Robust Electrospun Nanofibers from Chemosynthetic Poly(4-hydroxybutyrate) as Artificial Dural Substitute.

Abstract

Bioresorbable poly(4-hydroxybutyrate) (P4HB) may fulfill the specific requirements that are necessary for a dural substitute, including its high elasticity, long-term strength retention properties, and the biocompatibility without significant accumulation of acidic degradation products. However, commercial P4HB can only be produced by the bacterial fermentation, which limits its applications in the cerebrospinal system due to higher endotoxin restriction. Meanwhile, P4HB can be prepared via the ring-opening polymerization of γ-butyrolactone. In this contribution, high molecular weight P4HB from chemosynthesis is electrospun into fibrous membrane, showing good mechanical properties that match the natural dura mater. Such P4HB membrane induces fast cellular migration, adhesion, and proliferation of fibroblasts in vitro. Subcutaneous implantation in rats demonstrates excellent biocompatibility of the P4HB membrane with proper biodegradation behaviors. After implantation in the rabbit dural defect model as an onlay graft, the P4HB membranes prevent cerebrospinal fluid leakage and regenerate dura tissue without detecting any local or systematic infections or foreign body responses. Thus, the electrospun P4HB membranes may be particularly useful as artificial dural substitutes to induce wound closure and tissue regeneration, which will be of great benefit to neurosurgery in the future.