title: Human osteoprogenitor bone formation using encapsulated bone morphogenetic protein 2 in porous polymer scaffolds.
abstract: The ability to deliver, over time, biologically active osteogenic growth factors by means of designed scaffolds to sites of tissue regeneration offers tremendous therapeutic opportunities in a variety of musculoskeletal diseases. The aims of this study were to generate porous biodegradable scaffolds encapsulating an osteogenic protein, bone morphogenetic protein 2 (BMP-2), and to examine the ability of the scaffolds to promote human osteoprogenitor differentiation and bone formation in vitro and in vivo. BMP-2-encapsulated poly(DL-lactic acid) (PLA) scaffolds were generated by an innovative supercritical fluid process developed for solvent-sensitive and thermolabile growth factors. BMP-2 released from encapsulated constructs promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on three-dimensional scaffolds. Enhanced matrix synthesis and cell differentiation on growth factor-encapsulated scaffolds was observed after culture in an ex vivo model of bone formation developed on the basis of the chick chorioallantoic membrane model. BMP-2-encapsulated polymer scaffolds showed morphologic evidence of new bone matrix and cartilage formation after subcutaneous implantation and within diffusion chambers implanted into athymic mice as assessed by X-ray analysis and immunocytochemistry. The generation of three-dimensional biomimetic structures incorporating osteoinductive factors such as BMP-2 indicates their potential for de novo bone formation that exploits cell-matrix interactions and, significantly, realistic delivery protocols for growth factors in musculoskeletal tissue engineering.
authors.affiliation: University Orthopaedics, University of Southampton, General Hospital, Southampton S016 6YD, UK.
authors.forename: Xuebin B
authors.initials: XB
authors.lastname: Yang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Whitaker
authors.forename: Walter
authors.initials: W
authors.lastname: Sebald
authors.forename: Nicholas
authors.initials: N
authors.lastname: Clarke
authors.forename: Steven M
authors.initials: SM
authors.lastname: Howdle
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
authors.forename: Richard O C
authors.initials: RO
authors.lastname: Oreffo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011485:Protein Binding; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D011091:Polyesters; D011108:Polymers; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide)