Bone critical defect repair with poloxamine-cyclodextrin supramolecular gels.

The aim of this study was to evaluate the osteoinductive capacity of a poloxamine (Tetronic(®) 908, T) and α-cyclodextrin (αCD) supramolecular gel (T-CD) as scaffold in a critical size defect in rat calvaria. The T-CD gel was evaluated solely and after being loaded with simvastatin (SV) and bone morphogenetic protein (BMP-2) separately and in combinations in order to reduce the doses of the active substances. Three doses of SV (7.5, 75, 750 µg) and two doses of BMP-2 (3 and 6 µg) were tested. The histology and histomorphometrical analysis showed improved bone repair with T-CD compared to T, probably due to better release control of both SV and BMP-2. In addition, as T-CD eroded more slowly than poloxamine alone, it remained longer in the defect site. Although synergism was not obtained with BMP-2 and SV, according to the observed regeneration of the defect, the dose of BMP-2 and SV can be reduced to 3 µg and 7.5 µg, respectively.

Bone regeneration induced by an in situ gel-forming poloxamine, bone morphogenetic protein-2 system.

The aim of this study was to confirm previously shown, in vitro osteogenic induction by the Tetronics T908 and T1307 in a critical-size, rat calvaria defect. In vivo, the osteogenic activity of the hydrogels was comparable to in vitro, but less pronounced. However, similar to in vitro, the system was strongly potentiated by incorporating 6.5 microg of bone morphogenetic protein-2 in solution or pre-encapsulated in poly(lactic-co-glycolic) acid microspheres. These two systems extended the in vivo release of bone morphogenetic protein-2, determined with 125I- bone morphogenetic protein-2, for one and two additional weeks, respectively, time enough to fill approximately 40% and 90% of the defect with well-organized bone. Furthermore, the structural characteristics of Tetronic hydrogels together with their biocompatibility, injectability, and adaptability to multiple defect sizes and shapes suggest their role as new, potential bone morphogenetic protein-2 delivery, low-cost scaffolds for minor as well as critical bone defects.

Osteogenic effect of local, long versus short term BMP-2 delivery from a novel SPU-PLGA-ßTCP concentric system in a critical size defect in rats.

A concentric delivery system, composed of the three biomaterials SPU, PLGA, and ßTCP (segmented polyurethane, poly[lactic-co-glycolic acid], and ß-tricalcium phosphate) was fabricated as an external, porous ring of ßTCP with a pasty core of a new SPU, mixed with PLGA microspheres. The regenerative effects of two distinct doses of either immediately available or continuously released rhBMP-2 were evaluated in an 8mm, critical calvaria defect in rats. Protein dose and release kinetics affected material resorption rates and the progression of the regeneration process. Groups treated with the empty system alone or in conjunction with free rhBMP-2 did not respond. By contrast, after 12 weeks, approximately 20% and 60% of the defects implanted with systems loaded with 1.6 µg and 6.5 µg rhBMP-2, respectively were healed, with all the growth factor being released in the course of 6 weeks. The NMR, FTIR, GPC, DSC, and histological analyses showed that PLGA microsphere degradation occurred independently of the regenerative process. However, the resorption rate of the SPU and ßTCP did depend on the regeneration process, which was governed by dose and release rate of rhBMP-2. Furthermore, the biocompatibility and high capacity of adaptation to the defect convert the herein proposed, new SPU polymer into a potential material for applications in tissue engineering and regenerative medicine.