In situ gel-forming system for dual BMP-2 and 17 beta-estradiol controlled release for bone regeneration in osteoporotic rats

The aim of this study was to evaluate the bone regeneration capacity of a Pluronic (R) F127 (P)-Tetronic (R) 1307 (T) and cxcyclodextrin (CD) supramolecular gel (P-T-CD) in a 11/7/7 ratio containing BMP-2 and 17 beta-estradiol pre-encapsulated in poly-lactide-co-glycolide (PLGA) and poly-lactic acid (PLA-S) microspheres, respectively. Ovariectomy combined with dexamethasone treatment was used to induce an osteoporotic (OP) animal model of calvaria critical size defect in female rats to test the system. The two active substances showed a biphasic in vitro release profile characterized by an initial fast phase followed by a slow and prolonged release. The bone morphogenetic protein-2 (BMP-2) in vivo release was faster than in vitro. The in vivo experimental design included four groups of sham rats and other four groups of OP rats treated with the blank system, BMP-2, and one or two doses of BMP-2 combined with 17 beta-estradiol. After 12 weeks, histological and histomorphometric analyses showed that the combined treatment with BMP-2 and 17 beta-estradiol did not improve the repair response in sham, whereas in OP animals, a significant increase in the repair rate was observed with respect to the group treated with BMP-2 alone. However, the low values of osteocalcin, showed an immature and poorly mineralized new bone in OP animals. The second dose of the system with BMP-2 and 17 beta-estradiol did not improve the repair response in any case.