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Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits.

机译:基于多层胶原蛋白的支架,用于兔骨软骨缺损的修复。

摘要

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 × 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 SIGNIFICANCE: Osteochondral 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.
机译:简介:由于现有的局限性,确定合适的骨软骨修复治疗方法面临着重大挑战,并且迫切需要现成的低成本一步法临床需求。一种仿生方法,其中生物材料本身鼓励细胞从下面的骨髓浸润,并提供物理和化学线索来指导这些细胞再生受损组织,提供了一种潜在的解决方案。为了满足这一需求,我们小组中开发了一种多层胶原基骨软骨缺损修复支架。目的:本研究的目的是评估该支架在体内的反应,并确定其在每个支架中指导再生反应的能力。方法:多层支架,由I型胶原蛋白(牛源)和羟基磷灰石(HA)组成的骨层组成,中间层由胶原蛋白组成。 I型和II型胶原蛋白和HA;然后将由I型和II型胶原蛋白(猪源)和透明质酸(HyA)组成的表皮层植入新西兰白膝关节内侧股骨con中形成的临界尺寸(3×5 mm)骨软骨缺损中兔子并与空对照组进行比较。植入后第12周,通过肉眼,组织学和显微CT分析评估修复效果。结果:与空组相比,多层支架组的修复组织分析显示宏观外观有所增强。此外,支架组中的弥漫性宿主细胞浸润导致组织再生,具有区域性组织,软骨下骨的修复,上层软骨层的形成以及中间潮痕的证据。结论:这些结果证明了这种仿生技术的潜力多层支架可支持和指导宿主在骨软骨缺损治疗中的修复反应。意义:由于疾病或损伤,年轻的活跃患者经常发生骨软骨缺损,包括软骨和下方的软骨下骨。尽管有一些治疗选择可用,但成功的局限性有限,患者通常最终需要关节置换。为了满足这一临床需求,我们小组中已开发出一种多层胶原基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。本研究调查了在兔子膝盖的临界大小缺陷中对该支架的体内反应。结果显示支架引导宿主修复反应的能力,从而导致区域组织的组织再生,软骨下骨的修复,上层软骨层的形成以及中间潮痕的迹象。

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