Fabrication of MSC-laden composites of hyaluronic acid hydrogels reinforced with MEW scaffolds for cartilage repair.
Fabrication of MSC-laden composites of hyaluronic acid hydrogels reinforced with MEW scaffolds for cartilage repair.
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DOI：
10.1088/1758-5090/ac3acb
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发表时间：
2021-12-01
期刊：
影响因子：
9
通讯作者：
Burdick JA
中科院分区：
文献类型：
--
作者：
Galarraga JH;Locke RC;Witherel CE;Stoeckl BD;Castilho M;Mauck RL;Malda J;Levato R;Burdick JA
由于水凝胶能够支持间充质基质细胞(MSCs)的包裹和软骨形成，因此水凝胶在软骨组织工程中引起了人们的兴趣。然而，在水凝胶设计中，必须考虑水凝胶的交联度等特性，这些特性会影响营养物质的运输、新生基质的分布，以及植入过程中和植入后结构的稳定性。在这里，我们首先证明了更松散的交联度(即，更软的~2kPa)降冰片烯修饰的透明质酸(NorHA)水凝胶与更密集的(即，更坚硬的，~6-60kPa)水凝胶相比，支持促进软骨的形成和成熟，在56天的培养后，压缩模数增加了100倍。虽然柔软的NorHA水凝胶成熟为适合关节软骨修复的新材料，但它们的初始模数太低，无法处理，并且没有表现出承受关节载荷环境所需的稳定性。为了解决这个问题，我们用熔融电写(MEW)法制备的聚己内酯(PCL)微纤维增强了NorHA水凝胶。重要的是，用间距为400μm的MEW网制备的复合材料使软质NorHA水凝胶的模数增加了约50倍，同时保持了水凝胶的软骨形成潜力。复合水凝胶与单纯水凝胶在成软骨基因表达和生物化学含量(如DNA、GAG、胶原)方面差异不大，而复合水凝胶在培养56d后压缩模量值增加到约350kPa.最后，对复合材料与天然组织的整合进行了体外评估；与无细胞复合材料相比，预培养28天后植入的MSC复合材料显示出更高的整合强度和接触面积。这种方法对于设计细胞负载的植入物具有巨大的潜力，这些植入物既具有初始的机械完整性，又具有支持软骨修复的新骨形成和整合的能力。
Hydrogels are of interest in cartilage tissue engineering due to their ability to support the encapsulation and chondrogenesis of mesenchymal stromal cells (MSCs). However, features such as hydrogel crosslink density, which can influence nutrient transport, nascent matrix distribution, and the stability of constructs during and after implantation must be considered in hydrogel design. Here, we first demonstrate that more loosely crosslinked (i.e., softer, ~2 kPa) norbornene-modified hyaluronic acid (NorHA) hydrogels support enhanced cartilage formation and maturation when compared to more densely crosslinked (i.e., stiffer, ~6–60 kPa) hydrogels, with a >100-fold increase in compressive modulus after 56 days of culture. While soft NorHA hydrogels mature into neocartilage suitable for the repair of articular cartilage, their initial moduli are too low for handling and they do not exhibit the requisite stability needed to withstand the loading environments of articulating joints. To address this, we reinforced NorHA hydrogels with polycaprolactone (PCL) microfibers produced via melt-electrowriting (MEW). Importantly, composites fabricated with MEW meshes of 400 μm spacing increased the moduli of soft NorHA hydrogels by ~50-fold while preserving the chondrogenic potential of the hydrogels. There were minimal differences in chondrogenic gene expression and biochemical content (e.g., DNA, GAG, collagen) between hydrogels alone and composites, whereas the composites increased in compressive modulus to ~350 kPa after 56 days of culture. Lastly, integration of composites with native tissue was assessed ex vivo; MSC-laden composites implanted after 28 days of pre-culture exhibited increased integration strengths and contact areas compared to acellular composites. This approach has great potential towards the design of cell-laden implants that possess both initial mechanical integrity and the ability to support neocartilage formation and integration for cartilage repair.
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DOI：
10.1016/j.jmbbm.2012.03.006
发表时间：
2012-07
影响因子：
3.9
作者：
Kim M;Erickson IE;Choudhury M;Pleshko N;Mauck RL
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DOI：
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发表时间：
2012-04
期刊：
Biomedical materials (Bristol, England)
影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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