title: Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation.
abstract: The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or (125)I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15224, USA. greg.cooper@chp.edu
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Eric D
authors.initials: ED
authors.lastname: Miller
authors.forename: Gary E
authors.initials: GE
authors.lastname: Decesare
authors.forename: Arvydas
authors.initials: A
authors.lastname: Usas
authors.forename: Emily L
authors.initials: EL
authors.lastname: Lensie
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bykowski
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
authors.forename: Lee E
authors.initials: LE
authors.lastname: Weiss
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: Phil G
authors.initials: PG
authors.lastname: Campbell
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects*; D012886:Skull / Q000187:drug effects* / Q000254:growth & development*; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2