Utilizing Robust Design to Optimize Composite Bioadhesive for Promoting Dermal Wound Repair

Catechol-modified bioadhesives generate hydrogen peroxide (H₂O₂) during the process of curing. A robust design experiment was utilized to tune the H₂O₂ release profile and adhesive performance of a catechol-modified polyethylene glycol (PEG) containing silica particles (SiP). An L₉ orthogonal array was used to determine the relative contributions of four factors (the PEG architecture, PEG concentration, phosphate-buffered saline (PBS) concentration, and SiP concentration) at three factor levels to the performance of the composite adhesive. The PEG architecture and SiP wt% contributed the most to the variation in the results associated with the H₂O₂ release profile, as both factors affected the crosslinking of the adhesive matrix and SiP actively degraded the H₂O₂. The predicted values from this robust design experiment were used to select the adhesive formulations that released 40-80 µM of H₂O₂ and evaluate their ability to promote wound healing in a full-thickness murine dermal wound model. The treatment with the composite adhesive drastically increased the rate of the wound healing when compared to the untreated controls, while minimizing the epidermal hyperplasia. The release of H₂O₂ from the catechol and soluble silica from the SiP contributed to the recruitment of keratinocytes to the wound site and effectively promoted the wound healing.