Short‐ and long‐term peripheral nerve regeneration using a poly‐lactic‐co‐glycolic‐acid scaffold containing nerve growth factor and glial cell line‐derived neurotrophic factor releasing microspheres

Abstract

Addition of neural growth factors to bioengineered scaffolds may improve peripheral nerve regeneration. The aim of this study is to evaluate the short- and long term effect of microsphere delivered nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF) in the 10 mm rat sciatic nerve gap. Eighty-four rats were assigned to seven groups (n = 6) at two endpoints (6 and 16 weeks): saline, saline NGF, saline NGF-microspheres, saline GDNF, saline GDNF-microspheres, saline blank microspheres, and autologous nerve graft. Total fascicular area and total number of myelinated fibers at mid-tube increased in all conduit groups between 6 and 16 weeks. Autologous, saline NGF-microsphere and saline GDNF-microsphere groups reached maximal histomorphometric values by 6 weeks (p < 0.05). Compound muscle action potentials returned after 6 weeks for the autologous graft and continued to increase to a level of 3.6 ± 1.9 mV at endpoint. No significant differences were found between study groups as measured by ankle angle. These experiments show an initial beneficial effect of incorporation of NGF- or GDNF-microspheres in a PLGA 85/15 nerve conduit, since histomorphometric values reached their maximum by 6 weeks compared to control groups. These results do not yet extrapolate into improved electrophysiological or functional improvement.

Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

“…The axon diameters in a random sample of 10% of each cross section were measured using ImageJ software, which would result in a representative sample. [33][34][35] Statistical analysis…”

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

“…Thus, the combination of a nerve conduit with NTFs appears as a good option to enhance nerve regeneration. However, NTFs added within a nerve conduit can be rapidly degraded (Ejstrup et al, 2010;Tria et al, 1994), diffuse outside the conduit or get diluted after liquid infiltration resulting in sub-optimal concentrations, and thus poor regeneration outcome (de Boer et al, 2012;Wood et al, 2013). Hence, a better way to apply NTFs and prolong their presence in close contact with regenerating axons and Schwann cells is still needed to optimize the effects of NTFs on regeneration.…”

Tissue engineering of the peripheral nervous system

“…NC were also functionalized by the incorporation of growth factors and/or essential ECM and/or peptide sequences within the biomaterials. These growth factors were incorporated within the NCs wall [144][145][146][147][148], encapsulated into intraluminal biodegradable microspheres [149][150][151][152] and combined with aligned biomaterials [68,117,[153][154][155]. The incorporation of chitosan and chondroitin sulfate into the wall of the poly-DL-lactic acidbased NC showed an improvement of the nerve regeneration, but comparable results to the autograft were only obtained by the immobilization of NGF into the inner NCs wall [148].…”

“…The incorporation of growth factors is an efficient experimental alternative to improve the nerve regeneration of NC [68,141,142,[146][147][148][149]. These growth factors have some limitations that could be solved by the use of controlled delivery systems, where they are efficiently immobilized or cross-linked into NC and/or intraluminal fillers [139,145,147,[152][153][154][155].…”