Motasem Refaat1, Eric O Klineberg1, Michael C Fong1, Tanya C Garcia2, J Kent Leach1,3, Dominik R Haudenschild1. 1. Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA. 2. J.D. Wheat Veterinary Orthopaedic Laboratory, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, CA. 3. Department of Biomedical Engineering, University of California Davis, Davis, CA.
Abstract
STUDY DESIGN: The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. OBJECTIVE: To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. SUMMARY OF BACKGROUND DATA: BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. METHODS: Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 μg) was tested with or without "low-dose" rhBMP-2 (2 μg), and the results were compared with the "low-dose" (2 μg rhBMP-2) and "high-dose" (10 μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. RESULTS: Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. CONCLUSION: COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes. LEVEL OF EVIDENCE: N/A.
STUDY DESIGN: The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats. OBJECTIVE: To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP. SUMMARY OF BACKGROUND DATA: BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications. METHODS: Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 μg) was tested with or without "low-dose" rhBMP-2 (2 μg), and the results were compared with the "low-dose" (2 μg rhBMP-2) and "high-dose" (10 μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro. RESULTS: Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold. CONCLUSION: COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes. LEVEL OF EVIDENCE: N/A.
Authors: Brook I Martin; Sohail K Mirza; Bryan A Comstock; Darryl T Gray; William Kreuter; Richard A Deyo Journal: Spine (Phila Pa 1976) Date: 2007-02-01 Impact factor: 3.468
Authors: Dominik R Haudenschild; Eunmee Hong; Jasper H N Yik; Brett Chromy; Matthias Mörgelin; Kaylene D Snow; Chitrangada Acharya; Yoshikazu Takada; Paul E Di Cesare Journal: J Biol Chem Date: 2011-09-22 Impact factor: 5.157
Authors: Payam Moazzaz; Munish C Gupta; Mudit M Gilotra; Mohit N Gilotra; Sukanta Maitra; Thongchai Theerajunyaporn; James L Chen; A Hari Reddi; R Bruce Martin Journal: Spine (Phila Pa 1976) Date: 2005-08-01 Impact factor: 3.468
Authors: Chananit Sintuu; Robert J Simon; Masashi Miyazaki; Yuichiro Morishita; Henry J Hymanson; Cyrus Taghavi; Elsa J Brochmann; Samuel S Murray; Jeffrey C Wang Journal: J Bone Joint Surg Am Date: 2011-06-01 Impact factor: 5.284
Authors: Richard A Deyo; Brook I Martin; William Kreuter; Jeffrey G Jarvik; Heather Angier; Sohail K Mirza Journal: J Bone Joint Surg Am Date: 2011-11-02 Impact factor: 5.284
Authors: Dennis G Crandall; Jan Revella; Jason Patterson; Eric Huish; Michael Chang; Ryan McLemore Journal: Spine (Phila Pa 1976) Date: 2013-06-01 Impact factor: 3.468
Authors: Shay Bess; Breton G Line; Virginie Lafage; Frank Schwab; Christopher I Shaffrey; Robert A Hart; Oheneba Boachie-Adjei; Behrooz A Akbarnia; Christopher P Ames; Douglas C Burton; Vedat Deverin; Kai-Ming G Fu; Munish Gupta; Richard Hostin; Khaled Kebaish; Eric Klineberg; Gregory Mundis; Michael O'Brien; Alexis Shelokov; Justin S Smith Journal: Spine (Phila Pa 1976) Date: 2014-02-01 Impact factor: 3.468
Authors: Jia Shen; Aaron W James; Janette N Zara; Greg Asatrian; Kevork Khadarian; James B Zhang; Stephanie Ho; Hyun Ju Kim; Kang Ting; Chia Soo Journal: Tissue Eng Part A Date: 2013-07-17 Impact factor: 3.845
Authors: Victoria Tran; Arpad Karsai; Michael C Fong; Weiliang Cai; Jasper H N Yik; Eric Klineberg; Dominik R Haudenschild; Gang-Yu Liu Journal: J Phys Chem B Date: 2018-12-28 Impact factor: 2.991
Authors: Lara Schorn; Christoph Sproll; Michelle Ommerborn; Christian Naujoks; Norbert R Kübler; Rita Depprich Journal: Head Face Med Date: 2017-06-07 Impact factor: 2.151
Authors: Christian Deininger; Andrea Wagner; Patrick Heimel; Elias Salzer; Xavier Monforte Vila; Nadja Weißenbacher; Johannes Grillari; Heinz Redl; Florian Wichlas; Thomas Freude; Herbert Tempfer; Andreas Herbert Teuschl-Woller; Andreas Traweger Journal: Int J Mol Sci Date: 2021-12-28 Impact factor: 5.923