Genipin cross-linked type II collagen/chondroitin sulfate composite hydrogel-like cell delivery system induces differentiation of adipose-derived stem cells and regenerates degenerated nucleus pulposus

Publication date: Available online 16 March 2018
Source:Acta Biomaterialia
Author(s): Xiaopeng Zhou, Jingkai Wang, Weijing Fang, Yiqing Tao, Tengfei Zhao, Kaishun Xia, Chengzhen Liang, Jianming Hua, Fangcai Li, Qixin Chen
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro, and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo. The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease.Statement of significanceNucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent low back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSCs (CCSA) delivery system with genipin cross-linking. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is pre-loaded with ADSCs and can be injected into the NP with needle, followed by in situ gelation. Genipin is used as a cross-linker to improve the bio-stability of scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on ADSCs differentiation in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo.

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