Peptide Enhanced Bone Graft Substitute Presents Improved Short-Term Increase in Bone Volume and Construct Stiffness Compared to Iliac Crest Autologous Bone in an Ovine Lumbar Interbody Fusion Model
Arjan C Y Loenen, Jerome Connor, Scott Johnson, Katherine Davis, Nolan Hannigan, Tristan Barnes, Jacobus J Arts, Bert van Rietbergen, Arjan C Y Loenen, Jerome Connor, Scott Johnson, Katherine Davis, Nolan Hannigan, Tristan Barnes, Jacobus J Arts, Bert van Rietbergen
Abstract
Study design: Preclinical ovine model.
Objective: To assess the in vivo efficacy and safety of the P-15 L bone graft substitute and compare its performance to autologous iliac crest bone graft (ICBG) for lumbar interbody fusion indications.
Methods: Thirty skeletally mature sheep underwent lumbar interbody fusion surgery. Half of the sheep received autologous ICBG and the other half the peptide enhanced bone graft substitute (P-15 L). Following termination at 1, 3, and 6 months after surgery, the operated segments were analyzed using micro computed tomography (µCT), histology, and destructive mechanical testing. Additional systemic health monitoring was performed for the P-15 L group.
Results: One month after surgery, there was only minor evidence of bone remodeling and residual graft material could be clearly observed within the cage. There was active bone remodeling between 1 and 3 months after surgery. At 3 months after surgery significantly denser and stiffer bone was found in the P-15 L group, whereas at 6 months, P-15 L and ICBG gave similar fusion results. The P-15 L bone graft substitute did not have any adverse effects on systemic health.
Conclusions: The drug device combination P-15 L was demonstrated to be effective and save for lumbar interbody fusion as evidenced by this ovine model. Compared to autologous ICBG, P-15 L seems to expedite bone formation and remodeling but in the longer-term fusion results were similar.
Keywords: bone graft substitute; lumbar interbody fusion; morphological analysis; ovine; p-15 peptide.
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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References
- Walker BF. The prevalence of low back pain: a systematic review of the literature from 1966 to 1998. J Spinal Disord. 2000;13(3):205–217. doi:10.1097/00002517-200006000-00003
- Hoy D, Bain C, Williams G, et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012;64(6):2028–2037. doi:10.1002/art.34347
- Fritzell P, Hägg O, Wessberg P, Nordwall A. 2001 Volvo award winner in clinical studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group. Spine (Phila Pa 1976). 2001;26(23):2521–2532; discussion 2532-4. doi:10.1097/00007632-200112010-00002
- Kraft CN, Krauspe R. Spondylolisthesis. In: Boos N, Aebi M, eds. Spinal Disorders: Fundamentals of Diagnosis and Treatment. Springer Berlin Heidelberg; 2008:733–763. doi:10.1007/978-3-540-69091-7_27
- Bhalla A, Schoenfeld AJ, George J, Moghimi M, Bono CM. The influence of subgroup diagnosis on radiographic and clinical outcomes after lumbar fusion for degenerative disc disorders revisited: a systematic review of the literature. Spine J. 2017;17(1):143–149. doi:10.1016/j.spinee.2016.09.021
- Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine (Phila Pa 1976). 2012;37(1):67–76. doi:10.1097/BRS.0b013e31820cccfb
- Laurencin C, Khan Y, El-Amin SF. Bone graft substitutes. Expert Rev Med Devices. 2006;3(1):49–57. doi:10.1586/17434440.3.1.49
- Summers BN, Eisenstein SM. Donor site pain from the ilium. A complication of lumbar spine fusion. J Bone Joint Surg Br. 1989;71(4):677–680. doi:10.1302/0301-620x.71b4.2768321
- Hsu WK, Nickoli MS, Wang JC, et al. Improving the clinical evidence of bone graft substitute technology in lumbar spine surgery. Global Spine J. 2012;2(4):239–248. doi:10.1055/s-0032-1315454
- Duarte RM, Varanda P, Reis RL, Duarte ARC, Correia-Pinto J. Biomaterials and Bioactive agents in spinal fusion. Tissue Eng Part B Rev. 2017;23(6):540–551. doi:10.1089/ten.TEB.2017.0072
- Sehgal D, Vijay IK. A method for the high efficiency of water-soluble carbodiimide-mediated amidation. Anal Biochem. 1994;218(1):87–91. doi:10.1006/abio.1994.1144
- Bhatnagar RS, Qian JJ, Wedrychowska A, Sadeghi M, Wu YM, Smith N. Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen. Tissue Eng. 1999;5(1):53–65. doi:10.1089/ten.1999.5.53
- Bhatnagar RS, Qian JJ, Gough CA. The role in cell binding of a beta-bend within the triple helical region in collagen alpha 1 (I) chain: structural and biological evidence for conformational tautomerism on fiber surface. J Biomol Struct Dyn. 1997;14(5):547–560. doi:10.1080/07391102.1997.10508155
- Qian JJ, Bhatnagar RS. Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen. J Biomed Mater Res. 1996;31(4):545–554. doi:10.1002/(sici)1097-4636(199608)31:4<545:: Aid-jbm15>;2-f
- Kübler A, Neugebauer J, Oh JH, Scheer M, Zöller JE. Growth and proliferation of human osteoblasts on different bone graft substitutes: an in vitro study. Implant Dent. 2004;13(2):171–179. doi:10.1097/01.id.0000127522.14067.11
- Yang XB, Bhatnagar RS, Li S, Oreffo RO. Biomimetic collagen scaffolds for human bone cell growth and differentiation. Tissue Eng. 2004;10(7-8):1148–1159. doi:10.1089/ten.2004.10.1148
- Gomar F, Orozco R, Villar JL, Arrizabalaga F.P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial. Int Orthop. 2007;31(1):93–99. doi:10.1007/s00264-006-0087-x
- Sherman BP, Lindley EM, Turner AS, et al. Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model. Eur Spine J. 2010;19(12):2156–2163. doi:10.1007/s00586-010-1546-z
- Mobbs RJ, Maharaj M, Rao PJ. Clinical outcomes and fusion rates following anterior lumbar interbody fusion with bone graft substitute i-FACTOR, an anorganic bone matrix/P-15 composite. J Neurosurg Spine. 2014;21(6):867–876. doi:10.3171/2014.9.spine131151
- Lauweryns P, Raskin Y. Prospective analysis of a new bone graft in lumbar interbody fusion: results of a 2- year prospective clinical and radiological study. Int J Spine Surg. 2015;9:2. doi:10.14444/2002
- Jacobsen MK, Andresen AK, Jespersen AB, et al. Randomized double blind clinical trial of ABM/P-15 versus allograft in noninstrumented lumbar fusion surgery. Spine J. 2020;20(5):677–684. doi:10.1016/j.spinee.2020.01.009
- Arnold PM, Sasso RC, Janssen ME, et al. Efficacy of i-factor bone graft versus autograft in anterior cervical discectomy and fusion: results of the prospective, randomized, single-blinded food and drug administration investigational device exemption study. Spine (Phila Pa 1976). 2016;41(13):1075–1083. doi:10.1097/brs.0000000000001466
- Arnold PM, Sasso RC, Janssen ME, et al. i-Factor™ bone graft vs autograft in anterior cervical discectomy and fusion: 2-year follow-up of the randomized single-blinded food and drug administration investigational device exemption study. Neurosurgery. 2018;83(3):377–384. doi:10.1093/neuros/nyx432
- ISO. Biological evaluation of medical devices—part 6: tests for local effects after implantation. International Standardization Organization. 2007;10993-6(E).
- Walsh WR, Pelletier MH, Bertollo N, Christou C, Tan C. Does PEEK/HA enhance bone formation compared with peek in a sheep cervical fusion model? Clin Orthop Relat Res. 2016;474(11):2364–2372. doi:10.1007/s11999-016-4994-x
- Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M. The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3–11. doi:10.1002/jbmr.5650040103
- van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. 1995;28(1):69–81. doi:10.1016/0021-9290(95)80008-5
- Brantigan JW, Steffee AD. A carbon fiber implant to aid interbody lumbar fusion. Two-year clinical results in the first 26 patients. Spine (Phila Pa 1976). 1993;18(14):2106–2107. doi:10.1097/00007632-199310001-00030
- Steffen T, Stoll T, Arvinte T, Schenk RK. Porous tricalcium phosphate and transforming growth factor used for anterior spine surgery. Eur Spine J. 2001;10(2):S132–S140. doi:10.1007/s005860100325
- Santos ER, Goss DG, Morcom RK, Fraser RD. Radiologic assessment of interbody fusion using carbon fiber cages. Spine (Phila Pa 1976). 2003;28(10):997–1001. doi:10.1097/01.Brs.0000061988.93175.74
- Smit TH, Muller R, van Dijk M, Wuisman PI. Changes in bone architecture during spinal fusion: three years follow-up and the role of cage stiffness. Spine (Phila Pa 1976). 2003;28(16):1802–1808; discussion 1809. doi:10.1097/01.Brs.0000083285.09184.7a
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