Heparinoid hydrogels for cardiovascular tissue regeneration

Heparin (Hep) and heparan sulfate (HS) have been shown to possess anticoagulative properties, inhibit smooth muscle cell proliferation, moderate inflammation and control angiogenesis by stabilization and potentiation of growth factors (GF). These properties are potentially very useful for the treatment of cardiovascular diseases, especially when delivered as injectable hydrogels that can form in situ. This project focused on developing Hep and HS hydrogels for localized GF delivery. Hep and HS were acrylated, characterized and crosslinked with PEG tetra-thiols, either directly (10m% Hep/HS-Ac, Type 1) or by copolymerization with 20PEG8Ac or 20PEG8VS (4m% copolymer; 1.5% Hep/HS-Ac) to form degradable (Type 2D) or non-degradable (Type 2N) gels, respectively. Gelation times, viscoelasticity, swelling, mesh size, Hep/HS elution and activity, as well as GF incorporation and release were studied in vitro. Type 2D gels with covalently incorporated (CI) Hep and GFs were evaluated in vivo as ingrowth matrices in porous polyurethane (PU) scaffolds for healing response in a rat subcutaneous model.National Research Foundatio