Nerve tissue engineering using blends of poly(3‐hydroxyalkanoates) for peripheral nerve regeneration

Abstract

The only types of polyhydroxyalkanoates (PHAs) that have been explored for use in nerve regeneration are poly(3‐hydroxybutyrate), P(3HB), and poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (P(3HB‐co‐3HHx)). However, nerve regeneration induced by these PHAs is inferior to that of autologous nerve grafting. The aim of this work was to study novel PHA blends as resorbable biomaterials for the manufacture of nerve guidance conduits. PHA blend films with varying ratios of poly(3‐hydroxyoctanoate)/poly(3‐hydroxybutyrate) (P(3HO)/P(3HB)) were produced using the solvent‐casting method. Neat films of P(3HO) and P(3HB), along with 25:75, 50:50, and 75:25 blend films of P(3HO)/P(3HB), were characterized with respect to chemical, material, and biological properties. On surface analysis, the blends exhibited higher values of roughness compared with the neat films. The differential scanning calorimetry characterization of the blends confirmed that P(3HO) and P(3HB) formed immiscible blends. FTIR and XRD analysis of the blends showed a decrease in crystallinity along with an increase of the proportion of P(3HO) . However, an increase in the stiffness of the blends was observed when the proportion of P(3HB) increased. Although all of the blends were biocompatible with NG108‐15 neuronal cells, the 25:75 P(3HO)/P(3HB) blend showed significantly better support for growth and differentiation of these cells. The mechanical properties of PHA blends correspond to the reported properties of peripheral nerves. Therefore, they could serve as base material for the manufacture of nerve guidance conduits.

Additive manufactured biodegradable poly(glycerol sebacate methacrylate) nerve guidance conduits

“…Compression results on PGSm conduits showed an average Young's modulus of 3.2 MPa, similar to that of the native nerve (0.45 MPa) [44]. This similarity is further understood when compared with polycaprolactone (PCL), poly-L-lactide (PLLA) and poly(3-hydroxybutyrate) (P3HB), materials widely researched for peripheral nerve repair, with reported modulus values of 400 MPa, 668.4 MPa, 1160 MPa, respectively, far stiffer than that of the native nerve [25,[45][46][47][48]. Suture retention mechanical tests found PGSm conduits to have an average suture retention strength of 12.3 MPa, similar to the value reported for clinically used poly(tetrafluoroethylene) (as Gore-Tex vascular grafts), 23 MPa [49][50][51].…”

Unidirectional neuronal cell growth and differentiation on aligned polyhydroxyalkanoate blend microfibres with varying diameters

“…An in‐depth study on the effect of the PHA blend fibre diameter on cell growth and differentiation of NG108‐15 neuronal and RN22 Schwann cells was carried out. The choice of this particular PHA blend was driven by our work that we have published earlier (Lizarraga‐Valderrama et al, ), in which this blend was shown to be the most biocompatible with respect to neuronal cells when compared with the widely commercialized PCL and other P(3HO)/P(3HB) blend compositions. The biodegradation product resulting from the breakdown of P(3HB), 3‐hydroxybutyric acid, is a known natural metabolite found in the human body, hence is expected to have minimal toxicity and immunogenic response (Newman & Verdin, ).…”

Third generation poly(hydroxyacid) composite scaffolds for tissue engineering

“…Functional recovery was achieved following implantation of an oriented porous micropatterned Schwann cell seeded‐PHB nerve conduit into a 30 mm gap in sciatic nerves of rats . Blends of poly(3‐hydroxyoctanoate) (PHO) with PHB were able to support neuronal growth with the 25:75 blend film displaying tensile strength close to that of peripheral nerve . Peptide functionalized PHB/PHBV fibrous substrates resulted in enhanced SCs metabolic activity and proliferation.…”