Docosahexaenoic Acid-Infused Core–Shell Fibrous Membranes for Prevention of Epidural Adhesions

Abstract

Avoiding epidural adhesion following spinal surgery can reduce clinical discomfort and complications. As the severity of epidural adhesion is positively correlated with the inflammatory response, implanting a fibrous membrane after spinal surgery, which can act as a physical barrier to prevent adhesion formation while simultaneously modulates postoperative inflammation, is a promising approach to meet clinical needs. Toward this end, we fabricated an electrospun core–shell fibrous membrane (CSFM) based on polylactic acid (PLA) and infused the fiber core region with the potent natural anti-inflammatory compound docosahexaenoic acid (DHA). The PLA/DHA CSFM can continuously deliver DHA for up to 36 days in vitro and reduce the penetration and attachment of fibroblasts. The released DHA can downregulate the gene expression of inflammatory markers (IL-6, IL-1β, and TNF-α) in fibroblasts. Following an in vivo study that implanted a CSFM in rats subjected to lumbar laminectomy, the von Frey withdrawal test indicates the PLA/DHA CSFM treatment can successfully alleviate neuropathic pain-like behaviors in the treated rats, showing 3.60 ± 0.49 g threshold weight in comparison with 1.80 ± 0.75 g for the PLA CSFM treatment and 0.57 ± 0.37 g for the untreated control on day 21 post-implantation. The histological analysis also indicates that the PLA/DHA CSFM can significantly reduce proinflammatory cytokine (TNF-α and IL-1β) protein expression at the lesion and provide anti-adhesion effects, indicating its vital role in preventing epidural fibrosis by mitigating the inflammatory response.