Search Results (25)

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

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

In this study, a novel composite hydrogel was developed based on oxidized sodium alginate (OSA), synthesized via sodium periodate oxidation, and incorporated into a carboxymethyl chitosan (CMCS) matrix. Scallop active peptides (SAPs), a marine-derived bioactive component with outstanding antioxidant and pro-regenerative activities, was introduced to endow the hydrogel with enhanced biological functions, which is of great significance for breaking the functional limitations of traditional single-component hydrogels. The construction of a dynamic covalent network, driven by the Schiff base reaction, was confirmed through structural characterization using FT-IR and ¹H-NMR. The hydrogel exhibited favorable physicochemical properties, including shear-thinning behavior, significant self-healing capability, and a uniform porous microstructure that effectively mimics the extracellular matrix (ECM). In vitro evaluations revealed excellent biocompatibility and potent pro-angiogenic potential, as evidenced by enhanced HUVEC migration and tube formation. In a rat model of full-thickness skin wounds, the CMCS/OSA/SAPs hydrogel significantly accelerated wound closure and promoted re-epithelialization and organized collagen deposition. Furthermore, immunohistochemical analysis confirmed upregulated VEGF and α-SMA expression, alongside reduced inflammatory levels (decreased iNOS), indicating potent tissue-regenerative and immunomodulatory functions. Overall, this work presents a multifunctional hydrogel system that integrates antioxidant, anti-inflammatory, and tissue-regenerative properties, offering a promising strategy for deep-wound healing. This study highlights the significant potential of marine-derived bioactive proteins/peptides in the development of advanced biomedical materials. Full article

Gelatin–alginate composite hydrogels are some of the most prevalent bioinks used for extrusion-based three-dimensional (3D) bioprinting because of their combined bioactivity and ability to ionically crosslink. Ionically crosslinked gelatin–alginate constructs containing human bone marrow–derived mesenchymal stem cells (hBM-MSCs) were characterised over time under standardised in vitro conditions to assess physicochemical properties and resultant cell behaviour. Water uptake and degradation were quantified over time in phosphate-buffered saline (PBS) and collagenase type II media for up to 21 days. Cell viability and metabolic activity were quantified, and osteogenic gene expression (RUNX2, COL1A1, OCN) was assessed. Raman spectroscopy and compressive mechanical characterisation were performed. Collagen and glycosaminoglycan-related peaks were observed from extracellular matrix (ECM)-associated components, with an increased presence of protein-associated signatures later in culture. Hydrogels displayed nonlinear elastic behaviour with increased stress after longer incubation times, suggesting no degradation of mechanical integrity over the duration of the study. Hydrogels experienced rapid hydration followed by decreased swelling over time, with a maximum swelling ratio at 24 h. Degradation rates significantly increased over longer incubation times (p < 0.001) and in collagenase media compared to PBS (p < 0.001). Observed differences were likely due to both ion-exchange-mediated network disassembly and the dissolution of gelatin components. Cell metabolic activity decreased under osteogenic culture conditions, while changes in osteogenic marker expression were sequential, suggesting a transition from proliferation to early osteogenic commitment in this 3D system. This work provides both physicochemical and biological characterisation of a commonly utilised gelatin–alginate bioink system, to provide future optimisations within the field of extrusion-based bone tissue engineering, a reproducible baseline for future optimisation of bioink systems in extrusion-based bone tissue engineering. Full article

Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up. Full article

Background/Objectives: Wound healing represents a pervasive and urgent clinical challenge. Hard-to-heal chronic wounds are frequently complicated by infections, inflammatory responses, and oxidative stress. Currently, wound dressings are broadly categorized into dry and moist types, with moist wound dressings for chronic wounds accounting for approximately 70% of market revenue. Recently, adipose-derived stem cells (ADSCs), which possess self-renewal and multi-lineage differentiation capabilities, have emerged as a promising strategy for promoting tissue regeneration and wound repair. Methods: In this study, we developed a novel luteolin nanoparticle–ADSCs composite hydrogel (GelCA@LUT@ADSCs). This system was constructed by first encapsulating ADSCs within a chitosan/alginate hydrogel (GelCA), followed by coating the hydrogel with luteolin-loaded nanoparticles (LUT@NPs). Results: The sustained release of LUT@NPs from the hydrogel modulates the wound microenvironment, enhancing the pro-healing functions of ADSCs at the wound site. The GelCA hydrogel exhibited excellent biocompatibility. Both in vitro and in vivo results demonstrated that GelCA@LUT@ADSCs treatment effectively reduced inflammation, promoted angiogenesis and collagen deposition, stimulated cell proliferation and migration, and polarized macrophages toward an anti-inflammatory, pro-healing M₂ phenotype, thereby accelerating wound healing. Conclusions: Overall, this innovative therapeutic approach provides a novel strategy for wound management through a synergistic division of labor between pharmaceutical agents and stem cells. Full article

Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In this study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests performed on crosslinked hydrogels confirm the formation of solid-like structures, consistently indicating a superior storage modulus in relation to the loss modulus. The swelling behavior analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlue^TM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favored a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2) in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and therefore provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro. Full article

The management of vision-threatening retinal diseases remains challenging due to the lack of an effective drug delivery system. Encapsulated cell therapy (ECT) offers a promising approach for the continuous delivery of therapeutic agents without the need for immunosuppressants. In this context, an injectable and terminable collagen–alginate composite (CAC) ECT gel, designed with a Tet-on pro-caspase-8 system, was developed as a safe intraocular drug delivery platform for the sustained release of glial-cell-line-derived neurotrophic factor (GDNF) to treat retinal degenerative diseases. This study examined the potential clinical application of the CAC ECT gel, focusing on its safety, performance, and termination through doxycycline (Dox) administration in the eyes of healthy New Zealand White rabbits, as well as its therapeutic efficacy in rabbits with sodium-iodate (SI)-induced retinal degeneration. The findings indicated that the CAC ECT gel can be safely implanted without harming the retina or lens, displaying resistance to degradation, facilitating cell attachment, and secreting bioactive GDNF. Furthermore, the GDNF levels could be modulated by the number of implants. Moreover, Dox administration was effective in terminating gel function without causing retinal damage. Notably, rabbits with retinal degeneration treated with the gels exhibited significant functional recovery in both a-wave and b-wave amplitudes and showed remarkable efficacy in reducing photoreceptor apoptosis. Given its biocompatibility, mechanical stability, controlled drug release, terminability, and therapeutic effectiveness, our CAC ECT gel presents a promising therapeutic strategy for various retinal diseases in a clinical setting, eliminating the need for immunosuppressants. Full article

This paper reports an experimental study on the compatibility of human bronchial epithelial (HBE) cells in a collagen–alginate bioink. The compatibility was assessed using the culture well method with three bioink compositions prepared from a 10% alginate solution and neutralized TeloCol-10 mg/mL collagen stock solution. Cell viability, quantified by (live cell count—dead cell count)/live cell count within the HBE cell-laden hydrogel, was evaluated using the live/dead assay method from Day 0 to Day 6. Experimental results demonstrated that the collagen–alginate 4:1 bioink composition exhibited the highest cell viability on Day 6 (85%), outperforming the collagen–alginate 1:4 bioink composition and the alginate bioink composition, which showed cell viability of 75% and 45%, respectively. Additionally, the live cell count was highest for the collagen–alginate 4:1 bioink composition on Day 0, a trend that persisted through Days 1 to 6, underscoring its superior performance in maintaining cell viability and promoting cell proliferation. These findings show that the compatibility of HBE cells with the collagen–alginate 4:1 bioink composition was higher compared with the other two bioink compositions. Full article

Hydrogel materials based on sodium alginate find versatile applications in regenerative medicine and tissue engineering due to their unique properties, such as biocompatibility and biodegradability, and the possibility of the customization of their mechanical properties, such as in terms of the individual requirements of separate clinical applications. These materials, however, have numerous limitations in the area of biological activity. In order to eliminate their limitations, sodium alginate is popularly applied in combination with added gelatin, which represents a product of collagen hydrolysis. Despite numerous beneficial biological properties, matrix materials based on gelatin have poor mechanical properties and are characterized by their ability for rapid degradation in an aqueous environment, particularly at the physiological temperature of the body, which significantly limits the independent application opportunities of this type of composition in the range of scaffolding production dedicated for tissue engineering. Collagen hydrogels, unlike gelatin, are characterized by higher bioactivity, dictated by a greater number of ligands that allow for cell adhesion, as well as better stability under physiological conditions. Fish-derived collagen provides a material that may be efficiently extracted without the risk of mammalian prion infection and can be used in all patients without religious restrictions. Considering the numerous advantages of collagen indicating its superiority over gelatin, within the framework of this study, the compositions of hydrogel materials based on sodium alginate and fish collagen in different concentrations were developed. Prepared hydrogel materials were compared with the properties of a typical composition of alginate with the addition of gelatin. The rheological, mechanical, and physicochemical properties of the developed polymer compositions were evaluated. The first trials of 3D printing by extrusion technique using the analyzed polymer solutions were also conducted. The results obtained indicate that replacing gelatin with fish collagen at an analogous concentration leads to obtaining materials with a lower swelling degree, better mechanical properties, higher stability, limited release kinetics of calcium ions cross-linking the alginate matrix, a slowed process of protein release under physiological conditions, and the possibility of extrusion 3D printing. The conducted analysis highlights that the optimization of the applied concentrations of fish collagen additives to composition based on sodium alginate creates the possibility of designing materials with appropriate mechanical and rheological properties and degradation kinetics adjusted to the requirements of specific applications, leading to the prospective opportunity to produce materials capable of mimicking the properties of relevant soft tissues. Thanks to its excellent bioactivity and lower-than-gelatin viscosity of the polymer solution, fish collagen also provides a prospective solution for applications in the field of 3D bioprinting. Full article

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies. Full article

Hydrogels prepared from natural polymer have attracted extensive attention in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability, and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid, starch, guar gum, agarose, and dextran. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical applications of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing, and other biomedical fields are summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymers, novel technologies such as enzymatic and biological methods have been developed to improve their structural properties, and the development of new natural-based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels, and hydrogel microrobots have been designed to meet the advanced requirements in biomedical applications, and new strategies such as dual-cross-linking, microfluidic chip, micropatterning, and 3D/4D bioprinting have been explored to fabricate advanced hydrogel materials with designed properties for biomedical applications. Overall, natural polymeric hydrogels have attracted increasing interest in biomedical applications, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication are highly desirable and still challenging. Full article

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm⁻¹ and of collagen around 1430 cm⁻¹. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely. Full article

A new drug delivery system consisting of clindamycin phosphate entrapped in acid-etched halloysite nanotubes was successfully prepared and characterized. It was then used as an antibacterial component of the multicomponent hydrogel designed as a material for bone regeneration. First, halloysite (HNT) was etched and clindamycin phosphate (CP) was entrapped in both raw and modified nanotubes, resulting in HNT-CP and EHNT-CP systems. They were characterized using SEM, TEM, TGA and FTIR; the entrapment efficiency and release of CP from both systems were also studied. EHNT-CP was then used as an antibacterial component of the two hydrogels composed of alginate, collagen and β-TCP. The hydrogels were prepared using different crosslinking procedures but had the same composition. The morphology, porosity, degradation rate, CP release profile, cytocompatibility, antibacterial activity and ability to induce biomineralization were studied for both materials. The hydrogel obtained by a chemical crosslinking with EDC followed by the physical crosslinking with calcium ions had better properties and was shown to have potential as a bone repair material. Full article

Natural bone tissue is composed of calcium-deficient carbonated hydroxyapatite as the inorganic phase and collagen type I as the main organic phase. The biomimetic approach of scaffold development for bone tissue engineering application is focused on mimicking complex bone characteristics. Calcium phosphates are used in numerous studies as bioactive phases to mimic natural bone mineral. In order to mimic the organic phase, synthetic (e.g., poly(ε-caprolactone), polylactic acid, poly(lactide-co-glycolide acid)) and natural (e.g., alginate, chitosan, collagen, gelatin, silk) biodegradable polymers are used. However, as materials obtained from natural sources are accepted better by the human organism, natural polymers have attracted increasing attention. Over the last three decades, chitosan was extensively studied as a natural polymer suitable for biomimetic scaffold development for bone tissue engineering applications. Different types of chitosan-based biomaterials (e.g., molded macroporous, fiber-based, hydrogel, microspheres and 3D-printed) with specific properties for different regenerative applications were developed due to chitosan’s unique properties. This review summarizes the state-of-the-art of biomaterials for bone regeneration and relevant studies on chitosan-based materials and composites. Full article