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将胰岛素样生长因子 I 的生物响应性释放与 3D 可打印温敏水凝胶融合。

Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels.

机构信息

Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany.

Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany; Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy, Julius-Maximilians-University Würzburg, Röntgenring 11, DE-97070 Würzburg, Germany.

出版信息

J Control Release. 2022 Jul;347:115-126. doi: 10.1016/j.jconrel.2022.04.028. Epub 2022 May 6.

DOI:10.1016/j.jconrel.2022.04.028
PMID:35489547
Abstract

3D printing of biomaterials enables spatial control of drug incorporation during automated manufacturing. This study links bioresponsive release of the anabolic biologic, insulin-like growth factor-I (IGF-I) in response to matrix metalloproteinases (MMP) to 3D printing using the block copolymer of poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine) (POx-b-POzi). For that, a chemo-enzymatic synthesis was deployed, ligating IGF-I enzymatically to a protease sensitive linker (PSL), which was conjugated to a POx-b-POzi copolymer. The product was blended with the plain thermogelling POx-b-POzi hydrogel. MMP exposure of the resulting hydrogel triggered bioactive IGF-I release. The bioresponsive IGF-I containing POx-b-POzi hydrogel system was further detailed for shape control and localized incorporation of IGF-I via extrusion 3D printing for future applications in biomedicine and biofabrication.

摘要

3D 打印生物材料可在自动化制造过程中实现药物掺入的空间控制。本研究通过使用聚(2-甲基-2-恶唑啉)和温敏性聚(2-正丙基-2-恶嗪)(POx-b-POzi)嵌段共聚物,将生物响应性释放生物活性物质胰岛素样生长因子-I(IGF-I)以响应基质金属蛋白酶(MMP)与 3D 打印联系起来。为此,采用化学酶合成方法,将 IGF-I 酶促连接到蛋白酶敏感连接子(PSL)上,该连接子与 POx-b-POzi 共聚物偶联。所得水凝胶与普通温敏性 POx-b-POzi 水凝胶混合。MMP 暴露于所得水凝胶中会触发生物活性 IGF-I 的释放。进一步详细研究了含有生物响应性 IGF-I 的 POx-b-POzi 水凝胶系统,通过挤出 3D 打印进行形状控制和 IGF-I 的局部掺入,以用于生物医学和生物制造的未来应用。

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