Role for interleukin 1α in the inhibition of chondrogenesis in autologous implants using polyglycolic acid-polylactic acid scaffolds
Role for interleukin 1α in the inhibition of chondrogenesis in autologous implants using polyglycolic acid-polylactic acid scaffolds
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DOI：
10.1089/ten.2005.11.192
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Bonassar, LJ
中科院分区：
文献类型：
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作者：
Rotter, N;Ung, F;Bonassar, LJ
在具有免疫能力的动物体内生成组织工程化软骨仍然存在重大挑战。聚乙醇酸等支架材料会导致明显的炎症反应，抑制均质基质的合成。这项研究使用聚乙醇酸-聚乳酸共聚物(德国Norderstedt的Therisorb)在自体免疫能力猪模型中检测了组织工程化软骨的生成。本研究的目的是确定白介素1α(IL-1α)在该系统中的作用，并评估血清处理对组织生成的影响。将猪耳软骨细胞接种于含胎牛血清或无血清胰岛素-转铁蛋白-硒的培养液中培养1周。将标本自体植入猪体内，并以未接种支架为对照。术后1、4、8周，每组取6例标本进行组织学(苏木精-伊红、藏红O、三色染色、Verhoff‘s染色)和生化(糖胺多糖含量)分析。免疫组织化学方法检测IL-1α的存在和分布。组织学检查显示降解支架周围有急性炎症。软骨形成早在植入后1周就可观察到，并随着时间的推移继续增加；然而，所有标本中都没有出现均一的基质合成。IL-1α在种植体周围的软骨细胞和降解聚合物附近的细胞中有较强的表达。组织学上，在基质合成量或炎性浸润量方面，实验组之间没有显著差异。无血清培养组糖胺多糖含量显著高于无血清培养组。这些结果表明，在自体移植模型中，针对支架材料和血清成分的炎症反应会导致IL-1α等细胞因子的产生，这可能会抑制软骨组织的形成。
Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid - polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1 alpha (IL-1 alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin - transferrin - selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically ( hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically ( glycosaminoglycan content). The presence and distribution of IL-1 alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1 alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1 alpha that may inhibit cartilage tissue formation in autologous transplant models.