Biologically Active Cryogel Coatings as Novel Thromboresistant Biomaterials
Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
BACKGROUND: Prosthetic vascular graft coated with a thin non-thrombogenic biomaterial membrane, such as a heparin-based cryogel, could increase the long-term patency of the graft by preventing or minimizing restenosis caused from thrombosis and intimal hyperplasia (IH), by functioning as a delivery vehicle for small interfering RNA (siRNA) while providing a heparin-basedthromboresistant platform.
AIMS: Synthesis and characterization of the physical properties of three heparinized cryogel formulations and assess cell-matrix interactions in vitro. Evaluate siRNA adsorption to the negatively charged cryogels and examine anticoagulant activities ex vivo.
METHODS: Biopolymers (heparin, alginate, hyaluronic acid and gelatin) were chemically modified with methacrylate residues and used to fabricate heparin-based cryogels. Cryogel microstructure, swelling ratio, pore connectivity and mechanics were measured. Additionally, the interaction of cryogels with human aortic endothelial cells (HAoECs) and dendritic cells (DCs) was investigated. Cryogels were also dip-coated with siRNA in the absence or presence of transfection reagent polyethyleneimine (PEI) to measure siRNA adsorption, while the anticoagulant properties of the developed cryogels were evaluated using unheparinized whole blood from rabbits.
RESULTS: Preliminary results indicate that, cryogels exhibit shape-memory and water-retaining properties, with highly interconnected large pores, high elasticity and a moderate swelling ratio. HAoECs successfully adhered and proliferated on the cryogels while, and DCs showed minimal activation suggesting biocompatibility. SiRNA complexed with PEI was significantly adsorbed by the cryogels compared to siRNA alone. Finally, heparinized cryogels showed anticoagulant activity.
CONCLUSION: Preliminary results suggest the potential therapeutic use of heparinized cryogels in blood-contacting medical devices, as a novel delivery vehicle. Further studies need to be performed to confirm these results and evaluate siRNA transfection of cells, and prevention of smooth muscle cell (SMC) migration, a hallmark of IH.
Place, publisher, year, edition, pages
2014. , 37 p.
cryogel, hydrogel, thromboresistant, heparin, alginate, hyaluronic acid, gelatin, vascular graft, intimal hyperplasia, siRNA
Pharmaceutical Sciences Pharmacology and Toxicology Cardiac and Cardiovascular Systems Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-231603OAI: oai:DiVA.org:uu-231603DiVA: diva2:745083
Harvard Medical School, Harvard School of Engineering and Applied Sciences
Subject / course
Master of Science Programme in Pharmacy
Pradhan-Nabzdyk, Leena, PhDBencherif, Sidi, PhD
Hallberg, Mathias, PhD