Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA.
Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR, 97006, USA.
Biomaterials. 2021 Jun;273:120806. doi: 10.1016/j.biomaterials.2021.120806. Epub 2021 Apr 9.
Within tissue exposed to the systemic immune system, lymphocytes and fibroblasts act against biomaterials via the development of a fibrous capsule, known as the foreign body reaction (FBR). Inspired by the natural tolerance that the uterine cavity has to foreign bodies, our study explores the role of microenvironment across classical (subcutaneous) and immune privileged (uterine) tissues in the development of the FBR. As a model biomaterial, we used electrospun fibers loaded with sclerosing agents to provoke scar tissue growth. Additionally, we integrated these materials onto an intrauterine device as a platform for intrauterine biomaterial studies. Polyester materials in vitro achieved drug release up to 10 days, greater pro-inflammatory and pro-healing cytokine expression, and the addition of gelatin enabled greater fibroblast attachment. We observed the materials that induced the greatest FBR in the mouse, had no effect when inserted at the utero-tubal junction of non-human primates. These results suggest that the FBR varies across different tissue microenvironments, and a dampened fibrotic response exists in the uterine cavity, possibly due to immune privilege. Further study of immune privileged tissue factors on biomaterials could broaden our understanding of the FBR and inform new methods for achieving biocompatibility in vivo.
在暴露于全身免疫系统的组织中,淋巴细胞和成纤维细胞通过形成纤维囊(即异物反应,FBR)来对抗生物材料。受子宫腔对异物天然耐受的启发,我们的研究探索了经典(皮下)和免疫特权(子宫)组织中的微环境在 FBR 发展中的作用。作为一种模型生物材料,我们使用负载有硬化剂的静电纺纤维来引发瘢痕组织生长。此外,我们将这些材料整合到宫内节育器上,作为宫内生物材料研究的平台。聚酯材料在体外实现了长达 10 天的药物释放,表现出更强的促炎和促修复细胞因子表达,并且添加明胶可增强成纤维细胞附着。我们观察到在小鼠中引起最强 FBR 的材料,在非人类灵长类动物的输卵管-子宫交界处插入时没有效果。这些结果表明,FBR 在不同的组织微环境中存在差异,并且子宫腔中存在减弱的纤维化反应,这可能是由于免疫特权。对生物材料的免疫特权组织因素的进一步研究可以拓宽我们对 FBR 的理解,并为体内实现生物相容性提供新方法。