Heparin microparticle effects on presentation and bioactivity of bone morphogenetic protein-2

• Type of Material: Article
• Authors: Marian H. Hettiaratchi, Georgia Institute of Technology; Tobias Miller, Georgia Institute of Technology; Johnna Sue Temenoff, Emory University; Robert E. Guldberg, Emory University; Todd McDevitt, Emory University
• Language: English
• Date: 2014-08-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2014.05.011
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 35
• Issue: 25
• Start Page: 7228
• End Page: 7238
• Grant/Funding Information: MHH is supported by funding from the Natural Science and Engineering Research Council (NSERC) of Canada.; This work was supported by a Transformative Research Award from the National Institutes of Health (TR01 AR062006); and a grant from the National Science Foundation (NSF DMR 1207045).
• Keywords: OSTEOGENIC ACTIVITY; Bone tissue engineering; POLY(ETHYLENE GLYCOL); Science & Technology; ACID-BASED HYDROGELS; GELATIN MICROSPHERES; Materials Science; Glycosaminoglycan; OSTEOBLAST DIFFERENTIATION; FIBROBLAST-GROWTH-FACTOR; Technology; Bone morphogenetic protein; Engineering, Biomedical; STEM-CELLS; BIOMATERIAL CARRIERS; CONTROLLED-RELEASE; Heparin; Microparticle; Materials Science, Biomaterials; Alkaline phosphatase; Engineering; EXTRACELLULAR-MATRIX
• Research Categories: Engineering, Biomedical

Abstract

Biomaterials capable of providing localized and sustained presentation of bioactive proteins are critical for effective therapeutic growth factor delivery. However, current biomaterial delivery vehicles commonly suffer from limitations that can result in low retention of growth factors at the site of interest or adversely affect growth factor bioactivity. Heparin, a highly sulfated glycosaminoglycan, is an attractive growth factor delivery vehicle due to its ability to reversibly bind positively charged proteins, provide sustained delivery, and maintain protein bioactivity. This study describes the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. HMAm microparticles were shown to efficiently bind several heparin-binding growth factors (e.g. bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (FGF-2)), including a wide range of BMP-2 concentrations that exceeds the maximum binding capacity of other common growth factor delivery vehicles, such as gelatin. BMP-2 bioactivity was assessed on the basis of alkaline phosphatase (ALP) activity induced in skeletal myoblasts (C2C12). Microparticles loaded with BMP-2 stimulated comparable C2C12 ALP activity to soluble BMP-2 treatment, indicating that BMP-2-loaded microparticles retain bioactivity and potently elicit a functional cell response. In summary, our results suggest that heparin microparticles stably retain large amounts of bioactive BMP-2 for prolonged periods of time, and that presentation of BMP-2 via heparin microparticles can elicit cell responses comparable to soluble BMP-2 treatment. Consequently, heparin microparticles present an effective method of delivering and spatially retaining growth factors that could be used in a variety of systems to enable directed induction of cell fates and tissue regeneration.