Bone marrow mesenchymal stem cell-loaded HAMA hydrogel within highly bionic nerve guidance conduits for peripheral nerve regeneration

Abstract Nerve guidance conduits (NGCs) effectively support and guide the regeneration of injured nerves. However, traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth. This study develops a highly bionic nerve guidance conduit (HB-NGC) using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic (EHD) printing. The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes, while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing. The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl (HAMA) hydrogel encapsulating bone marrow mesenchymal stem cells (BMSCs). This highly biomimetic NGC is conductive, capable of guiding axon growth, and sustainably releases growth factors, effectively mimicking the structure, function, and characteristics of natural peripheral nerves. Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways, facilitating electrical signal conduction, and supplying an extracellular matrix (ECM) environment enriched with essential growth factors. Additionally, the HB-NGC’s morphology, along with its physicochemical and mechanical properties, effectively bridges the gap between severed nerve ends. In vivo animal studies validate the HB-NGC’s effectiveness, highlighting its significant potential to enhance peripheral nerve regeneration.