Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein‐2 (rhBMP‐)

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Abstract
In the current investigation, we report osseous regeneration in critical‐size rat calvarial defects using recombinant human bone morphogenetic protein‐2(rhBMP‐) and novel delivery systems based on biomaterials. The novel systems combine rhBMP‐ with dry powder microparticles of poly(D, L‐lactide‐co‐glycolide) (PLGA). The mixture of rhBMP‐ with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross‐linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0‐, 10‐, and 30‐µg doses of rhBMP‐ and implanted in 8‐mm‐diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP‐ restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP‐ yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21‐day time point. Although small differences between delivery systems were evident at 0‐ and 10‐µg rhBMP‐ doses, all test articles performed essentially equivalently at the 30‐µg dose. Thus, novel delivery systems for rhBMP‐ offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials. © 1994 John Wiley & Sons, Inc.