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Trevizani M, Leal LL, da Silva Barros RJ, de Paoli F, Nogueira BV, Costa FF, de Aguiar JAK, da Costa Maranduba CM. Effects of decellularization on glycosaminoglycans and collagen macromolecules in bovine bone extracellular matrix. Int J Biol Macromol 2025; 307:141007. [PMID: 39971037 DOI: 10.1016/j.ijbiomac.2025.141007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 01/27/2025] [Accepted: 02/12/2025] [Indexed: 02/21/2025]
Abstract
Bovine bones were decellularized to obtain extracellular matrices with potential use for Tissue Bioengineering. The objective of the present study was to develop a decellularization protocol for bovine trabecular bone while maintaining the integrity of the extracellular matrix (ECM). The protocol proved to be effective in significantly reducing the Amount of genetic material and cellular content, and it was considered innovative, being filed as a patent. The scaffold obtained showed a reduction in the content of glycosaminoglycans (GAGs) and collagen. Even with the loss of these ECM components, the material obtained can be considered an alternative for use in Tissue Engineering and Regenerative Medicine.
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Affiliation(s)
- Marizia Trevizani
- Department of Biology, Laboratory of Human Genetics and Cell Therapy, Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil
| | - Laís Lopardi Leal
- Department of Biology, Laboratory of Human Genetics and Cell Therapy, Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil
| | - Rodolpho José da Silva Barros
- Carlos Alberto Redins Cellular Ultrastructure Laboratory (LUCCAR), Department of Morphology, Health Sciences Center, Federal University of Espírito Santo, Espírito Santo, Brazil
| | - Flávia de Paoli
- Department of Morphology, Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil
| | - Breno Valentim Nogueira
- Carlos Alberto Redins Cellular Ultrastructure Laboratory (LUCCAR), Department of Morphology, Health Sciences Center, Federal University of Espírito Santo, Espírito Santo, Brazil
| | - Fabiano Freire Costa
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Minas Gerais, Brazil
| | - Jair Adriano Kopke de Aguiar
- Department of Biochemistry, Glycoconjugate Analysis Laboratory, Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil.
| | - Carlos Magno da Costa Maranduba
- Department of Biology, Laboratory of Human Genetics and Cell Therapy, Institute of Biological Sciences, Federal University of Juiz de Fora, Minas Gerais, Brazil.
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Ma T, Ren D, Wang J, Fu F, Sun WQ, Sun H. Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules. J Biomed Mater Res B Appl Biomater 2024; 112:e35358. [PMID: 38247243 DOI: 10.1002/jbm.b.35358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/16/2023] [Accepted: 11/24/2023] [Indexed: 01/23/2024]
Abstract
Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.
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Affiliation(s)
- Tong Ma
- Institute of Biothermal Science and Technology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Dangli Ren
- Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China
| | - Jingjing Wang
- Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China
| | - Feng Fu
- Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China
| | - Wendell Q Sun
- Institute of Biothermal Science and Technology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Hongtao Sun
- Tianjin Key Laboratory of Neurotrauma Repair, Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, China
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
- First Clinical Medical College of Lanzhou University, Lanzhou, China
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Wang JL, Eaton RG, Harrigan ME, Munjal V, Sette KN, Wilson SB, Grossbach AJ. Demineralized Bone Matrix and Fibers in Spinal Fusion. Int J Spine Surg 2023; 17:S28-S34. [PMID: 38135444 PMCID: PMC10753352 DOI: 10.14444/8558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 09/11/2023] [Indexed: 12/24/2023] Open
Abstract
Formation of bony fusion after arthrodesis depends on osteoinduction, osteoconduction, and osteogenesis. Traditionally, the patient's own bone, or autograft, has been used to provide biological material necessary for these steps. However, the amount of autograft obtainable is often inadequate. Modern spine surgery has adopted the use of many autograft extenders or replacements, such as demineralized bone matrix or fibers. The present article covers the history of bone grafting, the production and technical details of demineralized bone matrix, and the evidence supporting its use in spine fusions.
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Affiliation(s)
- Joshua L Wang
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Ryan G Eaton
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Markus E Harrigan
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Vikas Munjal
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Katelyn N Sette
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Seth B Wilson
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Andrew J Grossbach
- Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, OH, USA
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Broussolle T, Roux JP, Chapurlat R, Barrey C. Murine models of posterolateral spinal fusion: A systematic review. Neurochirurgie 2023; 69:101428. [PMID: 36871885 DOI: 10.1016/j.neuchi.2023.101428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/05/2023] [Accepted: 02/07/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Rodent models are commonly used experimentally to assess treatment effectiveness in spinal fusion. Certain factors are associated with better fusion rates. The objectives of the present study were to report the protocols most frequently used, to evaluate factors known to positively influence fusion rate, and to identify new factors. METHOD A systematic literature search of PubMed and Web of Science found 139 experimental studies of posterolateral lumbar spinal fusion in rodent models. Data for level and location of fusion, animal strain, sex, weight and age, graft, decortication, fusion assessment and fusion and mortality rates were collected and analyzed. RESULTS The standard murine model for spinal fusion was male Sprague Dawley rats of 295g weight and 13 weeks' age, using decortication, with L4-L5 as fusion level. The last two criteria were associated with significantly better fusion rates. On manual palpation, the overall mean fusion rate in rats was 58% and the autograft mean fusion rate was 61%. Most studies evaluated fusion as a binary on manual palpation, and only a few used CT and histology. Average mortality was 3.03% in rats and 1.56% in mice. CONCLUSIONS These results suggest using a rat model, younger than 10 weeks and weighing more than 300 grams on the day of surgery, to optimize fusion rates, with decortication before grafting and fusing the L4-L5 level.
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Affiliation(s)
- T Broussolle
- Department of Spine Surgery, P. Wertheimer University Hospital, GHE, hospices civils de Lyon, université Claude-Bernard Lyon 1, Lyon, France; Inserm UMR 1033, université Claude-Bernard Lyon 1, Lyon, France.
| | - Jean-Paul Roux
- Inserm UMR 1033, université Claude-Bernard Lyon 1, Lyon, France
| | - R Chapurlat
- Inserm UMR 1033, université Claude-Bernard Lyon 1, Lyon, France
| | - C Barrey
- Department of Spine Surgery, P. Wertheimer University Hospital, GHE, hospices civils de Lyon, université Claude-Bernard Lyon 1, Lyon, France; Arts et métiers ParisTech, ENSAM, 151, boulevard de l'Hôpital, 75013 Paris, France
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Jaramillo-Cañas W, Britto-Bisso F, Fernandez-Valiente C, Casado FL. Open-source perfusion system for medium-scale fabrication of demineralized bone matrix chip grafts. HARDWAREX 2023; 13:e00378. [PMID: 36483326 PMCID: PMC9722481 DOI: 10.1016/j.ohx.2022.e00378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 10/23/2022] [Accepted: 11/16/2022] [Indexed: 06/17/2023]
Abstract
Demineralized bone matrix (DBM) is considered one of the most reliable bone tissue grafts for regular surgical use, as it provides a scaffold that is structurally like native bone, and that enhances bone regeneration. However, commercially available DBM products are not suited for surgical restitutions of large bones. Therefore, each Tissue Bank is urged to implement their own demineralization protocol, which usually does not meet the high demand for bone grafting. In this project, we developed an open source system for medium-scale manufacturing of DBM grafts from human cadaveric donors to automate the demineralization protocol and improve its reproducibility. The device consists in (1) unidirectional flow reaction chamber, where the demineralization protocol takes place; (2) automated syringe pump, which controls the reagent́s inlet and vacuum; and (3) reagent dispenser, for the management of the reagents need for the demineralization protocol. Validation of the device included histological analysis, DNA quantification temperature regulation, electrochemiluminescence and colorimetric protocols, followed by the optimization of physicochemical parameters based on Response Surface Methodology. The results showed values of residual lipids and calcium within standardized ranges, and the maintenance of the structural integrity of the DBM, demonstrating the capacity of the system to support the proposed demineralization protocol.
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Affiliation(s)
| | - Frank Britto-Bisso
- Program of Biomedical Engineering PUCP-UPCH, Pontificia Universidad Catolica del Peru, Avenida Universitaria 1801, Lima 15088, Peru
| | - Cesar Fernandez-Valiente
- Program of Biomedical Engineering PUCP-UPCH, Pontificia Universidad Catolica del Peru, Avenida Universitaria 1801, Lima 15088, Peru
| | - Fanny L. Casado
- Institute of Omics Sciences and Applied Biotechnology, Pontificia Universidad Catolica del Peru, Avenida Universitaria 1801, Lima 15088, Peru
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Mustahsan VM, Anugu A, Komatsu DE, Kao I, Pentyala S. Biocompatible Customized 3D Bone Scaffolds Treated with CRFP, an Osteogenic Peptide. Bioengineering (Basel) 2021; 8:bioengineering8120199. [PMID: 34940352 PMCID: PMC8698998 DOI: 10.3390/bioengineering8120199] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/09/2021] [Accepted: 11/27/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Currently used synthetic bone graft substitutes (BGS) are either too weak to bear the principal load or if metallic, they can support loading, but can lead to stress shielding and are unable to integrate fully. In this study, we developed biocompatible, 3D printed scaffolds derived from µCT images of the bone that can overcome these issues and support the growth of osteoblasts. METHODS Cylindrical scaffolds were fabricated with acrylonitrile butadiene styrene (ABS) and Stratasys® MED 610 (MED610) materials. The 3D-printed scaffolds were seeded with Mus musculus calvaria cells (MC3T3). After the cells attained confluence, osteogenesis was induced with and without the addition of calcitonin receptor fragment peptide (CRFP) and the bone matrix production was analyzed. Mechanical compression testing was carried out to measure compressive strength, stiffness, and elastic modulus. RESULTS For the ABS scaffolds, there was a 9.8% increase in compressive strength (p < 0.05) in the scaffolds with no pre-coating and the treatment with CRFP, compared to non-treated scaffolds. Similarly, MED610 scaffolds treated with CRFP showed an 11.9% (polylysine pre-coating) and a 20% (no pre-coating) increase (p < 0.01) in compressive strength compared to non-treated scaffolds. CONCLUSIONS MED610 scaffolds are excellent BGS as they support osteoblast growth and show enhanced bone growth with enhanced compressive strength when augmented with CRFP.
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Affiliation(s)
- Vamiq M. Mustahsan
- Department of Anesthesiology, Stony Brook University, Stony Brook, NY 11794, USA; (V.M.M.); (A.A.)
- Department of Mechanical Engineering, Stony Brook University, Stony Brook, NY 11794, USA;
| | - Amith Anugu
- Department of Anesthesiology, Stony Brook University, Stony Brook, NY 11794, USA; (V.M.M.); (A.A.)
| | - David E. Komatsu
- Department of Orthopedics, Stony Brook University, Stony Brook, NY 11794, USA;
| | - Imin Kao
- Department of Mechanical Engineering, Stony Brook University, Stony Brook, NY 11794, USA;
| | - Srinivas Pentyala
- Department of Anesthesiology, Stony Brook University, Stony Brook, NY 11794, USA; (V.M.M.); (A.A.)
- Department of Mechanical Engineering, Stony Brook University, Stony Brook, NY 11794, USA;
- Department of Orthopedics, Stony Brook University, Stony Brook, NY 11794, USA;
- Correspondence:
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Abstract
BACKGROUND Back pain is a common chief complaint within the United States and is caused by a multitude of etiologies. There are many different treatment modalities for back pain, with a frequent option being spinal fusion procedures. The success of spinal fusion greatly depends on instrumentation, construct design, and bone grafts used in surgery. Bone allografts are important for both structural integrity and providing a scaffold for bone fusion to occur. METHOD Searches were performed using terms "allografts" and "bone" as well as product names in peer reviewed literature Pubmed, Google Scholar, FDA-510k approvals, and clinicaltrials.gov. RESULTS This study is a review of allografts and focuses on currently available products and their success in both animal and clinical studies. CONCLUSION Bone grafts used in surgery are generally categorized into 3 main types: autogenous (from patient's own body), allograft (from cadaveric or living donor), and synthetic. This paper focuses on allografts and provides an overview on the different subtypes with an emphasis on recent product development and uses in spinal fusion surgery.
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Affiliation(s)
- Justin D. Cohen
- Department of
Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Linda E. Kanim
- Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, California
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Andrew J. Tronits
- Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, California
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Hyun W. Bae
- Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, California
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
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Chang DG, Park JB, Han Y. Surgical outcomes of two kinds of demineralized bone matrix putties/local autograft composites in instrumented posterolateral lumbar fusion. BMC Musculoskelet Disord 2021; 22:200. [PMID: 33596888 PMCID: PMC7890888 DOI: 10.1186/s12891-021-04073-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 02/08/2021] [Indexed: 11/10/2022] Open
Abstract
Background This study aimed to assess the surgical outcomes of two kinds of demineralized bone matrix (DBM) putties/local autograft composites in instrumented posterolateral lumbar fusion (PLF). Methods Twenty-seven fusion segments of 19 patients, who underwent decompression and instrumented PLF for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1, were included in this study. The PLF mass consisted of different two kinds of DBMs (Grafton® and DBX®) and local autograft. Next, 7.5 cc of Grafton® DBM/local autograft composite was implanted on the left side, and the same amount of DBX® DBM/local autograft composite was implanted on the right side in the same patient. The PLF masses of 54 total sides (27 Grafton® sides and 27 DBX® sides) were assessed for fusion based on both flexion/extension lateral radiographs and computed tomography images at 12 and 24 months postoperatively. Clinical symptoms were also evaluated. Results At 12 months postoperatively, the fusion rates for the Grafton® and DBX® sides were 59.5 and 51.9%, respectively; the difference was not statistically significant (P = 0.425). At 24 months postoperatively, the fusion rates for the Grafton® and DBX® sides increased to 70.4 and 66.7%, respectively, but the difference was still not statistically significant (P = 0.574). Diabetes mellitus, smoking, and obesity (body mass index ≥25) negatively affected the fusion rate of both the Grafton® and DBX® sides. Visual analog scores for lower back pain and leg pain and Oswestry Disability Index were significantly improved after surgery (both, P < 0.01). No deep or superficial infections occurred postoperatively. No patients underwent revision surgery due to nonunion during follow-up. Conclusions Our results suggest that two kinds of DBMs/local autograft composites might be considered as useful bone graft substitute in instrumented posterolateral fusion for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1.
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Affiliation(s)
- Dong-Gune Chang
- Department of Orthopaedic Surgery, College of Medicine, Inje University Sanggye Paik Hospital, Inje University, Seoul, South Korea
| | - Jong-Beom Park
- Department of Orthopaedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea. .,Department of Orthopaedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Korea, 271 Cheonbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, South Korea.
| | - Yangjun Han
- Department of Orthopaedic Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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Anterior Cervical Arthrodesis With Polyetheretherketone Spacers: What is the Role of the Grafting Material? Clin Spine Surg 2020; 33:E539-E544. [PMID: 32324673 DOI: 10.1097/bsd.0000000000000995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
STUDY DESIGN This was a retrospective study of 2 surgeons' use of a single polyetheretherketone (PEEK) device. OBJECTIVE Our objective was to investigate the fusion adjunct placed within PEEK devices to examine the likelihood of an arthrodesis, regardless of the PEEK interbody device itself. SUMMARY OF BACKGROUND DATA The effectiveness of PEEK interbody devices in anterior cervical arthrodesis has been questioned. METHODS The authors retrospectively reviewed the results of 121 patients with demineralized bone matrix (DBM) and 96 with local autograft bone placed within identical PEEK devices for anterior cervical arthrodesis (from 2011 to 2018); 1 surgeon used DBM and another local autograft bone. Arthrodesis was determined independently by a surgeon and 2 blinded neuroradiologists. RESULTS For DBM versus autograft; mean age was 60 versus 61 years, smoking status 42.1% versus 31%, diabetes mellitus 18.2% versus 28%, mean body mass index 31 versus 30, and follow up averaged 17 months in both groups. For DBM versus autograft; a radiographic arthrodesis was observed in 22.3% versus 76% of patients. Refusion at the index level was required in 5.8% of the DBM and 0% of the autograft patients. CONCLUSIONS A PEEK interbody device filled with local autograft resulted in a higher radiographic fusion rate and a lower need for reoperation at the index level than an identical device filled with DBM. Caution is warranted in assigning fusion failure to the PEEK device alone in anterior cervical discectomy and fusion surgery.
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Abstract
The biologic steps involved in creating a bony fusion between adjacent segments of the spine are a complex and highly coordinated series of events. There have been significant advancements in bone grafts and bone graft substitutes in order to augment spinal fusion. While autologous bone grafting remains the gold standard, allograft bone grafting, synthetic bone graft substitutes, and bone graft enhancers are appropriate in certain clinical situations. This article provides an overview of the basic biology of spinal fusion and strategies for enhancing fusion through innovations in bone graft material.
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McCarthy MH, Weiner JA, Patel AA. Strategies to Achieve Spinal Fusion in Multilevel Anterior Cervical Spine Surgery: An Overview. HSS J 2020; 16:155-161. [PMID: 32523483 PMCID: PMC7253572 DOI: 10.1007/s11420-019-09738-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 10/18/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Anterior cervical fusion offers surgeons a safe and reliable surgical option for single-level and multilevel pathology; however, multilevel fusions pose a higher risk of complications than single-level fusions, including possible pseudoarthrosis, adjacent segment disease, sagittal imbalance, and construct subsidence. Various techniques can be used to mitigate risk in multilevel anterior cervical fusion. QUESTIONS/PURPOSES We reviewed the literature to determine the best surgical strategies in multilevel anterior cervical fusion. METHODS We searched the PubMed database for articles published from January 1980 through July 2019. Two authors identified relevant articles and then manually screened them for others to include in this review. RESULTS We initially identified 1936 articles and included 48 in our review. We found that clinical outcomes of multilevel anterior cervical fusion can be optimized through the use of biologics and graft selection, the evaluation of pre-existing deformity, the assessment of comorbidities, and the selection of fusion levels. Meticulous surgical technique in conjunction with modern surgical tools, such as instrumentation and biologics, allow surgeons to address complex cervical problems while limiting morbidity and enhancing clinical outcomes. CONCLUSIONS Multilevel anterior cervical fusions offer a relatively safe and reliable treatment option for both single-level and multilevel pathology.
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Affiliation(s)
- Michael H. McCarthy
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair, Suite 1350, Chicago, IL 60611 USA
| | - Joseph A. Weiner
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair, Suite 1350, Chicago, IL 60611 USA
| | - Alpesh A. Patel
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair, Suite 1350, Chicago, IL 60611 USA
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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; 14:213-221. [PMID: 32355628 DOI: 10.14444/7026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Background To evaluate the comparative abilities of commercially available, viable, cellular bone allografts to promote posterolateral spinal fusion. Methods Human allografts containing live cells were implanted in the athymic rat model of posterolateral spine fusion. Three commercially available allogeneic cellular bone matrices (Trinity Evolution, Trinity ELITE and Osteocel Plus) were compared with syngeneic iliac crest bone as the control. All spines underwent radiographs, manual palpation, and micro-computed tomography (CT) analysis after excision at 6 weeks. Histological sections of randomly selected spines were subjected to semiquantitative histopathological scoring for bone formation. Results By manual palpation, posterolateral fusion was detected in 40% (6/15) of spines implanted with syngeneic bone, whereas spines implanted with Trinity Evolution and Trinity ELITE allografts yielded 71% (10/14) and 77% (10/13) fusion, respectively. Only 7% (1/14) of spines implanted with Osteocel Plus allografts were judged fused by manual palpation (statistically significantly less than ELITE, P < .0007, and Evolution, P < .0013). The mineralized cancellous bone component of the allografts confounded radiographic analysis, but Trinity Evolution (0.452 ± 0.064) and Trinity ELITE (0.536 ± 0.109) allografts produced statistically significantly higher bone fusion mass volumes measured by quantitative micro-CT than did syngeneic bone (0.292 ± 0.109, P < .0001 for ELITE and P < .003 for Evolution) and Osteocel Plus (0.258 ± 0.103, P < .0001). Semiquantitative histopathological scores supported these findings because the total bone and bone marrow scores reflected significantly better new bone and marrow formation in the Trinity groups than in the Osteocel Plus group. Conclusions The Trinity Evolution and Trinity ELITE cellular bone allografts were more effective at creating posterolateral fusion than either the Osteocel Plus allografts or syngeneic bone in this animal model. Clinical Relevance The superior fusion rate of Trinity cellular bone allografts may lead to better clinical outcome of spinal fusion surgeries.
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Affiliation(s)
- Brian Johnstone
- Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, Oregon
| | | | | | | | | | - Marcel Betsch
- Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, Oregon
| | - Paolo Punsalan
- Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, Oregon
| | - Holly Cho
- Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, Oregon
| | | | - Jung Yoo
- Department of Orthopaedics and Rehabilitation, Oregon Health & Science University, Portland, Oregon
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Russell N, Walsh WR, Lovric V, Kim P, Chen JH, Larson MJ, Vizesi F. In-vivo Performance of Seven Commercially Available Demineralized Bone Matrix Fiber and Putty Products in a Rat Posterolateral Fusion Model. Front Surg 2020; 7:10. [PMID: 32266283 PMCID: PMC7099880 DOI: 10.3389/fsurg.2020.00010] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/28/2020] [Indexed: 12/13/2022] Open
Abstract
Introduction: Demineralized bone matrix (DBM) is a widely used bone graft in spinal fusion. Most commercial DBMs are composed of demineralized bone particles (~125–800 microns) suspended in a carrier that provides improved handling but dilutes the osteoinductive component. DBM fibers (DBF) provide improved osteoconductivity and do not require a carrier. It has been suggested that 100% DBF may offer improved performance over particulate-based DBMs with carrier. Study Design: Seven commercially available DBM products were tested in an athymic rat posterolateral fusion model. There were four 100% DBFs, two DBFs containing a carrier, and one particulate-based DBM containing carrier. Objective: The study objectives were to evaluate the in vivo performance: (1) compare fusion rate and fusion maturity of six commercially available DBFs and one particulate-based DBM, and (2) assess the effect of carrier on fusion outcomes for DBFs in a posterolateral fusion model. Methods: The DBF/DBM products evaluated were: StrandTM Family, Propel® DBM Fibers, Vesuvius® Demineralized Fibers, Optium® DBM Putty, Grafton® DBF, Grafton Flex, and DBX® Putty. Single-level posterolateral fusion was performed in 69 athymic rats. Fusion was assessed bilaterally after 4 weeks by manual palpation, radiograph and CT for bridging bone. Fusion mass maturity was assessed with a CT maturity grading scale and by histology. Statistical analysis was performed using Fishers Exact Test for categorical data and Kruskal-Wallis Test for non-parametric data. Results: Strand Family achieved 100% fusion (18/18) by manual palpation, radiographic and CT evaluation, significantly higher than Propel Fibers, Vesuvius Fibers, Optium Putty, and DBX Putty, and not statistically higher than Grafton DBF and Grafton Flex. Strand Family provided the highest fusion maturity, with CT maturity grade of 2.3/3.0 and 89% mature fusion rate. Fusion results suggest a detrimental effect of carrier on fusion performance. Conclusions: There were large variations in fusion performance for seven commercially available DBM products in an established preclinical fusion model. There were even significant differences between different 100% DBF products, suggesting that composition alone does not guarantee in vivo performance. In the absence of definitive clinical evidence, surgeons should carefully consider available data in valid animal models when selecting demineralized allograft options.
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Affiliation(s)
| | - William R Walsh
- Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Vedran Lovric
- Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Peter Kim
- SeaSpine Inc., Carlsbad, CA, United States
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14
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Lee MS, Lee DH, Jeon J, Tae G, Shin YM, Yang HS. Biofabrication and application of decellularized bone extracellular matrix for effective bone regeneration. J IND ENG CHEM 2020. [DOI: 10.1016/j.jiec.2019.12.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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15
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Waibl B. Aspekte der Verwendung von homologem Knochen bei Korrekturosteotomien. ARTHROSKOPIE 2019. [DOI: 10.1007/s00142-019-00313-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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16
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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; 13:437-458. [PMID: 31745449 DOI: 10.14444/6059] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background Insufficient data exist on bone graft substitute materials efficacy; two thirds lack any clinical data.1,2 This prospective animal study identified efficacy differences among commercially available materials of several classes. Methods Historically validated muscle pouch osteoinduction study (OIS) and posterolateral fusion (PLF) were performed in an athymic rat model. Grafting material products implanted were demineralized bone matrix (DBM)-based allografts (Accell EVO3, DBX Mix, DBX Strip, Grafton Crunch, Grafton Flex, Grafton Matrix, Grafton Putty, Magnifuse, and Progenix Plus), allografts (OsteoSponge, MinerOss), cellular allograft (Osteocel Plus), ceramics (Mozaik Strip), or activated ceramics (Actifuse ABX Putty, Vitoss BA). After 4 weeks, OIS specimens were evaluated ex vivo by histologic osteoinductivity. After 8 weeks, PLF ex vivo specimens were evaluated for fusion by manual palpation (FMP), radiography (FXR), and histology (FHISTO). Results OIS: No materials exhibited a rejection reaction on histology. All DBM-based materials exhibited osteoinductive potential as new bone formation at > 88% of implanted sites. One plain allograft (OsteoSponge) formed bone at 25% of sites. No bone formed for one ceramic (Mozaik Strip), three activated ceramics (Actifuse ABX Putty), or one cellular allograft, regardless of human bone marrow aspirate (hBMA) when added. PLF: Among the 10 DBMs, 6 had FMP of 100% (Accell EVO3, DBX Mix, DBX Strip, Grafton Flex, Grafton Putty, Magnifuse), 2 had FMP of 94% (Grafton Crunch, Grafton Matrix), and 2 conditions had FMP of 0% (Progenix Plus, Progenix Plus + athymic rat iliac crest bone graft [arICBG]). Ceramics (Mozaik Strip), activated ceramics (Actifuse ABX Putty, Vitoss BA), plain allograft (OsteoSponge, MinerOss (PLF study), and cellular allograft (Osteocel Plus) demonstrated 0% FMP. ArICBG demonstrated 13% FMP. Conclusions Eight DBM-based materials (Accell EVO3, DBX Mix, DBX Strip, Grafton Crunch, Grafton Flex, Grafton Matrix, Grafton Putty, Magnifuse) demonstrated excellent (> 90% FMP) efficacy in promoting fusion via bone healing. Two DBM conditions (Progenix Plus, Progenix Plus + arICBG) showed no manual palpation fusion (FMP). Systematically, over the 2 studies (OIS and PLF), cellular (Osteocel Plus), plain allografts (OsteoSponge, MinerOss; PLF study), ceramic (Mozaik Strip), and activated ceramics (Actifuse ABX Putty, Vitoss BA) demonstrated poor FMP efficacy (< 10%). Clinical Relevance When selecting DBMs, clinicians must be cognizant of variability in DBM efficacy by product and lot. While theoretically osteoinductive, cellular allograft and activated ceramics yielded poor in vivo efficacy. Whole allograft and ceramics may provide osteoconductive scaffolding for mixed-material grafting; however, surgeons should be cautious in using them alone. Direct clinical data are needed to establish efficacy for any bone graft substitute.
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Affiliation(s)
- Neil Bhamb
- Cedars-Sinai Medical Center, Los Angeles, California
| | - Linda E A Kanim
- Translational and Clinical Research, Spine Center, Cedars-Sinai Medical Center, Los Angeles, California
| | | | | | | | | | | | - Hyun W Bae
- Cedars-Sinai Medical Center, Los Angeles, California
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Sharma A, Faubion WA, Dietz AB. Regenerative Materials for Surgical Reconstruction: Current Spectrum of Materials and a Proposed Method for Classification. Mayo Clin Proc 2019; 94:2099-2116. [PMID: 31515102 DOI: 10.1016/j.mayocp.2019.03.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 02/12/2019] [Accepted: 03/15/2019] [Indexed: 10/26/2022]
Abstract
Chronic wound management is an enormous economic strain and quality-of-life issue for patients. Current treatments are ineffective or expensive and invasive. Materials (native and artificial) can act as the basis to enhance wound repair but often fall short of complete healing. The therapeutic index of materials have often been enhanced by combining them with drug or biologic elution technologies. Combination of materials with living drugs (cells) presents a new paradigm for enhancing therapy. Cell material interaction and therapeutic output will depend on variables ascribed to the living drug as well as variables ascribed to the underlying matrix. In this article, we review medical matrices currently approved by the US Food and Drug Administration (FDA) that would likely be the first generation of materials to be used in this manner. Currently there are hundreds of different materials on the market. Identification of the right combinations would benefit from a classification scheme to group materials with similar composition or derivation. We provide a classification scheme and FDA documentation references that should provide researchers and clinicians a starting point for testing these materials in the laboratory and rapidly transitioning cell therapies to the bedside.
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Affiliation(s)
- Ayushman Sharma
- Division of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Allan B Dietz
- Division of Experimental Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN; Division of Transfusion Medicine, Mayo Clinic, Rochester, MN; Department of Immunology, Mayo Clinic, Rochester, MN.
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18
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Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-assisted Cervical Spinal Interbody Fusion. Clin Spine Surg 2019; 32:71-79. [PMID: 30234566 DOI: 10.1097/bsd.0000000000000720] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
STUDY DESIGN This was a retrospective study. OBJECTIVE To radiographically demonstrate the distinct fusion pattern of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the setting of anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA Studies investigating spinal fusion assisted with rhBMP-2 have yielded promising results, suggesting rhBMP-2 is an efficacious alternative to iliac crest autografts. rhBMP-2-assisted spinal fusion both hastens healing and eliminates patient morbidity from iliac crest autograft. Unique to rhBMP-assisted spinal fusion is its distinct radiographic fusion pattern as fusion is achieved. Despite promising results and increased clinical use of rhBMP-2, there remains a paucity of literature documenting this radiographic process. MATERIALS AND METHODS This study included 26 patients who underwent single-level anterior cervical discectomy and fusion using rhBMP-2. All data used for this study was collected from a prior FDA Investigational Device Exemption study. RESULTS A polyetheretherketone cage was used as an interbody disk spacer in all 26 patients. Patients were evaluated between 2 and 6 weeks after surgery and subsequently at 3, 6, 12, and 24 months postoperative. All patients underwent plain radiography at every follow-up visit, and computed tomograhy evaluation was performed at 3, 6, 12, and 24 months as part of the study protocol. Earliest fusion was observed at 3 months in 38% of patients. Likely fusion was observed in all patients by 12 months postoperative. CONCLUSIONS rhBMP-2 leads to both successful interbody fusion and an enhanced fusion rate with unique imaging characteristics. Additional characteristics of BMP observed in 100% of patients included prevertebral soft-tissue swelling and early endplate resorption. Other common features included polyetheretherketone cage migration, heterotopic bone formation and cage subsidence.
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19
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Homayounfar N, Khan MM, Ji Y, Khoury ZH, Oates TW, Goodlett DR, Chellaiah M, Masri R. The effect of embryonic origin on the osteoinductive potential of bone allografts. J Prosthet Dent 2018; 121:651-658. [PMID: 30598313 DOI: 10.1016/j.prosdent.2018.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 11/15/2022]
Abstract
STATEMENT OF PROBLEM Allografts with osteoinduction potential are widely used to augment bone in surgical and prosthetic rehabilitations. However, osteoinduction potential varies among commercially available allografts. Donor bones are derived from different embryonic origins, either the neural crest or mesoderm. Whether the origin of the bones affects the osteoinductivity of allograftsis is unclear. PURPOSE The purpose of this ex vivo study was to investigate the osteoinduction potential of allografts derived from bones with distinct embryonic origins. MATERIAL AND METHODS Allografts were obtained from human frontal and parietal bones at 2 different ages (fetal and adult). The specimens were divided into 4 groups: adult frontal (n=5), adult parietal (n=5), fetal frontal (n=10), and fetal parietal (n=10). Two investigations were conducted to assess the osteoinductive potential of these allografts. First, the osteogenesis of human osteoblasts exposed to these allografts were evaluated by analyzing the expression of runt-related transcription factor 2 (RUNX2), collagen type 1 alpha 2 chain (COL1A2), and bone gamma-carboxyglutamate protein (BGLAP) genes using quantitative real-time polymerase chain reaction (qRT-PCR). Second, the protein content of the adult frontal and parietal bone matrices was analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). One-way ANOVA and the t test were used for statistical analyses of the gene and protein expression of the groups (α=.05). RESULTS No difference was found in the gene expression of the cells exposed to frontal or parietal bones. However, all 3 genes were significantly overexpressed in cells treated with fetal bones compared with adult bones. No difference was found in protein expression between adult frontal and adult parietal bones. CONCLUSIONS No difference was found in the osteoinductive capacity of frontal and parietal bones used as allografts. However, the osteoinductivity of fetal bones can be higher than that of adult bones. Further microanalyses are needed to determine the protein content of fetal bones.
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Affiliation(s)
- Negar Homayounfar
- Assistant Professor, Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, Md.
| | - Mohd M Khan
- Graduate student, University of Maryland School of Medicine, Baltimore, Md
| | - Yadong Ji
- Research Scientist, Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, Md
| | - Zaid H Khoury
- Graduate student, Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, Md
| | - Thomas W Oates
- Professor, Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, Md
| | - David R Goodlett
- Professor, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Md
| | - Meenakshi Chellaiah
- Professor, Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, Md
| | - Radi Masri
- Associate Professor, Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, Md
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20
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Abjornson C, Brecevich A, Callanan T, Dowe C, Cammisa FP, Lorio MP. ISASS Recommendations and Coverage Criteria for Bone Graft Substitutes used in Spinal Surgery. Int J Spine Surg 2018; 12:757-771. [PMID: 30619681 DOI: 10.14444/5095] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Autologous bone graft remains the gold standard by which bone graft substitutes are compared in spine fusion surgery. The utilization of bone graft substitutes, either as (1) an extender for spinal fusion constructs or (2) an alternative to minimize morbidity while maximizing outcomes, is changing. Moreover, current procedures technology (CPT) code 20939 became effective in 2018 defining bone marrow aspirate for bone grafting, spine surgery only. Changes in the complex landscape of grafting materials have prompted ISASS to provide category guidance for bone graft substitutes by comparing and contrasting US regulatory pathways, mechanisms of action, and supportive clinical evidence for these bone grafting materials.
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21
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Parrilla-Almansa A, García-Carrillo N, Ros-Tárraga P, Martínez CM, Martínez-Martínez F, Meseguer-Olmo L, De Aza PN. Demineralized Bone Matrix Coating Si-Ca-P Ceramic Does Not Improve the Osseointegration of the Scaffold. MATERIALS 2018; 11:ma11091580. [PMID: 30200440 PMCID: PMC6163991 DOI: 10.3390/ma11091580] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 07/28/2018] [Accepted: 08/26/2018] [Indexed: 12/19/2022]
Abstract
The aim of this study was to manufacture and evaluate the effect of a biphasic calcium silicophosphate (CSP) scaffold ceramic, coated with a natural demineralized bone matrix (DBM), to evaluate the efficiency of this novel ceramic material in bone regeneration. The DBM-coated CSP ceramic was made by coating a CSP scaffold with gel DBM, produced by the partial sintering of different-sized porous granules. These scaffolds were used to reconstruct defects in rabbit tibiae, where CSP scaffolds acted as the control material. Micro-CT and histological analyses were performed to evaluate new bone formation at 1, 3, and 5 months post-surgery. The present research results showed a correlation among the data obtained by micro-CT and the histomorphological results, the gradual disintegration of the biomaterial, and the presence of free scaffold fragments dispersed inside the medullary cavity occupied by hematopoietic bone marrow over the 5-month study period. No difference was found between the DBM-coated and uncoated implants. The new bone tissue inside the implants increased with implantation time. Slightly less new bone formation was observed in the DBM-coated samples, but it was not statistically significant. Both the DBM-coated and the CSP scaffolds gave excellent bone tissue responses and good osteoconductivity.
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Affiliation(s)
- Andrés Parrilla-Almansa
- Image Diagnostic Service, Virgen de la Arrixaca University Hospital, UCAM-Universidad Catolica San Antonio de Murcia, Guadalupe, 30107 Murcia, Spain.
| | - Nuria García-Carrillo
- Preclinical Imaging Unit, Laboratory Animal Service, University of Murcia, 30107 Murcia, Spain.
| | - Patricia Ros-Tárraga
- Tissue Regeneration and Repair Group: Orthobiology, Biomaterials and Tissue Engineering, UCAM-San Antonio Catholic University of Murcia, Guadalupe, 30107 Murcia, Spain.
| | | | | | - Luis Meseguer-Olmo
- Department of Orthopaedic Surgery and Trauma, School of Medicine, Lab of Regeneration and Tissue Repair, UCAM-Universidad Catolica San Antonio de Murcia, Guadalupe, 30107 Murcia, Spain.
| | - Piedad N De Aza
- Instituto de Bioingeniería, Universidad Miguel Hernández-UMH, Avda. Ferrocarril s/n. Elche, 03202 Alicante, Spain.
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22
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Kowalczewski CJ, Saul JM. Biomaterials for the Delivery of Growth Factors and Other Therapeutic Agents in Tissue Engineering Approaches to Bone Regeneration. Front Pharmacol 2018; 9:513. [PMID: 29896102 PMCID: PMC5986909 DOI: 10.3389/fphar.2018.00513] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 04/27/2018] [Indexed: 12/14/2022] Open
Abstract
Bone fracture followed by delayed or non-union typically requires bone graft intervention. Autologous bone grafts remain the clinical "gold standard". Recently, synthetic bone grafts such as Medtronic's Infuse Bone Graft have opened the possibility to pharmacological and tissue engineering strategies to bone repair following fracture. This clinically-available strategy uses an absorbable collagen sponge as a carrier material for recombinant human bone morphogenetic protein 2 (rhBMP-2) and a similar strategy has been employed by Stryker with BMP-7, also known as osteogenic protein-1 (OP-1). A key advantage to this approach is its "off-the-shelf" nature, but there are clear drawbacks to these products such as edema, inflammation, and ectopic bone growth. While there are clinical challenges associated with a lack of controlled release of rhBMP-2 and OP-1, these are among the first clinical examples to wed understanding of biological principles with biochemical production of proteins and pharmacological principles to promote tissue regeneration (known as regenerative pharmacology). After considering the clinical challenges with such synthetic bone grafts, this review considers the various biomaterial carriers under investigation to promote bone regeneration. This is followed by a survey of the literature where various pharmacological approaches and molecular targets are considered as future strategies to promote more rapid and mature bone regeneration. From the review, it should be clear that pharmacological understanding is a key aspect to developing these strategies.
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Affiliation(s)
| | - Justin M Saul
- Department of Chemical, Paper and Biomedical Engineering, Miami University, Oxford, OH, United States
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23
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Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: Comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion. PLoS One 2018; 13:e0197969. [PMID: 29795650 PMCID: PMC5967748 DOI: 10.1371/journal.pone.0197969] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Accepted: 05/13/2018] [Indexed: 01/25/2023] Open
Abstract
The potential use of bone progenitors, multipotential stromal cells (MSCs) helping spine fusion is increasing, but convenient MSC sources and effective processing methods are critical factors yet to be optimised. The aim of this study was to test the effect of bone marrow processing on the MSC abundance and to compare the differentiation capabilities of vertebral body-bone marrow (VB-BM) MSCs versus iliac crest-bone marrow (IC-BM) MSCs. We assessed the effect of the red blood cell lysis (ammonium chloride, AC) and density-gradient centrifugation (Lymphoprep™, LMP), on the extracted VB-BM and IC-BM MSC numbers. The MSC abundance (indicated by colony counts and CD45lowCD271high cell numbers), phenotype, proliferation and tri-lineage differentiation of VB-BM MSCs were compared with donor-matched IC-BM MSCs. Importantly, the MSC attachment and osteogenesis were examined when VB-BM and IC-BM samples were loaded on a beta-tricalcium phosphate scaffold. In contrast to LMP, using AC yielded more colonies from IC-BM and VB-BM aspirates (p = 0.0019 & p = 0.0201 respectively). For IC-BM and VB-BM, the colony counts and CD45lowCD271high cell numbers were comparable (p = 0.5186, p = 0.2640 respectively). Furthermore, cultured VB-BM MSCs exhibited the same phenotype, proliferative and adipogenic potential, but a higher osteogenic and chondrogenic capabilities than IC-BM MSCs (p = 0.0010 and p = 0.0005 for calcium and glycosaminoglycan (GAG) levels, respectively). The gene expression data confirmed higher chondrogenesis for VB-BM MSCs than IC-BM MSCs, but osteogenic gene expression levels were comparable. When loaded on Vitoss™, both MSCs showed a similar degree of attachment and survival, but a better osteogenic ability was detected for VB-BM MSCs as measured by alkaline phosphatase activity (p = 0.0386). Collectively, the BM processing using AC had more MSC yield than using LMP. VB-BM MSCs have a comparable phenotype and proliferative capacity, but higher chondrogenesis and osteogenesis with or without using scaffold than donor-matched IC-BM MSCs. Given better accessibility, VB-BM could be an ideal MSC source for spinal bone fusion.
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Fernandez de Grado G, Keller L, Idoux-Gillet Y, Wagner Q, Musset AM, Benkirane-Jessel N, Bornert F, Offner D. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng 2018; 9:2041731418776819. [PMID: 29899969 PMCID: PMC5990883 DOI: 10.1177/2041731418776819] [Citation(s) in RCA: 433] [Impact Index Per Article: 61.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 04/24/2018] [Indexed: 12/13/2022] Open
Abstract
Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can be used. They can be either derived from biological products such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (like bone morphogenetic protein) or synthetic such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes. All these substitutes are not suitable for every clinical use, and they have to be chosen selectively depending on their purpose. Thus, this review aims to highlight the principal characteristics of the most commonly used bone substitutes and to give some directions concerning their clinical use, as spine fusion, open-wedge tibial osteotomy, long bone fracture, oral and maxillofacial surgery, or periodontal treatments. However, the main limitations to bone substitutes use remain the management of large defects and the lack of vascularization in their central part, which is likely to appear following their utilization. In the field of bone tissue engineering, developing porous synthetic substitutes able to support a faster and a wider vascularization within their structure seems to be a promising way of research.
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Affiliation(s)
- Gabriel Fernandez de Grado
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
- Hôpitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, F-67000 Strasbourg
| | - Laetitia Keller
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
| | - Ysia Idoux-Gillet
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
| | - Quentin Wagner
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
| | - Anne-Marie Musset
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
- Hôpitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, F-67000 Strasbourg
| | - Nadia Benkirane-Jessel
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
| | - Fabien Bornert
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
- Hôpitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, F-67000 Strasbourg
| | - Damien Offner
- INSERM (French National Institute of Health and Medical Research), “Regenerative Nanomedicine” laboratory, http://www.regmed.fr, UMR 1260, Faculté de Médecine, FMTS, F-67085 Strasbourg Cedex
- Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Ste Elisabeth, F-67000 Strasbourg
- Hôpitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, F-67000 Strasbourg
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Kuznetsova VS, Vasilyev AV, Grigoriev TE, Zagoskin YD, Chvalun SN, Buharova TB, Goldshtein DV, Kulakov AA. [The prospects of hydrogels usage as a basis for curable osteoplastic materials]. STOMATOLOGII︠A︡ 2017; 96:68-74. [PMID: 29260770 DOI: 10.17116/stomat201796668-74] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The article deals with the main types of the polymers used in hydrogel preparation. Their biological, physical and chemical properties was compared. Ways of polymers hardening and prospects of medical application were considered. The prospect of use of chitosan hydrogels activated by osteoinductors as a material for bone augmentation were concluded.
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Affiliation(s)
- V S Kuznetsova
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
| | - A V Vasilyev
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia; Research Centre for Medical Genetics, Moscow, Russia
| | | | | | | | - T B Buharova
- Research Centre for Medical Genetics, Moscow, Russia
| | | | - A A Kulakov
- Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Russia
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Thrivikraman G, Athirasala A, Twohig C, Boda SK, Bertassoni LE. Biomaterials for Craniofacial Bone Regeneration. Dent Clin North Am 2017; 61:835-856. [PMID: 28886771 PMCID: PMC5663293 DOI: 10.1016/j.cden.2017.06.003] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Functional reconstruction of craniofacial defects is a major clinical challenge in craniofacial sciences. The advent of biomaterials is a potential alternative to standard autologous/allogenic grafting procedures to achieve clinically successful bone regeneration. This article discusses various classes of biomaterials currently used in craniofacial reconstruction. Also reviewed are clinical applications of biomaterials as delivery agents for sustained release of stem cells, genes, and growth factors. Recent promising advancements in 3D printing and bioprinting techniques that seem to be promising for future clinical treatments for craniofacial reconstruction are covered. Relevant topics in the bone regeneration literature exemplifying the potential of biomaterials to repair bone defects are highlighted.
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Affiliation(s)
- Greeshma Thrivikraman
- Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, OHSU School of Dentistry, 2730 SW Moody Avenue, Portland, OR 97201, USA
| | - Avathamsa Athirasala
- Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, OHSU School of Dentistry, 2730 SW Moody Avenue, Portland, OR 97201, USA
| | - Chelsea Twohig
- Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, OHSU School of Dentistry, 2730 SW Moody Avenue, Portland, OR 97201, USA
| | - Sunil Kumar Boda
- Mary and Dick Holland Regenerative Medicine Program, Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, NE 68198-5965, USA
| | - Luiz E Bertassoni
- Division of Biomaterials and Biomechanics, Department of Restorative Dentistry, OHSU School of Dentistry, 2730 SW Moody Avenue, Portland, OR 97201, USA; Department of Biomedical Engineering, OHSU School of Medicine, 3303 SW Bond Avenue, Portland, OR 97239, USA; OHSU Center for Regenerative Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
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Pacelli S, Basu S, Whitlow J, Chakravarti A, Acosta F, Varshney A, Modaresi S, Berkland C, Paul A. Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration. Adv Drug Deliv Rev 2017; 120:50-70. [PMID: 28734899 PMCID: PMC5705585 DOI: 10.1016/j.addr.2017.07.011] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Revised: 07/05/2017] [Accepted: 07/16/2017] [Indexed: 02/07/2023]
Abstract
A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration.
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Affiliation(s)
- Settimio Pacelli
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Sayantani Basu
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Jonathan Whitlow
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Aparna Chakravarti
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Francisca Acosta
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Arushi Varshney
- Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
| | - Saman Modaresi
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
| | - Cory Berkland
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA; Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
| | - Arghya Paul
- Department of Chemical and Petroleum Engineering, Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
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Lee TC, Wang YH, Huang SH, Chen CH, Ho ML, Fu YC, Wang CK. Evaluations of clinical-grade bone substitute-combined simvastatin carriers to enhance bone growth: In vitro and in vivo analyses. J BIOACT COMPAT POL 2017. [DOI: 10.1177/0883911517720813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We demonstrated in a value-added study that the combination of calcium phosphate–based bone substitute (MaxiBone® bioceramics) and simvastatin/poly lactic- co-glycolic acid (SIMm) carriers which were fabricated by GMP pharmaceutical company and underwent our patterned double-emulsion technique can promote bone growth. The average size distribution of SIMm, the encapsulation efficacy, and the in vitro release profile of simvastatin in SIMm over 14 days were investigated in this study. Based on the results of Alizarin Red S staining and alkaline phosphatase activity, the released simvastatin of SIMm can effectively induce osteogenesis of bone marrow mesenchymal stem cells (D1 cells). In the non-union fracture model of animal study, the MaxiBone bioceramics group and MaxiBone bioceramics with SIMm group showed a significant increase in the percentages of new bone matrix compared with the control group and SIMm groups at the 8th and 10th weeks. Moreover, the MaxiBone bioceramics with SIMm group showed the strongest effect in new bone formation among these groups. We concluded that the calcium phosphate–based ceramics of MaxiBone combined with SIMm can accelerate osteogenic differentiation and bone growth in vitro and in vivo. Our results provide a proof of concept that SIMm can play as an osteoinductive material and the combination with bone substitutes with osteoconductive property effectively enhance bone growth, and this treatment is value added for clinical application, especially in the healing of large bone defects or non-union. Graphical abstract. The clinical-grade calcium phosphate–based bone substitute combined SIM/PLGA/HAp microspheres were fabricated by GMP pharmaceutical company to promote bone growth in bone defect model of mice.
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Affiliation(s)
- Tien-Ching Lee
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yan-Hsiung Wang
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shih-Hao Huang
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Hwan Chen
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mei-Ling Ho
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yin-Chih Fu
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Orthopaedics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Kuang Wang
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan
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Buser Z, Drapeau S, Stappenbeck F, Pereira RC, Parhami F, Wang JC. Effect of Oxy133, an osteogenic oxysterol, on new bone formation in rat two-level posterolateral fusion model. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2017; 26:2763-2772. [PMID: 28547574 DOI: 10.1007/s00586-017-5149-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 05/10/2017] [Accepted: 05/18/2017] [Indexed: 12/16/2022]
Abstract
PURPOSE The aim of our study was to determine the effect of Oxy133 and rhBMP2 on fusion rates and new bone formation in a rat posterolateral fusion (PLF) model. Furthermore, we examined whether Oxy133 could inhibit the adipogenesis that is often present in rhBMP2-induced fusions. METHODS Sixty-four male Lewis rats underwent two levels PLF (L3-L5). All animals were randomly divided into eight groups based on the test compound that they received: control (DMSO), low-dose rhBMP2 (0.5 µg), high-dose rhBMP2 (5 µg), low-dose Oxy133 (5 mg), high-dose Oxy133 (20 mg), low rhBMP2 + high Oxy133, high rhBMP2 + high Oxy133, and low rhBMP2 + low Oxy133. Fusion rates were assessed 8 weeks after surgery with manual palpation and plain radiographs. Bone parameters were measured using microCT. Histology was used to evaluate adipogenesis. RESULTS No fusion was observed in the control group. Based on the manual palpation, 100% fusion was observed in all other groups except in the low-dose rhBMP2 group (69%). At 8 weeks based on X-rays, 100% fusion was observed in the following groups: high-dose rhBMP2, low-dose Oxy133, and low rhBMP2 + low Oxy133. In the other groups, the fusion rates were between 95 and 97%, except for the low rhBMP2 group (72%). We observed similar values in BV/TV ratio at L3-4 when Oxy133 groups were compared to rhBMP2 groups alone (44.62% in high-dose Oxy133 vs. 41.47% in high-dose rhBMP2 and 47.18% in low-dose Oxy133 vs. 54.98% in low-dose rhBMP2). Trabecular thickness was slightly lower in Oxy133 groups compared to rhBMP2 when comparing low- and high-dose groups from each group (118.44 µm for high-dose Oxy133 vs. 122.39 µm for high-dose rhBMP2 and 123.51 µm for low-dose Oxy133 vs. 135.74 µm for low-dose rhBMP2). At the same time, trabecular separation was lower in Oxy133 groups compared to rhBMP2 groups. Similar trends in bone parameters were observed at the L4-5 levels. Fusion masses with low- and high-dose Oxy133 had significantly less adipocytes than rhBMP2 groups that showed robust adipocyte formation. CONCLUSION In our study, both low-dose and high-dose Oxy133 produced solid fusions with bone densities similar or higher than in the BMP2 groups. High-dose Oxy133 group had significantly less adipocytes than high- or low-dose rhBMP2 groups. Furthermore, high-dose Oxy133 was able to significantly inhibit high-dose BMP2-induced adipogenesis when combined together. Consistent with the previous reports, our preliminary findings suggest that Oxy133 has a significant potential as an alternative to rhBMP2 in spine fusion.
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Affiliation(s)
- Zorica Buser
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, HMR 710, 2011 Zonal Ave., Los Angeles, CA, 90033, USA.
| | - Susan Drapeau
- Vericel Corporation, Cambridge, MA, USA.,Medtronic, Minneapolis, MN, USA
| | | | - Renata C Pereira
- Department of Pediatric Nephrology, University of California Los Angeles, Los Angeles, CA, USA
| | - Farhad Parhami
- Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Jeffrey C Wang
- Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, HMR 710, 2011 Zonal Ave., Los Angeles, CA, 90033, USA
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Khader BA, Towler MR. Common treatments and procedures used for fractures of the distal radius and scaphoid: A review. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 74:422-433. [DOI: 10.1016/j.msec.2016.12.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 12/08/2016] [Indexed: 10/20/2022]
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Alom N, Peto H, Kirkham GR, Shakesheff KM, White LJ. Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12 myoblasts and mouse primary calvarial cells. J Biomed Mater Res B Appl Biomater 2017; 106:900-908. [PMID: 28429412 DOI: 10.1002/jbm.b.33894] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 02/01/2017] [Accepted: 03/25/2017] [Indexed: 12/20/2022]
Abstract
Hydrogel scaffolds derived from the extracellular matrix (ECM) of mammalian tissues have been successfully used to promote tissue repair in vitro and in vivo. The objective of this study was to evaluate the osteogenic potential of ECM hydrogels prepared from demineralized and decellularized bovine bone in the presence and absence of osteogenic medium. Culture of C2C12 and mouse primary calvarial cells (mPCs) on decellularized bone ECM (bECM) and demineralized bone matrix (DBM) gels resulted in increased expression of osteogenic gene markers, including a 3.6- and 13.4-fold increase in osteopontin and 15.7- and 27.1-fold increase in osteocalcin when mPCs were cultured upon bECM with basal and osteogenic media, respectively. bECM hydrogels stimulated the osteogenic differentiation of C2C12 and mPCs even in the absence of osteogenic medium. These results suggest that bECM hydrogel scaffolds may have great utility in future clinical applications for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 900-908, 2018.
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Affiliation(s)
- Noura Alom
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
| | - Heather Peto
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
| | - Glen R Kirkham
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
| | - Kevin M Shakesheff
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
| | - Lisa J White
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, University of Nottingham University Park, Nottingham, United Kingdom
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Zhang Y, Wang J, Ma Y, Niu X, Liu J, Gao L, Zhai X, Chu K, Han B, Yang L, Wang J. Preparation and biocompatibility of demineralized bone matrix/sodium alginate putty. Cell Tissue Bank 2017; 18:205-216. [DOI: 10.1007/s10561-017-9627-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 04/13/2017] [Indexed: 10/19/2022]
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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; 10:35. [PMID: 27909656 DOI: 10.14444/3035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Multiple studies have demonstrated that a significant amount of variability exists in various demineralized bone matrix (DBM) formulations, which casts doubts on its reliability in consistently promoting fusion. Bone marrow aspirate (BMA) is a cellular based graft that contains mesenchymal stem cells (MSCs) and growth factors can confer osteogenic and osteoinductive potential to DBM. The goal of this study was to describe the outcome of DBM enriched with concentrated BMA in patients undergoing combined lumbar interbody and posterolateral fusion. METHODS Eighty patients with a minimum of 12 months of follow-up were evaluated. Fusion and rates of complication were evaluated. Functional outcomes were assessed based on the modified Odom's criteria. Multiple logistic regression analysis was used to examine the effects of independent variables on fusion outcome. RESULTS The overall rate of solid fusion (i.e patients with both solid posterolateral and interbody fusion) was 81.3% (65/80). Specifically, the radiographic evidence of solid posterolateral and interbody fusions were 81.3% (65/80) and 92.5% (74/80), respectively. Seven (8.75%) patients developed hardware-related complications, 2 (2.5%) patients developed a postoperative infection and 2 (2.5%) patients developed clinical pseudarthrosis. Charlson comorbidity index (CCI) scores of 3 and 4 were associated with non-solid unions (CCI-3, p = 0.048; CCI-4, p = 0.03). Excellent or good outcomes were achieved in 58 (72.5%) patients. CONCLUSIONS Patients undergoing lumbar fusion using an enriched bone graft containing concentrated BMA added to DBM can achieve successful fusion with relatively low complications and good functional outcomes. Despite these findings, more studies with higher level of evidence are needed to better understand the efficacy of this promising graft option.
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Affiliation(s)
- Remi M Ajiboye
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Mark A Eckardt
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Jason T Hamamoto
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Benjamin Plotkin
- UCLA Medical Center, Department of Orthopaedic Surgery, Santa Monica, CA
| | - Michael D Daubs
- University of Nevada School of Medicine, Department of Orthopaedic Surgery, Las Vegas, NV
| | - Jeffrey C Wang
- Keck Medicine of USC, Department of Orthopaedic Surgery, Los Angeles, CA
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Chung HJ, Hur JW, Ryu KS, Kim JS, Seong JH. Surgical Outcomes of Anterior Cervical Fusion Using Deminaralized Bone Matrix as Stand-Alone Graft Material: Single Arm, Pilot Study. KOREAN JOURNAL OF SPINE 2016; 13:114-119. [PMID: 27799989 PMCID: PMC5086461 DOI: 10.14245/kjs.2016.13.3.114] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/24/2016] [Accepted: 08/29/2016] [Indexed: 12/18/2022]
Abstract
Objective To investigate the safety and efficacy of demineralized bone matrix (DBM) as a bone graft substitute for anterior cervical discectomy and fusion (ACDF) surgery. Methods Twenty consecutive patients treated with ACDF using stand-alone polyestheretherketone (PEEK) cages (Zero-P) with DBM(CGDBM100) were prospectively evaluated with a minimum of 6 months of follow-up. Radiologic efficacy was evaluated with a 6-point scoring method for osseous fusion using plain radiograph and computed tomogrpahy scans. Clinical efficacy was evaluated using the visual analogue scale (VAS), Owestry disability index (ODI), and short-form health questionnaire-36. The safety of the bone graft substitute was assessed with vital sign monitoring and a survey measuring complications at each follow-up visit. Results There were significant improvements in VAS and ODI scores at a mean 6-month follow-up. Six months after surgery, solid fusion was achieved in all patients. Mean score on the 6-point scoring system was 5.1, and bony formation was found to score at least 4 points in all patients. There was no case with implant-related complications such as cage failure or migration, and no complications associated with the use of CGDBM100. Conclusion ACDF using CGDBM100 demonstrated good clinical and radiologic outcomes. The fusion rate was comparable with the published results of traditional ACDF. Therefore, the results of this study suggest that the use of a PEEK cage packed with DBM for ACDF is a safe and effective alternative to the gold standard of autologous iliac bone graft.
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Affiliation(s)
- Ho-Jung Chung
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jung-Woo Hur
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kyeong-Sik Ryu
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin-Sung Kim
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ji-Hoon Seong
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Ishida W, Elder BD, Holmes C, Lo SFL, Witham TF. Variables Affecting Fusion Rates in the Rat Posterolateral Spinal Fusion Model with Autogenic/Allogenic Bone Grafts: A Meta-analysis. Ann Biomed Eng 2016; 44:3186-3201. [PMID: 27473706 DOI: 10.1007/s10439-016-1701-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 07/21/2016] [Indexed: 01/14/2023]
Abstract
The rat posterolateral spinal fusion model with autogenic/allogenic bone graft (rat PFABG) has been increasingly utilized as an experimental model to assess the efficacy of novel fusion treatments. The objective of this study was to investigate the reliability of the rat PFABG model and examine the effects of different variables on spinal fusion. A web-based literature search from January, 1970 to September, 2015, yielded 26 studies, which included 40 rat PFABG control groups and 449 rats. Data regarding age, weight, sex, and strain of rats, graft volume, graft type, decorticated levels, surgical approach, institution, the number of control rats, fusion rate, methods of fusion assessment, and timing of fusion assessment were collected and analyzed. The primary outcome variable of interest was fusion rate, as evaluated by manual palpation. Fusion rates varied widely, from 0 to 96%. The calculated overall fusion rate was 46.1% with an I 2 value of 62.4, which indicated moderate heterogeneity. Weight >300 g, age >14 weeks, male rat, Sprague-Dawley strain, and autogenic coccyx grafts increased fusion rates with statistical significance. Additionally, an assessment time-point ≥8 weeks had a trend towards statistical significance (p = 0.070). Multi-regression analysis demonstrated that timing of assessment and age as continuous variables, as well as sex as a categorical variable, can predict the fusion rate with R 2 = 0.82. In an inter-institution reliability analysis, the pooled overall fusion rate was 50.0% [44.8, 55.3%], with statistically significant differences among fusion outcomes at different institutions (p < 0.001 and I 2 of 72.2). Due to the heterogeneity of fusion outcomes, the reliability of the rat PFABG model was relatively limited. However, selection of adequate variables can optimize its use as a control group in studies evaluating the efficacy of novel fusion therapies.
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Affiliation(s)
- Wataru Ishida
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Benjamin D Elder
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA.
| | - Christina Holmes
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Sheng-Fu L Lo
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
| | - Timothy F Witham
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1800 Orleans St., Room 6007, Baltimore, MD, 21287, USA
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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; 41:1075-1083. [PMID: 26825787 DOI: 10.1097/brs.0000000000001466] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN A prospective, randomized, controlled, parallel, single-blinded noninferiority multicenter pivotal FDA IDE trial. OBJECTIVE The objective of this study was to investigate efficacy and safety of i-Factor Bone Graft (i-Factor) compared with local autograft in single-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. SUMMARY OF BACKGROUND DATA i-Factor is a composite bone substitute material consisting of the P-15 synthetic collagen fragment adsorbed onto anorganic bone mineral and suspended in an inert biocompatible hydrogel carrier. P-15 has demonstrated bone healing efficacy in dental, orthopedic, and nonhuman applications. METHODS Patients randomly received either autograft (N = 154) or i-Factor (N = 165) in a cortical ring allograft. Study success was defined as noninferiority in fusion, Neck Disability Index (NDI), and Neurological Success endpoints, and similar adverse events profile at 12 months. RESULTS At 12 months (follow-up rate 87%), both i-Factor and autograft subjects demonstrated a high fusion rate (88.97% and 85.82%, respectively, noninferiority P = 0.0004), significant improvements in NDI (28.75 and 27.40, respectively, noninferiority P < 0.0001), and high Neurological Success rate (93.71% and 93.01%, respectively, noninferiority P < 0.0001). There was no difference in the rate of adverse events (83.64% and 82.47% in the i-Factor and autograft groups, respectively, P = 0.8814). Overall success rate consisting of fusion, NDI, Neurological Success and Safety Success was higher in i-Factor subjects than in autograft subjects (68.75% and 56.94%, respectively, P = 0.0382). Improvements in VAS pain and SF-36v2 scores were clinically relevant and similar between the groups. A high proportion of patients reported good or excellent Odom outcomes (81.4% in both groups). CONCLUSION i-Factor has met all four FDA mandated noninferiority success criteria and has demonstrated safety and efficacy in single-level ACDF for cervical radiculopathy. i-Factor and autograft groups demonstrated significant postsurgical improvement and high fusion rates. LEVEL OF EVIDENCE 1.
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Parmaksiz M, Dogan A, Odabas S, Elçin AE, Elçin YM. Clinical applications of decellularized extracellular matrices for tissue engineering and regenerative medicine. Biomed Mater 2016; 11:022003. [DOI: 10.1088/1748-6041/11/2/022003] [Citation(s) in RCA: 149] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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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; 25:133-7. [PMID: 26967986 DOI: 10.3171/2015.12.spine15737] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The efficacy of some demineralized bone matrix (DBM) substances has been demonstrated in the spinal fusion of rats; however, no previous comparative study has reported the efficacy of DBM with human mesenchymal stem cells (hMSCs). There is an added cost to the products with stem cells, which should be justified by improved osteogenic potential. The purpose of this study is to prospectively compare the fusion rates of 3 different commercially available DBM substances, both with and without hMSCs. METHODS Posterolateral fusion was performed in 32 mature athymic nude rats. Three groups of 8 rats were implanted with 1 of 3 DBMs: Trinity Evolution (DBM with stem cells), Grafton (DBM without stem cells), or DBX (DBM without stem cells). A fourth group with no implanted material was used as a control group. Radiographs were obtained at 2, 4, and 8 weeks. The rats were euthanized at 8 weeks. Overall fusion was determined by manual palpation and micro-CT. RESULTS The fusion rates at 8 weeks on the radiographs for Trinity Evolution, Grafton, and DBX were 8 of 8 rats, 3 of 8 rats, and 5 of 8 rats, respectively. A significant difference was found between Trinity Evolution and Grafton (p = 0.01). The overall fusion rates as determined by micro-CT and manual palpation for Trinity Evolution, Grafton, and DBX were 4 of 8 rats, 3 of 8 rats, and 3 of 8 rats, respectively. The Trinity Evolution substance had the highest overall fusion rate, however no significant difference was found between groups. CONCLUSIONS The efficacies of these DBM substances are demonstrated; however, the advantage of DBM with hMSCs could not be found in terms of posterolateral fusion. When evaluating spinal fusion using DBM substances, CT analysis is necessary in order to not overestimate fusion.
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Affiliation(s)
- Tetsuo Hayashi
- Department of Orthopaedic Surgery, University of California, Los Angeles, California;,Department of Orthopaedic Surgery, Japan Labour Health and Welfare Organization, Spinal Injuries Center, Fukuoka, Japan
| | - Elizabeth L Lord
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Akinobu Suzuki
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Shinji Takahashi
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Trevor P Scott
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Kevin Phan
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Haijun Tian
- Department of Orthopaedic Surgery, University of California, Los Angeles, California
| | - Michael D Daubs
- Department of Orthopaedic Surgery, University of Nevada, Las Vegas, Nevada; and
| | - Keiichiro Shiba
- Department of Orthopaedic Surgery, Japan Labour Health and Welfare Organization, Spinal Injuries Center, Fukuoka, Japan
| | - Jeffrey C Wang
- Department of Orthopaedic Surgery, University of Southern California, Los Angeles, California
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Makhni MC, Caldwell JME, Saifi C, Fischer CR, Lehman RA, Lenke LG, Lee FY. Tissue engineering advances in spine surgery. Regen Med 2016; 11:211-22. [DOI: 10.2217/rme.16.3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Autograft, while currently the gold standard for bone grafting, has several significant disadvantages including limited supply, donor site pain, hematoma formation, nerve and vascular injury, and fracture. Bone allografts have their own disadvantages including reduced osteoinductive capability, lack of osteoprogenitor cells, immunogenicity and risk of disease transmission. Thus demand exists for tissue-engineered constructs that can produce viable bone while avoiding the complications associated with human tissue grafts. This review will focus on recent advancements in tissue-engineered bone graft substitutes utilizing nanoscale technology in spine surgery applications. An evaluation will be performed of bone graft substitutes, biomimetic 3D scaffolds, bone morphogenetic protein, mesenchymal stem cells and intervertebral disc regeneration strategies.
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Affiliation(s)
- Melvin C Makhni
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Jon-Michael E Caldwell
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Comron Saifi
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Charla R Fischer
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Ronald A Lehman
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Lawrence G Lenke
- The Spine Hospital, Department of Orthopedic Surgery, New York-Presbyterian Healthcare System, Columbia University Medical Center, 5141 Broadway, New York, NY 10034, USA
| | - Francis Y Lee
- Department of Orthopedic Surgery, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
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Ghodasra JH, Nickoli MS, Hashmi SZ, Nelson JT, Mendoza M, Nicolas JD, Bellary SS, Sonn K, Ashtekar A, Park CJ, Babu J, Yun C, Ghosh A, Kannan A, Stock SR, Hsu WK, Hsu EL. Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model. Global Spine J 2016; 6:60-8. [PMID: 26835203 PMCID: PMC4733376 DOI: 10.1055/s-0035-1556582] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 04/24/2015] [Indexed: 11/16/2022] Open
Abstract
Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 μg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.
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Affiliation(s)
- Jason H. Ghodasra
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Michael S. Nickoli
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Sohaib Z. Hashmi
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - John T. Nelson
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Marco Mendoza
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Joseph D. Nicolas
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Sharath S. Bellary
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Kevin Sonn
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Amruta Ashtekar
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Christian J. Park
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Jacob Babu
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Chawon Yun
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Anjan Ghosh
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Abhishek Kannan
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Stuart R. Stock
- Department of Materials Science and Engineering, Northwestern University Feinberg School of Medicine, Evanston, Illinois, United States
| | - Wellington K. Hsu
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States,Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
| | - Erin L. Hsu
- Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States,Address for correspondence Erin L. Hsu, PhD Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine676 N. St. Clair Street, Suite 1350, Chicago, IL 60611United States
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La WG, Jang J, Kim BS, Lee MS, Cho DW, Yang HS. Systemically replicated organic and inorganic bony microenvironment for new bone formation generated by a 3D printing technology. RSC Adv 2016. [DOI: 10.1039/c5ra20218c] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
3D-printed bioimplants for enhanced bone defect healing using decellularized and demineralized ECM coating.
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Affiliation(s)
- Wan-Gun La
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine
- Dankook University
- Cheonan 330-714
- Republic of Korea
| | - Jinah Jang
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Korea
| | - Byoung Soo Kim
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Korea
| | - Min Suk Lee
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine
- Dankook University
- Cheonan 330-714
- Republic of Korea
| | - Dong-Woo Cho
- Department of Mechanical Engineering
- Pohang University of Science and Technology (POSTECH)
- Pohang
- Korea
| | - Hee Seok Yang
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine
- Dankook University
- Cheonan 330-714
- Republic of Korea
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Gothard D, Smith EL, Kanczler JM, Black CR, Wells JA, Roberts CA, White LJ, Qutachi O, Peto H, Rashidi H, Rojo L, Stevens MM, El Haj AJ, Rose FRAJ, Shakesheff KM, Oreffo ROC. In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors. PLoS One 2015; 10:e0145080. [PMID: 26675008 PMCID: PMC4684226 DOI: 10.1371/journal.pone.0145080] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 11/27/2015] [Indexed: 12/21/2022] Open
Abstract
The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.
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Affiliation(s)
- David Gothard
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
- * E-mail: (DG); (ROCO)
| | - Emma L. Smith
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
| | - Janos M. Kanczler
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
| | - Cameron R. Black
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
| | - Julia A. Wells
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
| | - Carol A. Roberts
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
| | - Lisa J. White
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
| | - Omar Qutachi
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
| | - Heather Peto
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
| | - Hassan Rashidi
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
| | - Luis Rojo
- Department of Materials, Imperial College London, Royal School of Mines, London, SW7 2AZ, United Kingdom
- Department of Bioengineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom
- Institute for Biomedical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom
- Biomaterials, Biomimetics, Biophotonics Research Division, King's College London, Dental Institute, Guy's Hospital, Tower Wing, London Bridge, London SE1 9RT, United Kingdom
| | - Molly M. Stevens
- Department of Materials, Imperial College London, Royal School of Mines, London, SW7 2AZ, United Kingdom
- Department of Bioengineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom
- Institute for Biomedical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom
| | - Alicia J. El Haj
- Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Stoke-on-Trent, ST4 7BQ, United Kingdom
| | - Felicity R. A. J. Rose
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
| | - Kevin M. Shakesheff
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling, School of Pharmacy, University of Nottingham, Centre for Biomolecular Sciences, University Park, Nottingham, NG7 2RD, United Kingdom
- Locate Therapeutics Limited, MediCity, Nottingham, NG90 6BH, United Kingdom
| | - Richard O. C. Oreffo
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, United Kingdom
- * E-mail: (DG); (ROCO)
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Pensak M, Hong SH, Dukas A, Bayron J, Tinsley B, Jain A, Tang A, Rowe D, Lieberman JR. Combination therapy with PTH and DBM cannot heal a critical sized murine femoral defect. J Orthop Res 2015; 33:1242-9. [PMID: 25877402 DOI: 10.1002/jor.22896] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 03/10/2015] [Indexed: 02/04/2023]
Abstract
Orthopaedic surgeons continue to search for cost-effective bone graft substitutes to enhance bone repair. Teriparatide (PTH 1-34) and demineralized bone matrix (DBM) have been used in patients to promote bone healing. We evaluated the efficacy of PTH and DBM in healing a critical sized femoral defect in three lineage-specific transgenic mice expressing Col3.6GFPtopaz (pre-osteoblastic marker), Col2.3GFPemerald (osteoblastic marker) and α-SMA-Cherry (pericyte/myofibroblast marker). Mid-diaphyseal defects measuring 2 mm in length were created in the central 1/3 of mice femora using a circular saw and stabilized with an alveolar distractor device and cerclage wires. Three groups were evaluated: Group I, PTH 30 μg/kg injection daily, Group II, PTH 30 μg/kg injection daily + DBM, and Group III, DBM + 30μL saline injection. PTH was given for 28 days or until the time of sacrifice. Animals were sacrificed at 7, 14, 28, and 56 days. Radiographs at the time of sacrifice were evaluated using a 5-point scaled scoring system. Radiographs showed a lack of healing across all treatment groups at all time points: Group I, 1.57 +/- 0.68; Group II, 3.00 +/- 1.29; and Group III, 2.90 +/- 1.03. Bone formation in the defect as measured by radiographic healing score was significantly better at 56 days in Groups II (p = 0.01) and III (p < 0.01) compared to Group I. Across all treatment groups and time points the defects were largely absent of osteoprogenitor cells based on gross observation of frozen histology and quantitation of cellular based histomorphometric parameters. Quantitation of frozen histologic slides showed a limited osteoprogenitor response to PTH and DBM. Our results suggest that the anabolic agent teriparatide is unable to induce healing in a critical sized mouse femoral defect when given alone or in combination with the DBM preparation we used as a local bone graft substitute.
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Affiliation(s)
- Michael Pensak
- University of Connecticut Health Center, Farmington, Connecticut
| | | | - Alex Dukas
- University of Connecticut Health Center, Farmington, Connecticut
| | - Jennifer Bayron
- University of Connecticut Health Center, Farmington, Connecticut
| | - Brian Tinsley
- University of Connecticut Health Center, Farmington, Connecticut
| | | | - Amy Tang
- Keck School of Medicine, University of Southern California, Los Angeles, California
| | - David Rowe
- University of Connecticut Health Center, Farmington, Connecticut
| | - Jay R Lieberman
- Keck School of Medicine, University of Southern California, Los Angeles, California
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Gupta A, Kukkar N, Sharif K, Main BJ, Albers CE, III SFEA. Bone graft substitutes for spine fusion: A brief review. World J Orthop 2015; 6:449-456. [PMID: 26191491 PMCID: PMC4501930 DOI: 10.5312/wjo.v6.i6.449] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 04/17/2015] [Accepted: 05/16/2015] [Indexed: 02/06/2023] Open
Abstract
Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins (recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice.
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Bigham-Sadegh A, Karimi I, Oryan A, Mahmoudi E, Shafiei-Sarvestani Z. Spinal fusion with demineralized calf fetal growth plate as novel biomaterial in rat model: a preliminary study. Int J Spine Surg 2015; 8:14444-1005. [PMID: 25694913 PMCID: PMC4325481 DOI: 10.14444/1005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background Spinal fusions are being performed for various pathologies of the spine such as degenerative diseases, deformities, tumors and fractures. Recently, other bone substitutes such as demineralized bone matrix (DBM) have been developed for spinal fusion. Therefore, this study was conducted to evaluate the intertransverse posterolateral fusion with the Bovine fetal growth plate (DCFGP) and compare it with commercial DBM in rat model. Methods A total of 16 mature male rats (aged 4 months and weighing 200-300 g) were randomly divided in two groups. After a skin incision on posterolateral site, two separate fascial incisions were made 3 mm from the midline. A muscle-splitting approach was used to expose the transverse processes of L4 and L5. Group I (n = 8) underwent with implanted Bovine fetal growth plate among decorticated transverse processes. In group II (n = 8) commercial DBM was placed in the same manner. Fusion was evaluated by manual palpation, radiographical, gross and histopathological analysis. Results The manual palpation, radiological, gross and histopathological findings indicate high potential of the DCFGP in spinal fusion. At the 42nd postoperative day, new bone formation as evidenced by a bridge between L4 and L5 was visualized in all rats implanted with DCFGP and commercial DBM. The newly formed bone tissue was observed in all implanted areas on the 42nd day after operation in the two groups. Conclusions The spinal fusion of the animals of both groups demonstrated more advanced osteogenic potential and resulted in proper fusion of the transverse process of lumbar vertebra.
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Affiliation(s)
- Amin Bigham-Sadegh
- Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
| | - Iraj Karimi
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
| | - Ahmad Oryan
- Department of Veterinary Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Elena Mahmoudi
- Department of Veterinary Surgery, School of Veterinary Medicine, Tehran University, Tehran, Iran
| | - Zahra Shafiei-Sarvestani
- Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
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Sekar S, Mandal A, Manikandan R, Sankar S, Sastry TP. Synthesis and Characterization of Synthetic and Natural Nano Hydroxyapatite Composites Containing Poloxamer Coated Demineralized Bone Matrix as Bone Graft Material: A Comparative Study. INT J POLYM MATER PO 2015. [DOI: 10.1080/00914037.2014.977901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Dentin Matrix Proteins in Bone Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2015; 881:129-42. [PMID: 26545748 DOI: 10.1007/978-3-319-22345-2_8] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Dentin and bone are mineralized tissue matrices comprised of collagen fibrils and reinforced with oriented crystalline hydroxyapatite. Although both tissues perform different functionalities, they are assembled and orchestrated by mesenchymal cells that synthesize both collagenous and noncollagenous proteins albeit in different proportions. The dentin matrix proteins (DMPs) have been studied in great detail in recent years due to its inherent calcium binding properties in the extracellular matrix resulting in tissue calcification. Recent studies have shown that these proteins can serve both as intracellular signaling proteins leading to induction of stem cell differentiation and also function as nucleating proteins in the extracellular matrix. These properties make the DMPs attractive candidates for bone and dentin tissue regeneration. This chapter will provide an overview of the DMPs, their functionality and their proven and possible applications with respect to bone tissue engineering.
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Xie Y, Li H, Yuan J, Fu L, Yang J, Zhang P. A prospective randomized comparison of PEEK cage containing calcium sulphate or demineralized bone matrix with autograft in anterior cervical interbody fusion. INTERNATIONAL ORTHOPAEDICS 2014; 39:1129-36. [PMID: 25432324 DOI: 10.1007/s00264-014-2610-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 11/14/2014] [Indexed: 11/25/2022]
Abstract
PURPOSE A variety of bone substitutes have been successfully used to fill PEEK cages in cervical interbody fusion in order to avoid the complications related to bone harvesting from the donor site. However, no controlled study has previously been conducted to compare the effectiveness of PEEK interbody cages containing calcium sulphate/ demineralized bone matrix (CS/DBM) with autogenous cancellous bone for the treatment of cervical spondylosis. The objective of this prospective, randomized clinical study was to evaluate the effectiveness of implanting PEEK cages containing CS/DBM for the treatment of cervical radiculopathy and/or myelopathy. METHODS Sixty-eight patients with cervical radiculopathy and/or myelopathy were randomly assigned to receive one- or two-level discectomy and fusion with PEEK interbody cages containing CS/DBM or autogenous iliac cancellous bone (AIB). The patients were followed up for two years postoperatively. The radiological and clinical outcomes were assessed during a two-year follow-up. RESULTS The mean blood loss was 75 ± 18.5 ml in the CS/DBM group and 100 ± 19.6 ml (P < 0.01) in the AIB group. The fusion rate was 94.3 % in the CS/DBM group and 100 % in the AIB group at 12-month follow-up. The fusion rate was 100 % at final follow-up in both groups. No significant difference (P > 0.05) was found regarding improvement of JOA score and segmental lordosis as well as neck and arm pain at all time intervals between the two groups. The total complication rate was significantly higher (P < 0.05) in the AIB group than in the CS/DBM group, but there was no significant difference between the two groups (P > 0.05) when comparing the complications in the neck. CONCLUSIONS In conclusion, the PEEK interbody fusion cage containing CS/DBM or AIB following one- or two-level discectomy had a similar outcome for cervical spondylotic radiculopathy and/or myelopathy. The rate of fusion and the recovery rate of JOA score between the two groups were the same. The filling of CS/DBM in the PEEK cage instead of AIB has the advantage of less operative blood loss and fewer complications at the donor site.
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Affiliation(s)
- Youzhuan Xie
- Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People's Republic of China
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Hinsenkamp M, Collard JF. Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins. INTERNATIONAL ORTHOPAEDICS 2014; 39:137-47. [PMID: 25338109 DOI: 10.1007/s00264-014-2562-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 09/30/2014] [Indexed: 12/22/2022]
Abstract
During recent decades the utilisation of growth factors, especially BMPs, has received an increasing interest in orthopaedic surgery. For clinical implantation the two main options are demineralised bone matrix (DBM) and recombinant bone morphogenetic proteins (rhBMP). Many clinical studies agree on an equivalent osteoinductive effect between DBM, BMPs and autologous bone graft; however, the different origins and processing of DBM and rhBMP may introduce some fluctuations. Their respective characteristics are reviewed and possible interactions with their effectiveness are analysed. The main difference concerns the concentration of BMPs, which varies to an order of magnitude of 10(6) between DBM and rhBMPs. This may explain the variability in efficiency of some products and the adverse effects. Currently, considering osteoinductive properties, safety and availability, the DBM seems to offer several advantages. However, if DBM and rhBMPs are useful in some indications, their effectiveness and safety can be improved and more evidence-based studies are needed to better define the indications.
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Affiliation(s)
- Maurice Hinsenkamp
- Orthopaedic Research Laboratory (LROT) and Musculoskeletal Tissue Bank (BTE), Department of Orthopaedic Surgery, Hôpital Erasme, Université Libre de Bruxelles (ULB), 808, route de Lennik, Brussels, B-1070, Belgium,
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