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

Catechol-modified bioadhesives generate hydrogen peroxide (H 2 O 2 ) during the process of curing. A robust design experiment was utilized to tune the H 2 O 2 release profile and adhesive performance of a catechol-modified polyethylene glycol (PEG) containing silica particles (SiP). An L 9 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 H 2 O 2 release profile, as both factors affected the crosslinking of the adhesive matrix and SiP actively degraded the H 2 O 2 . The predicted values from this robust design experiment were used to select the adhesive formulations that released 40-80 µM of H 2 O 2 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 H 2 O 2 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.