Dynamic mechanical loading facilitated chondrogenic differentiation of rabbit BMSCs in collagen scaffolds

Mechanical signals have been played close attention to regulate chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In this study,dynamic mechanical loading simulation with natural frequencies and intensities were applied to the 3D cultured BMSCs–collagen scaffold constructs.We investigated the effects of dynamic mechanical loading on cell adhesion,uniform distribution,proliferation,secretion of extracellular matrix(ECM)and chondrogenic differentiation of BMSCs–collagen scaffold constructs.The results indicated that dynamic mechanical loading facilitated the BMSCs adhesion,uniform distribution,proliferation and secretion of ECM with a slight contraction,which significantly improved the mechanical strength of the BMSCs–collagen scaffold constructs for better mimicking the structure and function of a native cartilage.Gene expression results indicated that dynamic mechanical loading contributed to the chondrogenic differentiation of BMSCs with higher levels of AGG,COL2A1 and SOX9 genes,and prevented of hypertrophic process with lower levels of COL10A1,and reduced the possibility of fibrocartilage formation due to down-regulated COL1A2.In conclusion,this study emphasized the important role of dynamic mechanical loading on promoting BMSCs chondrogenic differentiation and maintaining the cartilage phenotype for in vitro reconstruction of tissue-engineered cartilage,which provided an attractive prospect and a feasibility strategy for cartilage repair.

BMSCs-assisted injectable Col I hydrogel-regenerated cartilage defect by reconstructing superficial and calcified cartilage

The self-healing capacity of cartilage was limited due to absence of vascular,nervous and lymphatic systems.Although many clinical treatments have been used in cartilage defect repair and shown a promising repair result in short term,however,regeneration of complete zonal structure with physiological function,reconstruction cartilage homeostasis and maintaining long-term repair was still an unbridgeable chasm.Cartilage has complex zonal structure and multiple physiological functions,especially,superficial and calcified cartilage played an important role in keeping homeostasis.To address this hurdle of regenerating superficial and calcified cartilage,injectable tissue-induced type I collagen(Col I)hydrogel-encapsulated BMSCs was chosen to repair cartilage damage.After 1 month implantation,the results demonstrated that Col I gel was able to induce BMSCs differentiation into chondrocytes,and formed hyaline-like cartilage and the superficial layer with lubrication function.After 3 months post-surgery,chondrocytes at the bottom of the cartilage layer would undergo hypertrophy and promote the regeneration of calcified cartilage.Six months later,a continuous anatomical tidemark and complete calcified interface were restored.The regeneration of neo-hyaline cartilage was similar with adjacent normal tissue on the thickness of the cartilage,matrix secretion,collagen type and arrangement.Complete multilayer zonal structure with physiological function remodeling indicated that BMSCs-assisted injectable Col I hydrogel could reconstruct cartilage homeostasis and maintain long-term therapeutic effect.