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A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications

机译:用于伤口愈合应用的光交联聚乙烯醇水凝胶生长因子释放载体

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摘要

The objective of this study was to develop and evaluate a hydrogel vehicle for sustained release of growth factors for wound healing applications. Hydrogels were fabricated using ultraviolet photo-crosslinking of acrylamide-functionalized nondegradable poly(vinyl alcohol) (PVA). Protein permeability was initially assessed using trypsin inhibitor (TI), a 21 000 MW model protein drug. TI permeability was altered by changing the solids content of the gel and by adding hydrophilic PVA fillers. As the PVA content increased from 10% to 20%, protein flux decreased, with no TI permeating through 20% PVA hydrogels. Further increase in model drug release was achieved by incorporating hydrophilic PVA fillers into the hydrogel. As filler molecular weight increased, TI flux increased. The mechanism for this is most likely an alteration in protein/gel interactions and transient variations in water content. The percent protein released was also altered by varying protein loading concentration. Release studies conducted using growth factor in vehicles with hydrophilic filler showed sustained release of platelet-derived growth factor (PDGF-β,β) for up to 3 days compared with less than 24 hours in the controls. In vitro bioactivity was demonstrated by doubling of normal human dermal fibroblas numbers when exposed to growth factor-loaded vehicle compared to control. The release vehicle developed in this study uses a rapid and simple fabrication method, and protein release can be tailored by modifying solid content, incorporating biocompatible hydrophilic fillers, and varying protein loading concentration.
机译:这项研究的目的是开发和评估用于伤口愈合应用的生长因子持续释放的水凝胶载体。使用丙烯酰胺官能化的不可降解的聚乙烯醇(PVA)的紫外光交联制备水凝胶。最初使用胰蛋白酶抑制剂(TI)(一种21000 MW模型蛋白药物)评估了蛋白的渗透性。通过改变凝胶的固体含量和添加亲水性PVA填料,可以改变TI的渗透性。当PVA含量从10%增加到20%时,蛋白质通量下降,而TI不会透过20%PVA水凝胶。通过将亲水性PVA填料掺入水凝胶中,可以进一步增加模型药物的释放。随着填料分子量的增加,TI通量增加。其机制很可能是蛋白质/凝胶相互作用的改变和水分含量的瞬时变化。释放的蛋白质百分比也通过改变蛋白质上样浓度而改变。在含有亲水性填充剂的赋形剂中使用生长因子进行的释放研究表明,血小板源性生长因子(PDGF-β,β)的持续释放长达3天,而对照组则少于24小时。与对照组相比,当暴露于负载有生长因子的媒介物时,正常人皮肤原纤维的数量增加了一倍,从而证明了体外生物活性。在这项研究中开发的释放载体使用了一种快速,简单的制造方法,可以通过改变固体含量,掺入生物相容性亲水性填充剂以及改变蛋白质的负载量来定制蛋白质的释放。

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