Soft-Tissue Augmentation with Injectable Alginate and Syngeneic Fibroblasts
Soft-Tissue Augmentation with Injectable Alginate and Syngeneic Fibroblasts
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DOI：
10.1097/00006534-200005000-00020
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发表时间：
2000-05
影响因子：
3.6
通讯作者：
J. Marler;A. Guha;J. Rowley;R. Koka;David Mooney;J. Upton;J. Vacanti
中科院分区：
文献类型：
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作者：
J. Marler;A. Guha;J. Rowley;R. Koka;David Mooney;J. Upton;J. Vacanti
组织工程是一个将聚合物支架和分离的细胞群结合起来创造新组织的领域，它可以应用于软组织扩增领域，在这个领域中，聚合物和细胞群是独立注射的。我们已经开发了一种近交系大鼠模型，其中在真空下皮下注射水凝胶（一种聚合物形式）允许直接比较不同材料的组织学行为及其保持结构特定形状和体积的能力。使用该模型，我们比较了三种形式的藻酸钙，一种合成水凝胶，在8周的时间内-标准藻酸盐，其在注射到动物中后凝胶化（藻酸盐后凝胶），标准藻酸盐，其在注射到动物中之前凝胶化（藻酸盐前凝胶）和藻酸盐-RGD，其与细胞粘附三肽RGD共价连接（RGD后凝胶）。还评估了包括悬浮在这三种凝胶中的每一种内的培养的同系成纤维细胞的平行组（藻酸盐后凝胶加细胞、藻酸盐前凝胶加细胞和RGD后凝胶加细胞）。该研究使用了54只近交系刘易斯大鼠（6组中每组n = 9）。在藻酸盐凝胶后组中，结构几何形状得到了最佳保持，其中在8周时保留了58%的原始体积，当凝胶中包含同源成纤维细胞时，在8周时增加到88%。在RGD凝胶后组中，体积没有保持得那么好（8周时为原始体积的25%），但当包括同基因成纤维细胞时，体积再次增加（8周时为原始体积的41%）。藻酸盐预凝胶组的体积维持最差（8周时为原始体积的31%），并且未能通过添加成纤维细胞（8周时为原始体积的19%）来增加。在组织学上，在藻酸盐后凝胶组中，凝胶保持由纤维囊包围的均匀片材。在藻酸盐预凝胶和RGD后凝胶组中，纤维血管基质显著向内生长到凝胶中，并使构建体破碎。在其中包括同源成纤维细胞的构建体中，细胞在整个凝胶中可见，但不延伸过程或似乎有助于新组织形成。材料压缩测试表明，藻酸盐和RGD后凝胶构建体在12周内变得更硬，特别是在含细胞组中。我们的研究结果表明，海藻酸钙可能是一个合适的代理软组织增强凝胶皮下注射后。加入同系成纤维细胞增强了凝胶保持构建体体积的能力;这似乎是由增加的凝胶硬度介导的，而不是由从头组织形成介导的。我们的动物模型结合材料测试数据，允许对用于软组织填充的不同材料进行严格比较。
Tissue engineering, a field that combines polymer scaffolds with isolated cell populations to create new tissue, may be applied to soft-tissue augmentation—an area in which polymers and cell populations have been injected independently. We have developed an inbred rat model in which the subcutaneous injection of a hydrogel, a form of polymer, under vacuum permits direct comparison of different materials in terms of both histologic behavior and their ability to maintain the specific shape and volume of a construct. Using this model, we compared three forms of calcium alginate, a synthetic hydrogel, over an 8-week period—standard alginate that was gelled following injection into animals (alginate post-gel), standard alginate that was gelled before injection into animals (alginate pre-gel) and alginate-RGD, to which the cell adhesion tripeptide RGD was linked covalently (RGD post-gel). Parallel groups that included cultured syngeneic fibroblasts suspended within each of these three gels were also evaluated (alginate post-gel plus cells, alginate pre-gel plus cells, and RGD post-gel plus cells). The study used 54 inbred Lewis rats (n = 9 for each of the six groups). Construct geometry was optimally maintained in the alginate post-gel group in which 58 percent of the original volume was preserved at 8 weeks and increased to 88 percent at 8 weeks when syngeneic fibroblasts were included within the gel. Volume was not as well preserved in the RGD post-gel group (25 percent of original volume at 8 weeks), but again increased when syngeneic fibroblasts were included (41 percent of original volume at 8 weeks). Maintenance of volume was poorest in the alginate pre-gel group (31 percent of original volume at 8 weeks) and failed to be augmented by the addition of fibroblasts (19 percent of original volume at 8 weeks). Histologically, the gel remained a uniform sheet surrounded by a fibrous capsule in the alginate post-gel groups. In the alginate pre-gel and RGD post-gel groups, there was significant ingrowth of a fibrovascular stroma into the gel with fragmentation of the construct. In constructs in which syngeneic fibroblasts were included, cells were visualized throughout the gel but did not extend processes or appear to contribute to new tissue formation. Material compression testing indicated that the alginate and RGD post-gel constructs became stiffer over a 12-week period, particularly in the cell-containing groups. Our results suggest that calcium alginate could be a suitable agent for soft-tissue augmentation when gelled subcutaneously following injection. The addition of syngeneic fibroblasts enhanced the ability of the gel to maintain the volume of a construct; this seems to be mediated by increased gel stiffness rather than by de novo tissue formation. Our animal model, in combination with material testing data, permits rigorous comparison of different materials used for soft-tissue augmentation.