title: Solvent free production of porous PDLLA/calcium carbonate composite scaffolds improves the release of bone growth factors.
abstract: OBJECTIVE
  Incorporation of alkaline nano-/microparticles for neutralization of acidic degradation products into degradable polymer foams requires the use of organic solvents, which may compromise biocompatibility and may be associated with biological hazards. The aim of the present study was to develop and validate a solvent-free method to produce porous poly (DL-lactic acid)/calcium carbonate composite scaffolds (PDLLA/CaCO3) for controlled release of incorporated osteogenic growth factors.
  
  
  METHODS
  Composite PDLLA/CaCO3 granules were produced using a milling process and compared to composite material fabricated through a solution precipitation process using organic solvents. Particle size and mineral content were comparable in both groups. Supercritical carbon dioxide pressure was used to incorporate rhBMP2 into both composites.
  
  
  RESULTS
  Gas foaming resulted in comparable pore structures in both groups exhibiting a homogenous distribution of CaCO3 microparticles in the polymer scaffolds. The elasticity modulus of both types of scaffolds was not significantly different whereas the bending strength of the solvent-free produced scaffolds was significantly lower. The pH values remained constant between 6.90 and 7.25 during degradation of both composites. Release of BMP2 was significantly higher and the induction of alkaline phosphatase was more reliable in the group of scaffolds produced without organic solvents.
  
  
  CONCLUSIONS
  Solvent-free fabrication of composite PDLLA/CaCO3 scaffolds for controlled release of bone growth factors through gas foaming significantly enhances the release of growth factors and improves the biological efficacy of the incorporated growth factors.
authors.affiliation: Department of Oral and Maxillofacial Surgery, George-Augusta-University, Robert-Koch-Str, 40 37075, Göttingen, Germany, Schliephake.Henning@med.uni-goettingen.de.
authors.forename: H
authors.initials: H
authors.lastname: Schliephake
authors.forename: M
authors.initials: M
authors.lastname: Vucak
authors.forename: J
authors.initials: J
authors.lastname: Boven
authors.forename: S
authors.initials: S
authors.lastname: Backhaus
authors.forename: T
authors.initials: T
authors.lastname: Annen
authors.forename: M
authors.initials: M
authors.lastname: Epple
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002119:Calcium Carbonate; D002460:Cell Line; D003692:Delayed-Action Preparations; D006801:Humans; D011091:Polyesters; D011994:Recombinant Proteins / Q000378:metabolism; D012997:Solvents; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D011091:Polyesters; D011994:Recombinant Proteins; D012997:Solvents; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C033616:poly(lactide); D000469:Alkaline Phosphatase; D002119:Calcium Carbonate