Hydrogels For Bone Tissue Engineering Research Articles

Harnessing potential of microwave-assisted ultrafast synthesis of reduced graphene oxide/Mn3O4 bioactive nanocomposite hydrogel for bone tissue engineering

The development of functional materials with the potential for bone tissue regeneration along with rapid synthesis and cost-effective approach has been challenging. In this regard, hydrogels have been explored as a potent candidate to behave as a 3D scaffold for bone repair. However, poor mechanical attributes impeded their clinical translation. Enthralling demonstration of the potential of carbon-based nanocomposites in bone tissue engineering has been constantly encouraging the fabrication of advanced nanocomposites. Here, we investigated the fabrication of reduced graphene/manganese (II, III) oxide (RGO/Mn3O4) nanocomposites by taking advantage of the microwave-assisted synthesis approach for cost effective, and ultrafast synthesis. Mn3O4 nanoparticles with uniform distribution in RGO sheets and ∼ 1.7 nm size was fabricated using the approach. Further, fine-tuning of the structural interaction and mechanical behavior of the GelMA-based hydrogels upon reinforcement with RGO/Mn3O4 nanocomposites was investigated as a function of different concentrations of the nanocomposites where upto 50 % increment in the compressive stress was observed compared to native GelMA hydrogel. The ability of these hydrogels was further investigated for their osteogenic behaviour on MC3T3-E1 preosteoblast cells where constant cell proliferation for up to 10 days was witnessed for the hybrid hydrogel with the highest concentration of the nanofillers.

Incorporation of calcium phosphate cement into decellularized extracellular matrix enhances its bone regenerative properties

Decellularized extracellular matrix (dECM) hydrogels are engineered constructs that are widely-used in the field of regenerative medicine. However, the development of ECM-based hydrogels for bone tissue engineering requires enhancement in its osteogenic properties. For this purpose, we initially employed bone-derived dECM hydrogel (dECM-Hy) in combination with calcium phosphate cement (CPC) paste to improve the biological and structural properties of the dECM hydrogel. A decellularization protocol for bovine bone was developed to prepare dECM-Hy, and the mechanically-tuned dECM/CPC-Hy was built based on both rheological and mechanical characteristics. The dECM/CPC-Hy displayed a double swelling ratio and compressive strength. An interconnected structure with distinct hydroxyapatite crystals was evident in dECM/CPC-Hy. The expression levels of Alp, Runx2 and Ocn genes were upregulated in dECM/CPC-Hy compared to the dECM-Hy. A 14-day follow-up of the rats receiving subcutaneous implanted dECM-Hy, dECM/CPC-Hy and mesenchymal stem cells (MSCs)-embedded (dECM/CPC/MSCs-Hy) showed no toxicity, inflammatory factor expression or pathological changes. Radiography and computed tomography (CT) of the calvarial defects revealed new bone formation and elevated number of osteoblasts-osteocytes and osteons in dECM/CPC-Hy and dECM/CPC/MSCs-Hy compared to the control groups. These findings indicate that the dECM/CPC-Hy has substantial potential for bone tissue engineering.

Nanoclay-Composite Hydrogels for Bone Tissue Engineering.

Nanoclay-composite hydrogels represent a promising avenue for advancing bone tissue engineering. Traditional hydrogels face challenges in providing mechanical strength, biocompatibility, and bioactivity necessary for successful bone regeneration. The incorporation of nanoclay into hydrogel matrices offers a potential unique solution to these challenges. This review provides a comprehensive overview of the fabrication, physico-chemical/biological performance, and applications of nanoclay-composite hydrogels in bone tissue engineering. Various fabrication techniques, including in situ polymerization, physical blending, and 3D printing, are discussed. In vitro and in vivo studies evaluating biocompatibility and bioactivity have demonstrated the potential of these hydrogels for promoting cell adhesion, proliferation, and differentiation. Their applications in bone defect repair, osteochondral tissue engineering and drug delivery are also explored. Despite their potential in bone tissue engineering, nanoclay-composite hydrogels face challenges such as optimal dispersion, scalability, biocompatibility, long-term stability, regulatory approval, and integration with emerging technologies to achieve clinical application. Future research directions need to focus on refining fabrication techniques, enhancing understanding of biological interactions, and advancing towards clinical translation and commercialization. Overall, nanoclay-composite hydrogels offer exciting opportunities for improving bone regeneration strategies.

Developing double-crosslinking 3D printed hydrogels for bone tissue engineering

Bone defects are one of the main causes of disability worldwide. Due to the disadvantages associated with autografts, the latest advances have been focused on tissue regeneration approaches that use injectable hydrogels or 3D printed hydrogel-based structures that could refill appropriately the bone gap area without the need for external fixatives, leading to bone formation in the long term. Injectable hydrogels could be applied in extrusion-based 3D printing as inks; in this sense, double-crosslinking hydrogels appear as ideal candidates. In this work, injectable and printable double crosslinkable hydrogels based on oxidized xanthan gum (XGox) and methacrylate polyaspartylhydrazide (PAHy-MA) were produced. The formation of dynamic hydrazone bonds, occurring between aldehyde groups on the polysaccharide backbone and hydrazine moieties of PAHy-MA, induced an instant gelation, conferring, also, injectability and self-healing properties to the hydrogels. The presence of methacrylic moieties on the synthetic polymer allowed further crosslinking upon UV irradiation that stabilized the hydrogel shape and mitigated its susceptibility to hydrolytic degradation. Obtained hydrogels showed pseudoplastic behaviour and good recovery of viscoelastic properties over time. The physicochemical and rheological characterization highlighted increased stability and higher viscoelastic moduli after photo-crosslinking. The hydrogels also showed good printability, cytocompatibility and the early formation of a bone-like matrix when osteosarcoma-derived cells (MG-63) were cultured in the scaffolds for 21 days, with an increased collagen I deposition, mineralization and the expression of characteristic osteogenic markers.

Fabrication and Biomedical Application of Alginate Composite Hydrogels in Bone Tissue Engineering: A Review.

Nowadays, as a result of the frequent occurrence of accidental injuries and traumas such as bone damage, the number of people causing bone injuries or fractures is increasing around the world. The design and fabrication of ideal bone tissue engineering (BTE) materials have become a research hotspot in the scientific community, and thus provide a novel path for the treatment of bone diseases. Among the materials used to construct scaffolds in BTE, including metals, bioceramics, bioglasses, biomacromolecules, synthetic organic polymers, etc., natural biopolymers have more advantages against them because they can interact with cells well, causing natural polymers to be widely studied and applied in the field of BTE. In particular, alginate has the advantages of excellent biocompatibility, good biodegradability, non-immunogenicity, non-toxicity, wide sources, low price, and easy gelation, enabling itself to be widely used as a biomaterial. However, pure alginate hydrogel as a BTE scaffold material still has many shortcomings, such as insufficient mechanical properties, easy disintegration of materials in physiological environments, and lack of cell-specific recognition sites, which severely limits its clinical application in BTE. In order to overcome the defects of single alginate hydrogels, researchers prepared alginate composite hydrogels by adding one or more materials to the alginate matrix in a certain proportion to improve their bioapplicability. For this reason, this review will introduce in detail the methods for constructing alginate composite hydrogels, including alginate/polymer composite hydrogels, alginate/bioprotein or polypeptide composite hydrogels, alginate/bioceramic composite hydrogels, alginate/bioceramic composite hydrogels, and alginate/nanoclay composite hydrogels, as well as their biological application trends in BTE scaffold materials, and look forward to their future research direction. These alginate composite hydrogel scaffolds exhibit both unexceptionable mechanical and biochemical properties, which exhibit their high application value in bone tissue repair and regeneration, thus providing a theoretical basis for the development and sustainable application of alginate-based functional biomedical materials.

Bone Morphogenetic Protein 7-Loaded Gelatin Methacrylate/Oxidized Sodium Alginate/Nano-Hydroxyapatite Composite Hydrogel for Bone Tissue Engineering.

Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration. Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models. The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups. Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.

Smart responsive in situ hydrogel systems applied in bone tissue engineering.

The repair of irregular bone tissue suffers severe clinical problems due to the scarcity of an appropriate therapeutic carrier that can match dynamic and complex bone damage. Fortunately, stimuli-responsive in situ hydrogel systems that are triggered by a special microenvironment could be an ideal method of regenerating bone tissue because of the injectability, in situ gelatin, and spatiotemporally tunable drug release. Herein, we introduce the two main stimulus-response approaches, exogenous and endogenous, to forming in situ hydrogels in bone tissue engineering. First, we summarize specific and distinct responses to an extensive range of external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) to form in situ hydrogels created from biocompatible materials modified by various functional groups or hybrid functional nanoparticles. Furthermore, "smart" hydrogels, which respond to endogenous physiological or environmental stimuli (e.g., temperature, pH, enzyme, etc.), can achieve in situ gelation by one injection in vivo without additional intervention. Moreover, the mild chemistry response-mediated in situ hydrogel systems also offer fascinating prospects in bone tissue engineering, such as a Diels-Alder, Michael addition, thiol-Michael addition, and Schiff reactions, etc. The recent developments and challenges of various smart in situ hydrogels and their application to drug administration and bone tissue engineering are discussed in this review. It is anticipated that advanced strategies and innovative ideas of in situ hydrogels will be exploited in the clinical field and increase the quality of life for patients with bone damage.

Biomimetic design of platelet-rich plasma controlled release bacterial cellulose/hydroxyapatite composite hydrogel for bone tissue engineering

Bacterial cellulose (BC) hydrogel is renowned in the field of tissue engineering for its high biocompatibility, excellent mechanical strength, and eco-friendliness. Herein, we present a biomimetic mineralization method for preparing BC/hydroxyapatite (HAP) composite hydrogel scaffolds with different mineralization time and ion concentration of the mineralized solution. Spherical HAP reinforcement enhanced bone mineralization, thereby imparting increased bioactivity to BC matrix materials. Subsequently, platelet-rich plasma (PRP) was introduced into the scaffold. The PRP-loaded hydrogel enhanced the release of growth factors, which promoted cell adhesion, growth, and bone healing. After 3 weeks of MC3T3-E1 cell-induced osteogenesis, PRP positively affected cell differentiation in BC/HAP@PRP scaffolds. Overall, these scaffolds exhibited excellent biocompatibility, mineralized nodule formation, and controlled release in vitro, demonstrating great potential for application in bone tissue repair.

A Combination of Flexible Modified Plant Virus Nanoparticles Enables Additive Effects Resulting in Improved Osteogenesis.

Plant virus nanoparticles (VNPs) genetically engineered to present osteogenic cues provide a promising method for biofunctionalizing hydrogels in bone tissue engineering. Flexible Potato virus X (PVX) nanoparticles substantially enhance the attachment and differentiation of human mesenchymal stem cells (hMSCs) by presenting the RGD motif, hydroxyapatite-binding peptide (HABP), or consecutive polyglutamates (E8) in a concentration-dependent manner. Therefore, it is hypothesized that Tobacco mosaic virus nanoparticles, which present 1.6 times more functional peptides than PVX, will meliorate such an impact. This study hypothesizes that cultivating hMSCs on a surface coated with a combination of two VNPs presenting peptides for either cell attachment or mineralization can achieve additionally enhancing effects on osteogenesis. Calcium minerals deposited by differentiating hMSCs increases two to threefold for this combination, while the Alkaline Phosphatase activity of hMSCs grown on the PVX-RGD/PVX-HABP-coated surface significantly surpasses any other VNP combination. Superior additive effects are observed for the first time by employing a combination of VNPs with varying functionalities. It is found that the flexible VNP geometry plays a more critical role than the concentration of functional peptides. In conclusion, various peptide-presenting plant VNPs exhibit an additive enhancing effect offering significant potential for effectively functionalizing cell-containing hydrogels in bone tissue engineering.

Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering.

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.

Metal Ion-Containing Hydrogels: Synthesis, Properties, and Applications in Bone Tissue Engineering.

Hydrogel, as a unique scaffold material, features a three-dimensional network system that provides conducive conditions for the growth of cells and tissues in bone tissue engineering (BTE). In recent years, it has been discovered that metal ion-containing hybridized hydrogels, synthesized with metal particles as the foundation, exhibit excellent physicochemical properties, osteoinductivity, and osteogenic potential. They offer a wide range of research prospects in the field of BTE. This review provides an overview of the current state and recent advancements in research concerning metal ion-containing hydrogels in the field of BTE. Within materials science, it covers topics such as the binding mechanisms of metal ions within hydrogel networks, the types and fabrication methods of various metal ion-containing hydrogels, and the influence of metal ions on the properties of hydrogels. In the context of BTE, the review delves into the osteogenic mechanisms of various metal ions, the applications of metal ion-containing hydrogels in BTE, and relevant experimental studies in vitro and in vivo. Furthermore, future improvements in bone repair can be anticipated through advancements in bone bionics, exploring interactions between metal ions and the development of a wider range of metal ions and hydrogel types.

The Application of Three-Dimensional-Printed Hydrogels in Bone Tissue Engineering.

Bone defects are a prevalent clinical issue that presents a serious medical challenge. Bone tissue engineering (BTE) has emerged as an effective approach for treating large bone defects. Hydrogels, as hydrophilic three-dimensional polymers, are recognized as suitable material for BTE due to their excellent biocompatibility and degradability. However, the submicron and nanoporous structure of hydrogels limits the survival of osteoblasts, hindering bone tissue regeneration. In recent years, 3D printing technology has attracted appreciable attention. The use of hydrogels as 3D-printed ink facilitates the printing of hydrogels in any desired shape, enabling personalized or more complex requirements. This article provides a systematic review of the latest applications of 3D-printed hydrogels in BTE. These hydrogels serve as a multifunctional platform for the next generation technology in treating bone defects. The advantages and limitations of 3D-printed hydrogels in BTE are discussed, and future research directions are explored. This review can form the basis for future hydrogel design.

A Dual Reversible Cross-Linked Hydrogel with Enhanced Mechanical Property and Capable of Proangiogenic and Osteogenic Activities for Bone Defect Repair.

The clinical treatment of bone defects presents ongoing challenges. One promising approach is bone tissue engineering (BTE), wherein hydrogels have garnered significant attention. However, the application of hydrogels in BTE is severely limited due to their poor mechanical properties, as well as their inferior proangiogenic and osteogenic activities. To address these limitations, our develop a dual cross-linked alendronate (ALN)-Ca2+ /Mg2+ -doped sulfated hyaluronic acid (SHA@CM) hydrogel, using a one-step mixing injection molding method known as "three-in-one" approach. This approach enabled the simultaneous formation of Schiff-Base crosslinking and electric attraction-based crosslinking within the hydrogel. The Schiff-Base crosslinking contributed to the majority of the hydrogel's mechanical strength, while the electric attraction-based crosslinking served as a release reservoir for Ca2+ /Mg2+ and ALN, promoting enhanced osteogenic activities and providing additional mechanical reinforcement to the hydrogel. These experimental data demonstrates several favorable properties of the SHA@CM hydrogel, including satisfactory injectability, rapid gelation, self-healing capacity, and excellent cytocompatibility. Moreover, the presence of sulfated groups and Mg2+ within the SHA@CM hydrogel exhibited pro-angiogenic effects, while the controlled release of nanoparticles formed by Ca2+ /Mg2+ and ALN further enhanced the osteogenesis of the hydrogel. Overall, these results indicate that the SHA@CM hydrogel holds significant potential for the clinical translation of BTE.

Synthesis of Silanized Bioactive Glass/Gelatin Methacrylate (GelMA/Si-BG) composite hydrogel for Bone Tissue Engineering Application

Bioactive glass (BG) has been widely employed in the field of bone tissue engineering owing to its osteoconductive properties. These properties increase the stiffness and bioactivity of polymeric hydrogels, making them ideal for the repair, replacement, and regeneration of damaged bones. In this study, we investigated the effects of incorporating silanized 45S5 bioactive glass (Si-BG) into gelatin methacrylate (GelMA) hydrogel (GelMA/Si-BG) for potential bone tissue engineering. Our findings revealed that crosslinking GelMA with Si-BG had a striking increase in bioactivity with and without osteogenic induction of human mesenchymal stem cells (hMSCs) when compared to GelMA/BG hydrogels. Meanwhile, both GelMA/Si-BG and GelMA/BG hydrogels were able to maintain the cell viability of hMSC for up to 14 days. Additionally, GelMA/Si-BG hydrogels were shown to have a significantly higher compressive modulus than GelMA/BG hydrogels. This study has demonstrated the introduction of silanized 45S5 BG into GelMA hydrogel bioactivity and mechanical properties of GelMA hydrogels, exemplifying the potential application of silanization of BG in bone tissue engineering.

Crosslinking strategies for biomimetic hydrogels in bone tissue engineering.

Bone tissue engineering has become a popular area of study for making biomimetic hydrogels to treat bone diseases. In this work, we looked at biocompatible hydrogels that can be injected into bone defects that require the smallest possible surgery. Mineral ions can be attached to polymer chains to make useful hydrogels that help bones heal faster. These ions are very important for the balance of the body. In the chemically-triggered sector, advanced hydrogels cross-linked by different molecular agents have many advantages, such as being selective, able to form gels, and having mechanical properties that can be modified. In addition, different photo-initiators can be used to make photo cross linkable hydrogels react quickly and moderately under certain light bands. Enzyme-triggered hydrogels are another type of hydrogel that can be used to repair bone tissue because they are biocompatible and gel quickly. We also look at some of the important factors mentioned above that could change how well bone tissue engineering works as a therapy. Finally, this review summarizes the problems that still need to be solved to make clinically relevant hydrogels.

Enhanced osteogenic and antibacterial properties of polyetheretherketone by ultraviolet-initiated grafting polymerization of a gelatin methacryloyl/epsilon-poly-L-lysine/laponite hydrogel coating.

Polyetheretherketone (PEEK) is a promising material for use in orthopedic implants, but its bio-inert character and lack of antibacterial activity limit its applications in bone repair. In the present study, considering the advantages of PEEK in self-initiated graft polymerization and of hydrogels in bone tissue engineering, we constructed a hydrogel coating (GPL) consisting of Gelatin methacryloyl (GelMA), methacrylamide-modified ε-poly-l-lysine (ε-PLMA) and Laponite on PEEK through UV-initiated crosslinking. The coating improved the hydrophilicity of PEEK, and the coating degraded slowly so that approximately 80% was retained after incubation in PBS for 8 weeks. In vitro studies revealed that as compared to culturing on PEEK, culturing on PEEK-GPL led to enhanced viability and adhesion of cultured human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs). Due to the synergistic effect of the micron-scale three-dimensional surface and Laponite, PEEK-GPL exhibited a significantly improved induction of osteogenic differentiation of hWJ-MSCs compared to PEEK, as demonstrated by increased alkaline phosphatase activity, matrix mineralization, and expression of osteogenesis-related genes. Furthermore, PEEK-GPL showed antibacterial activity upon contact with Staphylococcus aureus and Escherichia coli, and this activity would be maintained before complete degradation of the hydrogel because the ε-PLMA was cross-linked covalently into the coating. Thus, PEEK-GPL achieved both osteogenesis and infection prevention in a single simple step, providing a feasible approach for the extensive use of PEEK in bone implants.

Development of hybrid scaffolds with biodegradable polymer composites and bioactive hydrogels for bone tissue engineering

The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.

Recent Progress in Hyaluronic-Acid-Based Hydrogels for Bone Tissue Engineering.

Hydrogel-based bone tissue engineering is a potential strategy for treating bone abnormalities and fractures. Hyaluronic acid (HA) is a natural polymer that is widely distributed in the human body and plays a significant role in numerous physiological processes such as cell migration, tissue hydration, and wound healing. Hydrogels based on HA and its derivatives have gained popularity as potential treatments for bone-related diseases. HA-based hydrogels have been extensively studied for their ability to mimic the natural extracellular matrix of bone tissue and provide a suitable microenvironment for cell support and tissue regeneration. The physical and chemical properties of HA can be modified to improve its mechanical strength, biocompatibility, and osteogenic potential. Moreover, HA-based hydrogels combined with other biomaterials in the presence or absence of bioactive agents have been investigated as a means of improving the mechanical properties and bioactivity of the hydrogel scaffold. Therefore, HA-based hydrogels have shown great promise in bone tissue engineering due to their biocompatibility, osteogenic activity, and ability to mimic the natural extracellular matrix of bone tissue. Overall, this review provides a comprehensive overview of the current state of the art in HA-based hydrogels for bone tissue engineering, highlighting the key advances, challenges, and future directions in this rapidly evolving field.

Chitosan, Gelatin, and Collagen Hydrogels for Bone Regeneration.

Hydrogels are versatile biomaterials characterized by three-dimensional, cross-linked, highly hydrated polymeric networks. These polymers exhibit a great variety of biochemical and biophysical properties, which allow for the diffusion of diverse molecules, such as drugs, active ingredients, growth factors, and nanoparticles. Meanwhile, these polymers can control chemical and molecular interactions at the cellular level. The polymeric network can be molded into different structures, imitating the structural characteristics of surrounding tissues and bone defects. Interestingly, the application of hydrogels in bone tissue engineering (BTE) has been gathering significant attention due to the beneficial bone improvement results that have been achieved. Moreover, essential clinical and osteoblastic fate-controlling advances have been achieved with the use of synthetic polymers in the production of hydrogels. However, current trends look towards fabricating hydrogels from biological precursors, such as biopolymers, due to the high biocompatibility, degradability, and mechanical control that can be regulated. Therefore, this review analyzes the concept of hydrogels and the characteristics of chitosan, collagen, and gelatin as excellent candidates for fabricating BTE scaffolds. The changes and opportunities brought on by these biopolymers in bone regeneration are discussed, considering the integration, synergy, and biocompatibility features.

Injectable antibacterial Ag-HA/ GelMA hydrogel for bone tissue engineering.

Background: Fracture or bone defect caused by accidental trauma or disease is a growing medical problem that threats to human health.Currently, most orthopedic implant materials must be removed via follow-up surgery, which requires a lengthy recovery period and may result in bacterial infection. Building bone tissue engineering scaffolds with hydrogel as a an efficient therapeutic strategy has outstanding bionic efficiency.By combining some bionic inorganic particles and hydrogels to imitate the organic-inorganic characteristics of natural bone extracellular matrix, developing injectable multifunctional hydrogels with bone tissue repair effects and also displaying excellent antibacterial activity possesses attractive advantages in the field of minimally invasive therapy in clinical. Methods: In the present work, a multifunctional injectable hydrogel formed by photocrosslinking was developed by introducing hydroxyapatite (HA) microspheres to Gelatin Methacryloyl (GelMA) hydrogel. Results: The composite hydrogels exhibited good adhesion and bending resistance properties due to the existence of HA. In addition, when the concentration of GelMA is 10% and the concentration of HA microspheres is 3%, HA/GelMA hydrogel system displayed increased microstructure stability, lower swelling rate, increased viscosity, and improved mechanical properties. Furthermore, the Ag-HA/GelMA demonstrated good antibacterial activity against Staphylococcus aureus and Escherichia coli, which could signifificantly lower the risk of bacterial infection following implantation. According to cell experiment, the Ag-HA/GelMA hydrogel is capable of cytocompatibility and has low toxicity to MC3T3 cell. Conclusion: Therefore, the new photothermal injectable antibacterial hydrogel materials proposed in this study will provide a promising clinical bone repair strategy and is expected to as a minimally invasive treatment biomaterial in bone repair fields.