Macroporous Hydrogels for Stable Sequestration and Sustained Release of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Using Nucleic Acid Aptamers

被引:37
作者
Abune, Lidya [1 ]
Zhao, Nan [1 ]
Lai, Jinping [1 ]
Peterson, Benjamin [1 ]
Szczesny, Spencer [1 ]
Wang, Yong [1 ]
机构
[1] Penn State Univ, Dept Biomed Engn, University Pk, PA 16802 USA
基金
美国国家卫生研究院;
关键词
macroporous hydrogel; protein delivery; growth factor; angiogenesis; aptamer; THERAPEUTIC ANGIOGENESIS; SUPERPOROUS HYDROGELS; DELIVERY; CELLS; MECHANISMS; EXPRESSION; DIFFUSION; HEPARIN;
D O I
10.1021/acsbiomaterials.9b00423
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Macroporous hydrogels have been widely studied for biological and biomedical applications such as drug delivery and tissue engineering. However, these hydrogels cannot stably sequester molecules of interest due to their high permeability. The purpose of this work was to study the feasibility of using two aptamers to sequester two protein drugs, quantify the apparent diffusivity of the protein drugs in aptamer-functionalized macroporous hydrogels, and evaluate the function of aptamer-functionalized macroporous hydrogels in controlling protein release for angiogenesis. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were used as the model proteins. The data show that anti-VEGF and anti-bFGF aptamers could be uniformly incorporated into macroporous hydrogels for stable and specific sequestration of VEGF and bFGF. The aptamers could reduce the apparent diffusivity of VEGF and bFGF in the macroporous hydrogels by approximately 3 orders of magnitude. Moreover, as the aptamers could prolong the release of these growth factors, dual aptamer-functionalized macroporous hydrogels could stimulate synergistic angiogenesis. Therefore, this work has successfully demonstrated that aptamer-functionalized macroporous hydrogels hold great potential of stably sequestering multiple molecules of interest for various biological and biomedical applications.
引用
收藏
页码:2382 / 2390
页数:17
相关论文
共 57 条
[1]   Therapeutic angiogenesis in cardiovascular disease [J].
Al Sabti, Hilal .
JOURNAL OF CARDIOTHORACIC SURGERY, 2007, 2 (1)
[2]   Solute diffusion within hydrogels. Mechanisms and models [J].
Amsden, B .
MACROMOLECULES, 1998, 31 (23) :8382-8395
[3]   Aptamer-functionalized superporous hydrogels for sequestration and release of growth factors regulated via molecular recognition [J].
Battig, Mark R. ;
Huang, Yike ;
Chen, Niancao ;
Wang, Yong .
BIOMATERIALS, 2014, 35 (27) :8040-8048
[4]   Programmable Release of Multiple Protein Drugs from Aptamer-Functionalized Hydrogels via Nucleic Acid Hybridization [J].
Battig, Mark R. ;
Soontornworajit, Boonchoy ;
Wang, Yong .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2012, 134 (30) :12410-12413
[5]   Design of growth factor sequestering biomaterials [J].
Belair, David G. ;
Ngoc Nhi Le ;
Murphy, William L. .
CHEMICAL COMMUNICATIONS, 2014, 50 (99) :15651-15668
[6]   Injectable cryogel-based whole-cell cancer vaccines [J].
Bencherif, Sidi A. ;
Sands, R. Warren ;
Ali, Omar A. ;
Li, Weiwei A. ;
Lewin, Sarah A. ;
Braschler, Thomas M. ;
Shih, Ting-Yu ;
Verbeke, Catia S. ;
Bhatta, Deen ;
Dranoff, Glenn ;
Mooney, David J. .
NATURE COMMUNICATIONS, 2015, 6
[7]   Direct in vitro selection of a 2′-O-methyl aptamer to VEGF [J].
Burmeister, PE ;
Lewis, SD ;
Silva, RF ;
Preiss, JR ;
Horwitz, LR ;
Pendergrast, PS ;
McCauley, TG ;
Kurz, JC ;
Epstein, DM ;
Wilson, C ;
Keefe, AD .
CHEMISTRY & BIOLOGY, 2005, 12 (01) :25-33
[8]   Crystallization of bFGF-DNA aptamer complexes using a Sparse Matrix designed for protein-nucleic acid complexes [J].
Cannone, JJ ;
Barnes, CL ;
Achari, A ;
Kundrot, CE .
JOURNAL OF CRYSTAL GROWTH, 2001, 232 (1-4) :409-417
[9]   VEGF gene therapy: stimulating angiogenesis or angioma-genesis? [J].
Carmeliet, P .
NATURE MEDICINE, 2000, 6 (10) :1102-1103
[10]  
Chen J, 1999, J BIOMED MATER RES, V44, P53, DOI 10.1002/(SICI)1097-4636(199901)44:1<53::AID-JBM6>3.3.CO