title: In vitro characterization of a slow release system of polylactic acid and rhBMP2.
abstract: The aim of the present report was to test a system for controlled release of recombinant human bone morphogenic protein (rhBMP2) incorporated into polylactic acid (PLA) implants. Incorporation of rhBMP2 into the polymer was accomplished by mixing rhBMP2 solution with granular powder of amorphous poly-DL-lactic acid, subsequent lyophilization, and high pressure CO(2) treatment at 100 bar. Porous cylindrical implants of 8 mm diameter and 3 mm thickness were fabricated with 100, 200, 400, and 800 microg BMP2/g polymer and submitted to in vitro testing. Polymer degradation was assessed during immersion of PLA implants into PBS for 176 days by measuring the inherent viscosity at days 0, 99, and 131. BMP2 release was evaluated by immersion of both the lyophilized powder and the implants into cell culture medium for up to 27 days. BMP2 release was assessed using a custom made ELISA. The biological activity of the released growth factor was determined by measuring the induction of alkaline phosphatase (AP) in C2C12 cells. There was a significant retardation in the release of BMP2 from the implants compared to the granular powder. Detectable amounts of BMP2 were found for all concentrations of BMP2 until the end of the observation period. Significant induction of AP was detected by BMP released from the implants after 3, 6, and 9 days. The present in-vitro study has shown that incorporation of rhBMP2 into PLA implants with subsequent slow release of biologically active growth factor is possible.
authors.affiliation: Department of Oral and Maxillofacial Surgery, George-Augusta-University, Göttingen, Germany. schliephake.henning@med.uni-goettingen.de
authors.forename: H
authors.initials: H
authors.lastname: Schliephake
authors.forename: H A
authors.initials: HA
authors.lastname: Weich
authors.forename: J
authors.initials: J
authors.lastname: Schulz
authors.forename: R
authors.initials: R
authors.lastname: Gruber
mesh_terms: D020341:Absorbable Implants; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000378:metabolism*; D004790:Enzyme Induction; D005740:Gases; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011091:Polyesters; D011108:Polymers / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D005740:Gases; D036341:Intercellular Signaling Peptides and Proteins; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide); D000469:Alkaline Phosphatase