Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair

Abstract

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

Lyophilized Platelet-Rich Fibrin Exudate-Loaded Carboxymethyl Chitosan/GelMA Hydrogel for Efficient Bone Defect Repair

“…71,72 The fast degradation rate of biomaterials shows no pro-osteogenic effect, while a slow degradation rate delays the progress of bone formation. 73 Here, the degradation time of the CGP hydrogels was similar to the time required for rat bone healing, suggesting the potential application of the hydrogels for bone defect repair. 74 Furthermore, H&E staining of hydrogel with surrounding tissues was performed to reveal adjacent tissue responses and histological changes after hydrogel implantation (Figure 6d).…”

“…The result suggested that the addition of LPRFe did not influence the biodegradation time of CG hydrogels. The degradation rate of biomaterials used for bone tissue engineering is expected to match the bone regeneration rate. , The fast degradation rate of biomaterials shows no pro-osteogenic effect, while a slow degradation rate delays the progress of bone formation . Here, the degradation time of the CGP hydrogels was similar to the time required for rat bone healing, suggesting the potential application of the hydrogels for bone defect repair …”

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

“…In the physiological milieu, alginate hydrogel degradation is uncontrolled, and the molecular weight of released alginate strands is often higher than the renal clearance threshold. To control the degradation rate, oxidized alginate and cleavable crosslinkers have been applied in smart hydrogels, making them sensitive to specific stimuli [ 36 , 37 ].…”

A review on the synthesis and development of alginate hydrogels for wound therapy

“…Studies have shown that the alginate gel can load and culture bone marrow stromal cells (BMSC), which can form bone structures. 207 Taking cartilage repair as an example, the implantation of mixed alginate hydrogel scaffolds into the knee joint defect can induce the promotion of cartilage reconstruction, 208 or the artificial composite alginate hydrogel is directly used to replace some cartilage tissues. 209,210 Adding hydroxyapatite into the sodium alginate hydrogel for wound healing can stimulate the natural growth of living tissue and the recovery of damaged parts of the body.…”