Sustained delivery of SDF-1伪 from heparin-based hydrogels to attract circulating pro-angiogenic cells

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• 作者：Silvana Prokoph^a ; Emmanouil Chavakis^b ; ^c ; Kandice R. Levental^a ; Andrea Zieris^a ; Uwe Freudenberg^a ; Stefanie Dimmeler^b ; Carsten Werner^a ; ^{werner@ipfdd.de}
• 关键词：Cardiac tissue engineering ; Chemotaxis ; Stromal cell-derived factor-1伪 ; Endothelial progenitor cell ; Biohybrid hydrogel
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：June, 2012
• 卷：33
• 期：19
• 页码：4792-4800
• 文件大小：1216 K

摘要

Enrichment of progenitor cells in ischemic tissue has become a promising therapeutic strategy in the treatment of myocardial infarction. Towards this aim, we report a biology-inspired concept using sulfated glycosaminoglycans to sustainably generate chemokine gradients for the localized accumulation of early endothelial progenitor cells (eEPCs). StarPEG-heparin hydrogels, which have been previously demonstrated to support angiogenesis, were functionalized with SDF-1伪, a potent chemoattractant known to act on EPCs. The gels were quantitatively shown to release the chemokine in amounts that are adjustable by the choice of loading concentrations and by matrix metalloprotease (MMP) mediated hydrogel cleavage. Transwell assays confirmed significantly enhanced migration of early EPCs towards concentration gradients of hydrogel-delivered SDF-1伪 in聽vitro. Subcutaneous implantation of SDF-1伪-releasing gels in mice resulted in massive infiltration of early EPCs and subsequently improved vascularization. In conclusion, sustained delivery of SDF-1伪 from pro-angiogenic starPEG-heparin hydrogels can effectively attract early EPCs, offering a powerful means to trigger endogenous mechanisms of cardiac regeneration.