The use of gelatin in a multiple drug delivery system

The use of gelatin for growth factor delivery was investigated. Protein-gelatin interactions were characterized using the Biomolecular Interaction Detection (BIND) system. Acidic gelatin sheets and basic gelatin microspheres were fabricated and optimized for delivering transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. The two delivery vehicles were then combined to produce two distinct release sequences and the effect of sequence on bone healing was determined.; Using the BIND system, TGF-beta1 was found to interact more strongly with acidic gelatin than basic gelatin whereas BMP-2 only slightly favors basic gelatin over acidic gelatin. Acidic gelatin sheets were fabricated by a casting technique. These sheets successfully delivered TGF-beta1 to a rabbit ulna defect to encourage new bone formation. Basic gelatin microspheres were fabricated by the precision particle fabrication (PPF) method. Uniform drug distribution within the microspheres lead to controlled release of BMP-2 that induced bone formation within the thigh muscle of mice. The sheets and microspheres were combined to deliver both drugs either simultaneously or with a four-day delay to a rabbit calvarial defect. Both sequences encouraged more bone regeneration than empty defects by 8 weeks.; Protein-gelatin interactions improved protein stability and lead to release through enzymatic degradation of the gelatin. Growth factors released either singly or in a dual system from gelatin successfully produced bone in vivo. However, single release systems require higher dosages to achieve similar healing results as observed in the dual release systems. No difference was observed between the dual release systems investigated.