Reconstruction of the macrophage and myelin debris ecosystem following spinal cord injury: a dual-matrix hydrogel/polycaprolactone platform

Spinal cord injury (SCI) causes severe trauma to the central nervous system (CNS), involving complex pathological processes such as oxidative stress, inflammation, demyelination, and scar formation. During SCI progression, ongoing myelin degeneration leads to the release of myelin debris, which directly inhibits neural regeneration and impairs functional recovery following the injury. Moreover, bone marrow-derived macrophages (BMDMs) infiltrate the injured site and extensively phagocytose myelin debris, transforming into lipid-laden foam cells. These foam cells accumulate at the lesion core, significantly promoting fibrotic scar formation. To address these challenges, we developed a composite scaffold consisting of a foam cell membrane-coated polycaprolactone (PCL) nanofiber membrane that was integrated with a dual-matrix human acellular amniotic membrane (HAAM) hydrogel. A comprehensive evaluation combining material characterization, in vitro assays, and in vivo assessment using a Sprague–Dawley rat spinal cord defect model demonstrated that the scaffold retains the bioactive properties of HAAM, effectively clearing myelin debris and mitigating foam cell accumulation while concurrently promoting neural regeneration following SCI. The proposed novel biomaterial-based strategy offers a promising approach to addressing the persistent accumulation of myelin debris after SCI.