Dataset Information

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

ABSTRACT: 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 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 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 three 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.

SUBMITTER: Abune L

PROVIDER: S-EPMC6900755 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Abune Lidya L Zhao Nan N Lai Jinping J Peterson Benjamin B Szczesny Spencer S Wang Yong Y

ACS biomaterials science & engineering 20190417 5

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 protein drugs in aptamer-functionalized macroporous hydrogels, and evaluate the function of aptamer-functionalized m ...[more]

PMID: 31819896

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Project description:Extracellular matrix (ECM)-derived bioscaffolds have been shown to elicit tissue repair through retention of bioactive signals. Given that the adventitia of large blood vessels is a richly vascularized microenvironment, we hypothesized that perivascular ECM contains bioactive signals that influence cells of blood vessel lineages. ECM bioscaffolds were derived from decellularized human and porcine aortic adventitia (hAdv and pAdv, respectively) and then shown have minimal DNA content and retain elastin and collagen proteins. Hydrogel formulations of hAdv and pAdv ECM bioscaffolds exhibited gelation kinetics similar to ECM hydrogels derived from porcine small intestinal submucosa (pSIS). hAdv and pAdv ECM hydrogels displayed thinner, less undulated, and fibrous microarchitecture reminiscent of native adventitia, with slight differences in ultrastructure visible in comparison to pSIS ECM hydrogels. Pepsin-digested pAdv and pSIS ECM bioscaffolds increased proliferation of human adventitia-derived endothelial cells and this effect was mediated in part by basic fibroblast growth factor (FGF2). Human endothelial cells cultured on Matrigel substrates formed more numerous and longer tube-like structures when supplemented with pAdv ECM bioscaffolds, and FGF2 mediated this matrix signaling. ECM bioscaffolds derived from pAdv promoted FGF2-dependent in vivo angiogenesis in the chick chorioallantoic membrane model. Using an angiogenesis-focused protein array, we detected 55 angiogenesis-related proteins, including FGF2 in hAdv, pAdv and pSIS ECMs. Interestingly, 19 of these factors were less abundant in ECMs bioscaffolds derived from aneurysmal specimens of human aorta when compared with non-aneurysmal (normal) specimens. This study reveals that Adv ECM hydrogels recapitulate matrix fiber microarchitecture of native adventitia, and retain angiogenesis-related actors and bioactive properties such as FGF2 signaling capable of influencing processes important for angiogenesis. This work supports the use of Adv ECM bioscaffolds for both discovery biology and potential translation towards microvascular regeneration in clinical applications.

Project description:Low back pain caused by degenerative disc disease affects many people worldwide and brings huge economical burden. Thus, attentions have focused on annulus fibrosus (AF) tissue engineering for treatment of intervertebral disc degeneration. To engineer a functional replacement for the AF, it is important to fabricate scaffolds that mimic the structural and mechanical properties of native tissue. AF-derived stem cells are promising seed cells for AF tissue engineering due to their tissue specificity. In the present study, decellularized AF matrix (DAFM)/chitosan hybrid hydrogels were fabricated using genipin as a crosslinker. AF stem cells were cultured on hydrogel scaffolds with or without basic fibroblast growth factor (bFGF), and cell proliferation, morphology, gene expression, and AF tissue synthesis were examined. Overall, more collagen-I, collagen-II, and aggrecan were secreted by AF stem cells grown on hydrogels with bFGF compared to those without. These results support the application of DAFM/chitosan hybrid hydrogels as an appropriate candidate for AF tissue engineering. Furthermore, incorporation of bFGF into hydrogels promoted AF-related tissue synthesis. Impact Statement The investigation of annulus fibrosus (AF)-related tissue secretion and gene expression in extracellular matrix (ECM) of AF-derived stem cells (AFSCs) provided theoretical and practical basis for the choice of scaffold materials and growth factors for AF tissue engineering. The innovations of the present work are obvious. First, AFSCs were used because they are more easily differentiated into AF cells, thereby producing more AF-related ECM. Second, the decellularized AF matrix (DAFM) was derived from native AF tissue, but had reduced immunogenicity after decellularization. Furthermore, the DAFM structure mimicked the fibrous network of actual AF tissue, which was advantageous to AFSC adhesion and growth. Third, basic fibroblast growth factor was successfully incorporated into the DAFM, showed gradual sustained release, and effectively promoted production of AF tissue ECM factors collagen-I, collagen-II, aggrecan, and glycosaminoglycan.

Dataset Information

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

Publications

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

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