title: Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice.
abstract: BACKGROUND
  A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing.
  
  
  METHODS
  Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1β (SDF-1β), transforming growth factor-β1 (TGF-β1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1β co-delivery enhances BMP-2 and TGF-β1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model.
  
  
  RESULTS
  Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-β1 was less effective compared to BMP-2, and SDF-1β therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2+SDF-1β was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-β1+SDF-1β decreased bone healing compared to TGF-β1 alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts.
  
  
  CONCLUSIONS
  Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1β augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1β is detrimental to TGF-β1-driven osteogenesis, its effect on osteogenesis is not universal.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Herberg
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Kondrikova
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA.
authors.forename: Sudharsan
authors.initials: S
authors.lastname: Periyasamy-Thandavan
authors.affiliation: Department of Oral Biology, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA.
authors.forename: R Nicole
authors.initials: RN
authors.lastname: Howie
authors.affiliation: Department of Oral Biology, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA; The Institute for Regenerative and Reparative Medicine, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Elsalanty
authors.affiliation: The Robotics Institute, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, 450 Technology Drive, Pittsburgh, PA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Weiss
authors.affiliation: The Institute for Complex Engineered Systems, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, 450 Technology Drive, Pittsburgh, PA, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Campbell
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA; Department of Orthopaedic Surgery, Georgia Regents University, 1120 15th St., Augusta, GA, USA; The Institute for Regenerative and Reparative Medicine, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA; Department of Oral Biology, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA; Department of Orthopaedic Surgery, Georgia Regents University, 1120 15th St., Augusta, GA, USA; Department of Orthodontics and Surgery, Division of Plastic Surgery, Georgia Regents University, 1120 15th St., Augusta, GA, USA; The Institute for Regenerative and Reparative Medicine, Georgia Regents University, 1459 Laney Walker Blvd., Augusta, GA, USA. Electronic address: crayj@musc.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Cray
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D053773:Transforming Growth Factor beta1
keywords: BMP-2; Biopatterning; Bone; Healing; SDF-1β; TGF-β1