Hydrogels For Bone Tissue Engineering Research Articles

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.

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.

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.

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.

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.