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仿生关节软骨修复片:去细胞软骨基质与丝弹性蛋白样蛋白(SELP)水凝胶的结合。

Biomimetic approach for an articular cartilage patch: Combination of decellularized cartilage matrix and silk-elastin-like-protein (SELP) hydrogel.

机构信息

Department of Veterinary Science, University of Parma, Italy.

Centre of Molecular and Environmental Biology (CBMA), Department of Biology and Institute of Science and Innovation for Bio-Sustainability (IB-S), University of Minho, Braga, Portugal.

出版信息

Ann Anat. 2023 Oct;250:152144. doi: 10.1016/j.aanat.2023.152144. Epub 2023 Aug 23.

Abstract

Articular cartilage degradation due to injury, disease and aging is a common clinical issue as current regenerative therapies are unable to fully replicate the complex microenvironment of the native tissue which, being avascular, is featured by very low ability to self-regenerate. The extracellular matrix (ECM), constituting almost 90% of the entire tissue, plays a critical role in its function and resistance to compressive forces. In this context, the current tissue engineering strategies are only partially effective in restoring the biology and function of the native tissue. A main issue in tissue regeneration is treatment failure due to scarce integration of the engineered construct, often following a gradual detachment of the graft. In this scenario, we aimed to create an adhesive patch able to adequately support cartilage regeneration as a promising tool for the treatment of cartilage injuries and diseases. For this, we produced an engineered construct composed of decellularized ECM (dECM) obtained from horse joint cartilage, to support tissue regeneration, coupled with a Silk-Elastin-Like Proteins (SELP) hydrogel, which acts as a biological glue, to guarantee an adequate adherence to the host tissue. Following the production of the two biomaterials we characterized them by assessing: 1) dECM morphological, chemical, and ultrastructural features along with its capability to support chondrocyte proliferation, specific marker expression and ECM synthesis; 2) SELP microarchitecture, cytocompatibility and mechanical properties. Our results demonstrated that both materials hold unique properties suitable to be exploited to produce a tailored microenvironment to support cell growth and differentiation providing a proof of concept concerning the in vitro biological and mechanical efficacy of the construct. The SELP hydrogel displayed a very interesting physical behavior due to its high degree of resistance to mechanical stress, which is generally associated with physiological mechanical load during locomotion. Intriguingly, the shear-thinning behavior of the hydrogel may also make it suitable to be applied and spread over non-homogeneous surfaces, therefore, we hypothesize that the hybrid biomaterial proposed may be a real asset in the treatment of cartilage defects and injuries.

摘要

由于损伤、疾病和衰老,关节软骨退化是一个常见的临床问题,因为目前的再生疗法无法完全复制天然组织的复杂微环境,而天然组织是无血管的,自我再生能力非常低。细胞外基质 (ECM) 构成了整个组织的近 90%,对其功能和抗压能力起着至关重要的作用。在这种情况下,目前的组织工程策略在恢复天然组织的生物学和功能方面仅部分有效。组织再生的一个主要问题是由于工程构建体的整合不足导致治疗失败,通常是在移植物逐渐分离之后。在这种情况下,我们旨在创建一种能够充分支持软骨再生的粘性贴片,作为治疗软骨损伤和疾病的有前途的工具。为此,我们制作了一种由马关节软骨脱细胞细胞外基质 (dECM) 组成的工程构建体,以支持组织再生,再加上一种丝素弹性蛋白样蛋白 (SELP) 水凝胶,作为生物胶,以保证与宿主组织的充分粘附。在生产出这两种生物材料后,我们对其进行了表征,评估了:1)dECM 的形态、化学和超微结构特征,以及其支持软骨细胞增殖、特异性标志物表达和细胞外基质合成的能力;2)SELP 微结构、细胞相容性和机械性能。我们的结果表明,这两种材料都具有独特的特性,可用于制造定制的微环境,以支持细胞生长和分化,为构建体的体外生物学和机械功效提供了概念验证。SELP 水凝胶由于其对机械应力的高度抵抗力而表现出非常有趣的物理行为,这通常与运动过程中的生理机械负荷有关。有趣的是,水凝胶的剪切稀化行为也可能使其适合应用和涂覆在非均匀表面上,因此,我们假设所提出的混合生物材料可能是治疗软骨缺陷和损伤的真正资产。

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