Search Results (77)

The development of hydrogel bioinks that combine structural stability with biological compatibility remains a major challenge in extrusion-based 3D printing for tissue engineering. In this proof-of-concept study, bacterial cellulose (BC) obtained from kombucha fermentation was explored as a sustainable nanofibrillar component for alginate/chondroitin sulfate (CS)/silicon-substituted hydroxyapatite (Si-HA) composite inks. Following alkaline purification, mechanical processing, and freeze-drying, BC was characterized by scanning electron microscopy (SEM), ATR-FTIR spectroscopy, and X-ray diffraction (XRD), revealing a highly entangled nanofibrillar architecture with high crystallinity (85.4%) and strong hydrogen-bonding potential. Four hydrogel formulations were developed as a comparative 2 × 2 matrix, contrasting BC-containing systems with methylcellulose (MC)-containing reference systems at two Si-HA loadings. Reduced-viscosity measurements of the uncrosslinked precursor formulations showed higher values at the lower Si-HA loading in both formulation series. All formulations could be extruded as acellular inks into grid-like constructs and retained identifiable macroporous architectures after ionic crosslinking. Swelling increased between 24 and 48 h, while mass loss remained limited after the initial 24 h incubation period. In direct-contact testing with L929 fibroblasts, cell viability remained above 84% after 48 h, meeting the ISO 10993-5 non-cytotoxicity criterion. These findings support the feasibility of incorporating physically processed kombucha-derived BC into alginate-based composite inks. Full article

Articular cartilage defects remain a significant clinical challenge due to the limited intrinsic regenerative capacity of cartilage and the inability of many current therapeutic approaches to restore the structure and function of native hyaline tissue. As a result, considerable research efforts have been directed toward the development of tissue-engineering and biomaterial-based strategies capable of promoting more effective regeneration. Among these, hydroxyapatite–hydrogel (HAp–hydrogel) composites have emerged as particularly promising candidates because they combine the biological functionality of HAp with the structural versatility of hydrogel networks. Hydrogels provide a highly hydrated, extracellular matrix-like environment that supports cell survival, facilitates matrix deposition, and enables the localized delivery of therapeutic agents. At the same time, their physicochemical properties can be tailored through a variety of crosslinking approaches and advanced responsive design strategies. The incorporation of HAp, either in nano- or microscale form, contributes to mechanical reinforcement, supports subchondral bone regeneration, and influences cellular behavior through both biochemical and mechanotransductive mechanisms. Beyond promoting chondrogenic differentiation, HAp–hydrogel composites have also been investigated for their capacity to modulate inflammation, stimulate angiogenesis within the subchondral region, provide antibacterial protection, and maintain a microenvironment conducive to tissue repair. This review critically examines recent advances in the development and application of HAp–hydrogel composites for cartilage regeneration, highlighting material design principles, fabrication strategies, healing mechanisms, and the key challenges that continue to influence their clinical translation. Full article

The aim of this mini-review is to highlight the significant medicinal potential of camphor coordination compounds as anticancer and antimicrobial agents. The appropriate selection of the metal center and rational design of the camphor derivatives can optimize the biological properties of these compounds, leading to the development of molecules with combined anticancer and antimicrobial activities. A promising area for future research is the incorporation of biologically active camphor coordination compounds into biocompatible materials (e.g., hydroxyapatite or hydrogels) to develop functional composites and wound dressings with enhanced therapeutic properties. 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

This investigation addressed challenges in the delivery of poorly soluble drugs, and the colloidal processing of polymer–ceramic composites by fabrication of advanced supramolecular hydrogels. Polygalacturonic acid (PGA) polymer and 18β-glycyrrhetinic acid (GA) drug, both characterized by poor aqueous solubility, were selected as model building blocks for supramolecular hydrogels. Meglumine (MG) served as a multifunctional component in the gels, acting as a building block as well as an alkalizing and solubilizing agent for PGA and GA. Investigations revealed gel formation mechanisms, which were based on the electrostatic interactions of deprotonated anionic carboxylic groups of PGA and GA with protonated amino groups of MG and the hydrogen bonding of PGA polymer and GA molecules. The feasibility of the fabrication of PGA-MG and GA-MG gels opened an avenue for the fabrication of PGA-GA-MG gels. The composite gels provided a platform for drug delivery, and the kinetics of drug release from the composite gels containing MG excipient were investigated. Composite gels were obtained from colloidal dispersions, containing bioceramics, such as hydroxyapatite, silica, and titania, and bioglass in the PGA solutions in the presence of MG. The results of this investigation pave the way for the fabrication of novel supramolecular and composite gels loaded with various functional materials. Full article

Although amorphous calcium phosphate (ACP) has been extensively employed as a biomaterial in dental and orthopedic fields, its exploration for environmental applications—particularly in potentially toxic element remediation—remains notably limited in the scientific literature. This study reports the rational design of a multifunctional adsorbent by integrating sodium citrate-stabilized ACP (Cit-ACP) nanoparticles into calcium-crosslinked sodium alginate (SA) hydrogel beads for selective Cu²⁺ sequestration from aqueous systems. Comprehensive sorption assessments revealed that equilibrium uptake aligned with the Freundlich isotherm (indicating heterogeneous surface interactions), while kinetic profiles adhered to pseudo-second-order behavior, characteristic of chemisorption-driven processes. Under optimized operational parameters (pH 5.0, 45 °C), the Cit-ACP/SA composite attained an exceptional maximum adsorption amount of 307.76 mg/g. Thermodynamic analysis further confirmed the spontaneity (ΔG° < 0) and endothermic nature (ΔH° > 0) of the process. Multi-technique characterization (XPS, FTIR, XRD, pH trajectory) elucidated a dual-mode adsorption mechanism: (i) ion exchange between aqueous Cu²⁺ and structural Ca²⁺ within both the alginate matrix and ACP framework; and (ii) in situ surface precipitation yielding copper-substituted hydroxyapatite. Owing to its facile aqueous-phase synthesis, superior adsorption performance, biodegradability, macroscopic bead morphology enabling rapid separation, and robust selectivity in complex matrices, the Cit-ACP/SA composite presents a sustainable, scalable, and eco-compatible platform for practical remediation of copper-contaminated wastewater. 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

Bone regeneration focuses on the creation of functional tissue to repair bone defects. Creating a biodegradable scaffold hydrogel that combines a hemostatic agent with bioactive ceramics can afford the biological and mechanical benefits of both components. In the present study, we developed an injectable gelatin–alginate dual-composite hydrogel, loaded with two functional fillers: hydroxyapatite (HA) and the hemostatic agent montmorillonite (MMT). HA (microparticles and nanoparticles) was incorporated at concentrations of 10–30 mg/mL, with and without MMT at 20 mg/mL. The effects of functional fillers and their concentration on the microstructure and resulting physical and mechanical properties were studied, and a qualitative model summarising these effects was developed. All formulations exhibited clinically appropriate gelation times (5–29 s). n-HA significantly prolonged gelation time, reaching 29 ± 3 s at 30 mg/mL, while MMT reduced gelation time at all concentrations. The tensile strength of the unloaded hydrogel reached 20 kPa and increased to 57 kPa with 30 mg/mL of n-HA. The tensile strength even increased further with the addition of MMT (77 kPa). The results indicate that the combination of HA and MMT produced dual micro-composite hydrogels with moderate reinforcement, whereas the combination of n-HA and MMT generated dual nano–micro composites with combined reinforcing effects. The latter exhibited the highest strength and sealing ability while maintaining clinically relevant gelation times and controlled swelling behaviour. In conclusion, the combination of MMT with n-HA or HA enables the creation of functional hydrogels with controlled properties, tailored to specific applications in bone regeneration. Full article

Maxillary sinus augmentation is a key procedure for rehabilitating the atrophic posterior maxilla and enabling predictable implant-supported restorations. Although autogenous bone remains the biological gold standard due to its osteogenic potential, its clinical use has declined because of donor-site morbidity, limited availability, and increased surgical burden. Deproteinized bovine bone mineral (DBBM) is currently the most widely used substitute, providing excellent biocompatibility and long-term volumetric stability. However, its inert nature, limited bioactivity, and slow resorption have driven the development of next-generation graft materials. Recent biomaterial innovations aim to enhance vascularization, accelerate osteogenesis, modulate immune responses, and achieve controlled resorption while maintaining favorable handling properties. These include ion-releasing bioactive ceramics, growth factor-enhanced allografts, polysaccharide–hydroxyapatite composites, smart hydrogels, and synthetic scaffolds with tunable degradation profiles. Given the complexity of bone regeneration, effective clinical translation requires an integrated framework combining in vitro assays, animal models, and human clinical studies. This review synthesizes evidence published since 2018 on emerging biomaterials for sinus floor elevation, critically evaluating their potential to overcome the limitations of DBBM and highlighting the importance of a coordinated preclinical-to-clinical research continuum. Full article

Bone infections, including osteomyelitis, prosthetic joint infections, and fracture-related infections, represent a persistent and growing clinical problem associated with substantial morbidity, mortality, and healthcare costs. Their management is complicated by limited bone vascularization, biofilm formation, intracellular bacterial persistence, dysregulated host immune responses and reduced antibiotic delivery to the infection site, which promote chronic infection and recurrence. The limitations of conventional treatment strategies based on surgical debridement and prolonged systemic antibiotic therapy, together with their association with antimicrobial resistance and systemic toxicity, have led to growing interest in alternative and adjunctive therapeutic approaches. Local antibiotic delivery systems, such as polymethyl methacrylate, calcium sulfate, hydroxyapatite-based composites, hydrogels, antibiotic-impregnated bone grafts, and nanoparticle carriers, enable high local antimicrobial concentrations while minimizing systemic exposure. From a different therapeutic perspective, immunomodulatory strategies, including mesenchymal stem cell-based therapies, cytokine-targeted interventions, bacteriophages, quorum-sensing inhibitors, and non-antibiotic antimicrobials, represent emerging approaches aimed at improving infection control and supporting bone regeneration. Advances in biomarker profiling, molecular diagnostics, and artificial intelligence-assisted analyses further support personalized approaches to diagnosis, monitoring, and treatment. Despite encouraging early results, clinical translation remains limited by methodological and regulatory challenges, underscoring the need for integrated, innovative treatment strategies. Full article

This study aimed to develop and characterize novel 3D-printed chitosan methacryloyl (CSMA) hydrogel-functionalized nano-hydroxyapatite/polycaprolactone (nHA/PCL) scaffolds for controlled release of bone marrow mesenchymal stem cell-exosomes (BMSC-Exos), with the objective of enhancing osteogenic and angiogenic capabilities in vitro. We fabricated a biomimetic, highly porous scaffold composed of nHA/PCL using high-temperature fused deposition modeling. An interfacial bioactive layer was formed via ultraviolet-induced crosslinking of CSMA hydrogel on the scaffold and loaded bone marrow mesenchymal stem cell-exosomes. We characterized the composite scaffold to evaluate its physicochemical properties, cytocompatibility, cell migration ability, osteogenic capacity, and angiogenic capacity. The 3D-printed 20%nHA/PCL scaffold has a porosity of approximately 75%, with its surface containing four elements: carbon, oxygen, calcium, and phosphorus. The compressive strength is (13.76 ± 1.33) MPa. The CSMA hydrogel exhibits good injectability and degrades slowly over time. Exosomes with a negative charge are released slowly within the extracellular matrix hydrogel. The contact angle of the scaffold material is below 90 degrees, and the hemolysis rate is below 5%. In vitro assays demonstrated that the nHA/PCL-CSMA-Exos composite exhibited excellent biocompatibility, markedly enhanced cell proliferation and migration, and robust pro-angiogenic and osteogenic activity. The fabricated nHA/PCL-CSMA-Exos composite scaffolds demonstrated excellent physicochemical properties, biocompatibility, and cell migration ability, promoting angiogenesis, bone tissue formation and mineralization. Full article

Despite extensive exploration of gelatin methacryloyl (GelMA)-based hydrogels for bone tissue engineering, their clinical translation is hindered by a critical trade-off: poor precursor stability leads to rapid sedimentation of bioactive fillers like hydroxyapatite (HAp), while formulations optimized for injectability often sacrifice mechanical integrity or handling precision. To overcome this challenge, we report a rheologically engineered, injectable composite hydrogel scaffold that integrates unmodified gelatin as a thermoresponsive viscosity modulator into a GelMA/HAp matrix. The incorporation of gelatin yields a stable, paste-like precursor at physiological temperature, which effectively prevents HAp sedimentation and enables precise, filamentous extrusion. Subsequent UV crosslinking locks the homogeneous structure in place, resulting in a mechanically robust scaffold with significantly enhanced compressive modulus. In vitro studies demonstrate that this biomimetic microenvironment not only supports high viability and proliferation of bone marrow stromal cells (BMSCs) but also potently enhances their osteogenic differentiation, as evidenced by upregulated alkaline phosphatase activity, Runx2 expression, and matrix mineralization. This simple, one-step strategy successfully reconciles injectability, structural fidelity, and bioactivity, offering a highly promising and clinically translatable platform for minimally invasive bone regeneration. 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

Chronic and complex wounds, including diabetic foot ulcers, venous leg ulcers, burns and post-surgical defects, remain difficult to manage due to persistent inflammation, impaired angiogenesis, microbial colonization and insufficient extracellular matrix (ECM) remodeling. Conventional dressings provide protection, but they do not supply the necessary biochemical and structural signals for effective tissue repair. This review examines recent advances in hydroxyapatite–collagen (HAp–Col) composite dressings, which combine the architecture of collagen with the mechanical reinforcement and ionic bioactivity of hydroxyapatite. Analysis of the literature indicates that in situ and biomimetic mineralization, freeze-drying, electrospinning, hydrogel and film processing, and emerging 3D printing approaches enable precise control of pore structure, mineral dispersion, and degradation behavior. Antimicrobial functionalization remains critical: metallic ions and locally delivered antibiotics offer robust early antibacterial activity, while plant-derived essential oils (EOs) provide broad-spectrum antimicrobial, antioxidant and anti-inflammatory effects with reduced risk of resistance. Preclinical studies consistently report enhanced epithelialization, improved collagen deposition and reduced bacterial burden in HAp–Col systems; however, translation is limited by formulation variability, sterilization sensitivity and the lack of standardized clinical trials. Overall, HAp–Col composites represent a versatile framework for next-generation wound dressings that can address both regenerative and antimicrobial requirements. Full article