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Injectable fibroblast growth factor-2 coacervate for persistent angiogenesis

Chu, H and Gao, J and Chen, CW and Huard, J and Wang, Y (2011) Injectable fibroblast growth factor-2 coacervate for persistent angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 108 (33). 13444 - 13449. ISSN 0027-8424

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Abstract

Enhancing the maturity of the newly formed blood vessels is critical for the success of therapeutic angiogenesis. The maturation of vasculature relies on active participation of mural cells to stabilize endothelium and a basal level of relevant growth factors. We set out to design and successfully achieved robust angiogenesis using an injectable polyvalent coacervate of a polycation, heparin, and fibroblast growth factor-2 (FGF2). FGF2 was loaded into the coacervate at nearly 100% efficiency. In vitro assays demonstrated that the matrix protected FGF2 from proteolytic degradations. FGF2 released from the coacervate was more effective in the differentiation of endothelial cells and chemotaxis of pericytes than free FGF2. One injection of 500 ng of FGF2 in the coacervate elicited comprehensive angiogenesis in vivo. The number of endothelial and mural cells increased significantly, and the local tissue contained more and larger blood vessels with increased circulation. Mural cells actively participated during the whole angiogenic process: Within 7 d of the injection, pericytes were recruited to close proximity of the endothelial cells. Mature vasculature stabilized by vascular smooth muscle cells persisted till at least 4 wk. On the other hand, bolus injection of an identical amount of free FGF2 induced weak angiogenic responses. These results demonstrate the potential of polyvalent coacervate as a new controlled delivery platform.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Chu, H
Gao, Jjig22@pitt.eduJIG220000-0002-6200-4141
Chen, CW
Huard, J
Wang, Yyaw20@pitt.eduYAW20orcid.org/0000-0003-2067-382X
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLanger, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 16 August 2011
Date Type: Publication
Journal or Publication Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 108
Number: 33
Page Range: 13444 - 13449
DOI or Unique Handle: 10.1073/pnas.1110121108
Schools and Programs: School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0027-8424
MeSH Headings: Cell Differentiation; Chemotaxis; Drug Carriers--chemistry; Drug Carriers--pharmacology; Endothelial Cells--cytology; Fibroblast Growth Factor 2--administration & dosage; Heparin--therapeutic use; Humans; Neovascularization, Physiologic--drug effects; Pericytes
Other ID: NLM PMC3158148
PubMed Central ID: PMC3158148
PubMed ID: 21808045
Date Deposited: 04 Apr 2014 16:33
Last Modified: 25 Jan 2019 21:55
URI: http://d-scholarship.pitt.edu/id/eprint/20900

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