Recombinant human bone morphogenetic protein 2/poIy(Iactic-co-gIycoIic acid) copoIymer microspheres with different particIe sizes:preparation and reIease performance in vivo and in vitro / 中国组织工程研究

ABSTRACT

BACKGROUND: The technology of biodegradable materials covering growth factors can be used to make sustained-release microspheres, which provides the feasibility for the efficient utilization of growth factors. OBJECTIVE: To prepare nano/micron-sized spheres using recombinant human bone morphogenetic protein 2/poly(lactic-co-glycolic acid) (rhBMP-2/PLGA)copolymer and to compare their release behaviors by in vivo and in vitro release experiments. METHODS: The rhBMP-2/PLGA nano/micron-sized spheres were prepared by emulsion solvent evaporation method to control the rate of pulp mixing.(1)In vitro release experimentPrepared nano/micron-sized spheres were dissolved in PBS for 70 days,and then ELISA method was used to detect the rhBMP-2 concentration in the supernatant at different time.(2)In vivo release experimentForty-four New Zealand rabbits were divided into two groups, and rhBMP-2/PLGA nano/micron-sized spheres were respectively implanted into trochanteric defects. The concentration of rhBMP-2 in the defect site was detected by ELISA within 70 days after implantation. RESULTS AND CONCLUSION:In vitro sustained release experimentThere was a sudden release of nanospheres in the former 3 days,and the cumulative release nearly reached 41%, followed by a steady and slow release, and then the cumulative release was up to approximately 83% at 70 days. The initial release of micron-sized spheres was less than that of nanospheres, and the cumulative release was about 20% within the former 3 days and reached to 70% at 70 days.In vivo sustained release testThere was a sudden release of the nanospheres,the cumulative release was nearly 35%, followed by a steady and slow release, and then the cumulative release was up to approximately 72% at 70 days. The initial release of micron-sized spheres was less than that of nanospheres, and the cumulative release was about 21% in the former 3 days and increased to about 63% at 70 days.In both in vivo and in vitro release experiments,the release duration of micron-sized spheres was longer than that of nanospheres in the former 3 days. To conclude, the release time of rhBMP-2/PLGA micron-sized spheres fulfills the need of bone growth cycle, therefore, rhBMP-2/PLGA micron-sized spheres are more favorable than rhBMP-2/PLGA nanospheres for bone defect repair in clinical practice.