Combination of a human articular cartilage-derived extracellular matrix scaffold and microfracture techniques for cartilage regeneration: A proof of concept in a sheep model

人类关节软骨衍生的细胞外基质支架与微骨折技术相结合用于软骨再生:在绵羊模型中的概念验证

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作者:Liqing Peng, Hao Li, Haoyuan Deng, Tianze Gao, Runmeng Li, Ziheng Xu, Qinyu Tian, Tianyuan Zhao, Jianwei Li, Yongkang Yang, Chao Wang, Shuyun Liu, Quanyi Guo

Background

The utilization of decellularized extracellular matrix has gained considerable attention across numerous areas in regenerative research. Of particular interest is the human articular cartilage-derived extracellular matrix (hACECM), which presents as a promising facilitator for cartilage regeneration. Concurrently, the microfracture (MF) ​technique, a well-established marrow stimulation method, has proven efficacious in the repair of cartilage defects. However, as of the current literature review, no investigations have explored the potential of a combined application of hACECM and the microfracture technique in the repair of cartilage defects within a sheep model. Hypothesis: The combination of hACECM scaffold and microfracture will result in improved repair of full-thickness femoral condyle articular cartilage defects compared to the use of either technique alone. Study design: Controlled laboratory study.

Conclusion

hACECM scaffolds combined with/without microfracture facilitate chondral defect repair. The translational potential of this article: Preclinical large animal models represent an important adjunct and surrogate for studies on articular cartilage repair, while the sheep stifle joint reflects many key features of the human knee and are therefore optimal experimental model for future clinical application in human. In this study, we developed a human articular cartilage-derived extracellular matrix scaffold and to verify the viability of its use in sheep animal models. Clinical studies are warranted to further quantify the effects of hACECM scaffolds in similar settings.

Methods

Full-thickness femoral condyle articular cartilage defect (diameter, 7.0 ​mm; debrided down to the subchondral bone plate) were created in the weight-bearing area of the femoral medial and lateral condyles (n ​= ​24). All of defected sheep were randomly divided into four groups: control, microfracture, hACECM scaffold, and hACECM scaffold ​+ ​microfracture. After 3, 6 and 12 months, the chondral repair was assessed for standardized (semi-) quantitative macroscopic, imaging, histological, immunohistochemical, mechanics, and biochemical analyses in each group. Result: At 3, 6 and 12 months after implantation, the gross view and pathological staining of regenerative tissues were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than in the microfracture and control groups; Micro-CT result showed that the parameters about the calcified layer of cartilage and subchondral bone were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than the others, and excessive subchondral bone proliferation in the microfracture group. The

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