Investigating Strategies to Prevent Alveolar Osteitis Using Electrospinning Technology and Tissue Engineered Gingival Models

Third molar extraction, a common surgical procedure in the UK, is notorious for post-operative complications with one in six patients experiencing alveolar osteitis (AO). AO is characterised by loss of the blood clot from the tooth extraction socket leading to post operative pain, which often results in repeated hospital visits, imposing a substantial time and financial burden on the NHS.
To address this clinical problem, a novel AO preventative measure was designed and fabricated in the form of a drug-loaded mucoadhesive patch composed of dual electrospun polyvinyl pyrrolidone (PVP)/Eudragit RS100 and poly-N-isopropylacrylamide (PNIPAM) fibres that are protected by a poly(ε-caprolactone) (PCL) backing layer. These patches demonstrated the rapid release of prednisolone along with controlled release of bupivacaine, while maintaining the pharmacological functionality of these drugs.

Human gingival mucosal equivalents (GME) made from immortalised gingival keratinocytes was used as a test platform. The GME displayed a well-differentiated, stratified squamous epithelium on top of a fibroblast-populated lamina propria and was validated for key tissue markers (e.g., cytokeratin, laminin) against native human gingiva. In addition, a polyHIPE scaffold made from poly(glycerol sebacate)-methacrylate (PGS-M) that contained osteoblast-differentiated periodontal ligament stem cells was developed to mimic alveolar bone. GME was successfully grown on a the polyHIPE scaffold and was also used to generate a post-tooth extraction model that incorporated human coagulum to model a blood clot.

Upon topical application of the patches to the surface of gingival epithelium both prednisolone and bupivacaine were released and permeated through the tissue in a time-dependent manner, suggesting that these patches are able to deliver their drug to tissues effectively. Xenobiotic metabolising enzymes (XME) are known for their ability to prepare drugs for their excretion. Human gingival tissue as well as GME were found to express a number of XME including those known to modify prednisolone and bupivacaine, indicating that drugs might be inactivated as they pass through the epithelium, a factor that needs to be taken into account in further patch development.

Taken together, these data show that dual electrospun patches have the potential to provide a mucoadhesive covering to prevent blood clot loss while delivering pain relief and anti-inflammatory drugs to post-tooth extraction sites in order to prevent AO. This study not only offers a future clinical avenue for the prevention of AO but also contributes valuable insights into tissue engineering, drug delivery and xenobiotic metabolism, laying the groundwork for future advancements in periodontal and local drug delivery research.