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纤维蛋白原修饰的具有不同刚度的区域分层脱钙骨支架用于膝关节缺损的骨软骨再生

Zonally Stratified Decalcified Bone Scaffold with Different Stiffness Modified by Fibrinogen for Osteochondral Regeneration of Knee Joint Defect.

作者信息

Chen Zhenyin, Du Wenjiang, Lv Yonggang

机构信息

Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, P. R. China.

State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan 430200, P. R. China.

出版信息

ACS Biomater Sci Eng. 2022 Dec 12;8(12):5257-5272. doi: 10.1021/acsbiomaterials.2c00813. Epub 2022 Nov 6.

DOI:10.1021/acsbiomaterials.2c00813
PMID:36335510
Abstract

Articular cartilage is generally known to be a complex tissue with multiple layers. Each layer has different composition, structure, and mechanical properties, making regeneration after knee joint defects a troubling clinical problem. A novel integrated stratified decalcified bone matrix (SDBM) scaffold with different stiffness to mimic the mechanical properties of articular cartilage is presented herein. This SDBM scaffold was modified using fibrinogen (Fg) (Fg + SDBM) to enhance its vascularization ability and improve its repair efficiency for osteochondral defects of knee joints. A Fg + SDBM scaffold with different elastic modulus in each layer (high-stiffness DBM (HDBM) layer, 174.208 ± 44.330 MPa (Fg + HDBM); medium-stiffness DBM (MDBM) layer, 21.214 ± 6.922 MPa (Fg + MDBM); and low-stiffness DBM (LDBM) layer, 0.678 ± 0.269 MPa (Fg + LDBM)) was constructed by controlling the stratified decalcification time with layered embedding paraffin (0, 3, and 5 days). The low- and medium-stiffness layers of the Fg + SDBM scaffold remarkably promoted the cartilage differentiation of bone marrow mesenchymal stem cells . Subcutaneous transplantation and rabbit knee joint osteochondral defect repair experiments revealed that the low- and medium-stiffness layers of the Fg + SDBM scaffold exhibited wonderful cartilage capacity, whereas the high-stiffness layer of Fg + SDBM scaffold exhibited good osteogenesis ability. Furthermore, this scaffold could promote blood vessel formation in subchondral bone area. This study presents a feasible strategy for osteochondral regeneration of defective knee joints, which is of great clinical value for tissue repair.

摘要

关节软骨通常被认为是一种具有多层结构的复杂组织。每层都有不同的组成、结构和力学性能,这使得膝关节缺损后的再生成为一个棘手的临床问题。本文提出了一种新型的集成分层脱钙骨基质(SDBM)支架,其具有不同的刚度,以模拟关节软骨的力学性能。这种SDBM支架用纤维蛋白原(Fg)进行了改性(Fg + SDBM),以增强其血管化能力并提高其对膝关节骨软骨缺损的修复效率。通过分层包埋石蜡(0、3和5天)控制分层脱钙时间,构建了每层具有不同弹性模量的Fg + SDBM支架(高刚度DBM(HDBM)层,174.208±44.330 MPa(Fg + HDBM);中刚度DBM(MDBM)层,21.214±6.922 MPa(Fg + MDBM);低刚度DBM(LDBM)层,0.678±0.269 MPa(Fg + LDBM))。Fg + SDBM支架的低刚度和中刚度层显著促进了骨髓间充质干细胞的软骨分化。皮下移植和兔膝关节骨软骨缺损修复实验表明,Fg + SDBM支架的低刚度和中刚度层表现出良好的软骨形成能力,而Fg + SDBM支架的高刚度层表现出良好的成骨能力。此外,这种支架可以促进软骨下骨区域的血管形成。本研究为膝关节缺损的骨软骨再生提出了一种可行的策略,对组织修复具有重要的临床价值。

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