Biophysically Optimized Nanofiber‐Hydrogel Scaffold Composite Acts as “Bio‐Bonsai” for Peripheral Nerve Simulation and Regeneration via Orienting Adipose Derived Stem Cells into Schwann‐Like Cell Differentiation

Abstract Efficient repairment of peripheral nerve injury (PNI) remains a severe clinical challenge worldwide, and recovering the regenerative capability of neurons in peripheral nervous system is hindered by the slow rate and inaccurate direction of axonal elongation. Schwann cells (SCs) loaded nerve guidance conduit has been proven to improve PNI repair, but the low cell survival rate and incomplete differentiation of SCs limited its practical application. To address these hurdles, a biophysically optimized nanofiber‐hydrogel scaffold composite (APML@PC) is prepared in this study, the “bio”bonsai“”inspired strategy integrates topological and biological cues to promote adipose‐derived mesenchymal stem cells (ADSCs) adhesion, proliferation, and Schwann‐like cell differentiation. In vitro and in vivo experiments confirmed the favorable biocompatibility and reasonable biodegradation behavior of this inducible platform, and the robust capability to promote axonal growth, remyelination regeneration, as well as nerve function recovery. This novel composite can serve as a promising candidate for the development of advanced stem cell‐based peripheral nerve regeneration, thereby paving a new avenue for clinically effective PNI therapy.