Development of an In Vitro Diabetic Keratinocyte Wound-Relevant Model Incorporating a Mechanical Microenvironment

In diabetes, these cues are disrupted, impairing signaling pathways and contributing to complications such as nonhealing skin wounds. Conventional <i>in vitro</i> models using plastic tissue culture plates (TCP) fail to replicate the mechanical interface of human skin, particularly the altered substrate rigidity associated with diabetic skin, and typically expose cells to supraphysiological glucose levels, limiting their physiological relevance.

To address these gaps, we developed a diabetic-like wound-relevant model integrating polyacrylamide hydrogels engineered to mimic skin-relevant substrate stiffness with human keratinocytes acclimatized to physiological glucose (NG) and subsequently exposed to diabetic glucose conditions (DG). This tunable cell–material interface enabled assessment of how substrate mechanics and glucose milieu jointly govern keratinocyte viability, proliferation, and migration.