Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold.

Autor: Dumanian ZP; Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America., Tollemar V; 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., Ye J; Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America., Lu M; Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America., Zhu Y; 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., Liao J; 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., Ameer GA; 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., He TC; Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States of America., Reid RR; Department of Surgery, Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Mar 01; Vol. 12 (3), pp. e0172327. Date of Electronic Publication: 2017 Mar 01 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0172327
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: