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无细胞多层胶原基支架在山羊关节中显示出功能性骨软骨组织的层特异性再生。

Cell-free multi-layered collagen-based scaffolds demonstrate layer specific regeneration of functional osteochondral tissue in caprine joints.

作者信息

Levingstone Tanya J, Ramesh Ashwanth, Brady Robert T, Brama Pieter A J, Kearney Clodagh, Gleeson John P, O'Brien Fergal J

机构信息

Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.

Section Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Dublin, Ireland.

出版信息

Biomaterials. 2016 May;87:69-81. doi: 10.1016/j.biomaterials.2016.02.006. Epub 2016 Feb 9.

DOI:10.1016/j.biomaterials.2016.02.006
PMID:26901430
Abstract

Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions. In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: namely critical sized lateral trochlear ridge (TR) and medial femoral condyle (MC) defects in the caprine stifle joint. The study thus presents the first data in a clinically applicable large animal model. Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation. Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months. Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark. Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions.

摘要

由于骨软骨组织的界面性质和复杂的分层结构(包括软骨下骨、中间钙化软骨和表层软骨区域),开发骨软骨组织修复策略面临着复杂的挑战。在本研究中,在大型动物模型中研究了一种多层仿生胶原基支架修复骨软骨缺损的长期能力:即山羊膝关节关键尺寸的外侧滑车嵴(TR)和内侧股骨髁(MC)缺损。因此,该研究提供了临床适用的大型动物模型中的首批数据。植入后2周证明了支架固定和早期整合。宏观分析表明,与植入后6个月和12个月的空缺损组和市售合成聚合物骨软骨支架组相比,多层支架组的愈合情况有所改善。放射学分析表明,多层支架组两个缺损部位的软骨下骨形成早在3个月时就更优,到12个月时软骨下骨完全再生。组织学分析证实,多层支架组在12个月时形成了结构良好的软骨下小梁骨和透明软骨样组织,解剖学潮标得以恢复。通过募集宿主细胞而无需预培养,用这种天然聚合物支架治疗后愈合情况得到改善,这表明该装置在治疗骨软骨损伤患者方面具有潜力。

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