Institute for Biomedical Engineering, University of Rostock, Friedrich-Barnewitz-Str. 4, D-18119 Rostock, Germany.
J Biomed Mater Res B Appl Biomater. 2011 May;97(2):388-95. doi: 10.1002/jbm.b.31826. Epub 2011 Mar 22.
Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 μm outer and 200 μm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems.
青光眼引流系统的植入是一些青光眼患者的适当治疗干预措施。然而,这种方法的一个缺点是植入材料的纤维组织反应,导致房水液体流动减少或引流系统完全堵塞。作为开发水分流器的基础,我们在此报告了使用聚(3-羟基丁酸酯)(P(3HB))和聚(4-羟基丁酸酯)(P(4HB))作为聚合物基质的研究,以及紫杉醇(PTX)和曲安奈德(TA)作为药物的研究,这些药物可能通过降低成纤维细胞活性来延迟或预防纤维化过程。将 P(3HB)和 P(4HB)制成具有 500μm 外径和 200μm 内径和约 1cm 长度的测试原型。将抗增殖剂 PTX 和抗炎剂 TA 掺入聚合物基质中,并通过扩散释放。体外细胞试验表明,这些聚合物具有降低成纤维细胞活力的潜力,而 TA 显示出对 Tenon 成纤维细胞的差异抑制作用,但对角膜角膜细胞没有抑制作用。将聚合物盘和原型装置植入兔眼证实了材料的良好生物相容性。聚(羟基丁酸酯)聚合物与 PTX 或 TA 的联合使用有可能减少与传统青光眼引流系统相关的纤维化。