title: Study of mesenchymal stem cells cultured on a poly(lactic-co-glycolic acid) scaffold containing simvastatin for bone healing.
abstract: BACKGROUND
  Tissue engineering is a promising alternative for the development of bone substitutes; for this purpose, three things are necessary: stem cells, a scaffold to allow tissue growth and factors that induce tissue regeneration.
  
  
  METHODS
  To congregate such efforts, we used the bioresorbable and biocompatible polymer poly(lactic-co-glycolic acid) (PLGA) as scaffold. For the osteoinductive factor, we used simvastatin (SIM), a drug with a pleiotropic effect on bone growth. Mesenchymal stem cells (MSCs) were cultured in PLGA containing SIM, and the bone substitute of PLGA/SIM/MSC was grafted into critical defects of rat calvaria.
  
  
  RESULTS
  The in vitro results showed that SIM directly interfered with the proliferation of MSC promoting cell death, while in the pure PLGA scaffold the MSC grew continuously. Scaffolds were implanted in the calvaria of rats and separated into groups: control (empty defect), PLGA pure, PLGA/SIM, PLGA/MSC and PLGA/SIM/MSC. The increase in bone growth was higher in the PLGA/SIM group.
  
  
  CONCLUSIONS
  We observed no improvement in the growth of bone tissue after implantation of the PLGA/SIM/MSC scaffold. As compared with in vitro results, our main hypothesis is that the microarchitecture of PLGA associated with low SIM release would have created an in vivo microenvironment of concentrated SIM that might have induced MSC death. However, our findings indicate that once implanted, both PLGA/SIM and PLGA/MSC contributed to bone formation. We suggest that strategies to maintain the viability of MSCs after cultivation in PLGA/SIM will contribute to improvement of bone regeneration.
authors.affiliation: Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.
authors.forename: Dario
authors.initials: D
authors.lastname: Mendes Junior
authors.affiliation: Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.|Department of Cell Biology and Structural Biology, Biology Institute, University of Campinas, São Paulo - Brazil.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Domingues
authors.affiliation: Post Graduation Program of Biotechnology and Environmental Monitoring, Federal University of Sao Carlos, Sorocaba, São Paulo - Brazil.
authors.forename: Moema A
authors.initials: MA
authors.lastname: Hausen
authors.affiliation: Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.
authors.forename: Silvia M M
authors.initials: SMM
authors.lastname: Cattani
authors.affiliation: Department of Materials Engineering, Faculty of Mechanical Engineering, University of Campinas, São Paulo - Brazil.
authors.forename: Aguedo
authors.initials: A
authors.lastname: Aragones
authors.affiliation: Department of Cell Biology and Structural Biology, Biology Institute, University of Campinas, São Paulo - Brazil.
authors.forename: Alexandre L R
authors.initials: ALR
authors.lastname: Oliveira
authors.affiliation: Department of Cell Biology and Structural Biology, Biology Institute, University of Campinas, São Paulo - Brazil.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Inácio
authors.affiliation: Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.
authors.forename: Maria L P
authors.initials: MLP
authors.lastname: Barbo
authors.affiliation: Department of Physiological Sciences, Biomaterials Laboratory, Pontifical Catholic University, Sorocaba, São Paulo - Brazil.|Department of Materials Engineering, Faculty of Mechanical Engineering, University of Campinas, São Paulo - Brazil.
authors.forename: Eliana A R
authors.initials: EAR
authors.lastname: Duek
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D002478:Cells, Cultured; D006018:Glycols; D019344:Lactic Acid; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D006018:Glycols; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019821:Simvastatin