Bioengineered and functionalized silk proteins accelerate wound healing in rat and human dermal fibroblasts.

IF 1.5 4区 生物学 Q4 CELL BIOLOGY Integrative Biology Pub Date : 2022-12-01 DOI:10.1093/intbio/zyac014
Chitra Manoharan, Dyna Susan Thomas, Rasalkar Sandhya Yashwant, Manjunatha Panduranga Mudagal, Suresh Janadri, Gourab Roy, Vijayan Kunjupillai, Rakesh Kumar Mishra, Ravikumar Gopalapillai
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引用次数: 1

Abstract

Wound healing is an intrinsic process directed towards the restoration of damaged or lost tissue. The development of a dressing material having the ability to control the multiple aspects of the wound environment would be an ideal strategy to improve wound healing. Though natural silk proteins, fibroin, and sericin have demonstrated tissue regenerative properties, the efficacy of bioengineered silk proteins on wound healing is seldom assessed. Furthermore, silk proteins sans contaminants, having low molecular masses, and combining with other bioactive factors can hasten the wound healing process. Herein, recombinant silk proteins, fibroin and sericin, and their fusions with cecropin B were evaluated for their wound-healing effects using in vivo rat model. The recombinant silk proteins demonstrated accelerated wound closure in comparison to untreated wounds and treatment with Povidone. Among all groups, the treatment with recombinant sericin-cecropin B (RSC) showed significantly faster healing, greater than 90% wound closure by Day 12 followed by recombinant fibroin-cecropin B (RFC) (88.86%). Furthermore, histological analysis and estimation of hydroxyproline showed complete epithelialization, neovascularization, and collagenisation in groups treated with recombinant silk proteins. The wound healing activity was further verified by in vitro scratch assay using HADF cells, where the recombinant silk proteins induced cell proliferation and cell migration to the wound area. Additionally, wound healing-related gene expression showed recombinant silk proteins stimulated the upregulation of EGF and VEGF and regulated the expression of TGF-β1 and TGF-β3. Our results demonstrated the enhanced healing effects of the recombinant silk fusion proteins in facilitating complete tissue regeneration with scar-free healing. Therefore, the recombinant silks and their fusion proteins have great potential to be developed as smart bandages for wound healing.

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生物工程和功能化丝蛋白促进大鼠和人皮肤成纤维细胞的伤口愈合。
伤口愈合是一个内在的过程,旨在恢复受损或丢失的组织。开发一种能够控制伤口环境多个方面的敷料将是改善伤口愈合的理想策略。虽然天然蚕丝蛋白、丝素蛋白和丝胶蛋白已经证明了组织再生的特性,但生物工程蚕丝蛋白在伤口愈合方面的功效很少得到评估。此外,丝蛋白无污染物,具有低分子质量,并与其他生物活性因子结合,可以加速伤口愈合过程。本研究采用体内大鼠模型,对重组丝蛋白、丝素蛋白和丝胶蛋白及其与天蚕素B融合物的创面愈合效果进行了评价。与未处理的伤口和聚维酮治疗相比,重组丝蛋白显示加速伤口愈合。在所有组中,重组丝素-天蚕素B (RSC)治疗的愈合速度明显更快,第12天伤口愈合率超过90%,其次是重组丝素-天蚕素B (RFC)(88.86%)。此外,对羟基脯氨酸的组织学分析和估计显示,重组丝蛋白处理组的上皮化、新生血管和胶原形成完全。利用HADF细胞进行体外划伤实验,进一步验证了重组丝蛋白的创面愈合活性,重组丝蛋白诱导细胞增殖并向创面区域迁移。此外,伤口愈合相关基因表达显示重组丝蛋白刺激EGF和VEGF上调,调控TGF-β1和TGF-β3的表达。我们的研究结果表明,重组丝融合蛋白在促进组织完全再生和无疤痕愈合方面具有增强的愈合作用。因此,重组丝及其融合蛋白在伤口愈合智能绷带方面具有很大的发展潜力。
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来源期刊
Integrative Biology
Integrative Biology 生物-细胞生物学
CiteScore
4.90
自引率
0.00%
发文量
15
审稿时长
1 months
期刊介绍: Integrative Biology publishes original biological research based on innovative experimental and theoretical methodologies that answer biological questions. The journal is multi- and inter-disciplinary, calling upon expertise and technologies from the physical sciences, engineering, computation, imaging, and mathematics to address critical questions in biological systems. Research using experimental or computational quantitative technologies to characterise biological systems at the molecular, cellular, tissue and population levels is welcomed. Of particular interest are submissions contributing to quantitative understanding of how component properties at one level in the dimensional scale (nano to micro) determine system behaviour at a higher level of complexity. Studies of synthetic systems, whether used to elucidate fundamental principles of biological function or as the basis for novel applications are also of interest.
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