Silk fibroin-collagen hydrogel loaded with IGF1-CESCs attenuate intervertebral disc degeneration by accelerating annulus fibrosus healing in rats

Zhiqiang Tian ¹ Zigang Shen ² Hong Chen ³ Ping Zhao ^1*

• ¹ Southwest University, Chongqing, Chongqing Municipality, China
• ² Chongqing Sericulture Science and Technology Research Institute, Chongqing, China
• ³ 903 Hospital of Joint Logistic Support Force of The People's Liberation Army, Hangzhou, Jiangsu Province, China

The reduced self-healing capacity of a damaged annulus fibrosus (AF) leads to intervertebral disc (IVD) degeneration. AF wound treatment is challenging. The combination of biomaterials and stem cell-derived exosomes is a promising wound treatment strategy with significant clinical value. Collagen hydrogels are widely used in IVD disease research; however, their poor mechanical properties limit their clinical applications. Here, we used cartilage endplate stem cells (CESCs) combined with combined silk fibroin (SF) and a collagen-mixed hydrogel to release high-concentration insulin-like growth factor 1 (IGF1) exosomes for the treatment of AF wounds, which can quickly repair damaged AF. We found that both IGF1 and IGF1-rich exosomes (rIGF1 Exo) promoted the proliferation and migration of annulus fibrosus cells (AFCs). SF and collagen mixed hydrogels have excellent compressive mechanical properties and are suitable for IVD therapy. Our results showed that after the rIGF1-CESCs@SF-collagen hydrogel was filled in the damaged area of the AF, the wound healing speed was accelerated, nucleus pulposus overflow was inhibited, the IVD height was maintained, and degeneration was reduced. Our results indicate that the IGF1-CESCs@SF-collagen hydrogel can efficiently treat AF wounds.