Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits

Injuries to the nervous system account for the widespread morbidity, mortality, and discomfort worldwide. Artificial nerve guidance conduits (NGCs) offer a promising platform for nerve reconstruction, however, they require extracellular matrix (ECM)-like features to better mimic the in vivo microenvironment. Consequently, this research was aimed to fabricate heparin/growth factors (GFs)-immobilized artificial NGCs. Heparin was covalently immobilized onto aligned electrospun polycaprolactone/gelatin (PCL/Gel) nanofibers. Thereafter, basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were preferentially immobilized on heparinized nanofibers; the immobilization efficiency of GFs was found to be 50% with respect to (w.r.t.) their initial loaded amounts. The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention (~ 10% w.r.t the initial loaded amount) and bioactivity of NGF for up to 5 days. The permeability of bovine serum albumin (BSA) from nanofibrous membranes was further assessed and found to be comparable with the commercialized cellulose acetate membranes. The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term (1 week) and long-term (1-month). The NGCs displayed good structural stability and biocompatibility in vivo. The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs. Taken together; these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines. Graphical Abstract: [Figure not available: see fulltext.].