Hydrogels For Bone Tissue Engineering Research Articles

Fabrication of polycaprolactone/chitosan/hydroxyapatite structure to improve the mechanical behavior of the hydrogel‐based scaffolds for bone tissue engineering: Biscaffold approach

AbstractThe main idea of this study is to create a 3D printed scaffold to improve the mechanical behavior of hydrogels for bone tissue engineering. This paper investigated the effects of infill percentage and strand diameter on the 3D printed polycaprolactone/Chitosan/HA scaffold's mechanical properties. The printing parameters were optimized by central composite design in response surface methodology. The X, Y, and Z axes measured stiffness (N/m), compressive strength (MPa), and elongation at break (%). The results showed that the highest stiffness of all samples (in both vertical (65 MPa) and horizontal (32 MPa) loading dimensions) could be found in the scaffolds with 40% infill and the strands with 400 μm diameter. It was also indicated that the degradability of the samples could be improved (0.33%–1.03%) with a reduction of strand diameter from 600 to 400 μm. The most swelling was attributed to the scaffold with 50% infill and strand diameter of 600 μm. Hydrophilicity was improved by employing chitosan (78.3°–66.3°). Results depicted good biocompatibility (>80%) of the samples. To sum up, the idea of a biscaffold with suitable engineering can be a good idea to enhance the mechanical behavior of hydrogel‐based scaffolds.

Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering.

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.

In vitro and in vivo evaluation of hydrogel-based scaffold for bone tissue engineering application

The main objective of the current assay was to fabricate a sophisticated and effective scaffold based on the nanofibrous structure in combination with the 3D structure of hydrogels for bone tissue engineering. In this scenario, we fabricated nanofibers using electrospinning and carbonized them. The processed nanofibers were added to the polymeric solution and cross-linked to embedded nanofibers into the 3D structure of hydrogel. The obtained constructs were characterized using the most relevant characterization techniques. The results showed that as-prepared nanofibers have a diameter of 185 ± 63 nm and some breakages and fusions in the nanofiber's structure are apparent. The electron microscopy showed that the obtained 3D structure has a porous architecture with interconnected pores that are beneficial for bone regeneration. The biological evaluations also showed that the fabricated 3D scaffold was hemocompatible, cytocompatible, and regenerated new bone tissue in an animal model. In conclusion, these results implied that the fabricated NFC-integrated 3D scaffold exhibited promising characteristics beneficial for bone regeneration and can be applied as the bone tissue engineering scaffold.

Application of Hydrogels as Three-Dimensional Bioprinting Ink for Tissue Engineering.

The use of three-dimensional bioprinting technology combined with the principle of tissue engineering is important for the construction of tissue or organ regeneration microenvironments. As a three-dimensional bioprinting ink, hydrogels need to be highly printable and provide a stiff and cell-friendly microenvironment. At present, hydrogels are used as bioprinting inks in tissue engineering. However, there is still a lack of summary of the latest 3D printing technology and the properties of hydrogel materials. In this paper, the materials commonly used as hydrogel bioinks; the advanced technologies including inkjet bioprinting, extrusion bioprinting, laser-assisted bioprinting, stereolithography bioprinting, suspension bioprinting, and digital 3D bioprinting technologies; printing characterization including printability and fidelity; biological properties, and the application fields of bioprinting hydrogels in bone tissue engineering, skin tissue engineering, cardiovascular tissue engineering are reviewed, and the current problems and future directions are prospected.

Synthesis and Characterizations of Bioactive Glass Nanoparticle-Incorporated Triblock Copolymeric Injectable Hydrogel for Bone Tissue Engineering.

Recently, injectable hydrogels have attracted much interest in tissue engineering (TE) applications because of their controlled flowability, adaptability, and easy handling properties. This work emphasizes the synthesis and characterizations of bioactive glass (BAG) nanoparticle-reinforced poly(ethylene glycol) (PEG)- and poly(N-vinylcarbazole) (pNVC)-based minimally invasive composite injectable hydrogel suitable for bone regeneration. First, the copolymer was synthesized from a combination of PEG and pNVC through reversible addition-fragmentation chain-transfer (RAFT) polymerization and nanocomposite hydrogel constructs were subsequently prepared by conjugating BAG particles at varying loading concentrations. Gel permeation chromatography (GPC) analysis confirmed the controlled nature of the polymer. Various physicochemical characterization results confirmed the successful synthesis of copolymer and nanocomposite hydrogels that showed good gelling and injectability properties. Our optimal nanocomposite hydrogel formulation showed excellent swelling properties in comparison to the copolymeric hydrogel due to the presence of hydrophilic BAG particles. The bone cell proliferation rate was found to be evidently higher in the nanocomposite hydrogel than in the copolymeric hydrogel. Moreover, the enhanced level of ALP activity and apatite mineralization for the nanocomposite in comparison to that for the copolymeric hydrogel indicates accelerated in vitro osteogenesis. Overall, our study findings indicate BAG particle-conjugated nanocomposite hydrogels can be used as promising grafting materials in orthopedic reconstructive surgeries complementary to conventional bone graft substitutes in cancellous bone defects due to their 3D porous framework, minimal invasiveness, and ability to form any desired shape to match irregular bone defects.

The fabrication of hydroxyapatite mineralized hydrogels for bone tissue engineering

The fabrication of hydroxyapatite mineralized hydrogels for bone tissue engineering

Chitosan/POSS Hybrid Hydrogels for Bone Tissue Engineering.

Hybrid hydrogels composed of chitosan (CS) have shown great potential in bone tissue engineering and regeneration. The introduction of polyhedral oligomeric silsesquioxanes (POSS) in the biopolymeric matrix has been demonstrated to improve the rheological and biological properties of the hybrid composites. In this work, we have integrated the favourable features of chitosan (CS) and POSS nanoparticles to design new nanocomposites for bone tissue regeneration, focusing our attention on the effect of POSS concentration within the CS matrix (0.5, 1, and 1.5 equivalents in weight of POSS with respect to CS) on the chemical, physical, rheological, and in vitro biological properties of the final composites. The drug release ability of the synthesized hydrogel scaffolds were also investigated using, as the model drug, ketoprofen, that was included in the scaffold during the gelling procedure, showing a more controlled release for the hybrids with respect to CS (86-91% of drug released after two weeks). The results of the in vitro biological tests performed on human fetal osteoblastic cells (hFOB 1.19) culture demonstrated the great biocompatibility of the hybrid materials. The hybrids, at the different POSS concentrations, showed values of cell mortality superimposable with control cells (11.1 vs. 9.8%), thus revealing the CS/POSS hydrogels as possible candidates for bone tissue engineering applications.

Enzyme-Triggered Crosslinked Hybrid Hydrogels for Bone Tissue Engineering.

The quest to develop state-of-the-art hydrogels for bone tissue engineering has accompanied substantial innovation and significant progression in the field of bioactive hydrogels. Still, there is scope for advancement in this cell-friendly and biocompatible scaffold system. The crosslinking approaches used for hydrogel synthesis plays a decisive role in guiding and regulating the mechanical stability, network framework, macroscopic architect, immunological behaviors, and cellular responses. Until recently, enzyme-based crosslinking strategies were considered as the pinnacle in designing efficient hybrid hydrogel systems. A variety of enzymes have been explored for manufacturing hydrogels while taking the advantage of the biocompatible nature, specificity, ability to produce nontoxic by products and high efficiency of enzymes. The current review focuses on the utility of different enzymes as crosslinking agents for hydrogel formation with their application in bone tissue engineering. The field of enzyme crosslinked hydrogel synthesis is rapidly maturing with a lot of opportunities to be explored in bone tissue engineering. Enzyme-based in situ and externally crosslinked hydrogels for bone regeneration is an attractive field, and with innovation in using engineered enzymes this field will continue to flourish with clinical orientation.

3D Bioprinted GelMA-Gelatin-Hydroxyapatite Osteoblast Laden Composite Hydrogels for Bone Tissue Engineering.

Introduction 3D bioprinting offers a novel solution to critical sized bone defects by allowing the placement of osteogenic cells, additive biomaterials and bioactive signaling that mimic native tissue. We describe the suitability of an extrusion-based 3D bioink composed of gelatin methacryloyl (GelMA), gelatin, hydroxyapatite (HA), and osteoblasts for bone tissue engineering. Methods A mouse calvarial osteoblast-laden GelMA-gelatin-LAP bioink consisting of various concentrations of HA was 3D-bioprinted into a porous hydrogel construct. After days 1, 14, and 28, five constructs from each HA concentration were analyzed. The water weight percent differences of the hydrogels and the degradation behavior in enzyme solution were characterized. An ALP assay and histological analysis were performed. Cell survivability was determined using a LIVE/DEAD Viability/Cytoxicity Kit and AlamarBlue Cell Viability reagent. Real-time polymerase chain reaction (RT-qPCR) was performed to measure expression levels of bone morphogenetic protein-7 (BMP-7) and Osteocalcin (BGLAP). Results The addition of 5, 10, and 20 mg/ml of HA significantly reduced hydrogel swelling (p ≤ 0.01) from baseline GelMA-Gelatin hydrogels (Figure 3A). HA significantly decreased hydrogel breakdown in a concentration dependent manner (Figure 3B, p ≤ 0.001). A significant increase in cell proliferation at day 28 was noted in all groups (Figure 3D). ALP activity (Figure 3E) significantly increased with the addition of 5mg/ml and 20mg/ml of HA at days 7 and 28 (p ≤ 0.05). Live/dead staining at 1, 14, and 28 days showed high chondrocyte viability. The addition of 20mg/ml of HA demonstrated significantly greater BMP7 and BGLAP gene expression at both 14 and 28 days over the hydrogels without HA (Figure 5, p ≤ 0.05). Conclusion The addition of HA to GelMA-gelatin hydrogels significantly decreased hydrogel swelling, improved the ability of the hydrogel to resist enzymatic degradation, increased osteoblastic differentiation and mineralization, and increased osteogenic gene expression while maintaining equal cell viability and proliferation to non-HA hydrogels.

Application of Graphene Oxide-Based Hydrogels in Bone Tissue Engineering.

As an important derivative of graphene-based materials, graphene oxide (GO) not only plays an important role not only in optoelectronics and sensing but also in biology due to its unique mechanical, electronic, and optical properties. This article reviews the application of GO-based hydrogels in bone tissue engineering. Whether it is a hydrogel synthesized with natural polymer compounds, synthetic polymer chemicals, bioceramics, bioactive factors, or other materials, the addition of GO can significantly improve various properties of the hydrogel. We also introduce some high-performance GO-based hydrogels in this paper, proposing some insights into materials that may be applied to bone tissue engineering in the future.

Stiff and Tough Hydrogels Prepared Through Integration of Ionic Cross-linking and Enzymatic Mineralization

Enzymatic mineralization has become an effective approach to enhancing the stiffness of hydrogels for bone tissue engineering, but generally with limited toughness. On the other hand, double network cross-linking provides hydrogel with enhanced toughness. In this study, we integrated double cross-linking method with enzymatic mineralization to synthesize stiff and tough hydrogels. We have synthesized three kinds of sodium alginate-polyacrylamide (SA-PAM) double-network hydrogels and systematically compared the composition and structure differences, mechanical properties, and biological properties of the different hydrogels in the absence and presence of mineralization. In particular, we examined the role of specific cross-linking ions, i.e., calcium, zinc and strontium ions, in modulating the mineralization process. Synergistic effect of ionic cross-linking and enzymatic mineralization was clearly observed with dramatic increase in compressive modulus. In particular, mineralized hydrogel cross-linked with Sr2+ showed the highest compressive Young's modulus of 17.28 ± 3.56 MPa, which was 37 times of that of the original hydrogel. In addition, it had the highest tensile Young's modulus at 2.60 ± 0.25 MPa and 84 ± 5.5% elongation at break. Such synergistic effect from Sr2+ was attributed to a more uniformed mineralization process due to the early initiation of a more homogeneous nucleation process and subsequent denser mineralized structure. Cellular study also suggested that cell proliferation, adhesion and osteogenic differentiation were improved as a result of enzymatic mineralization. Our results provided an effective way for the preparation of stiff and tough hydrogels with osteogenesis, and demonstrated potential in bone tissue engineering applications. Statement of significanceHydrogels with excellent stiffness, stability and biocompatibility have attracted significant attentions in the bone tissue engineering applications. Our results suggested that the synergistic effect of ionic cross-linking and enzymatic mineralization rendered more enhancement of the compressive and tensile stiffness of SA-PAM DN hydrogels, as well as the toughness, swelling stability and cellular response. In particular, mineralized hydrogel cross-linked with Sr2+ showed the highest compressive Young's modulus of 17.28 ± 3.56MPa, which was 37 times of that of the original hydrogel. Such synergistic effect from Sr2+ was attributed to a more uniformed mineralization process. The cell proliferation, adhesion and osteogenic differentiation were greatly improved as a result of enzymatic mineralization, where the MSCs cultured on strontium ion cross-linked mineralized hydrogel showed the best performance.

3D-bioprinted GelMA-gelatin-hydroxyapatite osteoblast-laden composite hydrogels for bone tissue engineering

IntroductionThe treatment of large bone defects remains an area of significant challenge in orthopaedic surgery. In cases where critical-sized defects (CSDs) remain, current treatment options are underwhelming and are often fraught with complications. 3D bioprinting offers a novel solution to CSDs by allowing the placement of osteogenic cells, additive biomaterials and bioactive signaling that mimic native tissue. We describe the suitability of an extrusion-based 3D bioink composed of gelatin methacryloyl (GelMA), gelatin, hydroxyapatite (HA), and osteoblasts for bone tissue engineering. MethodsA MC3T3-E1 Subclone 4 mouse calvarial osteoblast-laden GelMA-gelatin bioink consisting of various concentrations of HA was 3D-bioprinted into porous hydrogel constructs using an in-lab modified BIO-X 3D Bioprinter. The 3D-fabricated constructs were cross-linked via photopolymerization in the presence of Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) under UV light (1000 mW/cm2) cultured in complete osteogenic medium. After 1, 14, and 28 days, a cohort of constructs were harvested for analysis. An ALP assay and histological analysis were performed. Cell survivability and proliferation in the composite hydrogels was determined. Real-time polymerase chain reaction (RT-qPCR) was performed to measure expression levels of osteogenic genes bone morphogenetic protein-7 (BMP-7) and Osteocalcin (BGLAP) relative to a housekeeping gene (GAPDH). ResultsThe addition of HA to the bioink significantly decreased swelling from baseline GelMA-Gelatin hydrogels with a slight trend of decreased swelling with increasing HA content. The addition of 5, 10, and 20 mg/mL of HA significantly reduced hydrogel swelling (p ≤ 0.01). There was no difference among the HA groups. Degradation analysis with Type IV collagenase demonstrated that HA significantly decreased hydrogel breakdown in a concentration dependent manner (p ≤ 0.001). Results of the Alamar Blue assay demonstrated significantly increased cell proliferation in all groups at day 28, including the hydrogels without any HA. There was no difference in metabolic activity among the groups (p ≤ 0.01). ALP activity for days 7, 14, and 28 was normalized to Day 1 and found that the addition of 5 mg/mL and 20 mg/mL of HA significantly increased ALP expression at days 7 and 28 (p ≤ 0.05). Live/dead staining at 1, 14, and 28 days after printing showed, in all groups, the majority of the osteoblasts were alive at each time-point. The addition of 20 mg/mL of HA (GG20HA) demonstrated significantly greater BMP7 and BGLAP gene expression at both 14 and 28 days over the hydrogels without HA (p ≤ 0.05). ConclusionIn order for tissue-engineered bone defect repair materials to be successful they need to be biocompatible, biodegradable, similar in strength to bone while allowing for good bone induction, and a three-dimensional porous network structure for host tissue ingrowth. Therefore, 3D bioprinting for bone tissue engineering is an exciting possibility in the treatment of critical-sized bone defects as it presents an opportunity to fulfill these qualities. Although there are many reports on 3D bioprinting of bone-like structures, the ideal bioink(s) for bone tissue regeneration have yet to be discovered. Here we report on the use of a cellular GelMA-gelatin bioink with the addition of HA. In this report we demonstrated the suitability of a GelMA-gelatin-HA bioink for 3D bioprinting of bone tissue engineering applications. The addition of HA to GelMA-gelatin hydrogels significantly (1) decreased hydrogel swelling, (2) improved upon the ability of the hydrogel to resist enzymatic degradation, (3) increased osteoblastic differentiation and mineralization, and (4) increased osteogenic gene expression while maintaining equal cell viability and proliferation to non HA hydrogels. GelMA-gelatin-HA is a promising hydrogel for bone tissue repair.Significance/Clinical Relevance: We demonstrated the suitability of a GelMA-gelatin-HA bioink for 3D bioprinting of bone tissue engineering applications. The addition of HA to GelMA-gelatin hydrogels significantly decreased hydrogel swelling, improved the ability of the hydrogel to resist enzymatic degradation, increased osteoblastic differentiation and mineralization, and increased osteogenic gene expression while maintaining equal cell viability and proliferation to non-HA hydrogels. GelMA-gelatin-HA is a promising hydrogel for bone tissue repair.

Injectable pH-responsive adhesive hydrogels for bone tissue engineering inspired by the underwater attachment strategy of marine mussels

A major challenge in tissue engineering is the development of alternatives to traditional bone autografts and allografts that can regenerate critical-sized bone defects. Here we present the design of injectable pH-responsive double-crosslinked adhesive hydrogels inspired by the molecular mechanism and environmental post-processing of marine mussel adhesive. Nine adhesive hydrogel formulations were developed through the conjugation of crosslinkable catechol functional groups (DOPA) and the synthetic oligomer oligo[poly(ethylene glycol) fumarate] (OPF), varying the DOPA content (w/w%) and molecular weight (MW) of the OPF backbone to produce formulations with a range of swelling ratios, porosities, and crosslink densities. DOPA incorporation altered the surface chemistry, mechanical properties, and surface topography of hydrogels, resulting in an increase in material stiffness, slower degradation, and enhanced pre-osteoblast cell attachment and proliferation. When injected within simulated bone defects, DOPA-mediated interfacial adhesive interactions also prevented the displacement of scaffolds, an effect that was maintained even after swelling within physiological conditions. Taken together, OPF-DOPA hydrogels represent a promising new material to enhanced tissue integration and the prevention of the post-implantation migration of scaffolds that can occur due to biomechanical loading in vivo.

Methods of improving the mechanical properties of hydrogels and their research progress in bone tissue engineering

To review the methods of improving the mechanical properties of hydrogels and the research progress in bone tissue engineering. The recent domestic and foreign literature on hydrogels in bone tissue engineering was reviewed, and the methods of improving the mechanical properties of hydrogels and the effect of bone repair in vivo and in vitro were summarized. Hydrogels are widely used in bone tissue engineering, but their mechanical properties are poor. Improving the mechanical properties of hydrogels can enhance bone repair. The methods of improving the mechanical properties of hydrogels include the construction of dual network structures, inorganic nanoparticle composites, introduction of conductive materials, and fiber network reinforcement. These methods can improve the mechanical properties of hydrogels to various degrees while also demonstrating a significant bone repair impact. The mechanical properties of hydrogels can be effectively improved by modifying the system, components, and fiber structure, and bone repair can be effectively promoted.

Injectable eggshell-derived hydroxyapatite-incorporated fibroin-alginate composite hydrogel for bone tissue engineering

Tissue engineering is a promising approach to repair and regenerate damaged or lost tissues or organs. In dental aspect, reconstruction of the resorbed alveolar bone after tooth extraction plays an important role in the success of dental substitution, especially in dental implant treatment. The hydroxyapatite (HA)-incorporated fibroin-alginate composite injectable hydrogel was fabricated to be used as scaffold for bone regeneration. HA was synthesized from eggshell biowaste. Fibroin was extracted from Bombyx mori cocoon. The synthesized HA, fibroin and alginate hydrogel were characterized. HA-incorporated fibroin-alginate hydrogel had decreased pore size and porosity compared with pure alginate hydrogel. Thermal analysis showed that hydrogel had a degradation peak of approximately 250 °C. Hydrogel could absorb water, with a swelling ratio of around 300% at 24 h. Hydrogel was degraded as time passed and almost completely degraded at day 7. Its compressive Young's modulus was approximately 0.04 ± 0.02 N/mm2 to 0.10 ± 0.02 N/mm2. Primary cytotoxicity test indicated non-toxic potential of the fabricated hydrogel. Increased ALP activity was observed in MC3T3-E1 cultured in HA-incorporated fibroin-alginate hydrogel. Results suggested the potential use of injectable HA fibroin-alginate hydrogel as dental scaffolding material. Further studies including in vivo examinations are needed prior to its clinical application.

Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering.

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications.

Withdrawal Notice: Application of Graphene Oxide-Based Hydrogels in Bone Tissue Engineering

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Fabrication and Characterization of Biodegradable Gelatin Methacrylate/Biphasic Calcium Phosphate Composite Hydrogel for Bone Tissue Engineering.

In the field of bone tissue, maintaining adequate mechanical strength and tissue volume is an important part. Recently, biphasic calcium phosphate (BCP) was fabricated to solve the shortcomings of hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP), and it is widely studied in the field of bone-tissue engineering. In this study, a composite hydrogel was fabricated by applying BCP to gelatin methacrylate (GelMA). It was tested by using a mechanical tester, to characterize the mechanical properties of the prepared composite hydrogel. The fabricated BCP was analyzed through FTIR and XRD. As a result, a different characteristic pattern from hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) was observed, and it was confirmed that it was successfully bound to the hydrogel. Then, the proliferation and differentiation of preosteoblasts were checked to evaluate cell viability. The analysis results showed high cell viability and relatively high bone differentiation ability in the composite hydrogel to which BCP was applied. These features have been shown to be beneficial for bone regeneration by maintaining the volume and shape of the hydrogel. In addition, hydrogels can be advantageous for clinical use, as they can shape the structure of the material for custom applications.

Nanohydroxyapatite incorporated photocrosslinked gelatinmethacryloyl/poly(ethyleneglycol)diacrylate hydrogel for bone tissue engineering.

The development of novel strategies that aim to augment the regenerative potential of bone is critical for devising better treatment options for bone defects or injuries. Facilitation of bone repair and regeneration utilizing composite hydrogels that simulates bone matrix is emerging as a viable approach in bone tissue engineering. The present study aimed to develop nanohydroxyapatite-incorporated gelatinmethacryloyl (GelMA)/poly(ethylene glycol) diacrylate (PEGDA) hydrogel (GMPHhydrogel). A facile blending and photocrosslinking approach was employed to incorporate nanohydroxyapatite into the inter-crosslinked polymeric hydrogel network to obtain an ECM mimicking matrix for assisting bone tissue regeneration. Chemical characterization of GelMA and the GMPH hydrogel was carried out using FTIR and 1H NMR. Physical properties of GMPH, such as gelation, swelling and degradation ratios, and internal morphology, signified the suitability of GMPH hydrogel for tissue engineering. Cell viability assay demonstrated a healthy proliferation of MG63 osteoblast cells in GMPH hydrogel extracted growth medium, indicating the hydrogel's cytocompatibility and suitability for bone tissue engineering. Our study documented the fabrication of a novel GelMA/PEGDA-nanohydroxyapatite hydrogel that possesses ideal physicochemical and biological properties for bone tissue engineering.

Recent Advances in Design of Functional Biocompatible Hydrogels for Bone Tissue Engineering

AbstractBone related diseases have caused serious threats to human health owing to their complexity and specificity. Fortunately, owing to the unique 3D network structure with high aqueous content and functional properties, emerging hydrogels are regarded as one of the most promising candidates for bone tissue engineering, such as repairing cartilage injury, skull defect, and arthritis. Herein, various design strategies and synthesis methods (e.g., 3D‐printing technology and nanoparticle composite strategy) are introduced to prepare implanted hydrogel scaffolds with tunable mechanical strength, favorable biocompatibility, and excellent bioactivity for applying in bone regeneration. Injectable hydrogels based on biocompatible materials (e.g., collagen, hyaluronic acid, chitosan, polyethylene glycol, etc.) possess many advantages in minimally invasive surgery, including adjustable physicochemical properties, filling irregular shapes of defect sites, and on‐demand release drugs or growth factors in response to different stimuli (e.g., pH, temperature, redox, enzyme, light, magnetic, etc.). In addition, drug delivery systems based on micro/nanogels are discussed, and its numerous promising designs used in the application of bone diseases (e.g., rheumatoid arthritis, osteoarthritis, cartilage defect) are also briefed in this review. Particularly, several key factors of hydrogel scaffolds (e.g., mechanical property, pore size, and release behavior of active factors) that can induce bone tissue regeneration are also summarized in this review. It is anticipated that advanced approaches and innovative ideas of bioactive hydrogels will be exploited in the clinical field and increase the life quality of patients with the bone injury.