Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
J Mech Behav Biomed Mater. 2013 Dec;28:320-31. doi: 10.1016/j.jmbbm.2013.08.009. Epub 2013 Aug 22.
Promising treatment approaches in repairing tissue defects include implementation of regenerative medicine strategies, particularly delivery of preadipocytes to sites where adipose tissue damage needs to be repaired or where fat needs to be generated. In this study, we suggest that the injectable hyaluronic acid/adipic acid dihydrazide (HA/ADH) hydrogel may be an adipose-tissue-like material in terms of biological compatibility as well as mechanical behavior. First, we show that the hydrogel enables and supports growth, proliferation and differentiation of 3T3-L1 preadipocytes. Second, given that adipose tissue is a weight-bearing biological structure, we investigate the large deformation mechanical behavior of the hydrogel with and without embedded preadipocytes, by performing confined and unconfined compression tests and then calibrating a strain energy density (SED) function to the results. Four test groups were examined: (1) Hydrogel specimens right after the preparation without cells, (2) and (3) 3-days-cultured hydrogel specimens with and without cells, respectively, and (4) 6-days-cultured hydrogel specimens with cells. A one-term Ogden SED was found to adequately describe the hyperelastic behavior of the hydrogel specimens in all experimental groups. Importantly, we found that the mechanical properties of the hydrogel, when subjected to compression, are in good agreement with those of native adipose tissue, with the better fit occurring 3-6 days after preparation of the hydrogel. Third, computational finite element studies of the mechanical (stress-strain) behavior of the HA/ADH hydrogel when containing mature adipocytes indicated that the stiffnesses of the constructs were mildly affected by the presence of the adipocytes. Hence, we conclude that injectable HA/ADH hydrogel may serve as a vessel for protecting preadipocytes during, and at a short-term after delivery to native tissues, e.g. in research towards regenerative medicine in tissue reconstructions.
有前途的组织缺损修复方法包括实施再生医学策略，特别是将前体脂肪细胞递送到需要修复脂肪组织损伤的部位或需要生成脂肪的部位。在这项研究中，我们认为可注射透明质酸/己二酸二酰肼（HA/ADH）水凝胶在生物相容性和机械性能方面可能是一种类似脂肪组织的材料。首先，我们表明水凝胶能够支持和促进 3T3-L1 前体脂肪细胞的生长、增殖和分化。其次，鉴于脂肪组织是一种承重的生物结构，我们通过进行受限和无约束压缩测试来研究水凝胶及其嵌入的前体脂肪细胞的大变形力学行为，然后根据结果校准应变能密度（SED）函数。研究了四个测试组：（1）制备后立即不含细胞的水凝胶标本，（2）和（3）分别培养 3 天和 6 天的含细胞和不含细胞的水凝胶标本，（4）含细胞的培养 6 天的水凝胶标本。发现一个项的 Ogden SED 能够充分描述所有实验组中水凝胶标本的超弹性行为。重要的是，我们发现水凝胶在压缩时的机械性能与天然脂肪组织非常吻合，在水凝胶制备后 3-6 天拟合效果更好。第三，对含有成熟脂肪细胞的 HA/ADH 水凝胶的机械（应力-应变）行为进行的计算有限元研究表明，构建体的刚度受到脂肪细胞存在的轻微影响。因此，我们得出结论，可注射 HA/ADH 水凝胶可作为前体脂肪细胞在递送到天然组织过程中的载体，例如在组织重建的再生医学研究中。
