On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage.
On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage.
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DOI：
10.1016/j.jmbbm.2012.10.016
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发表时间：
2013-03
影响因子：
3.9
通讯作者：
Vernerey, Franck J.
中科院分区：
文献类型：
--
作者：
Dhote, Valentin;Skaalure, Stacey;Akalp, Umut;Roberts, Justine;Bryant, Stephanie J.;Vernerey, Franck J.
受伤或疾病引起的软骨损伤会导致疼痛和活动能力丧失，从而降低人们的生活质量。由于软骨的自我修复能力有限，因此正在研究组织工程策略（例如将细胞封装在合成水凝胶中）作为恢复受损软骨的方法。然而，迄今为止的策略并不理想，部分原因是可降解水凝胶的设计因凝胶的结构和时间复杂性以及沿多个长度尺度演化的组织而变得复杂。为了解决这个问题，本研究提出了一种多尺度力学模型，使用基于降解水凝胶内单个软骨细胞释放细胞外基质分子的三相配方（固体、流体、未结合的基质分子）。该模型描述了包含不同长度尺度的水凝胶内生物系统的关键参与者（细胞、蛋白聚糖、胶原蛋白）。其中包括两种机制：由于水凝胶降解导致的体积特性的时间变化和基质传输。数值结果表明，体积特性的时间变化是未结合基质分子通过水凝胶扩散的决定性因素。水凝胶中基质分子的运输有助于细胞周基质和细胞外基质的发育，并且取决于基质分子和水凝胶网的相对大小。数值结果还表明，导致网格尺寸变化的渗透压是水凝胶中基质分子实现更大扩散率的关键参数。该数值模型得到了可生物降解的聚乙二醇水凝胶中软骨细胞基质合成的实验结果的证实。该模型最终可用于预测关键的水凝胶设计参数，以实现最佳的软骨生长。
Damage to cartilage caused by injury or disease can lead to pain and loss of mobility, diminishing one’s quality of life. Because cartilage has a limited capacity for self-repair, tissue engineering strategies, such as cells encapsulated in synthetic hydrogels, are being investigated as a means to restore the damaged cartilage. However, strategies to date are suboptimal in part because designing degradable hydrogels is complicated by structural and temporal complexities of the gel and evolving tissue along multiple length scales. To address this problem, this study proposes a multi-scale mechanical model using a triphasic formulation (solid, fluid, unbound matrix molecules) based on a single chondrocyte releasing extracellular matrix molecules within a degrading hydrogel. This model describes the key players (cells, proteoglycans, collagen) of the biological system within the hydrogel encompassing different length scales. Two mechanisms are included: temporal changes of bulk properties due to hydrogel degradation, and matrix transport. Numerical results demonstrate that the temporal change of bulk properties is a decisive factor in the diffusion of unbound matrix molecules through the hydrogel. Transport of matrix molecules in the hydrogel contributes both to the development of the pericellular matrix and the extracellular matrix and is dependent on the relative size of matrix molecules and the hydrogel mesh. The numerical results also demonstrate that osmotic pressure, which leads to changes in mesh size, is a key parameter for achieving a larger diffusivity for matrix molecules in the hydrogel. The numerical model is confirmed with experimental results of matrix synthesis by chondrocytes in biodegradable poly(ethylene glycol)-based hydrogels. This model may ultimately be used to predict key hydrogel design parameters towards achieving optimal cartilage growth.
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影响因子：
--
作者：
Hootman, JM;Helmick, CG
通讯作者：
Helmick, CG
影响因子：
6.2
作者：
Lin-Gibson, S;Bencherif, S;Washburn, NR
通讯作者：
Washburn, NR
DOI：
10.1002/nme.4335
发表时间：
2012-10-19
影响因子：
2.9
作者：
Farsad, Mehdi;Vernerey, Franck J.
通讯作者：
Vernerey, Franck J.
影响因子：
4
作者：
Foucard, Louis;Vernerey, Franck J.
通讯作者：
Vernerey, Franck J.
影响因子：
2.4
作者：
KWAN, MK;LAI, WM;MOW, VC
通讯作者：
MOW, VC