肌腱衍生基质和碳二亚胺交联的应用使工程肌腱样蛋白质组在熔喷支架上成熟

IF 3.1 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Thomas Lee Jenkins, Sadhana Venkataraman, Aya Saleh, Sarah Calve, Behnam Pourdeyhimi, Dianne Little
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引用次数: 0

摘要

背景:肌腱损伤越来越常见,通过纤维化而非无疤痕再生愈合。组织工程旨在利用具有仿生因子的合成聚合物支架来改善修复,以增强再生潜力。方法:在本研究中,我们比较了三组,即聚乳酸(PLA)熔喷支架,PLA熔喷支架涂覆肌腱衍生基质(TDM), PLA熔喷支架与碳二亚胺交联TDM (2.5:1:1 EDC:NHS:COOH比例)(EDC-TDM),并确定了它们在工程肌腱发育方面的潜力。我们将人脂肪干细胞(hASCs)在熔吹支架上培养28天(n = 4-6 /组),并使用生化分析和蛋白质组学测量拉伸力学功能、基质合成和基质组成。结果:与PLA相比,TDM涂层PLA熔喷支架在28天的屈服拉伸和应力均有所改善。TDM或EDC-TDM的基质合成速率与PLA相似。蛋白质组学分析显示,hASCs产生了富含胶原的细胞外基质,其中含有许多与肌腱相关的基质蛋白。与其他组相比,TDM涂层支架导致I型胶原增加,而EDC-TDM支架的糖蛋白和ECM调节因子增加,这与新沉积基质的成熟度增加一致。结论:TDM涂层和熔喷支架的交联显示出对工程肌腱发育蛋白质组的基质细胞益处,但在机械、生化和基质积累速度方面的明显益处比预期的要少,这与之前的电纺丝支架的研究结果一致。然而,电纺丝支架的纤维结构和微结构与熔喷支架不同,这表明需要进一步考虑这些差异,并改进TDM在熔喷支架中的应用方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Application of Tendon-Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon-Like Proteome on Meltblown Scaffolds

Application of Tendon-Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon-Like Proteome on Meltblown Scaffolds

Background: Tendon injuries are increasingly common and heal by fibrosis rather than scar-less regeneration. Tissue engineering seeks to improve repair using synthetic polymer scaffolds with biomimetic factors to enhance the regenerative potential.

Methods: In this study, we compared three groups, namely, poly(lactic acid) (PLA) meltblown scaffolds, PLA meltblown scaffolds coated with tendon-derived matrix (TDM), and PLA meltblown scaffolds with carbodiimide crosslinked TDM (2.5:1:1 EDC:NHS:COOH ratio) (EDC-TDM) and determined their potential for engineered tendon development. We cultured human adipose stem cells (hASCs) for 28 days on meltblown scaffolds (n = 4–6/group) and measured tensile mechanical function, matrix synthesis, and matrix composition using biochemical assays and proteomics.

Results: Coating PLA meltblown scaffolds with TDM improved yield stretch and stress at 28 days compared with PLA. Matrix synthesis rates for TDM or EDC-TDM were similar to PLA. Proteomic analysis revealed that hASCs produced a collagen-rich extracellular matrix, with many tendon-related matrix proteins. Coating scaffolds with TDM led to an increase in collagen type I whereas EDC-TDM scaffolds had an increase in glycoproteins and ECM regulators compared with other groups, consistent with increased maturity of the newly deposited matrix.

Conclusions: TDM coating and crosslinking of meltblown scaffolds demonstrated matricellular benefits for the proteome of engineered tendon development but provided fewer clear benefits toward mechanical, biochemical, and rate of matrix accumulation than expected, and that previous work with electrospun scaffolds would suggest. However, electrospun scaffolds have different fiber structure and microarchitecture than meltblown, suggesting that further consideration of these differences and refinement of TDM application methods to meltblown scaffolds is required.

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来源期刊
CiteScore
7.50
自引率
3.00%
发文量
97
审稿时长
4-8 weeks
期刊介绍: Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.
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