Rationally designed, self-assembly, multifunctional hydrogel depot repairs severe spinal cord injury

ABSTRACT: Following severe spinal cord injury (SCI), dysregulated neuroinflammation causes neuronal and glial apoptosis, resulting in scar and cystic cavity formation during wound healing process and ultimately atrophic nerve regrowth inhibitory microenvironment. Because of this complex and dynamic nature of SCI pathophysiology, a systemic solution for scar and cavity free wound healing while remodeling microenvironment for nerve regrowth has been rarely explored. To address this challenge, we provided a one-step solution through a self-assembly, multifunctional hydrogel depot punctually releasing the anti-inflammatory drug methylprednisolone sodium succinate (MPSS) and growth factors locally according to its pathophysiology to repair severe SCI. We found release of growth factors alone could only provide some tissues/axons protection, but failed to eliminate all cystic cavity formation. Sustained release of MPSS is sufficient to modulate dysregulated neuroinflammation and eliminate almost all cystic cavity but unable to alleviate impenetrable scar boundaries, which are largely responsive for nerve regrowth failure. Strikingly, synergically releasing anti-inflammatory drugs MPSS and growth factors in the hydrogel depot along SCI pathophysiology protected spared tissues/axons from secondary injury, promoted scar boundary and cavity free wound healing and made permissive bridges for remarkable axonal regrowth. Behavior and electrophysiology studies indicated that the remnant of spared axons but not regenerating axons mediated functional recovery, strongly suggesting that additional interventions are still required to make the rebuilt neuronal circuits perform functions. Taken together, these findings pave the way to develop a systemic solution to treat acute SCI.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE165635 | GEO | 2022/01/01

REPOSITORIES: GEO