Nair Ashwin, Zou Ling, Bhattacharyya Dhiman, Timmons Richard B, Tang Liping
Bioengineering Department, University of Texas at Arlington, Arlington, Texas 76019-0138, USA.
Langmuir. 2008 Mar 4;24(5):2015-24. doi: 10.1021/la7025973. Epub 2008 Jan 12.
Implant-associated fibrotic capsule formation presents a major challenge for the development of long-term drug release microspheres and implantable sensors. Since material properties have been shown to affect in vitro cellular responses and also to influence short-term in vivo tissue responses, we have thus assumed that the type and density of surface chemical groups would affect the degree of tissue responses to microsphere implants. To test this hypothesis, polypropylene particles with different surface densities of -OH and -COOH groups, along with the polypropylene control (-CH2 groups) were utilized. The influence of functional groups and their surface densities on fibrotic reactions were analyzed using a mice subcutaneous implantation model. Our comparative studies included determination and correlation of the extents of fibrotic capsule formation, cell infiltration into the particles, and recruitment of CD11b+ inflammatory cells for all of the substrates employed. We have observed major differences among microspheres coated with different surface functionalities. Surfaces with -OH surface groups trigger the strongest responses, while -COOH-rich surfaces prompt the least tissue reactions. However, variation of the surface density of either functional group has a relatively minor influence on the extent of fibrotic tissue reactions. The present results show that surface functionality can be used as a powerful tool to alter implant-associated fibrotic reactions and, potentially, to improve the efficacy and function of drug-delivery microspheres, implantable sensors, and tissue-engineering scaffolds.
植入相关的纤维化包膜形成是长效药物释放微球和可植入传感器研发面临的一项重大挑战。由于材料特性已被证明会影响体外细胞反应,也会影响短期体内组织反应,因此我们推测表面化学基团的类型和密度会影响组织对微球植入物的反应程度。为了验证这一假设,我们使用了具有不同-OH和-COOH基团表面密度的聚丙烯颗粒,以及聚丙烯对照物(-CH2基团)。利用小鼠皮下植入模型分析了官能团及其表面密度对纤维化反应的影响。我们的比较研究包括对所有所用底物的纤维化包膜形成程度、细胞向颗粒内浸润以及CD11b+炎性细胞募集情况的测定和相关性分析。我们观察到涂覆有不同表面功能基团的微球之间存在重大差异。具有-OH表面基团的表面引发的反应最强,而富含-COOH的表面引发的组织反应最少。然而,任一官能团表面密度的变化对纤维化组织反应程度的影响相对较小。目前的结果表明,表面功能可作为一种强大的工具来改变植入相关的纤维化反应,并有可能提高药物递送微球、可植入传感器和组织工程支架的功效和功能。