Dual-therapeutic niraparib-loaded chitosan nanoparticle–alginate hydrogel with adipose-derived stromal cells promotes functional and histological recovery after spinal cord injury

Background: Spinal cord injury (SCI) triggers oxidative stress, inflammation, and progressive neurodegeneration. Methods: Here, we developed a dual-therapy composite hydrogel that integrates niraparib-loaded chitosan nanoparticles (NICNPs) and adipose-derived stromal cells (ASCs) into a calcium alginate scaffold for sustained drug release and cell delivery. Results: NICNPs demonstrated comparable encapsulation efficiencies across formulations (44.97% ± 7.23%, 41.54% ± 4.70%, and 44.67% ± 8.81% for 1%, 3%, and 5% loading, respectively), with biphasic sustained drug release over 168 h. All hydrogels supported ASC viability; under oxidative stress, NICNP hydrogels significantly improved cell survival compared with ASC-only hydrogels. In vitro, NICNP–ASC constructs markedly reduced LPS-induced cytokines (TNF-α, IL-6, and IL-1β). In vivo, in a rat SCI model, NICNP–ASC hydrogels significantly reduced lesion volume and enhanced gray and white matter preservation compared to other formulations and the control group. Alginate hydrogel incorporating ASCs and niraparib-loaded chitosan nanoparticles at 5% w/w drug loading (HY–ASC–NICNPs-5) demonstrated maximal efficacy, showing robust parenchymal bridging, dense myelin preservation, and angiogenesis. Behavioral recovery improved significantly, with BBB scores highest in HY–ASC–NICNPs-5 at both 4 and 8 weeks. ELISA confirmed elevated neurotrophic factors and antioxidant enzymes alongside reduced inflammatory cytokines in NICNP–ASC groups, particularly in the 5% formulation. Conclusion: Overall, these dual-functional hydrogel systems created a pro-regenerative microenvironment, attenuated secondary injury cascades, and restored hindlimb motor function.