title: Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold.
abstract: Large skeletal defects caused by trauma, congenital malformations, and post-oncologic resections of the calvarium present major challenges to the reconstructive surgeon. We previously identified BMP-9 as the most osteogenic BMP in vitro and in vivo. Here we sought to investigate the bone regenerative capacity of murine-derived calvarial mesenchymal progenitor cells (iCALs) transduced by BMP-9 in the context of healing critical-sized calvarial defects. To accomplish this, the transduced cells were delivered to the defect site within a thermoresponsive biodegradable scaffold consisting of poly(polyethylene glycol citrate-co-N-isopropylacrylamide mixed with gelatin (PPCN-g). A total of three treatment arms were evaluated: PPCN-g alone, PPCN-g seeded with iCALs expressing GFP, and PPCN-g seeded with iCALs expressing BMP-9. Defects treated only with PPCN-g scaffold did not statistically change in size when evaluated at eight weeks postoperatively (p = 0.72). Conversely, both animal groups treated with iCALs showed significant reductions in defect size after 12 weeks of follow-up (BMP9-treated: p = 0.0025; GFP-treated: p = 0.0042). However, H&E and trichrome staining revealed more complete osseointegration and mature bone formation only in the BMP9-treated group. These results suggest that BMP9-transduced iCALs seeded in a PPCN-g thermoresponsive scaffold is capable of inducing bone formation in vivo and is an effective means of creating tissue engineered bone for critical sized defects.
authors.affiliation: Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Zari P
authors.initials: ZP
authors.lastname: Dumanian
authors.affiliation: Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America.|Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Viktor
authors.initials: V
authors.lastname: Tollemar
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Jixing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Minpeng
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL and the Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Yunxiao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL and the Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Biomedical Engineering, Northwestern University, Evanston, IL and the Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Ameer
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Reid
mesh_terms: D000818:Animals; D002460:Cell Line; D017102:Fracture Healing; D005780:Gelatin / Q000737:chemistry; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016348:Osseointegration; D011092:Polyethylene Glycols / Q000737:chemistry; D012886:Skull / Q000293:injuries*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014161:Transduction, Genetic
chemical_list: C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D011092:Polyethylene Glycols; D005780:Gelatin; C000595209:polyethylene glycol 1000