RESUMO
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.
Assuntos
Consolidação da Fratura , Fatores de Diferenciação de Crescimento , Células-Tronco Mesenquimais/metabolismo , Osseointegração , Crânio/lesões , Alicerces Teciduais/química , Transdução Genética , Animais , Linhagem Celular , Gelatina/química , Fator 2 de Diferenciação de Crescimento , Fatores de Diferenciação de Crescimento/biossíntese , Fatores de Diferenciação de Crescimento/genética , Humanos , Camundongos , Polietilenoglicóis/químicaRESUMO
BACKGROUND: The authors present a novel mesh suture design aimed at minimizing the early laparotomy dehiscence that drives ventral hernia formation. The authors hypothesized that modulation of the suture-tissue interface through use of a macroporous structure and increased aspect ratio (width-to-height ratio) would decrease the suture pull-through that leads to laparotomy dehiscence. METHODS: Incisional hernias were produced in 30 rats according to an established hernia model. The rat hernias were randomized to repair with either two 5-0 polypropylene sutures or two midweight polypropylene mesh sutures. Standardized photographs were taken before repair and 1 month after repair. Edge-detection software was used to define the border of the hernia defect and calculate the defect area. Histologic analysis was performed on all mesh suture specimens. RESULTS: Seventeen hernias were repaired with mesh sutures and 13 were repaired with conventional sutures. The mean area of the recurrent defects following repair with mesh suture was 177.8 ± 27.1 mm2, compared with 267.3 ± 34.1 mm2 following conventional suture repair. This correlated to a 57.4 percent reduction in defect area after mesh suture repair, compared with a 10.1 percent increase in defect area following conventional suture repair (p < 0.0007). None (zero of 34) of the mesh sutures pulled through the surrounding tissue, whereas 65 percent (17 of 26) of the conventional sutures demonstrated complete pull-through. Excellent fibrocollagenous ingrowth was observed in 13 of 17 mesh suture specimens. CONCLUSIONS: Mesh sutures better resisted suture pull-through than conventional polypropylene sutures. The design elements of mesh sutures may prevent early laparotomy dehiscence by more evenly distributing distracting forces at the suture-tissue interface and permitting tissue incorporation of the suture itself.