Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, Dresden, Germany.
Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
Biomaterials. 2014 Dec;35(37):9755-9766. doi: 10.1016/j.biomaterials.2014.08.023. Epub 2014 Sep 5.
Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue.
由明胶和赖氨酸二异氰酸酯乙酯制备的水凝胶提供了可调节的弹性性质和降解行为。研究了它们与人主动脉内皮细胞（HAEC）以及人巨噬细胞（Mɸ）和粒细胞（Gɸ）的相互作用。实验表明其具有良好的生物相容性、适当的细胞黏附和细胞浸润性。直接接触水凝胶，但不接触水解或酶解水凝胶降解产物，会导致所有细胞类型中环氧化酶-2（COX-2）的表达增强，表明体外存在较弱的炎症激活。只有 Mɸ 在直接接触水凝胶后改变了其细胞因子分泌谱，表明炎症激活较为显著。另一方面，在 HAEC 中，水凝胶并不影响紧密连接蛋白的表达、细胞因子和基质金属蛋白酶的分泌，表明内皮细胞功能得以维持。这与以下发现一致：在 HAEC 中，血栓调节蛋白的合成增加，但没有发生血栓调节蛋白的膜脱落。在免疫功能正常的小鼠中皮下植入这些材料后获得的首次体内数据表明，植入物与周围组织良好整合，没有进行性纤维囊形成，也没有体内炎症组织反应。总的来说，该研究表明基于明胶的水凝胶具有作为受损软组织的临时替代物和功能再生的潜力。
