Examination of the Role of Cells in Commercially Available Cellular Allografts in Spine Fusion: An in Vivo Animal Study.
Journal
The Journal of bone and joint surgery. American volume
ISSN: 1535-1386
Titre abrégé: J Bone Joint Surg Am
Pays: United States
ID NLM: 0014030
Informations de publication
Date de publication:
16 Dec 2020
16 Dec 2020
Historique:
pubmed:
21
10
2020
medline:
23
4
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Despite the extensive use of cellular bone matrices (CBMs) in spine surgery, there is little evidence to support the contribution of cells within CBMs to bone formation. The objective of this study was to determine the contribution of cells to spinal fusion by direct comparisons among viable CBMs, devitalized CBMs, and cell-free demineralized bone matrix (DBM). Three commercially available grafts were tested: a CBM containing particulate DBM (CBM-particulate), a CBM containing DBM fibers (CBM-fiber), and a cell-free product with DBM fibers only (DBM-fiber). CBMs were used in viable states (CBM-particulatev and CBM-fiberv) and devitalized (lyophilized) states (CBM-particulated and CBM-fiberd), resulting in 5 groups. Viable cell counts and bone morphogenetic protein-2 (BMP-2) content on enzyme-linked immunosorbent assay (ELISA) within each graft material were measured. A single-level posterolateral lumbar fusion was performed on 45 athymic rats with 3 lots of each product implanted into 9 animals per group. After 6 weeks, fusion was assessed using manual palpation, micro-computed tomography (μ-CT), and histological analysis. The 2 groups with viable cells were comparable with respect to cell counts, and pairwise comparisons showed no significant differences in BMP-2 content across the 5 groups. Manual palpation demonstrated fusion rates of 9 of 9 in the DBM-fiber specimens, 9 of 9 in the CBM-fiberd specimens, 8 of 9 in the CBM-fiberv specimens, and 0 of 9 in both CBM-particulate groups. The μ-CT maturity grade was significantly higher in the DBM-fiber group (2.78 ± 0.55) compared with the other groups (p < 0.0001), while none of the CBM-particulate samples demonstrated intertransverse fusion in qualitative assessments. The viable and devitalized samples in each CBM group were comparable with regard to fusion rates, bone volume fraction, μ-CT maturity grade, and histological features. The cellular component of 2 commercially available CBMs yielded no additional benefits in terms of spinal fusion. Meanwhile, the groups with a fiber-based DBM demonstrated significantly higher fusion outcomes compared with the CBM groups with particulate DBM, indicating that the DBM component is probably the key determinant of fusion. Data from the current study demonstrate that cells yielded no additional benefit in spinal fusion and emphasize the need for well-designed clinical studies on cellular graft materials.
Sections du résumé
BACKGROUND
BACKGROUND
Despite the extensive use of cellular bone matrices (CBMs) in spine surgery, there is little evidence to support the contribution of cells within CBMs to bone formation. The objective of this study was to determine the contribution of cells to spinal fusion by direct comparisons among viable CBMs, devitalized CBMs, and cell-free demineralized bone matrix (DBM).
METHODS
METHODS
Three commercially available grafts were tested: a CBM containing particulate DBM (CBM-particulate), a CBM containing DBM fibers (CBM-fiber), and a cell-free product with DBM fibers only (DBM-fiber). CBMs were used in viable states (CBM-particulatev and CBM-fiberv) and devitalized (lyophilized) states (CBM-particulated and CBM-fiberd), resulting in 5 groups. Viable cell counts and bone morphogenetic protein-2 (BMP-2) content on enzyme-linked immunosorbent assay (ELISA) within each graft material were measured. A single-level posterolateral lumbar fusion was performed on 45 athymic rats with 3 lots of each product implanted into 9 animals per group. After 6 weeks, fusion was assessed using manual palpation, micro-computed tomography (μ-CT), and histological analysis.
RESULTS
RESULTS
The 2 groups with viable cells were comparable with respect to cell counts, and pairwise comparisons showed no significant differences in BMP-2 content across the 5 groups. Manual palpation demonstrated fusion rates of 9 of 9 in the DBM-fiber specimens, 9 of 9 in the CBM-fiberd specimens, 8 of 9 in the CBM-fiberv specimens, and 0 of 9 in both CBM-particulate groups. The μ-CT maturity grade was significantly higher in the DBM-fiber group (2.78 ± 0.55) compared with the other groups (p < 0.0001), while none of the CBM-particulate samples demonstrated intertransverse fusion in qualitative assessments. The viable and devitalized samples in each CBM group were comparable with regard to fusion rates, bone volume fraction, μ-CT maturity grade, and histological features.
CONCLUSIONS
CONCLUSIONS
The cellular component of 2 commercially available CBMs yielded no additional benefits in terms of spinal fusion. Meanwhile, the groups with a fiber-based DBM demonstrated significantly higher fusion outcomes compared with the CBM groups with particulate DBM, indicating that the DBM component is probably the key determinant of fusion.
CLINICAL RELEVANCE
CONCLUSIONS
Data from the current study demonstrate that cells yielded no additional benefit in spinal fusion and emphasize the need for well-designed clinical studies on cellular graft materials.
Identifiants
pubmed: 33079897
pii: 00004623-202012160-00009
doi: 10.2106/JBJS.20.00330
doi:
Substances chimiques
Bmp2 protein, rat
0
Bone Morphogenetic Protein 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e135Informations de copyright
Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure: This work was supported by a research grant from SeaSpine Holdings. SeaSpine manufacturers one of the products investigated in the study, and two of the authors are employees of SeaSpine. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (including employment with SeaSpine Holdings) and “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, directly relevant to this work (http://links.lww.com/JBJS/G166).
Références
Buser Z, Chung AS, Abedi A, Wang JC. The future of disc surgery and regeneration. Int Orthop. 2019 Apr;43(4):995-1-10. Epub 2018 Nov 30.
Grabowski G, Cornett CA. Bone graft and bone graft substitutes in spine surgery: current concepts and controversies. J Am Acad Orthop Surg. 2013 Jan;21(1):51-1-10.
Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, Lattanzi W, Logroscino G. Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med. 2014 Oct;25(10):2445-1-10. Epub 2014 May 28.
Baumhauer J, Pinzur MS, Donahue R, Beasley W, DiGiovanni C. Site selection and pain outcome after autologous bone graft harvest. Foot Ankle Int. 2014 Feb;35(2):104-1-10. Epub 2013 Nov 13.
Zadegan SA, Abedi A, Jazayeri SB, Vaccaro AR, Rahimi-Movaghar V. Demineralized bone matrix in anterior cervical discectomy and fusion: a systematic review. Eur Spine J. 2017 Apr;26(4):958-1-10. Epub 2016 Nov 10.
Zadegan SA, Abedi A, Jazayeri SB, Bonaki HN, Vaccaro AR, Rahimi-Movaghar V. Clinical application of ceramics in anterior cervical discectomy and fusion: a review and update. Global Spine J. 2017 Jun;7(4):343-1-10. Epub 2017 Apr 20.
Zadegan SA, Abedi A, Jazayeri SB, Nasiri Bonaki H, Jazayeri SB, Vaccaro AR, Rahimi-Movaghar V. Bone morphogenetic proteins in anterior cervical fusion: a systematic review and meta-analysis. World Neurosurg. 2017 Aug;104:752-1-10. Epub 2017 Mar 16.
Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A. Mesenchymal stem cells: cell fate decision to osteoblast or adipocyte and application in osteoporosis treatment. Int J Mol Sci. 2018 Jan 25;19(2):E360.
Lopez MJ, McIntosh KR, Spencer ND, Borneman JN, Horswell R, Anderson P, Yu G, Gaschen L, Gimble JM. Acceleration of spinal fusion using syngeneic and allogeneic adult adipose derived stem cells in a rat model. J Orthop Res. 2009 Mar;27(3):366-1-10.
Piuzzi NS, Dominici M, Long M, Pascual-Garrido C, Rodeo S, Huard J, Guicheux J, McFarland R, Goodrich LR, Maddens S, Robey PG, Bauer TW, Barrett J, Barry F, Karli D, Chu CR, Weiss DJ, Martin I, Jorgensen C, Muschler GF. Proceedings of the signature series symposium “Cellular Therapies for Orthopaedics and Musculoskeletal Disease Proven and Unproven Therapies-Promise, Facts and Fantasy,” International Society for Cellular Therapies, Montreal, Canada, May 2, 2018. Cytotherapy. 2018 Nov;20(11):1381-1-10. Epub 2018 Oct 10.
Chu CR, Rodeo S, Bhutani N, Goodrich LR, Huard J, Irrgang J, LaPrade RF, Lattermann C, Lu Y, Mandelbaum B, Mao J, McIntyre L, Mishra A, Muschler GF, Piuzzi NS, Potter H, Spindler K, Tokish JM, Tuan R, Zaslav K, Maloney W. Optimizing clinical use of biologics in orthopaedic surgery: consensus recommendations from the 2018 AAOS/NIH U-13 Conference. J Am Acad Orthop Surg. 2019 Jan 15;27(2):e50-1-10.
Skovrlj B, Guzman JZ, Al Maaieh M, Cho SK, Iatridis JC, Qureshi SA. Cellular bone matrices: viable stem cell-containing bone graft substitutes. Spine J. 2014 Nov 1;14(11):2763-1-10. Epub 2014 Jun 11.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010 Jun 29;8(6):e1000412.
Grauer JN, Patel TC, Erulkar JS, Troiano NW, Panjabi MM, Friedlaender GE. 2000 Young Investigator Research Award winner. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine (Phila Pa 1976). 2001 Jan 15;26(2):127-1-10.
Robinson ST, Svet MT, Kanim LA, Metzger MF. Four-point bending as a method for quantitatively evaluating spinal arthrodesis in a rat model. Comp Med. 2015 Feb;65(1):46-1-10.
Ralis ZA, Watkins G. Modified tetrachrome method for osteoid and defectively mineralized bone in paraffin sections. Biotech Histochem. 1992 Nov;67(6):339-1-10.
Kosmas C, Hojjati M, Young PC, Abedi A, Gholamrezanezhad A, Rajiah P. Dual-layer spectral computerized tomography for metal artifact reduction: small versus large orthopedic devices. Skeletal Radiol. 2019 Dec;48(12):1981-1-10. Epub 2019 Jun 1.
Abedi A, Mokkink LB, Zadegan SA, Paholpak P, Tamai K, Wang JC, Buser Z. Reliability and validity of the AOSpine Thoracolumbar Injury Classification System: a systematic review. Global Spine J. 2019 Apr;9(2):231-1-10. Epub 2018 Oct 15.
Altman DG. Practical statistics for medical research. Chapman and Hall/CRC; 1990.
Hayashi T, Lord EL, Suzuki A, Takahashi S, Scott TP, Phan K, Tian H, Daubs MD, Shiba K, Wang JC. A comparison of commercially available demineralized bone matrices with and without human mesenchymal stem cells in a rodent spinal fusion model. J Neurosurg Spine. 2016 Jul;25(1):133-1-10. Epub 2016 Mar 11.
Bhamb N, Kanim LEA, Drapeau S, Mohan S, Vasquez E, Shimko D, McKAY W, Bae HW. Comparative efficacy of commonly available human bone graft substitutes as tested for posterolateral fusion in an athymic rat model. Int J Spine Surg. 2019 Oct 31;13(5):437-1-10.
Lin C, Zhang N, Waldorff EI, Punsalan P, Wang D, Semler E, Ryaby JT, Yoo J, Johnstone B. Comparing cellular bone matrices for posterolateral spinal fusion in a rat model. JOR Spine. 2020 Mar 15;3(2):e1084.
Johnstone B, Zhang N, Waldorff EI, Semler E, Dasgupta A, Betsch M, Punsalan P, Cho H, Ryaby JT, Yoo J. A comparative evaluation of commercially available cell-based allografts in a rat spinal fusion model. Int J Spine Surg. 2020 Apr 30;14(2):213-1-10.
Bae H, Zhao L, Zhu D, Kanim LE, Wang JC, Delamarter RB. Variability across ten production lots of a single demineralized bone matrix product. J Bone Joint Surg Am. 2010 Feb;92(2):427-1-10.
Baboolal TG, Boxall SA, El-Sherbiny YM, Moseley TA, Cuthbert RJ, Giannoudis PV, McGonagle D, Jones E. Multipotential stromal cell abundance in cellular bone allograft: comparison with fresh age-matched iliac crest bone and bone marrow aspirate. Regen Med. 2014;9(5):593-1-10. Epub 2014 Mar 12.
Neman J, Duenas V, Kowolik C, Hambrecht A, Chen M, Jandial R. Lineage mapping and characterization of the native progenitor population in cellular allograft. Spine J. 2013 Feb;13(2):162-1-10. Epub 2013 Jan 8.
Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Surgical technique. J Bone Joint Surg Am. 2006 Sep;88(Suppl 1 Pt 2):322-1-10.
Chung CG, James AW, Asatrian G, Chang L, Nguyen A, Le K, Bayani G, Lee R, Stoker D, Pang S, Zhang X, Ting K, Péault B, Soo C. Human perivascular stem cell-based bone graft substitute induces rat spinal fusion. Stem Cells Transl Med. 2014 Oct;3(10):1231-1-10. Epub 2014 Aug 25. Erratum in: Stem Cells Transl Med. 2015 May;4(5):538.
Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO. Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev. 2012 Sep;64(12):1063-1-10. Epub 2012 Jun 21.
Martin GJ Jr, Boden SD, Titus L, Scarborough NL. New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis. Spine (Phila Pa 1976). 1999 Apr 1;24(7):637-1-10.
Ajiboye RM, Eckardt MA, Hamamoto JT, Plotkin B, Daubs MD, Wang JC. Outcomes of demineralized bone matrix enriched with concentrated bone marrow aspirate in lumbar fusion. Int J Spine Surg. 2016 Oct 17;10:35.
Wang JC, Yoon ST, Brodke DS, Park JB, Hsieh P, Meisel HJ, Buser Z. Development of AOSpine BOnE (bone osteobiologics and evidence) classification. Global Spine J. 2020 Oct;10(7):871-1-10. Epub 2019 Oct 23.
Drespe IH, Polzhofer GK, Turner AS, Grauer JN. Animal models for spinal fusion. Spine J. 2005 Nov-Dec;5(6)(Suppl):209S-16S.
Sandhu HS, Khan SN. Animal models for preclinical assessment of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 2002 Aug 15;27(16 Suppl 1):S32-1-10.
Dang ABC, Hong H, Lee K, Luan T, Reddy S, Kuo AC. Repurposing human osteoarthritic cartilage as a bone graft substitute in an athymic rat posterolateral spinal fusion model. Int J Spine Surg. 2018 Dec 21;12(6):735-1-10.
Brecevich AT, Kiely PD, Yoon BV, Nguyen JT, Cammisa FP, Abjornson C. Efficacy comparison of Accell Evo3 and Grafton demineralized bone matrix putties against autologous bone in a rat posterolateral spine fusion model. Spine J. 2017 Jun;17(6):855-1-10. Epub 2017 Jan 23.