Abstract
BACKGROUND: Diabetic patients suffer from chronic wounds partly due to altered function of fibroblasts. Fibroblasts of diabetic patients synthesize collagen I (COLI) at a much higher level than collagen III (COLIII), resulting in delayed tissue granulation and, consequently, a delay in the overall wound healing process. METHODS: We aimed to revive the matrix protein productivity of diabetic fibroblasts by employing aligned, electrically conductive and biocompatible spider silk-CNT fibers as a cell culture matrix to mediate the electrical stimulation of fibroblasts to induce cell polarization and activation. RESULTS: A 5.2 and 42.7 fold increase in COLI and COLIII production was induced in diabetic fibroblasts. The stimulated cells synthesized a substantially high level of COLIII to reduce the abnormally high COLI/COLIII ratio, and the matrix metalloproteinases expression was markedly suppressed. The protein expression profile was consistent with favorable wound healing. The modulation effect was also demonstrated in normal fibroblasts of healthy individuals, suggesting that the developed method can be utilized generally for connective tissue repair. Silkworm silk-CNT fibers corroborated similar effects on restoring the function of diabetic fibroblasts. CONCLUSIONS: The approach of using an engineered biopolymer matrix to remedy dysfunctional fibroblasts of patients offers the opportunity of developing personalized cell therapy for noninvasive treatments and inspires the design of multi-functional biometrics for effective tissue regeneration.