Biomimetic tendon extracellular matrix composite gradient scaffold enhances ligament-to-bone junction reconstruction
Biomimetic tendon extracellular matrix composite gradient scaffold enhances ligament-to-bone junction reconstruction
复制标题
仿生肌腱细胞外基质复合梯度支架增强韧带骨连接重建
DOI：
10.1016/j.actbio.2017.05.027
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发表时间：
2017-07-01
影响因子：
9.7
通讯作者：
Ouyang, Hongwei
中科院分区：
文献类型：
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作者：
Liu, Huanhuan;Yang, Long;Ouyang, Hongwei
由于韧带/肌腱-骨连接处的血管供应不足和多组织过渡结构，韧带/肌腱-骨连接处愈合的管理至今仍是骨科医学领域的一个巨大挑战。已经采用了许多策略来改善韧带-骨连接处的愈合，包括干细胞、生物活性因子和合成材料的递送，但是这些方法通常不足以概括天然组织界面处的复杂结构-功能关系。在这里，我们开发了一种易于制造和有效的仿生复合材料，以促进韧带-骨连接的再生，通过物理改性肌腱细胞外基质（ECM）成随机排列的随机复合材料，使用超声处理。体外观察兔骨髓基质细胞在修饰的ECM上的分化潜能。结果表明，修饰的ECM增强了软骨形成和成骨相关的表观遗传基因（Jmjd 1c，Kdm 6 b），转录因子基因（Sox 9，Runx 2）和细胞外基质基因（Col 2a 1，Ocn）的表达，导致体外骨诱导性高于未处理的肌腱ECM。在兔前交叉韧带（ACL）体内重建模型中，显微计算机断层扫描（Micro-CT）和组织学分析表明，改良的Random-Aligned-Random复合支架比未改良的肌腱ECM更有效地促进了界面骨和纤维软骨的形成。因此，这些结果表明，仿生Random-Aligned-Random复合材料可能是一个有前途的支架韧带/tendon-bone junction repair.Statement的显著性声明天然过渡区由几个不同的但连续的组织区域，包括软组织，非钙化纤维软骨，钙化纤维软骨和骨。其相彼此互连的分层移植物对于支持功能连续的多组织区域的形成是必不可少的。已经尝试了各种技术来改善韧带/肌腱移植物与骨的粘附，包括利用干细胞、生长因子和生物材料，但是这些方法通常不足以概括天然组织界面处的复杂结构-功能关系。在这里，我们开发了一种易于制造和有效的仿生复合材料，以促进韧带-骨连接的再生，通过物理改性肌腱细胞外基质（ECM）成随机排列的随机复合材料，使用超声处理。修饰的ECM在体外增强软骨形成和成骨相关表观遗传基因的表达。在兔前交叉韧带重建体内模型中，结果表明，改性的Random-Aligned-Random复合材料增强了界面中骨和纤维软骨的形成，证明比未改性的肌腱ECM更有效。因此，这些结果表明，仿生Random-Aligned-Random复合材料可能是一种有前途的韧带/肌腱-骨连接修复支架。(C)2017由Elsevier Ltd代表Acta Materialia Inc.发布。
Management of ligament/tendon-to-bone-junction healing remains a formidable challenge in the field of orthopedic medicine to date, due to deficient vascularity and multi-tissue transitional structure of the junction. Numerous strategies have been employed to improve ligament-bone junction healing, including delivery of stem cells, bioactive factors, and synthetic materials, but these methods are often inadequate at recapitulating the complex structure-function relationships at native tissue interfaces. Here, we developed an easily-fabricated and effective biomimetic composite to promote the regeneration of ligament-bone junction by physically modifying the tendon extracellular matrix (ECM) into a Random-Aligned-Random composite using ultrasound treatment. The differentiation potential of rabbit bone marrow stromal cells on the modified ECM were examined in vitro. The results demonstrated that the modified ECM enhanced expression of chondrogenesis and osteogenesis-associated epigenetic genes (Jmjd1c, Kdm6b), transcription factor genes (Sox9, Runx2) and extracellular matrix genes (Col2a1, Ocn), resulting in higher osteoinductivity than the untreated tendon ECM in vitro. In the rabbit anterior cruciate ligament (ACL) reconstruction model in vivo, micro-computed tomography (Micro-CT) and histological analysis showed that the modified Random-Aligned-Random composite scaffold enhanced bone and fibrocartilage formation at the interface, more efficaciously than the unmodified tendon ECM. Therefore, these results demonstrated that the biomimetic Random-Aligned-Random composite could be a promising scaffold for ligament/tendon-bone junction repair.Statement of SignificanceThe native transitional region consists of several distinct yet contiguous tissue regions, composed of soft tissue, non-calcified fibrocartilage, calcified fibrocartilage, and bone. A stratified graft whose phases are interconnected with each other is essential for supporting the formation of functionally continuous multi-tissue regions. Various techniques have been attempted to improve adherence of the ligament/tendon graft to bone, including utilization of stem cells, growth factors and biomaterials, but these methods are often inadequate at recapitulating the complex structure-function relationships at native tissue interfaces. Here, we developed an easily-fabricated and effective biomimetic composite to promote the regeneration of ligament-bone junction by physically modifying the tendon extracellular matrix (ECM) into a Random-Aligned-Random composite using ultrasound treatment. The modified ECM enhanced expression of chondrogenesis and osteogenesis-associated epigenetic genes expression in vitro. In the rabbit anterior crucial ligament reconstruction model in vivo, results showed that the modified Random-Aligned-Random composite enhances the bone and fibrocartilage formation in the interface, proving to be more efficient than the unmodified tendon ECM. Therefore, these results demonstrated that the biomimetic Random-Aligned-Random composite could be a promising scaffold for ligament/tendon-bone junction repair. (C) 2017 Published by Elsevier Ltd on behalf of Acta Materialia Inc.