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Production of heparin-containing hydrogels for modulating cell responses.

机译:含肝素的水凝胶的生产,用于调节细胞反应。

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Successful tissue regeneration requires that biomaterials have optimal bioactivity and mechanical properties. Heparin-containing hydrogels that can be crosslinked in situ were designed to contain tunable amounts of biological components (e.g. heparin, arginine-glycine-aspartate (RGD)) as well as to exhibit controlled mechanical properties (e.g. shear modulus). These gel parameters can also be tuned to provide controlled delivery of proteins, such as growth factors, for regulating cellular behavior. Maleimide-functionalized low-molecular-weight heparin (LWMH) was conjugated to a poly(ethylene glycol) (PEG) hydrogel. The elastic shear modulus, as assessed via oscillatory rheology experiments, could be tuned by the concentration of polymer in the hydrogel, and by the end group functionality of PEG. Hydrogels of two different moduli (2.8 and 0.4kPa) were used to study differences in the response of human aortic adventitial fibroblasts (AoAF) in two-dimensional cell culture experiments. These experiments indicated that the AoAFs show improved adhesion to materials with the higher modulus. Evaluation of cell responses to hydrogels with RGD linked to the hydrogels via conjugation to PEG or to LMWH indicated improved cellular responses to these materials when the bioactive ligands were chemically attached through linkage to the PEG rather than to the LMWH. These results highlight important design considerations in the tailoring of these materials for cardiovascular tissue engineering applications.
机译:成功的组织再生需要生物材料具有最佳的生物活性和机械性能。可以原位交联的含肝素的水凝胶被设计成含有可调节量的生物成分(例如肝素,精氨酸-甘氨酸-天冬氨酸(RGD))以及表现出受控的机械性能(例如剪切模量)。还可以调节这些凝胶参数以提供蛋白质的受控递送,例如生长因子,以调节细胞行为。马来酰亚胺官能化的低分子量肝素(LWMH)与聚(乙二醇)(PEG)水凝胶结合。通过振荡流变学实验评估的弹性剪切模量可以通过水凝胶中聚合物的浓度以及PEG的端基官能团进行调节。在二维细胞培养实验中,使用两种不同模量(2.8和0.4kPa)的水凝胶研究人主动脉外膜成纤维细胞(AoAF)反应的差异。这些实验表明,AoAF对具有较高模量的材料显示出改善的粘附性。评估RGD通过与PEG或LMWH偶联而与水凝胶相连的细胞对水凝胶的反应表明,当生物活性配体通过化学键连接到PEG而不是LMWH上时,对这些物质的细胞反应得到改善。这些结果突出了为心血管组织工程应用定制这些材料时的重要设计考虑因素。

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