title: Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration.
abstract: Currently, functional treatment of fracture non-unions and bone loss remains a significant challenge in the field of orthopaedic surgery. Tissue engineering of bone has emerged as a new treatment alternative in bone repair and regeneration. Our approach is to combine a polymeric matrix with a cellular vehicle for delivery of bone morphogenetic protein-2 (BMP-2), constructed through retroviral gene transfer. The objective of this study is to develop an osteoinductive, tissue-engineered bone replacement system by culturing BMP-2-producing cells on an osteoconductive, biodegradable, polymeric-ceramic matrix. The hypothesis is that retroviral gene transfer can be used effectively in combination with a biodegradable matrix to promote bone formation. First, we examined the in vitro attachment and growth of transfected BMP-producing cells on a PLAGA-HA scaffold. Second, the bioactivity of the produced BMP in vitro was evaluated using a mouse model. It was found that the polymer-ceramic scaffold supported BMP-2 production, allowing the attachment and growth of retroviral transfected, BMP-2-producing cells. In vivo, the scaffold successfully functioned as a delivery vehicle for bioactive BMP-2, as it induced heterotopic bone formation in a SCID mouse model.
authors.affiliation: Department of Chemical Engineering, Center for Advanced Biomaterials and Tissue Engineering, Drexel University, Philadelphia, PA 19104, USA. laurencin@drexel.edu
authors.forename: C T
authors.initials: CT
authors.lastname: Laurencin
authors.forename: M A
authors.initials: MA
authors.lastname: Attawia
authors.forename: L Q
authors.initials: LQ
authors.lastname: Lu
authors.forename: M D
authors.initials: MD
authors.lastname: Borden
authors.forename: H H
authors.initials: HH
authors.lastname: Lu
authors.forename: W J
authors.initials: WJ
authors.lastname: Gorum
authors.forename: J R
authors.initials: JR
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis*; D001861:Bone Regeneration; D002448:Cell Adhesion; D002460:Cell Line; D017886:Durapatite / Q000008:administration & dosage* / Q000737:chemistry; D015316:Genetic Therapy; D051379:Mice; D016513:Mice, SCID; D011098:Polyglactin 910 / Q000008:administration & dosage* / Q000737:chemistry; D012190:Retroviridae / Q000235:genetics; D016212:Transforming Growth Factor beta
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D011098:Polyglactin 910; D017886:Durapatite