Self-Assembling Biohybrid Bands of Büngner for Axonal Regeneration in the Peripheral Nervous System

There is broad consensus that successful repair of severe peripheral nerve injuries requires recreating key structural and cellular features of the natural regenerative process, particularly the action of Bands of Büngner (BoB), longitudinal Schwann cell (SC) structures that guide regenerating axons. Current biomaterial-based strategies have shown limited efficacy, in part because they do not sufficiently reproduce the anisotropic and cellular microenvironment established by BoB, resulting in disorganized axonal growth and reduced regenerative efficiency across long gaps. To address this limitation, a biohybrid scaffold designed to promote Schwann cell self-organization into Büngner-like structures through defined physical cues. Rather than relying solely on biochemical supplementation is developed, this system leverages anisotropic fiber architecture to induce SC alignment and early activation-associated phenotypic modulation. In this study, a self-organizing biohybrid BoB (BBoB) construct formed by Schwann cells within an aligned fiber-based scaffold is presented. It is demonstrated that these engineered structures recapitulate key morphological features of native BoB in vitro and promote enhanced axonal regeneration across a 11 mm sciatic nerve defect in vivo. Together, these findings support the concept that physically programmed Schwann cell organization within biomaterial conduits can enhance peripheral nerve regeneration, using clinically accessible biomaterials and autologous Schwann cells.