Effect of shear on physicochemical properties of matrix metalloproteinase responsive silk-elastinlike hydrogels

剪切力对基质金属蛋白酶响应型丝素蛋白-弹性蛋白样水凝胶理化性质的影响

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Abstract

Silk-elastinlike protein polymers (SELPs) have been fabricated as matrices for controlled delivery of bioactive agents. In this application the need for an environmentally responsive, degradable polymer has risen to improve treatment outcomes. To satisfy this need, we have designed, synthesized, and expressed SELPs with matrix metalloproteinase (MMP) degradable sequences inserted in distinct regions of the polymer backbone. Upon characterization of the physicochemical properties of newly synthesized analogs, it was determined that conditioning of the polymers was necessary for normalization of batch properties, and to generate a more robust polymer network suitable for delivery. In this report we have examined the use of shear stress to condition synthesized material prior to application as a controlled release matrix. The application of high shear to SELPs results in significant changes in physiochemical properties as assayed by swelling ratio, soluble fraction release, rate of gel formation, stiffness of hydrogels, and nanoparticle release from matrices. These observed changes in material characteristics may be caused by the removal of semi-stable secondary and tertiary structures from single polymer strands leading to a more robust hydrogel with greater intermolecular interaction.

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