title: Sequential platelet-derived growth factor-simvastatin release promotes dentoalveolar regeneration.
abstract: OBJECTIVE
  Timely augmentation of the physiological events of dentoalveolar repair is a prerequisite for the optimization of the outcome of regeneration. This study aimed to develop a treatment strategy to promote dentoalveolar regeneration by the combined delivery of the early mitogenic factor platelet-derived growth factor (PDGF) and the late osteogenic differentiation factor simvastatin.
  
  
  METHODS
  By using the coaxial electrohydrodynamic atomization technique, PDGF and simvastatin were encapsulated in a double-walled poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) (PDLLA-PLGA) microspheres in five different modes: microspheres encapsulating bovine serum albumin (BB), PDGF alone (XP), simvastatin alone (SB), PDGF-in-core and simvastatin-in-shell (PS), and simvastatin-in-core and PDGF-in-shell (SP). The microspheres were characterized using scanning electronic microscopy, and the in vitro release profile was evaluated. Microspheres were delivered to fill large osteotomy sites on rat maxillae for 14 and 28 days, and the outcome of regeneration was evaluated by microcomputed tomography and histological assessments.
  
  
  RESULTS
  Uniform 20-μm controlled release microspheres were successfully fabricated. Parallel PDGF-simvastatin release was noted in the PS group, and the fast release of PDGF followed by the slow release of simvastatin was noted in the SP group. The promotion of osteogenesis was observed in XP, PS, and SP groups at day 14, whereas the SP group demonstrated the greatest bone fill, trabecular numbers, and thickest trabeculae. Bone bridging was evident in the PS and SP group, with significantly increased osteoblasts in the SP group, and osteoclastic cell recruitment was promoted in all bioactive molecule-treated groups. At day 28, osteogenesis was promoted in all bioactive molecule-treated groups. Initial corticalization was noted in the XP, PS, and SP groups. Osteoblasts appeared to be decreased in all groups, and significantly, a greater osteoclastic cell recruitment was noted in the SB and SP groups.
  
  
  CONCLUSIONS
  Both PDGF and simvastatin facilitate dentoalveolar regeneration, and sequential PDGF-simvastatin release (SP group) further accelerated the regeneration process through the enhancement of osteoblastogenesis and the promotion of bone maturation.
authors: 1 Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University , Taipei, Taiwan .
authors: Po-Chun
authors: PC
authors: Chang
authors: Li Yen
authors: LY
authors: Chong
authors: Alex S M
authors: AS
authors: Dovban
authors: Lum Peng
authors: LP
authors: Lim
authors: Jason C
authors: JC
authors: Lim
authors: Mark Yen-Ping
authors: MY
authors: Kuo
authors: Chi-Hwa
authors: CH
authors: Wang
mesh_terms: D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D010982:Platelet-Derived Growth Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019821:Simvastatin
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