Combining chitin biological conduits with injectable adipose tissue-derived decellularised matrix hydrogels loaded with adipose-derived mesenchymal stem cells for the repair of peripheral nerve defects in rats

Abstract

Mesenchymal stem cells (MSCs) have shown potential for the repair of defective tissues and peripheral nerve injuries. However, local treatment alone may lead to cell loss, low viability, and diminished paracrine action owing to the lack of effective biological scaffolds. To improve the therapeutic effects of MSCs, bioactive scaffolds that mimic the stem cell microenvironment in vivo should be constructed. We developed an injectable decellularised matrix hydrogel (DAM-gel) to simulate the stem cell microenvironment using combined physical, chemical, and enzymatic digestions of human adipose tissues. The DAM-gel was loaded with rat adipose-derived mesenchymal stem cells (ADSCs) to repair sciatic nerve defects. Compared with ADSCs alone, the ADSC-loaded DAM-gel promoted the proliferation of Schwann cells in vitro, which are important in sciatic nerve regeneration. Chitin biological conduits filled with ADSC-DAM-gel composites were designed to bridge the sciatic nerve defects. Axonal regeneration and the recovery of neurological function in the ADSC-DAM-gel group increased post-surgery compared with the control group (blank conduit, ADSCs, and DAM-gel group), as confirmed by a CatWalk gait analysis, electrophysiology, and nerve/muscle histology. The ADSC-loaded DAM-gel-treated rats retained the improved peripheral nerve regeneration. Therefore, DAM-gels have great potential for enhancing the repair capacity of ADSCs in peripheral nerve defects.