Autologous blood coagulum containing rhBMP6 induces new bone formation to promote anterior lumbar interbody fusion (ALIF) and posterolateral lumbar fusion (PLF) of spine in sheep.

Autor: Grgurevic L; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., Erjavec I; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., Gupta M; Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA., Pecin M; Clinics for Surgery, Orthopedics and Ophthalmology, School of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia., Bordukalo-Niksic T; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., Stokovic N; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., Vnuk D; Clinics for Surgery, Orthopedics and Ophthalmology, School of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia., Farkas V; Division of Molecular Biology, Rudjer Boskovic Institute, 10000 Zagreb, Croatia., Capak H; Department of Radiology, School of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia., Milosevic M; Department of Environmental and Occupational Health and Sports, School of Public Health 'Andrija Stampar', University of Zagreb School of Medicine, Rockefellerova 4, 10000 Zagreb, Croatia., Bubic Spoljar J; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia., Peric M; Center for Translational and Clinical Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia., Vuckovic M; Clinics for Surgery, Orthopedics and Ophthalmology, School of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia., Maticic D; Clinics for Surgery, Orthopedics and Ophthalmology, School of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia., Windhager R; Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria., Oppermann H; Genera Research Ltd, Kalinovica, 10436 Rakov Potok, Croatia., Sampath TK; perForm Biologics Inc., Holliston, MA 01746, USA., Vukicevic S; Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, University of Zagreb School of Medicine, 10000 Zagreb, Croatia. Electronic address: slobodan.vukicevic@mef.hr.
Jazyk: angličtina
Zdroj: Bone [Bone] 2020 Sep; Vol. 138, pp. 115448. Date of Electronic Publication: 2020 May 22.
DOI: 10.1016/j.bone.2020.115448
Abstrakt: In the present study, we evaluated an autologous bone graft substitute (ABGS) composed of recombinant human BMP6 (rhBMP6) dispersed within autologous blood coagulum (ABC) used as a physiological carrier for new bone formation in spine fusion sheep models. The application of ABGS included cervical cage for use in the anterior lumbar interbody fusion (ALIF), while for the posterolateral lumbar fusion (PLF) sheep model allograft devitalized bone particles (ALLO) were applied with and without use of instrumentation. In the ALIF model, ABGS (rhBMP6/ABC/cage) implants fused significantly when placed in between the L4-L5 vertebrae as compared to control (ABC/cage) which appears to have a fibrocartilaginous gap, as examined by histology and micro CT analysis at 16 weeks following surgery. In the PLF model, ABGS implants with or without ALLO showed a complete fusion when placed ectopically in the gutter bilaterally between two decorticated L4-L5 transverse processes at a success rate of 88% without instrumentation and at 80% with instrumentation; however the bone volume was 50% lower in the instrumentation group than without, as examined by histology, radiographs, micro CT analyses and biomechanical testing at 27 weeks following surgery. The newly formed bone was uniform within ABGS implants resulting in a biomechanically competent and histologically qualified fusion with an optimum dose in the range of 100 μg rhBMP6 per mL ABC, while in the implants that contained ALLO, the mineralized bone particles were substituted by the newly formed remodeling bone via creeping substitution. These findings demonstrate for the first time that ABGS (rhBMP6/ABC) without and with ALLO particles induced a robust bone formation with a successful fusion in sheep models of ALIF and PLF, and that autologous blood coagulum (ABC) can serve as a preferred physiological native carrier to induce new bone at low doses of rhBMP6 and to achieve a successful spinal fusion.
Competing Interests: Declaration of competing interest LG, HO and SV have an issued patent US8197840 licensed to Genera Research (GR). HO received grants and other from GR during the study, RW is a consultant for Pfizer, Stryker, Takeda, Depuy Synthes and Zimmer Biomet, TKS received grants and other from perForm Biologics during the study. MG is a consultant for Depuy Synthes, Innomed and Medtronic and receive royalties from Depuy Synthes and Innomed.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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