Tissue Engineered Combinatorial Therapeutics for Spinal Cord Injury Repair

Traumatic spinal cord injury (SCI) lead to temporary or permanent sensorimotor deficit due to the complex and multifaceted features of the injury site, making the treatments ineffective. Recent research emphasizes the potential of combinatorial therapeutics approaches combining different therapeutics, such as biomaterials and stem cell transplantation. In this context, nerve composite hydrogels, fabricated from decellularized sciatic nerve (dSN) and spinal cord (dSC) extracellular matrices (ECM), might be promising platforms due to their biocompatibility and ability to mimic native microenvironments. In this study, we developed and characterized nerve mimetic composite hydrogels embedded with human adipose-derived stem cells (hASCs) and investigated their neuro-regenerative potential. Histological and DNA analysis confirmed successful decellularization while retaining ECM architecture. The mechanical characterization indicated similar properties across hydrogel compositions. Importantly, embedded hASCs demonstrated sustained viability, secreted angiogenic and neurotrophic factors, and enhanced endothelial cell sprouting and neurite outgrowth. Proteomic analysis further identified specific ECM components influence in modulating cellular behaviors. These findings collectively highlighted the therapeutic potential of dSN:dSC composite hydrogels, particularly 1:2 ratio. Additionally, a comparative study evaluated various decellularization methods for dura mater to determine the optimal protocol for future use as a sealant or patch for neurosurgery or SCI repair. Altogether, promising hydrogel candidate was determined and optimal decellularization protocol for dura mater for the sealant/patch applications will be identified, however, further validation through in vivo studies is needed.