Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits
Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits
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DOI：
10.1016/j.actbio.2015.12.034
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发表时间：
2016-03-01
影响因子：
9.7
通讯作者：
O'Brien, Fergal J.
中科院分区：
文献类型：
--
作者：
Levingstone, Tanya J.;Thompson, Emmet;O'Brien, Fergal J.
简介：由于现有的局限性，确定骨软骨炎修复的合适治疗方法是一项重大挑战，迫切的临床需求仍然是现成的、低成本的一步法。仿生方法提供了一种潜在的解决方案，其中生物材料本身鼓励细胞从底层骨髓浸润，并提供物理和化学线索来指导这些细胞再生受损组织。为了满足这一需求，我们小组开发了一种基于胶原的多层骨软骨缺损修复支架。目的：本研究的目的是评估这种支架的体内反应，并确定其在每层中指导再生反应的能力，以修复兔膝关节关键尺寸缺损中的骨软骨组织。方法：多层支架，包括由I型胶原蛋白组成的骨层（牛源）和羟基磷灰石（HA）组成的中间层，由I型和II型胶原和HA组成的中间层;以及由I型和II型胶原蛋白组成的表层（猪源）和透明质酸（HyA），植入新西兰白色兔膝关节内侧股骨髁中产生的临界尺寸（3 × 5 mm）骨软骨缺损中，并与空白对照组进行比较。修复评估宏观，组织学和使用micro-CT分析在12周后implantation.Results：修复组织的分析表明，增强宏观外观的多层支架组相比，空组。此外，支架组中的弥漫性宿主细胞浸润导致组织再生，具有带状组织，修复了软骨下骨，形成了覆盖的软骨层和中间潮标的证据。这些结果证明了这种仿生多-在骨软骨缺损的治疗中，层状支架可支持和引导宿主的修复反应。由于疾病或受伤，年轻的活动患者经常出现涉及软骨和底层软骨下骨的缺陷。虽然有一些治疗选择，但成功是有限的，患者最终往往需要关节置换。为了解决这一临床需求，我们小组开发了一种基于胶原蛋白的多层骨软骨缺损修复支架，旨在指导每个区域内宿主干细胞介导的组织形成。本研究调查在兔膝关节的临界尺寸的缺陷，在体内反应，这种支架。结果表明，支架能够引导宿主修复反应，导致组织再生与带状组织，修复软骨下骨，形成覆盖软骨层和中间潮标的证据。(C)2015 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Introduction: Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group.Aim: The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee.Methods: Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 x 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation.Results: Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.Conclusion: These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects.Statement of SignificanceOsteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.