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oai:figshare.com:article/34038024 2026-10-01T04:07:03Z category_1 category_4 category_146 category_7 category_12 category_13 category_14 category_21 category_873 category_734 category_61 portal_63 item_type_6 month_year_10_2026

Development of an In Vitro Diabetic Keratinocyte Wound-Relevant Model Incorporating a Mechanical Microenvironment Ranjita R. Save (25151529) Kanchan S. Chitnis (25151532) Abhijit Majumder (302750) Biophysics Biochemistry Space Science Medicine Cell Biology Genetics Molecular Biology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Developmental Biology typically expose cells maintain healthy function living organisms respond impairing signaling pathways evaluate therapeutic effects engineering hydrogel substrates supraphysiological glucose levels relevant substrate stiffness relevant model incorporating optimized mechanical properties human keratinocytes acclimatized diabetic cell dynamics nonhealing skin wounds diabetic glucose conditions diabetic keratinocyte wound mechanical microenvironment cells vitro </ italic vitro </ human skin physiological glucose diabetic skin substrate mechanics model ’ mechanical interface like wound mimic skin validated using subsequently exposed phytochemical curcumin physiological relevance mechanical cues materials strategies drug evaluation dg ). Cells in living organisms respond to chemical and mechanical cues from their microenvironment to maintain healthy function. 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. The model’s utility was further validated using the standard antidiabetic drug metformin (MET) and the phytochemical curcumin (CUR) to evaluate therapeutic effects on diabetic cell dynamics. Beyond its application in drug evaluation, this work offers design insights for engineering hydrogel substrates with optimized mechanical properties, contributing to materials strategies for improving diabetic wound healing outcomes. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acsapm.6c02844.s001 https://figshare.com/articles/journal_contribution/Development_of_an_In_Vitro_Diabetic_Keratinocyte_Wound-Relevant_Model_Incorporating_a_Mechanical_Microenvironment/34038024 CC BY-NC 4.0