Development and evaluation of an injectable ChitHCl-MgSO4-DDA hydrogel for bone regeneration: In vitro and in vivo studies on cell migration and osteogenesis enhancement.

Nonunion and delayed union of the bone are situations in orthopedic surgery that can occur even if the bone alignment is correct and there is sufficient mechanical stability. Surgeons usually apply artificial bone grafts in bone fracture gaps or in bone defect sites for osteogenesis to improve bone healing; however, these bone graft materials have no osteoinductive or osteogenic properties, and fit the morphology of the fracture gap with difficulty. In this study, we developed an injectable chitosan-based hydrogel with MgSO4 and dextran oxidative, with the purpose to improve bone healing through introducing an engineered chitosan-based hydrogel. The developed hydrogel can gelate and fit with any morphology or shape, has good biocompatibility, can enhance the cell-migration capacity, and can improve extracellular calcium deposition. Moreover, the amount of new bone formed by injecting the hydrogel in the bone tunnel was assessed by an in vivo test. We believe this injectable chitosan-based hydrogel has great potential for application in the orthopedic field to improve fracture gap healing.

Injectable ChitHCl-DDA tissue adhesive with high adhesive strength and biocompatibility for torn meniscus repair and regeneration.

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.

Self-adaptable calcium-based bioactive phosphosilicate-infused gelatin-hyaluronic hydrogel for orthopedic regeneration.

Bone regeneration is a critical and intricate process vital for healing fractures, defects, and injuries. Although conventional bone grafts are commonly used, they may fall short of optimal outcomes, thereby driving the need for alternative therapies. This research endeavors to explore synergistically designed Hyalo Glass Gel (HGG), and its explicitly for bone tissue engineering and regenerative medicine. The HGG composite comprises a modifiable calcium-based bioactive phosphosilicates-incorporated/crosslinked gelatin-hyaluronic scaffold showcasing promising functional characteristics. The study underscores the distinct attributes of each constituent (gelatin (Gel), hyaluronic acid (HA), and 45S5 calcium sodium phosphosilicates (BG)), and their cooperative influences on the scaffold's performance. Careful manipulation of crosslinking methods facilitates customization of HGG's mechanical attributes, degradation kinetics, and structural features, aligning them with the requisites of bone tissue engineering applications. Moreover, the integration of BG augments the scaffold's bioactivity, thereby expediting tissue regenerative processes. This comprehensive evaluation encompasses HGG's physicochemical aspects, mechanical traits rooted in viscoelasticity, as well as its biodegradability, in-vitro bioactivity, and interactions with stem cells. The result obtained underscores the viscoelastic nature of HGG, substantiating its capacity to foster mesenchymal stem cell viability, proliferation, and differentiation. Significantly, HGG manifests biocompatibility and adjustable attributes, exhibits pronounced drug (vancomycin) retention abilities, rendering it apt for wound healing, drug delivery, and bone regeneration. Its distinctive composition, tailored attributes, and mimicry of bone tissue's extracellular matrix (ECM) due to its bioactive nature, collectively situate its potential as a versatile biomaterial for subsequent research and development endeavors with compelling prospects in bone tissue engineering and regenerative medicine.

Plasma-Enabled Graphene Quantum Dot Hydrogel-Magnesium Composites as Bioactive Scaffolds for In Vivo Bone Defect Repair.

Bioactive and mechanically stable metal-based scaffolds are commonly used for bone defect repair. However, conventional metal-based scaffolds induce nonuniform cell growth, limiting damaged tissue restoration. Here, we develop a plasma nanotechnology-enhanced graphene quantum dot (GQD) hydrogel-magnesium (Mg) composite scaffold for functional bone defect repair by integrating a bioresource-derived nitrogen-doped GQD (NGQD) hydrogel into the Mg ZK60 alloy. Each scaffold component brings major synergistic advantages over the current alloy-based state of the art, including (1) mechanical support of the cortical bone and calcium deposition by the released Mg2+ during degradation; (2) enhanced uptake, migration, and distribution of osteoblasts by the porous hydrogel; and (3) improved osteoblast adhesion and proliferation, osteogenesis, and mineralization by the NGQDs in the hydrogel. Through an in vivo study, the hybrid scaffold with the much enhanced osteogenic ability induced by the above synergy promotes a more rapid, uniform, and directional bone growth across the hydrogel channel, compared with the control Mg-based scaffold. This work provides insights into the design of multifunctional hybrid scaffolds, which can be applied in other areas well beyond the demonstrated bone defect repair.