Investigation of neuro-regenerative therapeutic potential of nerve composite matrix hydrogels embedded with adipose-derived stem cells

Abstract

Traumatic spinal cord injury (SCI) induces permanent sensorimotor deficit below the site of injury. There is various research conducted to provide effective therapy, however, SCI is still considered incurable due to the complex nature of the injury site. Recently, our lab developed a combinatorial therapeutic for SCI repair comprising human adipose-derived stem cell (hASC)-embedded nerve composite hydrogels using different ratios of decellularized sciatic nerve (dSN) and spinal cord (dSC) matrices. This study investigated angiogenic and neurotrophic effects of the combinatorial therapeutic in vitro. Compression testing was performed to analyze mechanical properties of the composite hydrogels and showed no significant difference between all hydrogel groups. Next, pro-angiogenic factors and neurotrophins secreted from hASCs within different ratios of the composite hydrogels were analyzed and we found culture durations and extracellular matrix (ECM) composition affect secretory behavior. Interestingly, ECM compositional difference between hydrogel groups had little influence on human brain microvascular endothelial cells (HBVECs) infiltration and dorsal root ganglia (DRG) neurite outgrowth. Finally, we conducted proteomic analysis to identify the ECM components potentially contributing to these observed effects. Taken together, dSN:dSC = 1:2 hydrogel showed slightly better therapeutic potentials, warranting validation using in vivo studies.