机械性能优越的基质促进兔前交叉韧带组织的骨整合和再生。

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits.

机构信息

Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, CT 06030.

Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT 06030.

出版信息

Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28655-28666. doi: 10.1073/pnas.2012347117. Epub 2020 Nov 3.

Abstract

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

摘要

前交叉韧带(ACL)重建的金标准治疗方法是使用肌腱移植物和同种异体移植物。这种治疗方法的限制因素包括供体部位发病率、潜在疾病传播和移植物质量的变化。为了解决这些限制,我们之前开发了一种现成的替代品,即聚(L-乳酸)(PLLA)生物工程 ACL 基质,并证明其具有再生 ACL 组织的可行性。本研究旨在:1)通过补充骨髓抽吸物浓缩物(BMAC)和生长因子(BMP-2、FGF-2 和 FGF-8)来加速生物工程 ACL 基质的再生速度,2)提高基质强度保留率。组织学评估显示所有组均有强劲的组织再生。在 BMAC 组中,存在类似于 ACL 成纤维细胞和软骨细胞的立方细胞,周围是富含阴离子大分子的细胞外基质,这在以前的研究中没有观察到,表明再生得到了增强。此外,关节内给予 FGF-2 和 FGF-8 被发现可以抑制关节炎症。为了提高基质强度保留率,我们将不可降解纤维,聚对苯二甲酸乙二醇酯(PET),掺入 PLLA 生物工程 ACL 基质中,以制造“虎形移植物”。与实验各组相比,虎形移植物表现出最大的峰值载荷,在兔模型中也是迄今为止最高的。此外,虎形移植物表现出优异的骨整合性,使其成为理想的生物工程 ACL 基质。本研究结果表明生物活性因子和 PET 掺入对 ACL 再生具有有益作用,并为功能性生物工程 ACL 基质的临床转化迈出了有希望的一步。

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