BT@PDA generates localized electrical microcurrents that recruit endogenous MSCs via electrotaxis and subsequently promote their chondrogenic differentiation. In vitro, ultrasound-triggered electrical cues upregulated chondrogenic markers (SOX9, collagen II, aggrecan) in MSCs and activated TGF-β signaling, demonstrating restoration of the pro-anabolic bioelectric microenvironment. In a murine DMM model, the adhesive hydrogel exhibited prolonged retention on cartilage surfaces and, with ultrasound, induced robust cartilage regeneration and OA reversal. Treated joints showed preserved proteoglycan and Type II collagen content, inhibited osteophyte formation, and protection of subchondral bone microarchitecture. In summary, this mussel-inspired piezoelectric hydrogel provides an electromechanical stimulation platform that effectively couples physical cues with bio-adhesion to regenerate cartilage. Full article

Gelatin-based hydrogels are promising matrices for wound management, but their direct application is constrained by insufficient structural stability and lack of intrinsic antimicrobial activity. Porcine and fish gelatin hydrogels were photochemically crosslinked with menadione sodium bisulfite (MSB), a water-soluble hemostatic derivative of vitamin K3, and characterized by ATR-FTIR and ¹H NMR spectroscopy, together with antimicrobial testing against Staphylococcus aureus, Candida albicans, Escherichia coli, and Salmonella enterica. FTIR analysis showed that MSB crosslinking retards the thermal disruption of collagen-like triple helices in both gelatins, with the effect being more pronounced in porcine gelatin owing to its higher imino acid content and more developed collagen-like network. NMR measurements confirmed that crosslinking increases the bound-water fraction approximately threefold in porcine and twofold in fish gelatin, while the bulk water mobility stays unchanged. MSB crosslinking enhanced antimicrobial activity against S. aureus and C. albicans by up to 5.6-fold relative to non-crosslinked controls and additionally conferred activity against E. coli, while S. enterica remained resistant in all variants. MSB, thus, simultaneously serves as a structural crosslinker and imparts intrinsic antimicrobial activity to the resulting hydrogels, making them a promising basis for multifunctional wound-healing materials. Full article

Impaired wound healing is often caused by persistent inflammation, bacterial infection, and insufficient extracellular matrix remodeling. Natural polymer-based hydrogels represent ideal wound dressings but often struggle to balance structural stability and biological activity. Herein, we report a dual-functional network regulation strategy enabled by highly soluble mussel foot protein (HMFP) that acts simultaneously as a structural crosslinking regulator and bioactive effector to fabricate synergistic hydrogels (CS-SH-H) from β-chitosan (CS) and sodium hyaluronate (SH). HMFP homogenizes the porous microstructure, strengthens intermolecular interactions, and significantly improves thermal and structural stability via multivalent non-covalent bonding. In vitro, CS-SH-H shows excellent cytocompatibility, significantly promotes fibroblast proliferation and migration, and exerts potent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In a mouse full-thickness skin defect model, the hydrogel dramatically accelerates wound closure, reducing the residual wound area to 25% on day 7, outperforming the control groups. Immunohistochemistry confirms that HMFP suppresses TNF-α-mediated inflammation and enhances Ki-67-positive cell proliferation, leading to accelerated re-epithelialization and collagen deposition. This study establishes HMFP as a promising marine-derived dual-functional network regulator for designing high-performance hydrogel dressings. This strategy is scalable and translatable for treating infected and inflammatory wounds. Full article

Infectious wounds are plagued by persistent infection, uncontrolled inflammation, and delayed repair, while traditional therapies suffer from the poor solubility of natural drugs, low bioavailability, and bacterial drug resistance. To address these issues, this study developed a photo-responsive chitosan composite hydrogel (BBR-AS@Ce6@Matrix) cross-linked by chitosan (CS) and oxidized sodium alginate (OSA), co-loaded with Berberine–Asiaticoside cocrystal (BBR-AS) and chlorin e6-loaded chitosan nanoparticles (Ce6@CS NPs). The BBR-AS co-crystal was prepared by solvent method and verified to significantly improve the solubility and dissolution of asiaticoside. The Ce6@CS NPs were fabricated via non-solvent-assisted counterion complexation, showing high encapsulation efficiency, uniform particle size, and efficient singlet oxygen generation under irradiation. The hydrogel exhibited a three-dimensional porous network, favorable rheology, high water content, pH-dependent swelling and erosion behaviors, and significantly promoted BBR/AS release in vitro. In vitro experiments demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus, good cytocompatibility, and enhanced migration of L929 and Hacat cells. In a rat infectious wound model, the hydrogel combined with light irradiation markedly accelerated wound closure, promoted collagen deposition and angiogenesis, upregulated VEGF/CD31, and downregulated TNF-α/IL-6. In conclusion, BBR-AS@Ce6@Matrix integrates co-crystal solubilization, nanoparticle-facilitated release, and photodynamic synergy to achieve antibacterial, anti-inflammatory, pro-angiogenic and tissue remodeling effects, providing a promising multifunctional platform for infectious wound repair. Full article

Surface functionalization of metallic implants is widely explored to enhance their performance and functionality. In this study, multifunctional hydrogel coatings based on poly(vinylpyrrolidone) and polyethylene glycol were developed and functionalized with a taxifolin (TAX) inclusion complex and collagen to introduce bioactive features. TAX, a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, was incorporated using β-cyclodextrin to improve its stability and enable controlled release. The coatings were applied to titanium-hydroxyapatite composites and titanium sheet substrates to evaluate their applicability across surfaces with varying morphologies, ranging from porous to relatively smooth. The ceramic phase was modified with magnesium ions to enhance its bioactivity and better mimic the composition of natural bone tissue. FTIR and SEM analyses confirmed hydrogel formation and effective surface coverage. Degradation and incubation studies in simulated physiological environments demonstrated the material’s stability, while UV–Vis analysis indicated TAX release, highlighting the system’s potential as a carrier for flavonoid-based compounds. Indirect cytotoxicity studies using MC3T3-E1 preosteoblasts indicated low cytotoxicity and a favorable biological response of collagen- and taxifolin-modified systems. The developed coatings represent a versatile platform for surface modification of titanium-based biomaterials and demonstrate potential for application across substrates with diverse surface characteristics. Further studies are required to assess their biological potential. Full article

Objectives: Skin wound repair has long remained a crucial clinical challenge, in response to which, in this study, we propose a novel injectable hydrogel delivery system. In particular, we focus on the efficient delivery of bioactive factors and modulation of the local wound microenvironment. Methods: The hydrogel integrates selenium nanoparticles (SeNPs) and basic fibroblast growth factor (bFGF), which serve as key therapeutic components in the proposed system, and are additionally co-integrated with oxidized hyaluronic acid (OHA) and heparin-grafted carboxymethyl chitosan (CMCS-g-Hep) to construct a multifunctional SeNPs/bFGF-loaded CMCS-g-Hep/OHA hydrogel network. Accordingly, this proposed hydrogel was systematically evaluated using chemical synthesis, physicochemical characterization, in vitro cellular assays, and C57BL6J mice studies, which we used to jointly assess the biocompatibility and wound-healing efficacy of the proposed system. Results: The results demonstrated that the hydrogel enabled sustained bFGF release and was capable of significantly enhancing fibroblast proliferation, migration, and collagen deposition. In a mouse skin defect model, treatment with the loaded hydrogel markedly accelerated wound closure. Additionally, we conducted mechanistic investigations to further illustrate that the hydrogel can modulate the wound microenvironment by regulating inflammatory and chemotactic signaling pathways. Conclusions: These findings suggest a promising therapeutic pathway for chronic wound repair. Full article

Rapid rewarming is the most conventional and primary treatment for frostbite, yet effective adjunctive strategies remain absent. Conventional wound dressings, such as therapeutic hydrogels, tend to freeze and lack the necessary rewarming ability, rendering them unsuitable for direct application. Herein, we engineered an environmentally tolerant photothermal hydrogel, named 5A-Gel, featuring anti-swelling, anti-pressure, antioxidant, anti-freezing, and anti-drying capacities, for the treatment of frostbite. 5A-Gel was formed via dynamic crosslinking between gelatin and tea polyphenols in a glycerol/water solvent system. The incorporation of glycerol endowed the hydrogel with superior anti-swelling, anti-freezing, and anti-drying performance (remaining flexible at −20 °C and 37 °C for at least 60 days), along with concentration-dependent antioxidant activity due to tea polyphenols. Furthermore, 5A-Gel exhibited excellent photothermal effects, maintaining stable temperature and softness under 808 nm laser irradiation with robust cyclic durability. In addition, 5A-Gel showed slow degradability, excellent hemocompatibility, and favorable in vivo biosafety. Functionally, in a mouse frostbite wound model, photothermal rewarming therapy using 5A-Gel markedly expedited frostbite healing, promoting re-epithelialization, enhancing collagen deposition, alleviating inflammatory response, and stimulating neovascularization. Therefore, the as-prepared 5A-Gel serves as a competent therapeutic platform for in situ frostbite treatment and offers innovative principles for the rational engineering of high-performance hydrogel systems targeting frostbite tissue injuries. Full article

Recent studies have highlighted the potential of urinary bladder matrix (UBM) derived from decellularized porcine urinary bladder as a bioactive hydrogel. Despite its complex composition of over 100 proteins, Type I collagen is the primary constituent of UBM. Caco-2 cells are widely used as an in vitro model of the intestinal epithelium; however, to date, no published study has evaluated the effects of UBM on Caco-2 cells. In this study, Electric Cell–Substrate Impedance Sensing (ECIS) was used to measure Caco-2 cell attachment and wound-healing migration on UBM-coated microelectrodes. Our results demonstrate that UBM hydrogel coating at 0.2 mg/mL significantly accelerates cell attachment and enhances migration rates compared to uncoated controls. These stimulatory effects were comparable to those observed with 0.2 mg/mL Type I collagen, suggesting that UBM can function as effectively as Type I collagen. We further monitored barrier formation in Caco-2 cells cultured on UBM-coated transwell membrane inserts using TEER measurements and scanning electron microscopy. The TEER values reached 300 Ω·cm² within three days, indicating the rapid establishment of mature tight junctions. Overall, these results show that UBM hydrogel coatings are effective substrates for Caco-2 cells, performing as well as Type I collagen in all our tests. Full article

Atherosclerosis begins with endothelial dysfunction, inflammatory activation, and immune-cell recruitment within a spatially organized vascular wall. Conventional static cultures and Transwell systems are advantageous for isolated readouts, but they fail to effectively recapitulate multicellular compartmentalization, extracellular matrix support, and dynamic perfusion within a singular platform. Here, we present a four-channel microfluidic vascular-wall chip designed to reconstitute an endothelial cell-extracellular matrix-smooth muscle cell arrangement and to model early atherosclerosis-related inflammatory endothelial dysfunction. The device comprises a perfusable endothelial channel, a collagen I hydrogel region embedded with human aortic smooth muscle cells, a cell-free matrix region, and a culture-medium supply channel. Under physiological conditions, HUVECs formed a ZO-1-positive endothelial barrier and maintained high cellular viability. Stimulation with TNF-α and IL-1β (10 ng/mL each) elevated IL-6 secretion, promoted the recruitment of THP-1-derived M0-like macrophages, disrupted ZO-1 continuity, and increased FITC-dextran permeability without causing extensive cell death. The chip was subsequently utilized to evaluate metformin and atorvastatin therapies. The combinational treatment produced a more pronounced attenuation of MCP-1 secretion than either monotherapy under the inflammatory background. While this platform does not recapitulate advanced plaque formation, lipid deposition, foam-cell formation, or disturbed arterial shear, it successfully provides a microfluidic model of early inflammatory endothelial dysfunction to facilitate mechanistic studies and preliminary anti-inflammatory drug evaluation. Full article

Diabetic wounds are characterized by persistent hyperglycemia, excessive ROS accumulation, sustained inflammation, and impaired angiogenesis, yet current treatments remain suboptimal. To address these challenges, we developed a mild heat stimulating and microenvironment reprogramming hydrogel (termed C-4-N) via a green synthetic strategy. L-Arginine (L-Arg) triggered the spontaneous self-polymerization of protocatechuic aldehyde (PA) into poly (protocatechuic aldehyde) (PPA) nanoparticles, onto which ginsenoside Compound K (CK) was subsequently loaded, yielding CK/L-Arg/PPA nanoparticles. These nanoparticles were then uniformly embedded into a dynamic disulfide network composed of α-lipoic acid (LA)-modified chitosan (CS-LA) and 4-arm-PEG-SH under UV irradiation without toxic photo-initiators, forming the C-4-N hydrogel. The C-4-N hydrogel reprogrammed the diabetic wound microenvironment through three synergistic mechanisms, lowering blood glucose and scavenging ROS via the coordinated actions of LA, CK and PPA, promoting M1-to-M2 macrophage polarization via downregulation of pro-inflammatory cytokines (TNF-α, IL-6) and upregulation of anti-inflammatory cytokines (IL-10, TGF-β1), further amplified by mild photothermal stimulation of 40–43 °C. In a diabetic rat model, the C-4-N hydrogel achieved a near-complete wound closure rate of 99.49 ± 0.10% on day 13 upon mild photothermal stimulation, accompanied by enhanced re-epithelialization, organized collagen deposition, vascular maturation, and systemic glucose regulation. In summary, this green synthesized, mild heat-stimulating hydrogel establishes a synergistic microenvironment reprogramming paradigm for chronic diabetic wound managements. Full article

The extracellular matrix (ECM) regulates skeletal muscle development through biochemical signaling and mechanical interactions. While Matrigel supplementation is commonly used to enhance engineered muscle formation, the contribution of specific ECM proteins remain incompletely defined in 3D systems. Here, we evaluated the effects of laminin and fibronectin supplementation on myogenic differentiation in collagen type I hydrogels and assessed their influence on passive tissue compaction and alignment in 3D constructs. Two-dimensional collagen hydrogels supplemented with increasing concentrations (0–100 µg/mL) of laminin or fibronectin were screened to maximize the myoblast fusion index. These concentrations were incorporated into 3D myocyte-seeded hydrogels cultured between flexible posts to quantify passive compaction forces via cantilever mechanics. Fibronectin supplementation (10 µg/mL) resulted in significantly greater early post displacement and sustained passive compaction compared to laminin-supplemented and unsupplemented controls. Constructs cultured under tension between posts exhibited enhanced alignment, with fibronectin further increasing the proportion of fibers oriented within 0–20° of the tension axis. Together, these findings demonstrate that fibronectin enhances early passive compaction dynamics and tension-mediated alignment in collagen-based skeletal muscle constructs. These results provide insight into how specific ECM components influence 3D tissue organization and may inform the design of engineered muscle models for regenerative applications. Full article

Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article

A composite hydrogel scaffold comprising chitosan, silk fibroin, Aloe vera extract, and Mimosa complex was fabricated and thoroughly characterized. Upon freeze-drying, the scaffolds displayed a uniform cylindrical geometry with a highly porous, interconnected polymeric network. Quantitative image analysis revealed a mean pore diameter of 43.09 ± 2.27 µm alongside an overall porosity of 61.4 ± 6.2%. ATR-FTIR and XRD analyses confirmed successful inclusion of the complex formation and the incorporation of all constituents into the final formulation. The scaffold exhibited a compressive modulus of 46.63 ± 22.71 kPa (dry) and 5.40 ± 3.73 kPa (hydrated), with a swelling ratio of 756.62 ± 114.08%, supporting its suitability for physiological applications. TGF-β3 loading via adsorption yielded an entrapment efficiency of approximately 79.18%, reflecting effective physical immobilization throughout the polymer matrix. Cytocompatibility was subsequently assessed using an indirect contact model combined with an MTT assay, both of which confirmed that TGF-β3-loaded scaffolds exerted no cytotoxic effects on chondrocytes. After 28 days in culture, scanning electron microscopy revealed pronounced cell adhesion, preservation of rounded cell morphology, and ECM deposition along pore walls and throughout interconnected channels. Immunofluorescence analysis further demonstrated a time-dependent accumulation of aggrecan and collagen type II within the three-dimensional scaffold architecture. Collectively, these findings suggest that the developed composite hydrogel scaffold is well-suited for cartilage-related in vitro culture applications. Full article

In ulcerative colitis (UC), the therapeutic efficacy of nanoparticle (NP)-based drug delivery systems is limited by premature drug release, uptake or degradation of NPs during their passage through the harsh gastrointestinal tract (GIT) environment, poor colon targeting, and rapid NP clearance caused by diarrhea symptoms. This study focused on designing an advanced spatiotemporally controlled nanohybrid hydrogel drug delivery system to overcome these challenges. We developed a pH- and temperature-responsive polysaccharide-based hydrogel composed of chitosan (CS), β-glycerol phosphate disodium salt pentahydrate (GP), hydroxypropyl cellulose (HPC), and collagen type I (Col I), designated as CS/HHPC/Col I-GP. The hydrogel exhibited a dense and uniform porous reticular structure, with an average pore diameter of 127.45 ± 2.22 μm. The equilibrium swelling ratio of the CS/HHPC/Col I-GP was determined to be 32.10 ± 1.11 g/g, indicating excellent swelling capacity and sustained structural stability over 6 h—making it suitable for sustained drug release in the intestinal tract. Then, the prepared curcumin nanoparticles (CurNPs) were encapsulated into the CS/HHPC/Col I-GP hydrogel to form the CS/HHPC/Col I-GP-CurNPs composite. The polysaccharide-based hydrogel shell of the formulation withstood harsh gastrointestinal conditions, enabled targeted adhesion to the colon, and was specifically degraded by colonic enzymes. The CurNPs released in the colon benefit from their negatively charged characteristics, enabling accumulation at the positively charged inflamed sites and achieving sustained Cur release. The results of the gastrointestinal digestion simulation experiment showed that the cumulative release of CS/HHPC/Col I-GP-CurNPs was only 12.33 ± 2.17% in simulated gastric fluid (SGF) and reached 96.91 ± 1.98% in simulated colonic fluid (SCF) after 60 h. Cell and animal experimental data confirmed that the formulation significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivating the TLR4/MyD88/NF-κB pathway. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced. This study provides a promising strategy for the oral drug treatment of UC. Full article