Dual properties of PEGDA-GelMA scaffold: Good long-term cerebral biocompatibility and motor outcome but limited potential for brain regeneration

BACKGROUND Acute brain injuries represent a major clinical challenge, as current therapeutic strategies are insufficient to promote tissue regeneration and fully restore lost neurological functions. In this context, biomaterials have shown promise in promoting tissue repair. METHODS This study introduces an innovative strategy involving the 3D DLP (Digital Light Processing) printing of a degradable scaffold composed of PEGDA (polyethylene ‑glycol diacrylate) and GelMA (gelatin methacryloyl). The neuro‑implant combines the mechanical stability of PEGDA with the bioactivity and biocompatibility of gelatin, forming a porous and guiding architecture. This scaffold is implanted in rat brains injured by malonate injection. RESULTS DLP technology enabled the complex scaffold architecture specific to the cortex. A longitudinal follow‑up using behavioural assays and MR imaging at 3‑ and 6‑months post‑injury revealed a favourable in ‑vivo safety profile, contralesional functional MR activation, and improved grip strength of the impaired forelimb at 6 months (p = 0.057). MRI provided high‑quality images revealing the scaffold’s fine architecture in vivo and showed no degradation. Histological analysis confirmed chronic biocompatibility, with complete colonisation by viable endogenous cells, including a stable vascular network persisting at 6 months and a high density of neural progenitors (Sox2⁺, Dcx⁺) and mature oligodendrocytes (OSP⁺), offset by a surprising absence of mature, functional neurons and astrocytes. CONCLUSION Our results highlight the long‑term biocompatibility of the PEGDA–GelMA scaffold in the brain, but its functional regenerative potential is limited. Nevertheless, this implant appears capable of improving functional motor outcome; this improvement was not explained by neuron or astrocyte attraction. PEGDA–GelMA can serve as a structural bridge between healthy and damaged brain tissue, attracting endogenous cells. The implant stabilises the lesion site and may enhance brain plasticity mechanisms such as contralesional motor ‑cortex involvement. These findings provide an acellular basis for developing a regenerative, brain‑compatible structural platform targeting central nervous system lesions.