title: Establishment and characterization of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model.
abstract: A large animal model is required for the assessment of minimally invasive, tissue-engineering-based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here, we develop a novel open mini-thoracotomy approach in an ovine model of thoracic interbody fusion that allows the assessment of various fusion constructs, with a focus on novel, tissue-engineering-based interventions. The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances that were required of the study. Six male Merino sheep aged 4-6 years and weighing 35-45 kg underwent the procedure mentioned earlier and were alloted a survival timeline of 6 months. Each sheep underwent a three-level discectomy (T6/7, T8/9, and T10/11) with a randomly allocated implantation of a different graft substitute at each of the following three levels: (1) polycaprolactone (PCL)-based scaffold plus 0.54 μg recombinant human bone morphogenetic protein-2 (rhBMP-2); (2) PCL-based scaffold alone; or (3) autograft. The sheep were closely monitored postoperatively for signs of pain (i.e., gait abnormalities/teeth gnawing/social isolation). Fusion assessments were conducted postsacrifice using computed tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol that was approved by the Institute's committee on animal research. All six sheep were successfully operated on and reached the allotted survival timeline, thereby demonstrating the feasibility of the surgical procedure and postoperative care. There were no significant complications and during the postoperative period, the animals did not exhibit marked signs of distress according to the previously described assessment criteria. Computed tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by a histological evaluation of the respective groups. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method that can reproducibly form the platform for research into various spine-tissue-engineered constructs and their fusion-promoting properties.
authors.affiliation: 1 QUT/Mater Paediatric Spine Research Group , Brisbane, Australia .
authors.forename: Mostyn R N O
authors.initials: MR
authors.lastname: Yong
authors.forename: Siamak
authors.initials: S
authors.lastname: Saifzadeh
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Askin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Labrom
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.forename: Clayton J
authors.initials: CJ
authors.lastname: Adam
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D011091:Polyesters / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D012272:Ribs / Q000000981:diagnostic imaging / Q000601:surgery; D012756:Sheep / Q000601:surgery*; D013123:Spinal Fusion; D013904:Thoracic Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D013908:Thoracotomy / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011091:Polyesters; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C016240:polycaprolactone