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小型猪模型中软骨修复及软骨下骨重塑对局部损伤的反应:对组织工程的启示

Cartilage repair and subchondral bone remodeling in response to focal lesions in a mini-pig model: implications for tissue engineering.

作者信息

Fisher Matthew B, Belkin Nicole S, Milby Andrew H, Henning Elizabeth A, Bostrom Marc, Kim Minwook, Pfeifer Christian, Meloni Gregory, Dodge George R, Burdick Jason A, Schaer Thomas P, Steinberg David R, Mauck Robert L

机构信息

1 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.

出版信息

Tissue Eng Part A. 2015 Feb;21(3-4):850-60. doi: 10.1089/ten.TEA.2014.0384. Epub 2014 Dec 11.

Abstract

OBJECTIVE

Preclinical large animal models are essential for evaluating new tissue engineering (TE) technologies and refining surgical approaches for cartilage repair. Some preclinical animal studies, including the commonly used minipig model, have noted marked remodeling of the subchondral bone. However, the mechanisms underlying this response have not been well characterized. Thus, our objective was to compare in-vivo outcomes of chondral defects with varied injury depths and treatments.

DESIGN

Trochlear chondral defects were created in 11 Yucatan minipigs (6 months old). Groups included an untreated partial-thickness defect (PTD), an untreated full-thickness defect (FTD), and FTDs treated with microfracture, autologous cartilage transfer (FTD-ACT), or an acellular hyaluronic acid hydrogel. Six weeks after surgery, micro-computed tomography (μCT) was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. A finite element model (FEM) was developed to assess load transmission.

RESULTS

Using μCT, substantial bone remodeling was observed for all FTDs, but not for the PTD group. The best overall histological scores and greatest type II collagen staining was found for the FTD-ACT and PTD groups. The FEM confirmed that only the FTD-ACT group could initially restore appropriate transfer of compressive loads to the underlying bone.

CONCLUSIONS

The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair.

摘要

目的

临床前大型动物模型对于评估新的组织工程(TE)技术和完善软骨修复的手术方法至关重要。一些临床前动物研究,包括常用的小型猪模型,已经注意到软骨下骨有明显的重塑。然而,这种反应的潜在机制尚未得到很好的描述。因此,我们的目的是比较不同损伤深度和治疗方法的软骨缺损的体内结果。

设计

在11只6个月大的尤卡坦小型猪中制造滑车软骨缺损。分组包括未治疗的部分厚度缺损(PTD)、未治疗的全层厚度缺损(FTD),以及接受微骨折、自体软骨移植(FTD-ACT)或无细胞透明质酸水凝胶治疗的FTD。术后六周,使用微型计算机断层扫描(μCT)定量评估缺损填充和软骨下骨重塑。使用国际软骨修复协会(ICRS-II)组织学评分系统和II型胶原免疫组织化学评估软骨修复质量。开发了有限元模型(FEM)来评估载荷传递。

结果

使用μCT观察到所有FTD组均有大量骨重塑,但PTD组未观察到。FTD-ACT组和PTD组的总体组织学评分最佳,II型胶原染色最强。FEM证实,只有FTD-ACT组能够最初恢复向下方骨骼的适当压缩载荷传递。

结论

在该模型系统中观察到的骨重塑似乎是一种生物学现象,而不是机械载荷改变的结果,局灶性软骨缺损的深度(部分厚度与全层厚度)决定了骨重塑反应。在利用该模型评估软骨修复的TE方法的研究中,应仔细控制软骨损伤的类型。

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