Biological Materials Laboratory, CSIR-Central Leather Research Institute (CSIR-CLRI), Adyar, Chennai 600020, Tamil Nadu, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Biological Materials Laboratory, CSIR-Central Leather Research Institute (CSIR-CLRI), Adyar, Chennai 600020, Tamil Nadu, India.
Int J Biol Macromol. 2022 Oct 31;219:907-918. doi: 10.1016/j.ijbiomac.2022.08.029. Epub 2022 Aug 8.
Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-β (TGF-β) activity during the process of wound healing leads to progressive fibrosis. Decorin is an extracellular matrix (ECM) protein which regulates collagen fibrillogenesis. However, targeted delivery and effective protein therapy remains a challenge owing to degradation byproteases. Hence, we aimed to deliver Decorin in a sustainable mode for the reduction of TGF-β levels and subsequent scar formation. Herein, we have fabricated PCL-Gelatin bio-mimetic scaffolds to optimize the bio-activity and provide localized delivery of recombinant Decorin. The degradation and drug release patterns reveals that this biomaterial is biodegradable and offers sustained release of the recombinant Decorin. Decorin loaded nanofiber displayed lower adhesion and proliferation rates in in-vitro conditions. Moreover, Decorin loaded scaffolds demonstrated morphological changes in cells, specifically targeting the myofibroblast. The expression of TGF-β was also scrutinized to understand the effect of Decorin loaded nanofibers. Besides, in the in-vitro fibrotic model, Decorin loaded nanofibers efficiently reduced the expression of ECM related proteins. Therefore, we report the sustained delivery of the recombinant Decorin from nanofiber dressing to potentially obstruct scar formation during the process of wound healing.
疤痕是组织损伤或手术后纤维化的结果,有报道称,在伤口愈合过程中转化生长因子-β(TGF-β)活性过度会导致进行性纤维化。聚集蛋白聚糖是一种细胞外基质(ECM)蛋白,可调节胶原原纤维的形成。然而,由于蛋白酶的降解,靶向递送和有效的蛋白质治疗仍然是一个挑战。因此,我们旨在以可持续的方式递送聚集蛋白聚糖,以降低 TGF-β水平并随后减少疤痕形成。在此,我们已经制备了 PCL-明胶仿生支架,以优化生物活性并提供重组聚集蛋白聚糖的局部递送。降解和药物释放模式表明,这种生物材料是可生物降解的,并提供重组聚集蛋白聚糖的持续释放。负载有聚集蛋白聚糖的纳米纤维在体外条件下显示出较低的黏附和增殖率。此外,负载有聚集蛋白聚糖的支架在细胞中表现出形态变化,特别是针对肌成纤维细胞。还研究了 TGF-β 的表达,以了解负载有聚集蛋白聚糖的纳米纤维的作用。此外,在体外纤维化模型中,负载有聚集蛋白聚糖的纳米纤维可有效降低 ECM 相关蛋白的表达。因此,我们报告了从纳米纤维敷料中持续递送重组聚集蛋白聚糖,以潜在地阻止伤口愈合过程中的疤痕形成。