Biodegradable Dual-Cross-Linked Hydrogels with Stem Cell Differentiation Regulatory Properties Promote Growth Plate Injury Repair via Controllable Three-Dimensional Mechanics and a Cartilage-like Extracellular Matrix

Abstract

Recent breakthroughs in cell transplantation therapy have revealed the promising potential of bone marrow mesenchymal stem cells (BMSCs) for promoting the regeneration of growth plate cartilage injury. However, the high apoptosis rate and the uncertainty of the differentiation direction of cells often lead to poor therapeutic effects. Cells are often grown under three-dimensional (3D) conditions in vivo, and the stiffness and components of the extracellular matrix (ECM) are important regulators of stem cell differentiation. To this end, a 3D cartilage-like ECM hydrogel with tunable mechanical properties was designed and synthesized mainly from gelatin methacrylate (GM) and oxidized chondroitin sulfate (OCS) via dynamic Schiff base bonding under UV. The effects of scaffold stiffness and composition on the survival and differentiation of BMSCs in vitro were investigated. A rat model of growth plate injury was developed to validate the effect of the GMOCS hydrogels encapsulated with BMSCs on the repair of growth plate injury. The results showed that 3D GMOCS hydrogels with an appropriate modulus significantly promoted chondrogenic differentiation of BMSCs, and GMOCS/ BMSC transplantation could effectively inhibit bone bridge formation and promote the repair of damaged growth plates. Accordingly, GMOCS/BMSC therapy can be engineered as a promising therapeutic candidate for growth plate injury.

Repair of Infected Bone Defects with Hydrogel Materials

“…Guan-synthesized three-dimensional hydrogels encapsulating bone marrow mesenchymal stem cells (BMSCs) use oxidized chondroitin sulfate via dynamic Schiff base bonding. The transformation of BMSCs into chondrocytes and the repair of damaged growth plates were facilitated [ 47 ]. Hao et al demonstrated that chondroitin sulfate is involved in biomineralization in its free state which promotes bone tissue repair [ 48 ].…”

Tissue engineering in growth plate cartilage regeneration: Mechanisms to therapeutic strategies

“…Thus, GMOCS hydrogels can achieve sustained release of active ingredients and affect the differentiation trend of MSCs, thus provide a good niche for promoting the repair of growth plates injury and cartilage regeneration. Their safety and feasibility for clinical conversion can be further evaluated in the future 167 (Table 2).…”