Silk-CNT Mediated Fibroblast Stimulation toward Chronic Wound Repair.

Naiwei Chi,Elwin Clutter,Rong Wang,Shuyao Zheng

doi:10.21926/rpm.1904007

Naiwei Chi, Elwin Clutter + Show 2 more

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https://doi.org/10.21926/rpm.1904007

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Abstract

BackgroundDiabetic 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.MethodsWe 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.ResultsA 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.ConclusionsThe 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.

Highlights

Diabetes is a debilitating condition that affects 9.4% of the U.S population [1]
matrix metalloproteinases (MMPs) are essential for clearing the wound bed and rapid turnover of growth factors, receptors, and extracellular matrix (ECM) proteins [5,6,7]; elevated MMP level in diabetic patients accelerates the degradation of newly synthesized matrix proteins and disrupts their proper deposition and maturation [8]
The difference between diabetic dermal fibroblasts (DDF) and non-diabetic dermal fibroblasts (NDF) cells in collagen synthesis was examined by collagen I (COLI) and collagen III (COLIII) immunostaining (Figure 1)

Summary

Introduction

Diabetes is a debilitating condition that affects 9.4% of the U.S population [1]. Twenty percent of patients with diabetes suffer chronic wounds that are painful and lead to a significant number of lower-limb amputations each year [2]. MMPs are synthesized by fibroblasts, which are the primary source of ECM proteins that are essential to the wound healing process [9]. During tissue growth in wound healing, COLIII synthesis is enhanced by fibroblasts to form granulation tissues to cover up the cleared wound area [12]. The COLI/COLIII ratio is much higher in the tissues of diabetic patients [13]. The elevated level of MMPs in diabetic patients causes rapid degradation of newly synthesized proteins, leading to the formation of chronic wounds [14, 15]. Fibroblasts of diabetic patients synthesize collagen I (COLI) at a much higher level than collagen III (COLIII), resulting in delayed tissue granulation and, a delay in the overall wound healing process

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