title: An experimental setup to evaluate innovative therapy options for the enhancement of bone healing using BMP as a benchmark--a pilot study.
abstract: Critical or delayed bone healing in rat osteotomy (OT) models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP) 2 guided positive control. Using external fixation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group)), transplantation of a BMP charged autologous blood clot (BMP-group) and the artificial blood clot only (ABC-group) into the OT-gap. In vivo micro-computer tomography (µCT) scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses. In µCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISH-group. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group. In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.
authors.affiliation: Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Berlin, Germany. bernd.preininger@charite.de
authors.forename: B
authors.initials: B
authors.lastname: Preininger
authors.forename: H
authors.initials: H
authors.lastname: Gerigk
authors.forename: J
authors.initials: J
authors.lastname: Bruckner
authors.forename: C
authors.initials: C
authors.lastname: Perka
authors.forename: H
authors.initials: H
authors.lastname: Schell
authors.forename: A
authors.initials: A
authors.lastname: Ellinghaus
authors.forename: K
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.forename: G
authors.initials: G
authors.lastname: Duda
mesh_terms: D000818:Animals; D019985:Benchmarking; D001777:Blood Coagulation / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery*; D023421:Models, Animal; D010027:Osteotomy / Q000379:methods*; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D055396:Bone Morphogenetic Protein 2