Photo-crosslinkable and biodegradable Pluronic/heparin hydrogels for local and sustained delivery of angiogenic growth factor

Photo-crosslinkable and biodegradable Pluronic/heparin composite hydrogels were fabricated for local and sustained delivery of basic fibroblast growth factor (bFGF) to induce angiogenesis. Terminally di-acrylated Pluronic F127 and vinyl group conjugated heparin were used as a mixed macromer precursor solution to prepare a photo-crosslinkable hydrogel. An aqueous solution containing the two macromers with different weight ratios was photo-crosslinked in the presence of bFGF to produce in situ formed bFGF loaded Pluronic/heparin hydrogels. Swelling, mass erosion, bFGF release characteristics of Pluronic/heparin hydrogels were thoroughly examined by varying the weight ratio of the two macromers. The incorporation of heparin in the composite hydrogel enabled the controlled release of bFGF over a one month period in a near zero order manner. The prolonged release of bFGF could be attributed to the specific interaction between bFGF and heparin in the hydrogel matrices. The released bFGF fraction from the degradable hydrogels also showed sufficient proliferation activity of human umbilical vein endothelial cell (HUVEC). When the Pluronic/heparin hydrogels were implanted in vivo, a significant extent of neovascularization was observed.