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基于鼻腔软骨细胞的工程化移植物修复关节软骨“亲吻”损伤:一项大型动物初步研究。

Nasal Chondrocyte-Based Engineered Grafts for the Repair of Articular Cartilage "Kissing" Lesions: A Pilot Large-Animal Study.

机构信息

Department of Histology and Embryology, School of Medicine, University of Zagreb, Zagreb, Croatia.

Investigation performed at the University of Zagreb, Zagreb, Croatia.

出版信息

Am J Sports Med. 2021 Jul;49(8):2187-2198. doi: 10.1177/03635465211014190. Epub 2021 May 28.

DOI:10.1177/03635465211014190
PMID:34048271
Abstract

BACKGROUND

Bipolar or "kissing" cartilage lesions formed on 2 opposite articular surfaces of the knee joint are commonly listed as exclusion criteria for advanced cartilage therapies.

PURPOSE

To test, in a pilot large-animal study, whether autologous nasal chondrocyte (NC)-based tissue engineering, recently introduced for the treatment of focal cartilage injuries, could provide a solution for challenging kissing lesions.

STUDY DESIGN

Controlled laboratory study.

METHODS

Osteochondral kissing lesions were freshly introduced into the knee joints of 26 sheep and covered with NC-based grafts with a low or high hyaline-like extracellular matrix; a control group was treated with a cell-free scaffold collagen membrane (SCA). The cartilage repair site was assessed at 6 weeks and 6 months after implantation by histology, immunohistochemistry, and magnetic resonance imaging evaluation.

RESULTS

NC-based grafts, independently of their composition, induced partial hyaline cartilage repair with stable integrity in surrounding healthy tissue at 6 months after treatment. The SCA repaired cartilage to a similar degree to that of NC-based grafts.

CONCLUSION

Kissing lesion repair, as evidenced in this sheep study, demonstrated the feasibility of the treatment of complex cartilage injuries with advanced biological methods. However, the potential advantages of an NC-based approach over a cell-free approach warrant further investigations in a more relevant preclinical model.

CLINICAL RELEVANCE

NC-based grafts currently undergoing phase II clinical trials have a high potential to replace existing cartilage therapies that show significant limitations in the quality and reproducibility of the repair method. We have brought this innovative concept to the next level by addressing a new clinical indication.

摘要

背景

膝关节的两个相对关节面上形成的双相或“亲吻”软骨病变通常被列为高级软骨治疗的排除标准。

目的

在一项大型动物初步研究中进行测试,即自体鼻软骨细胞(NC)为基础的组织工程学,最近被引入用于治疗局灶性软骨损伤,是否能为具有挑战性的“亲吻”病变提供解决方案。

研究设计

对照实验室研究。

方法

将新鲜的骨软骨“亲吻”病变引入 26 只绵羊的膝关节中,并覆盖基于 NC 的移植物,具有低或高透明样细胞外基质;对照组采用无细胞支架胶原膜(SCA)治疗。植入后 6 周和 6 个月通过组织学、免疫组织化学和磁共振成像评估评估软骨修复部位。

结果

无论组成如何,基于 NC 的移植物均诱导了部分透明软骨修复,并在治疗后 6 个月时在周围健康组织中保持稳定的完整性。SCA 修复的软骨与基于 NC 的移植物具有相似的程度。

结论

如本绵羊研究所示,“亲吻”病变的修复证明了使用先进的生物方法治疗复杂软骨损伤的可行性。然而,基于 NC 的方法与无细胞方法相比的潜在优势需要在更相关的临床前模型中进行进一步研究。

临床相关性

目前正在进行 II 期临床试验的基于 NC 的移植物具有很高的潜力,可以替代现有的软骨治疗方法,这些方法在修复方法的质量和可重复性方面存在显著局限性。我们通过解决新的临床适应证,将这一创新理念提升到了一个新的水平。

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