Biomaterials combined with Engineered Growth Factors with collagen binding affinity for tissue regeneration.

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We engineered growth factors (EGF, HGF, VEGF etc) to confer collagen binding activity by fusion of fibronectin collagen-binding domain (CBD). Resulting engineered growth factors showed stable binding activity. Cell growth promotion activity was also improved when they were combined with collagen. One of such fusion protein (CBD-HGF) immobilized to the culture vessels continued to stimulate growth of endothelial cells without medium change. That is, additional factor was unnecessary during prolonged culture. This will be suitable for developing culture system (or bioreactor) of growing large number of cells for cell-implantation therapy.We further examined CBD-HGF on the applicability to regenerative medicine by combining with tissue engineering materials as follows.1) Small caliber artificial blood vessels (3mm in diameter, ePTFE) were combined with CBD-HGF and implanted into dog femoral artery. The implanted vessels showed earlier endothelialization (4weeks) as compared to control vessels and native HGF treated vessels. The fusion HGF may be used to develop implantable vessels with long patency for bypass graft of coronary artery.2) Collagen sponges combined with CBD-HGF induced extensive angiogenesis by 2 weeks after implantation into rat subcutaneous tissue, while control and HGF-treated sponge showed minimal angiogenesis. The sponge may be useful to repair ischemic cardiac tissues, leg ulcer etc.3) CBD-HGF infused to balloon-injured carotid artery of rats promoted endothelialization of denuded areas. It may be used to prevent restenosis after angioplasty using balloon catheter.The results of the present study indicated the applicability of collagen-binding growth factor (s) in the following ways;1) Culture system for cell therapy, 2) biomaterial combined with growth factor activity to induce tissue repair and 3) medicine to induce tissue repair.