Role and characteristics of tissue-engineered cartilage in the treatment of growth plate injuries

doi:10.12307/2021.070

Abstract

Abstract: BACKGROUND: The growth plate regulates the longitudinal growth of long bones. Once damaged and replaced by bony bar formation, it will cause length discrepancy and angular deformity. Considering the unsatisfactory outcome of clinical treatments, it is potential for cartilage tissue engineering scaffolds in treatment of growth plate injuries.
OBJECTIVE: To introduce the physiological structure and functions of the growth plate, and discuss and summarize the progress of cartilage tissue engineering technology in the treatment of growth plate injury.
METHODS: The databases of PubMed, Web of Science, CNKI, and Wanfang were retrieved with “growth plate, physis, physeal, scaffold, cartilage tissue engineering” as key words in English and Chinese to collect relevant articles published from 2000 to 2020. Initially, 292 articles were retrieved, and 65 articles were selected for further analysis.
RESULTS AND CONCLUSION: Cartilage tissue engineering scaffolds perform well in treatment of growth plate injuries in animal models. The bioactive scaffold not only fills the defect, inhibits the formation of bone bridge, reduces angular deformity of the affected limb, but also induces the differentiation of mesenchymal stem cells into chondrocytes which are arranged in a columnar regular structure similar to natural growth plates. Many experimental results have found that the application of mesenchymal stem cells combined with appropriate cartilage inducing factors, such as transforming growth factor-β, insulin-like growth factor-1, can promote chondrocytes regeneration and arrange them in order. Regenerated cartilage tissue plays the normal function of growth plate and allows long bone to grow up. In addition, as the carrier of cells and growth factors, the scaffold in cartilage tissue engineering requires suitable mechanical strength and good biocompatibility. Since there are some shortcomings when natural biomaterials or synthetic polymer materials used alone, it is more effective to use scaffolds made of composite materials. However, to be applied to clinical treatment, more experimental researches are required in the future.

Key words: cartilage, materials, growth plate, cartilage tissue engineering, scaffold, mesenchymal stem cells, chondrocytes, extracellular matrix, review

CLC Number:

Wang Xianggang, Wan Qian, Liu He, Li Ronghang, Zhang Yan, Li Zuhao, Wang Jincheng. Role and characteristics of tissue-engineered cartilage in the treatment of growth plate injuries[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(28): 4539-4545.

Figures/Tables 3

在治疗生长板损伤实验时，骨髓间充质干细胞的表现优异。GULTEKIN等[21]将骨髓间充质干细胞细胞薄层植入家兔胫骨近端生长板缺损处，结果发现骨髓间充质干细胞能够有效抑制受损生长板的骨化，并促进长骨继续生长，见图2A。虽然单纯的骨髓间充质干细胞植入有一定的效果，但是由于生长板损伤处再生微环境较差，治疗效果有限，加入支架和活性物质提供支撑和再生微环境，效果会更好[6]。AZARPIRA等[26]通过切除家兔股骨远端50%的生长板进行造模，在壳聚糖支架上加入骨髓间充质干细胞并将复合支架植入缺损处，3个月后，空白对照组有骨桥形成，提示造模成功；而相比于仅植入壳聚糖支架组，支架与骨髓间充质干细胞细胞结合组的患肢成角畸形明显减轻，显示骨髓间充质干细胞与支架结合能更好地治疗缺损。LI等[23]使用生长板细胞外基质制备的支架搭载自体骨髓间充质干细胞植入家兔生长板缺损处，4，8和16周影像学结果显示，对比空白对照组和单纯支架植入组，含有骨髓间充质干细胞的治疗组家兔患肢成角畸形明显减轻，如图2B。更进一步的研究显示，加入软骨分化诱导因子后，通过定向诱导骨髓间充质干细胞的分化可以更有针对性地治疗软骨类损伤。CLARK等[25]通过使用胰岛素样生长因子1作为活性物质定向诱导骨髓间充质干细胞的分化，以聚乳酸-乙醇酸支架作为载体，植入家兔生长板骨桥形成处，结果显示相较于空白支架组和胰岛素样生长因子1支架组，加入了骨髓间充质干细胞和胰岛素样生长因子1的支架组更好地减轻了患肢畸形，并且组织染色分析显示有更多的新生软骨细胞形成，预示着临床应用时在支架和诱导因子的作用下，骨髓间充质干细胞能更好地治愈生长板损伤，见图2C，D。"

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