BIOMATERIAL PLATFORMS FOR MODULATING NEUROINFLAMMATION AND SUPPORTING NEUROREGENERATION

To achieve spinal cord repair after spinal cord injury (SCI), we are developing biomaterial-based approaches that promote neural regeneration while limiting neuroinflammation, to complement and enhance stem-cell-based therapies. We evaluated a human-derived photocrosslinkable hydrogel (derived from perinatal tissues) and custom-engineered nanoparticles for targeted immuno-modulation within the central nervous system and assessed their biocompatibility in vitro on primary murine neural cultures containing neurons and glia.
Upon exposure of the neural cultures to the hydrogel and nanoparticles, the neural viability and cell morphology were monitored by live imaging. Furthermore, inflammatory responses were assessed by qRT-PCR, and oxidative stress was quantified using CellROX.
The human-based hydrogel showed high neural compatibility, supported neuronal survival and neurite outgrowth. Establishing stable cell-laden 3D cultures required optimisation of hydrogel physical properties, as suboptimal cross-linking or polymer concentration impaired outgrowth and generated spatial viability gradients. Hydrogel components were per se immunologically inert, although elevated concentrations of the photoinitiator (LAP) induced a mild inflammatory response.
The nanoparticles displayed excellent neural compatibility. Concentrations up to 50 mg/L in the neural cultures did not affect the neural viability, nor induced expression of classical pro-inflammatory markers (Il6, Nos2, and Il1b).
These findings support combining our hydrogel and nanoparticles as a carrier system for stem cells in therapies for improved spinal cord regeneration.