A biodegradable piezoelectric scaffold excited by exercise promotes chondrogenesis and cartilage regeneration in rabbit osteochondral defects.

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.

Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR, 1 H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 mm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed B11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel.