Improved cartilage repair via in vitro pre-maturation of MSC-seeded hyaluronic acid hydrogels.

Improved cartilage repair via in vitro pre-maturation of MSC-seeded hyaluronic acid hydrogels.
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DOI:
10.1088/1748-6041/7/2/024110
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发表时间:
2012-04
期刊:
Biomedical materials (Bristol, England)
影响因子:
--
通讯作者:
Mauck RL
Mauck RL
中科院分区:
其他
文献类型:
--
作者:
Erickson IE;Kestle SR;Zellars KH;Dodge GR;Burdick JA;Mauck RL

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局灶性软骨缺损的功能性修复需要用具有与天然组织相当的压缩特性并与邻近宿主软骨整合的新组织填充空间。虽然整合不良是当前临床治疗的常见并发症,但有关组织工程在功能性压缩特性发展方面取得进展的报告很少包括对其整合潜力的分析。因此,我们的目标是评估体外软骨缺损模型中富含间充质干细胞(MSC)的透明质酸(HA)水凝胶的成熟和整合。此外,我们还考虑了预熟化初始阶段以及各种材料配方的影响,以最大限度地提高结构的抗压性能和集成强度。将 MSC 封装在 1%、3% 和 5% 甲基丙烯酸酯化 HA (MeHA) 或 2% 琼脂糖 (Ag) 中,并在体外软骨缺损内直接(原位)凝胶化,或者在植入前形成并预培养 4 周。结果显示,预培养的修复结构的整合强度等于(1% MeHA)或大于(2% Ag)原位修复软骨的整合强度。此外,MSC软骨形成和成熟受到原位修复环境的限制,其成熟程度比提前成熟的构建体要小得多。这些结果表明,结构提前成熟可能是功能性软骨修复的基本要素。
Functional repair of focal cartilage defects requires filling the space with neotissue that has compressive properties comparable to native tissue and integration with adjacent host cartilage. While poor integration is a common complication with current clinical treatments, reports of tissue engineering advances in the development of functional compressive properties rarely include analyses of their potential for integration. Our objective was thus to assess both the maturation and integration of mesenchymal stem cell (MSC) laden hyaluronic acid (HA) hydrogels in an in vitro cartilage defect model. Furthermore, we considered the effects of an initial period of pre-maturation as well as various material formulations to maximize both construct compressive properties and integration strength. MSCs were encapsulated in 1%, 3%, and 5% methacrylated HA (MeHA) or 2% agarose (Ag) and gelled directly (in situ) within an in vitro cartilage defect or were formed and then pre-cultured for 4 weeks before implantation. Results showed the integration strength of pre-cultured repair constructs was equal to (1% MeHA) or greater than (2% Ag) the integration of in situ repaired cartilage. Moreover, MSC chondrogenesis and maturation was restricted by the in situ repair environment with constructs maturing to a much lesser extent than pre-matured constructs. These results indicate that construct pre-maturation may be an essential element of functional cartilage repair.
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