Poly-L-lactic acid nanofiber/polyamidoamine composite hydrogel as novel strategy for in vitro neuroregeneration and neuroprotection

A purposely designed PLLA/H-AGMA₂₀ composite hydrogel incorporating an electrospun poly-L-lactic acid (PLLA) mat in a cell-adhesive polyamidoamine hydrogel (H-AGMA₂₀) was investigated as a novel biomaterial with neuroregenerative and neuroprotective properties. A PLLA mat was first functionalized by exposure to ethylenediamine vapors, introducing amine functions through ester group aminolysis, and then impregnated with an α,ω-acrylamide-terminated oligomer (AGMA₂₀) aqueous solution. The system was finally cured through UV-induced radical polymerization. The resulting H-AGMA₂₀ matrix was covalently grafted onto the PLLA nanofibers since a portion of the AGMA₂₀ acrylamide terminals reacted with their surface amine groups, leading to the soft and pliable PLLA/H-AGMA₂₀ composite. Biological investigations performed on preneuronal and immune cell lines demonstrated that PLLA/H-AGMA₂₀ exhibits promising neuroregenerative properties, effectively promoting both cell proliferation and neuronal differentiation. In addition, the composite demonstrated significant neuroprotective effects in vitro, counteracting neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺) and proinflammatory agent lipopolysaccharide (LPS)-induced cytotoxicity. These protective results appear to be mediated by modulation of inflammatory pathways, highlighting the combined capacity of biomaterial to support neuronal development while reducing neuroinflammatory damage.