Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

We hypothesize that the controlled delivery of rhVEGF using a microsphere/hydrogel combination system could be useful to achieve active blood vessel formation in the ischemic hindlimb mouse model, which is clinically relevant for therapeutic angiogenesis without multiple administrations. A combination of poly(d,l-lactide-co-glycolide) (PLGA) microspheres and alginate hydrogels containing rhVEGF was prepared and injected intramuscularly into the ischemic hindlimb site of mouse model, and new blood vessel formation near the ischemic site was evaluated. The controlled release of rhVEGF from the combination system effectively protected muscles in ischemic regions from tissue necrosis. Interestingly, the number of newly formed, active blood vessels was significantly increased in mice treated with the rhVEGF-releasing combination system. A microsphere/hydrogel combination system provided a useful means to deliver therapeutic angiogenic molecules into the body for the treatment of ischemic vascular diseases, which could reduce the number of administrations of many types of drugs.