Biocompatibility of PDGF‐simvastatin double‐walled PLGA (PDLLA) microspheres for dentoalveolar regeneration: A preliminary study

Abstract

Proper coordination of local signal to harmonize mitogenesis and osteogenic differentiation is one of the prerequisites to optimize dentoalveolar regeneration. In the study, we purpose to fabricate controlled-release microspheres encapsulating platelet-derived growth factor (PDGF) and simvastatin by coaxial electrohydrodynamic atomization. The microspheres demonstrated a distinct core and shell structure encapsulating PDGF and simvastatin respectively, and the encapsulation efficiency was 82.45-92.16% in-core and 51.37-71.34% in-shell. Sequential release of PDGF and simvastatin was seen in simvastatin-in-core and PDGF-in-shell (SP) design, and simultaneous release was achieved in PDGF-in-core and simvastatin-in-shell (PS) design. All microspheres demonstrated acceptable biocompatibility in vivo, with increased proliferation, reduced apoptosis, and reduced inflammation while PDGF or simvastatin was encapsulated. The PS design significantly reduced apoptosis than control, whereby significant and persistent enhanced proliferation was noted in SP group. The thickness of fibrotic capsules surrounding microspheres significantly reduced in both SP and PS group at day 14. The finding demonstrates that synergism of PDGF and simvastatin favored biocompatibility. Further investigations will aim on confirming the regenerative effect of SP and PS microspheres in a more clinically relevant model.