Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

• Published in: Scientific reports Vol. 7; no. 1; pp. 14351 - 9
• Main Authors: Choi, Won Il, Sahu, Abhishek, Vilos, Cristian, Kamaly, Nazila, Jo, Seong-Min, Lee, Jin Hyung, Tae, Giyoong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 639/301/54/152; 639/925/352/152; Animals; Anticoagulants; Bioavailability; Biological activity; Bone Morphogenetic Protein 2 - metabolism; Cell proliferation; Controlled release; Cross-Linking Reagents - chemistry; Delayed-Action Preparations - chemistry; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - metabolism; Growth factors; Heparin; Heparin - chemistry; Humanities and Social Sciences; Humans; Intercellular Signaling Peptides and Proteins - administration & dosage; multidisciplinary; Nanoparticles; Nanostructures - chemistry; Nanostructures - therapeutic use; Poloxamer - chemistry; Science; Science (multidisciplinary); Surface charge; Tissue Distribution; Tissue engineering; Vascular endothelial growth factor
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-14040-5

Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.