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Pharmacologically tunable polyethylene-glycol-based cell growth substrate

机译:药理学可调聚乙二醇基细胞生长底物

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摘要

Biohybrid materials combining synthetic polymers with biological components are highly suited for tissue engineering in order to emulate the behavior of natural materials such as the extracellular matrix (ECM). In order to allow for an optimal cell-material interplay, the physical and biological parameters of the artificial matrix need to be dynamically remodeled during cultivation. Current tissue engineering concepts are mainly based on passive remodeling mechanisms including the degradation of the hydrogel and the release of incorporated biomolecules and therefore do not enable external adjustment of cultivation conditions. We present a novel hydrogel material that is able to serve as a cell growth matrix, whose degradation and presentation of cell-interacting biomolecules can be externally controlled by the addition of a pharmacological substance. The hydrogel is based on branched polyethylene glycol that is covalently decorated with the aminocoumarin-antibiotic switchable gyrase B protein conferring stimulus-responsive degradation. ECM properties were conferred to the hydrogels with cell attachment motifs and a general approach for the incorporation and inducible release of therapeutic biomolecules. This smart biohybrid material has the potential to serve as a next-generation tissue engineering device which allows for dynamic external adjustment of the physical and biological parameters, resulting in optimally controlled tissue formation.
机译:生物混合材料将合成聚合物与生物成分结合在一起,非常适合组织工程设计,以模拟诸如细胞外基质(ECM)等天然材料的行为。为了允许最佳的细胞-材料相互作用,在培养过程中需要对人工基质的物理和生物学参数进行动态重塑。当前的组织工程学概念主要基于被动重塑机制,包括水凝胶的降解和结合的生物分子的释放,因此无法对培养条件进行外部调整。我们提出了一种新型的水凝胶材料,它能够用作细胞生长基质,其降解和与细胞相互作用的生物分子的表现可以通过添加药理学物质来外部控制。该水凝胶基于支化的聚乙二醇,并与氨基香豆素-抗生素可转换的促旋酶B蛋白共价修饰,赋予刺激响应性降解。 ECM特性被赋予具有细胞附着基序的水凝胶,以及掺入和诱导释放治疗性生物分子的一般方法。这种智能生物混合材料具有用作下一代组织工程设备的潜力,该设备可以动态地外部调节物理和生物学参数,从而实现对组织形成的最佳控制。

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