Chi Naiwei, Zheng Shuyao, Clutter Elwin, Wang Rong
Department of Chemistry, Illinois Institute of Technology, Chicago, Illinois 60616, USA.
Recent Prog Mater. 2019;1(4). doi: 10.21926/rpm.1904007. Epub 2019 Dec 18.
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.
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.
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.
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.
糖尿病患者患有慢性伤口,部分原因是成纤维细胞功能改变。糖尿病患者的成纤维细胞合成I型胶原蛋白(COLI)的水平远高于III型胶原蛋白(COLIII),导致组织肉芽形成延迟,进而导致整体伤口愈合过程延迟。
我们旨在通过使用排列整齐、具有导电性和生物相容性的蜘蛛丝-CNT纤维作为细胞培养基质来恢复糖尿病成纤维细胞的基质蛋白生产力,以介导对成纤维细胞的电刺激,诱导细胞极化和激活。
糖尿病成纤维细胞中COLI和COLIII的产量分别增加了5.2倍和42.7倍。受刺激的细胞合成了大量高水平的COLIII,以降低异常高的COLI/COLIII比值,并且基质金属蛋白酶的表达明显受到抑制。蛋白质表达谱与良好的伤口愈合一致。在健康个体的正常成纤维细胞中也证实了这种调节作用,表明所开发的方法可普遍用于结缔组织修复。蚕茧丝-CNT纤维对恢复糖尿病成纤维细胞的功能也有类似作用。
使用工程化生物聚合物基质来修复患者功能失调的成纤维细胞的方法,为开发用于非侵入性治疗的个性化细胞疗法提供了机会,并激发了用于有效组织再生的多功能生物计量学的设计。