Methods: Coaxial electrohydrodynamic atomization technique was utilized for the fabrication of double-walled poly-(D,L-lactide-co-glycolide) (PLGA) and poly D,L-lactide (PDLLA) hybrid microspheres. Platelet-derived growth factor (PDGF)and simvastatin were encapsulated in the shell and core respectively. The structure of microspheres was confirmed by confocal microscope and SEM. The encapsulation efficiency and in vitro releasing profile were further examined by ELISA and HPLC. The biocompatibility of microspheres was evaluated by descriptive histology and the expression of proliferating cell nuclear antigen (PCNA) as well as the apoptotic signals.
Results: We successfully encapsulated PDGF in the shell and simvastatin in the core, and the microspheres were approximately 20 μm in diameter with distinct bilayered structure. The encapsulation efficiency of simvastatin and PDGF is 82.45±1.13% and 51.37±1.37%. Fast release of PDGF in day 3-7 and slow release of simvastatin after day 7 was also achieved. Histologic sections demonstrated no obvious inflammation surrounding any implanted microsphere at day 10 and 14. PDGF-encapsulated micospheres showed strongest proliferating activities at day 10. The apoptotic signal was scanty and slightly elevated in all specimens at later stage, and PDGF group demonstrated less apoptotic signals among three groups.
Conclusions: We successfully fabricated double-walled PLGA(PDLLA) microspheres allowing early release of PDGF for cell proliferation and delayed release of simvastatin to promote differentiation with acceptable biocompatibility.