Gelatin–tricalcium phosphate membranes immobilized with NGF, BDNF, or IGF‐1 for peripheral nerve repair: An in vitro and in vivo study

Abstract

In the present study, NGF, BNDF from the neurotrophin family and IGF-1 were covalently immobilized on gelatin-tricalcium phosphate (GTG) membrane using carbodiimide. We investigated the effects of these growth factors released from the GTG composites on cultured PC12 cells and sciatic nerve regeneration across a 10-mm-long gap in rats. In PC12 cell culture, the total protein content and MTT assay indicated more cell attachment on the composites modified with growth factors. The IGF-1 group showed a higher survival promotion effect on PC12 cells than did BDNF and NGF groups. On the other hand, NGF released from the composite showed the highest level of neuritogenesis for PC12 cells in neurite outgrowth assay. In the animal study, the GTG conduits modified with various growth factors were well tolerated by the host tissue. In the regenerated nerves, the number of the axons per unit area of the BDNF group was significantly higher than that of NGF and GTG groups but similar to that of IGF-1 group. However, the average axon size was the largest in NGF group. This result was in concordance with the neurite outgrowth assay in which NGF showed the highest neuritogenic potential. In the assessment of motor and sensory recovery after nerve repair, conduits modified with various neurotrophic factors showed a more favorable outcome in compound muscle action potential. The BDNF group had a better gastrocnemic muscle weight ratio than blank GTG repair. Nevertheless, the different effects of GTG conduits modified with various neurotrophic factors on functional recovery cannot be simply illustrated in the sciatic function index.

Rat sciatic nerve repair with a poly‐lactic‐co‐glycolic acid scaffold and nerve growth factor releasing microspheres

“…Generally, half life of proteins in vivo is short, and their neurotrophic effect therefore concordant. A couple of delivery systems have been used by others: impregnated fibronectin mats,15 fibrin matrices,7 fibrin sealant,16 gelatin‐tricalcium phosphate membranes,17 growth factor eluting conduits,4, 18 subcutaneous reservoir implantation, and infusion at coaptation site19 and mini osmotic pumps 20. All were aimed at the long‐term delivery of NGF.…”

Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration

“…For instance, glial-derived neurotrophic factor (GDNF) supplementation of multiluminal conduits had a beneficial effect on inducing axon outgrowth and target reinnervation compared to GDNF-free conduits in a 4 cm nerve gap injury [ 18 ]. NGF, brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF) encapsulation into gelatin-based nerve guidance conduits (NGCs) showed promising potential for neurite guidance and extension, as well as functional recovery [ 19 ]. Compared with GFs or the application of grafted biomaterial alone in repairing PNI, combining them together has several advantages.…”

Chinese Medicine in Diabetic Peripheral Neuropathy: Experimental Research on Nerve Repair and Regeneration

“…Recent studies have shown that IGF-1 nourishes and supports motor and autonomic nerves. Decreased serum IGF-1 level and IGF-1 mRNA expression are shown in experimental diabetic rats, and administration of IGF-1 results in improvement of diabetic neuropathy [31]. Zeng et al [19] applied reverse transcription polymerase chain reaction assay and confirmed that the expression of IGF-1 mRNA was decreased in sciatic nerves in STZ-induced diabetic rats; the expression level of IGF-1 mRNA and glucose was negatively correlated; treatment with Xiaokelingnongsuoye resulted in increased expression of IGF-1 mRNA in sciatic nerves.…”