Abstract
Nerve guidance conduits (NGCs) are used as an alternative to the “gold standard” nerve autografting, preventing the need for surgical intervention required to harvest autologous nerves. However, the regeneration outcomes achieved with the current NGCs are only comparable with autografting when the gap is short (less than 10 mm). In the present study, we have developed NGCs made from a blend of polyhydroxyalkanoates, a family of natural resorbable polymers. Hollow NGCs made from a 75:25 poly(3‐hydroxyoctanoate)/poly(3‐hydroxybutyrate) blend (PHA‐NGCs) were manufactured using dip‐molding. These PHA‐NGCs showed appropriate flexibility for peripheral nerve regeneration. In vitro cell studies performed using RT4‐D6P2T rat Schwann cell line confirmed that the material is capable of sustaining cell proliferation and adhesion. PHA‐NGCs were then implanted in vivo to repair 10 mm gaps of the median nerve of female Wistar rats for 12 weeks. Functional evaluation of the regenerated nerve using the grasping test showed that PHA‐NGCs displayed similar motor recovery as the autograft, starting from week 7. Additionally, nerve cross‐sectional area, density and number of myelinated cells, as well as axon diameter, fiber diameter, myelin thickness and g‐ratio obtained using the PHA‐NGCs were found comparable to an autograft. This preclinical data confirmed that the PHA‐NGCs are indeed highly promising candidates for peripheral nerve regeneration.
Highlights
Peripheral nerve injuries (PNI) may have a dramatic impact on the patient's quality of life and can involve high health care expenses
PHA-Nerve guidance conduits (NGCs) were fabricated from P(3HO)/P(3HB) 75/25 blend whose biocompatibility with neuronal cells was previously assessed by LizarragaValderrama et al.[6]
The rat median nerve repair model was used as a preclinical test model to evaluate the performance of the PHA-NGCs in promoting peripheral nerve regeneration in vivo (Figure 2a)
Summary
Peripheral nerve injuries (PNI) may have a dramatic impact on the patient's quality of life and can involve high health care expenses. As a response to denervation, SCs located in the distal axonal segment secrete a range of growth factors to facilitate regenerating axons to reach their sensory end organ or target muscle. In this case, end-to-end epineurial neurorrhaphy is suitable if tension free coaptation can be achieved after suturing the two stumps. PHAs have shown superior biocompatibility with neuronal cells compared to the widely used synthetic polymers, polycaprolactone (PCL)[6] and PLA.[15,16] PHAs exhibit properties that may overcome some of the limitations of the available NGCs including controllable surface erosion, lower acidity of their degradation products and longer-lasting stability compared to their synthetic counterparts. We have carried out, for the first time, preclinical assessment of novel PHA blend-based NGCs, PHA-NGCs, for regeneration of median nerve gaps and functional repair by using the tubulation technique, with significantly promising results
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