Search Results (48)

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

The rapid emergence of antibiotic-resistant bacteria represents one of the most critical challenges in modern healthcare and has stimulated intense research into alternative antimicrobial strategies. Antibacterial hydrogels have emerged as versatile biomaterials due to their high water content, tunable physicochemical properties, and ability to function as multifunctional platforms for drug delivery and tissue regeneration. This review analyzes recent advances in antibacterial hydrogel systems through a conceptual framework based on three complementary pillars: biological antibacterial agents, inorganic functional components, and structural material engineering. Biological strategies, particularly bacteriophage-based approaches, provide highly specific antibacterial activity capable of targeting multidrug-resistant pathogens and disrupting bacterial biofilms. Inorganic components such as hydroxyapatite nanoparticles contribute additional functionalities including drug adsorption, modulation of the ionic microenvironment, and osteoconductive behavior relevant for bone-related infections. Structural design strategies based on electrospinning enable the fabrication of fibrous architectures that enhance mechanical stability, regulate therapeutic release, and mimic extracellular matrix organization. The integration of these three pillars within multifunctional hydrogel platforms offers promising opportunities for developing advanced antibacterial biomaterials capable of addressing infection control while supporting tissue 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

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

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

In this study, we present the synthesis and characterization of graphene oxide (GO)-based hydrogels reinforced with hydroxyapatite (HA), titanium dioxide (TiO₂), zinc oxide (ZnO), silicon oxide (SiO₂), silver (Ag), and graphitic carbon nitride (g-C₃N₄). The aim is to develop multifunctional hydrogels with enhanced structural and biological performance and photocatalytic activity, opening the way for applications in regenerative medicine. The structure and composition of the hydrogels were investigated using FTIR and UV–Vis spectroscopy, which highlighted the chemical interactions between GO and the incorporated nanoparticles. The morphology was analyzed through scanning electron microscopy (SEM) and metallographic optical microscopy (MOM), confirming a uniform distribution of the inorganic phases and an internal architecture optimized for stability and bioactivity. Antibacterial activity was evaluated against Gram-positive and Gram-negative strains, both in the absence and presence of photodynamic therapy. The latter was activated by a Woodpecker laser at a 420 nm wavelength. The results showed significant bacterial inhibition, further enhanced by laser exposure, suggesting a synergistic effect between photocatalytic activation and the hydrogel components. Overall, the obtained hydrogels demonstrate robust mechano-structural properties and promising biological activity, supporting their potential for innovative biomedical applications in the tissue regeneration field and for the emerging biofunctional technologies. Full article

Osteoporotic vertebrae are a uniquely challenging tissue for local delivery due to the complex geometry of cancellous bone, the proximity of the spinal cord, and the need for reliable site retention. These challenges can be met with the use of stimuli responsive, state transiting formulations by leveraging their unique capacity for minimally invasive implantation as a liquid, sol–gel transition in response to stimuli, and finally, release of a loaded therapeutic. Here, we present the formulation development of a thermosensitive methylcellulose–collagen hydrogel, functionalised with controlled release simvastatin, recently shown to enhance osteogenesis while also impeding osteoclast activity. We first optimised a formulation with collagen content of 0.4% w/v to achieve a thermosensitive system with sol–gel transition at 29 °C, shear-thinning/injectable properties, low cytotoxicity, and high biocompatibility. Incorporation of nano-hydroxyapatite for enhanced bone tissue mimicry revealed optimal performance at 100% w/collagen content, showing long-term hydrolytic stability, maintaining more than 100% of its mass after 28 days. A loading concentration of 1 mg of simvastatin to 1 g of hydrogel displayed sustained release of simvastatin over 35 days. Finally, the release of simvastatin from the hydrogel into in vitro conditions prevented the formation of osteoclasts but failed to boost osteogenesis. Together these findings reveal a series of desirable stimuli-responsive hydrogel properties, achieving minimally invasive application coupled with sustained release of a hydrophobic compound, which is potentially useful for spatially complex bone regeneration. Further this work demonstrates the challenge of dosing sustained release systems to achieve simultaneous osteogenesis and anti-osteoclastogenic effects. Full article

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

Periodontal disease in dogs leads to progressive bone loss and adversely impacts overall health. However, cost-effective regenerative strategies are still limited in veterinary practice. This study aimed to develop and evaluate a novel tannic acid (TA)–gelatin-based hydrogel (Gel), incorporating graphene oxide (GO) and hydroxyapatite nanoparticles (HA), as a potential barrier material for guided tissue regeneration (GTR) applications. The hydrogels—Gel, Gel-GO, Gel-HA, and Gel-GO-HA—were characterized for chemical structure, molecular interactions, surface morphology, nanoparticle dispersion, and tensile strength. Cytotoxicity was assessed using L929 fibroblasts (ISO 10993-5), while cell viability/proliferation, morphology, and alkaline phosphatase (ALP) production were evaluated using canine periodontal ligament-derived cells. Results show that crosslinking with tannic acid enhanced the incorporation of graphene oxide and hydroxyapatite nanoparticles via hydrogen bonding into TA–gelatin-based hydrogels. This combination increased surface roughness, reduced degradation rate, and enabled shape memory behavior, critical for guided tissue regeneration (GTR) membranes. The extracts from Gel-HA-GO showed that cytotoxicity was both time- and concentration-dependent in L929 fibroblasts, whereas enhanced cell proliferation and increased ALP production were observed in cultures derived from canine periodontal ligament cells. These findings suggest that TA–gelatin-based hydrogels incorporating GO and HA demonstrated favorable mechanical and physicochemical properties, biocompatibility, and osteogenic potential. These attributes suggest their viability as a promising composite for the development of innovative GTR strategies to address periodontal tissue loss in veterinary medicine. Full article

A varied family of polyphenolic chemicals, flavonoids, are becoming more and more important in bone tissue engineering because of their osteogenic, anti-inflammatory, and antioxidant effects. Recent developments incorporating flavonoids into different biomaterial platforms to improve bone regeneration are emphasized in this study. Osteocalcin (OCN) expression was 2.1-fold greater in scaffolds loaded with flavonoids—such as those made of polycaprolactone (PCL)—greatly increasing human mesenchymal stem cell (hMSC) proliferation and mineralization. Comparably, a threefold increase in calcium deposition indicates increased mineralization when hydroxyapatite (HA) was functionalized with flavonoids such as quercetin. These HA scaffolds with flavonoids also showed a 45% decrease in osteoclast activity, therefore promoting balanced bone remodeling. Concurrent with flavonoids like EGCG and quercetin, chitosan-based scaffolds encouraged osteogenic differentiation with increases in osteogenic markers like osteopontin (OPN) and alkaline phosphatase (ALP) expression by up to 82%. These scaffolds also showed 82% bone defect repair after six weeks in vivo, suggesting their promise in rapid bone regeneration. With an increase of up to 32% in the bone volume-to-total volume ratio (BV/TV) and 28% greater bone–implant contact (BIC), flavonoid coatings on titanium implants enhanced osteointegration in implantology. Displaying successful osteogenesis and immunomodulation, the addition of flavonoids into metal–organic frameworks (MOFs) and injectable hydrogels demonstrated a 72% increase in new bone formation in vivo. Though further research is required to confirm long-term clinical effectiveness, these findings show the great promise of flavonoid-functionalized biomaterials in bone regeneration. Full article

Rapid functional soft tissue restoration has shown considerable promise as a framework for stability and coordination in the human body. Inspired by the anisotropic arrangement of structures with soft and hard phases in biological tissues, such as tendon, cartilage, and ligament, many methods have been used to fabricate composite hydrogels with appropriate mechanical properties. The development of a high-strength hydrogel with strong bioactivity remains a key barrier to replace soft tissues with comparable synthetic structures. In this study, a highly dispersed hydroxyapatite nanofiber (HANF) reinforced polyvinyl alcohol-sodium alginate (PVA/SA) composite hydrogel is prepared for soft tissue replacement. The effect of the addition of HANF on the microstructure and properties of composite hydrogel is also investigated. The results show that the PVA/SA hydrogel, after the incorporation of HANF, combines well with the PVA/SA hydrogel (HANF@PVA/SA). SEM morphologies show that dispersed HANF can enter the holes of the three-dimensional structure of the composite hydrogel. Additionally, the addition of HANF can enhance the compressive strength of the PVA/SA composite hydrogel from 4.66 MPa to 7.72 MPa. At the same time, the HANF@PVA/SA hydrogel maintains the same excellent hydrophilicity as the original PVA/SA hydrogel. Finally, cytotoxicity and live/dead cell staining tests also confirmed its excellent biocompatibility, demonstrating its tremendous potential for use in soft tissue repair. Full article

Bone tissue engineering aims to restore lost bone and create an environment conducive to new bone formation. To address this challenge, we developed a novel biomimetic hydrogel that combines maleic anhydride–modified type I collagen (ColME) with maleic anhydride–modified demineralized and decellularized porcine bone matrix particles (mDBMp), forming a composite ColME–mDBMp (CMB) hydrogel. Chemical modification of collagen resulted in a high degree of substitution, thereby enhancing its photocrosslinkability. Integration of mDBMp into the ColME hydrogel via photocrosslinking resulted in enhanced physiological stability, reduced shrinkage, and improved mechanical strength compared to gelatin methacrylate (GelMA)-based hydrogels. Moreover, mineralization of the CMB hydrogel promoted the formation of pure hydroxyapatite (HAp) crystals, providing superior stiffness while maintaining ductility relative to GelMA-based hydrogels. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) encapsulated in CMB hydrogels exhibited enhanced proliferation, cell–matrix interactions, and osteogenic differentiation, as evidenced by increased calcium deposition and histological analysis. These results demonstrate that the CMB hydrogel, enriched with extracellular matrix (ECM) components, shows considerable promise over current GelMA-based hydrogels for bone tissue engineering. Full article

Alginate hydrogels have gathered significant attention in biomedical engineering due to their remarkable biocompatibility, biodegradability, and ability to encapsulate cells and bioactive molecules, but much less has been reported on the kinetics of gelation. Scarce experimental data are available on cross-linked alginates (AL) with bioactive components. The present study addressed a novel method for defining the crosslinking mechanism using rheological measurements for aqueous mixtures of AL and calcium chloride (CaCl₂) with the presence of hydroxyapatite (HAp) as filler particles. The time-dependent crosslinking behaviour of these mixtures was exploited using a plate–plate rheometer, when crosslinking occurs due to calcium ions (Ca²⁺) binding to the guluronic acid blocks within the AL polymer, forming a stable “egg-box” structure. To reveal the influence of HAp particles as filler on crosslinked sample morphology, after rheological measurement and crosslinking, crosslinked samples were freeze-dried and their morphology was assessed using an optical microscope and SEM. It was found that the addition of HAp particles, which are known to enhance the mechanical properties and biocompatibility of crosslinked AL gels, significantly decreased (usually rapidly) the interaction between the Ca²⁺ and AL chains. In this research, the physical “shielding” effect of HAp particles on the crosslinking of AL with Ca²⁺ ions has been observed for the first time, and its crosslinking behaviour was defined using rheological methods. After crosslinking and rheometer measurements, the samples were further evaluated for morphological properties and the observations were correlated with their dewatering properties. While the presence of HAp particles led to a slower crosslinking process and a more uniform development of the rheological parameters, it also led to a more uniform porosity and improved dewatering properties. The observed effects allow for a better understanding of the crosslinking process kinetics, which directly affects the physical and chemical properties of the AL gels. The shielding behaviour (retardation) of filler particles occurs when they physically or chemically block certain components in a mixture, delaying their interaction with other reactants. In hydrogel formulations, filler particles like hydroxyapatite (HAp) can act as barriers, adsorbing onto reactive components or creating physical separation, which slows the reaction rate and allows for controlled gelation or delayed crosslinking. This delayed reactivity is beneficial for precise control over the reaction timing, enabling the better manipulation of material properties such as crosslinking distribution, pore structure, and mechanical stability. In this research, the physical shielding effect of HAp particles was observed through changes in rheological properties during crosslinking and was dependent on the HAp concentration. The addition of HAp also enabled more uniform porosity and improved dewatering properties. The observed effects allow for a better understanding of the crosslinking process kinetics, which directly affects the physical and chemical properties of the AL gels. Full article