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基于去细胞半月板基质的纳米纤维支架的构建及其在半月板组织工程中的应用

Development of a decellularized meniscus matrix-based nanofibrous scaffold for meniscus tissue engineering.

机构信息

McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.

McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA.

出版信息

Acta Biomater. 2021 Jul 1;128:175-185. doi: 10.1016/j.actbio.2021.03.074. Epub 2021 Apr 3.

Abstract

The meniscus plays a critical role in knee mechanical function but is commonly injured given its central load bearing role. In the adult, meniscus repair is limited, given the low number of endogenous cells, the density of the matrix, and the limited vascularity. Menisci are fibrocartilaginous tissues composed of a micro-/nano- fibrous extracellular matrix (ECM) and a mixture of chondrocyte-like and fibroblast-like cells. Here, we developed a fibrous scaffold system that consists of bioactive components (decellularized meniscus ECM (dME) within a poly(e-caprolactone) material) fashioned into a biomimetic morphology (via electrospinning) to support and enhance meniscus cell function and matrix production. This work supports that the incorporation of dME into synthetic nanofibers increased hydrophilicity of the scaffold, leading to enhanced meniscus cell spreading, proliferation, and fibrochondrogenic gene expression. This work identifies a new biomimetic scaffold for therapeutic strategies to substitute or replace injured meniscus tissue. STATEMENT OF SIGNIFICANCE: In this study, we show that a scaffold electrospun from a combination of synthetic materials and bovine decellularized meniscus ECM provides appropriate signals and a suitable template for meniscus fibrochondrocyte spreading, proliferation, and secretion of collagen and proteoglycans. Material characterization and in vitro cell studies support that this new bioactive material is susceptible to enzymatic digestion and supports meniscus-like tissue formation.

摘要

半月板在膝关节机械功能中起着至关重要的作用,但由于其承担着中央负荷的作用,所以很容易受伤。在成年人中,由于内源性细胞数量少、基质密度大和血管有限,半月板修复的能力有限。半月板是由纤维软骨组织组成的,包含微观/纳米纤维细胞外基质(ECM)和类似于软骨细胞和成纤维细胞的细胞混合物。在这里,我们开发了一种纤维支架系统,该系统由生物活性成分(脱细胞半月板 ECM(dME)在聚己内酯材料内)构成,并采用仿生形态(通过静电纺丝)来支撑和增强半月板细胞功能和基质生成。这项工作表明,将 dME 掺入合成纳米纤维中会增加支架的亲水性,从而促进半月板细胞的铺展、增殖和纤维软骨生成基因表达。这项工作确定了一种新的仿生支架,用于替代或替换受伤的半月板组织的治疗策略。研究意义:在这项研究中,我们表明,由合成材料和牛脱细胞半月板 ECM 组合纺丝而成的支架为半月板纤维软骨细胞的铺展、增殖和胶原蛋白和蛋白聚糖的分泌提供了适当的信号和合适的模板。材料特性和体外细胞研究表明,这种新的生物活性材料易于酶消化,并支持半月板样组织的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a236/8474106/8b986aae0dd6/nihms-1702215-f0001.jpg

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