Peripheral nerve injury still remaining a major clinical surgical challenge, since the current clinical solutions lead to an often-unsatisfactory nerve regeneration. Despite autologous nerve grafts are considered the gold standard, tissue engineered nerve guidance grafts are valued, alternatives to overcome this unmet medical need. Neurotrophic factors can stimulate and control neurogenesis at the nerve injury site. Nerve growth factor (NGF) is the most prominent neurotrophic factor, being recognized to facilitate the survival and the innervation of autonomic nerves and sensory neurons. Therefore, the local delivery of NGF from NGG might enhance nerve regeneration.
In this work we demonstrate the selective retrieval of autologous NGF, derived from rat blood plasma, immobilized at the surface of an electrospun nanofibrous substrate (NFM). For that, anti-NGF antibody was immobilized at the surface of NFMs, at the maximum concentration of 10 mg/mL, capable to selectively immobilize autologous NGF. The neurogenesis potential of the NFM functionalized with autologous NGF (NFM-NGF) was further evaluated by culturing rat pheochromocytoma (PC12) cells during 7 days, without further induction. The biological results indicate that NFM-NGF promote neuronal differentiation of PC12 cells, being more effective than the control condition. Moreover, the promotion of neurite outgrowth of PC12 cells were also observed on NFM-NGF. In summary, autologous NGF immobilized at the surface of NFM for promoting functional peripheral nerve regeneration.
The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of M.R.C. (PD/BD/113797/2015) financed by the FCT Doctoral Program on Advanced Therapies for Health (PATH) (FSE/POCH/PD/169/2013), the IF grant of A.M. (IF/00376/2014), and the projects SPARTAN (PTDC/CTM-BIO/4388/2014) and FRONthera (NORTE-01-0145-FEDER-0000232).