How to Manage Bone Marrow Aspirate Concentrate to Treat Musculoskeletal Disorders: A Systematic Review

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1 How to Manage Bone Marrow Aspirate Concentrate to Treat Musculoskeletal Disorders: A Systematic Review Diego Costa Astur, Elton Luiz B. Cavalcante, Adilson Góes R. Júnior, Pedro Debieux, João Victor Novaretti, Camila Cohen Kaleka, Moises Cohen

2 CONFLICT OF INTEREST Diego Costa Astur, Elton Luiz B. Cavalcante, Adilson Góes R. Júnior, Pedro Debieux, João Victor Novaretti, Camila Cohen Kaleka, Moises Cohen The authors declare no financial conflicts to diclosure

3 INTRODUCTION Bone Marrow Aspirate Concentrate - BMAC: Bone marrow components derived from distinct cellular origins; Concentrated through centrifugation (minimal separation); Potential advantages: Self-renewal; Differentiation to numerous tissues; Cell migration to injured tissue; Modulation of inflammatory process.

4 PURPOSE To help establish the optimal collection and processing method, as well as explore the efficacy of BMAC to treat musculoskeletal disorders in humans.

5 METHODS A search was carried out in 2018 by two independent reviewers: PubMed, Lilacs and Cochrane. The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) checklist was used; Levels of evidence classification: Grading System of Recommendations Assessment, Development and Evaluation (GRADE) and Oxford Center for Evidence-Based Medicine.

6 METHODS Inclusion criteria: o Last 5 years; o Full text; o English written; o Humans Non Inclusion criteria o Evidence Level IV; o In vitro studies; o Revision articles. Extracted data included: production process, the site of acquisition, pathologies eligible for treatment, as well as the outcomes and effectiveness of the treatment.

7 Selected Articles: 333 Bone Marrow Aspirate Concentrate Excluded Articles: Did not use human subjects; - Did not mention musculoskeletal disorders; - Without mention of orthopedic use; - More than 5 years since publication; - Used animal subjects. Included Articles: 69 Selected Articles: 16 Duplicate Articles: 3 Excluded Articles: 51-19: low levels of evidence; - 25: mentioned, but without orthopedic use; - 4: full article not available; - 4: mentioned, but whitout; use in humans; - 1: review in progress. Reviewed Articles: 13

8 RESULTS 13 reviewed articles 10 from the last 2 years; 354 patients; Age: years; 5 studies were classified as level of evidence I (Oxford); Major pathologies: Osteochondral lesions; Femoral head osteonecrosis.

9 RESULTS Site and Quantity of Bone Marrow Aspirate: Anterior region of the iliac crest and 50 to 400 ml. Aspiration Technique: access incisions ranged from 3 to 10 cm, under either anesthesia; 3 to 10 aspirations (2 mm between punctures sites); 5 ml per aspiration; Syringes of 60 ml with anticoagulant and 11 mm needles.

10 RESULTS Processing Methodology: Centrifuge: Arteriocyte Magellan e Harvest SmartPreP 2 ; Speed: rpm; Time: 15 min; Final volume of processed: 12 to 50 ml; Applied volume: 5 50 ml; Application: immediately following processing.

11 RESULTS Review findings: Osteochondral lesions on the Knee: The articular cartilage resembled native conformation; Clinical and functional scores improvement; Lower risk of graft failure; Durable chondral repair when compared to microfractures. Femoral head osteonecrosis and Spinal arthrodesis: Without differences. Tibial pseudoarthrosis: Greater potential for consolidation; In infected pseudoarthrosis, the infectiot was treated without antibiotics. Partial rotator cuff tears: Increased proliferation ans cell migration to the injury

12 CONCLUSION Iliac Crest main place of aspiration; 60 ml syringe containing anticoagulant and 11 mm needle; Total volume aspirated between 50 and 60 ml; Centrifugation for 15 min (3200 rpm); Final volume applied from 5 to 6 ml.

13 REFERENCES Fortier LA, Potter HG, Rickey EJ, Schnabel LV, Foo LF, Chong LR, et al. Concentrated bone marrow aspirate improves full-tickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am. 2010; 92 (10): Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-induced autologous chondrocyte implatation versus sultipotent stem cells for the treatment of large patellofemoral chondral lesions: a nonrandomized prospective trial. Cartilage.2015; 6 (2): Kim JD, Lee GW, Jung GH, Kim CK, Kim T, Park JH, et al. Clinical outcome of autologous bone marrow aspirates concentrate (BMAC) injection on degenerative arthritis of the knee. Eur J Orthop Surg Traumatol. 2014; 24 (8): Moatshe G, Morris ER, Cinque ME, Pascual-Garrido C, Chahla J, Engebretsen L, et al. Biological treatment of the knee with platelet-rich plasma or boné marrow aspirate concentrates. Acta Orthop. 2017; 88 (6): Oliver KS, Bayes M, Crane D, Pathikonda C. Clinical outcome of bone marrow concentrate in knee osteoarthritis, Journal of Prolotherapy. 2015; 7 (2): Enea D, Cecconi S, Calcagno S, Busilacchi S, Manzotti S, Gigante A. One-step cartilage repair in the knee: collagen-covered microfracture and autologous bone marrow concentrate. A pilot study. Knee. 2015; 22 (1): Gobbi A, Whyte JP. One-stage cartilage repair using a hyaluronic acid-based scaffold with activated bone marrow-derived mesenchymal stem cells compared with microfracture: five-year follow-up. Am J Sports Med. 2016; 44. (11): Krych AJ, Nawabi DH, Farshad-Amacker NA, Jones KJ, Maak TG, Potter HG, et al. Bone marrow concentrate improves early cartilage phase maturation of a scaffold plug in the knee: a comparative magnetic resonance imaging analysis to platelet-rich plasma and control. Am J Sports Med. 2016; 44 (1): Dijkers M. Introducing GRADE: a systematic approach to rating evidence in systematic reviews and to guideline development. Adv Res Imp Edu. 2013; 1(5): 1-9. Burns PB, Rohrich RJ, Chung KC. The Levels of Evidence and their role in Evidence-Based Medicine. Plast Reconstr Surg. 2011; 128(1): Gobbi A, Scotti C, Karnatzikos G, Mudhigere A, Castro M, Peretti GM. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of fullthickness chondral defects of the knee in patients older than 45 years. Knee Surg Sports Traumatol Arthrosc. 2016; 25 (8): Kraeutler MJ, Chahla J, LaPrade RF, Pascual-Garrido C. Biologic options for articular cartilage wear (platelet-rich plasma, stem cells, bone marrow aspirate concentrate). Clin Sports Med. 2017; 36 (3): Oladeji LO, Stannard JP, Cook CR, Kfuri M, Crist BD, Smith MJ, et al. Effects of autogenous bone marrow aspirate concentrate on radiographic integration of femoral condylar osteochondral allografts. Am J Sports Med. 2017; 45 (12): Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O Connor MI. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med. 2017; 45 (1): Hernigou P, Trousselier M, Roubineau F, Bouthors C, Chevallier N, Rouard H, et al. Local transplantation of bone marrow concentrate granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect. Int Orthop. 2016; 40 (11): Hyer CF, Berlet GC, Bussewitz BW, Hankins T, Ziegler HL, Philbin TM. Quantitative assessment of the yield of osteoblastic connective tissue progenitors in bone marrow aspirate from the iliac crest, tibia, and calcaneus. J Bone Joint Surg Am. 2013; 95 (14): Marx RE, Tursun R. A qualitative and quantitative analysis of autologous human multipotent adult stem cells derived from three anatomic areas by marrow aspiration: tibia, anterior ilium, and posterior ilium. Int J Oral Maxillofac Implants. 2013; 28 (5): e Pierini L, Di Bella C, Dozza B, Frisoni T, Martella E, Bellotti C. The posterior iliac crest outperforms the anterior iliac crest when obtaining mesenchymal stem cells from bone marrow. 2013; 95 (12): Lee DH, Ryu KJ, Kim JW, Kang KC, Choi YR. Bone marrow aspirate concentrate and platelet-rich plasma enhanced bone healing in distraction osteogenesis of the tibia. Clin Orthop Relat Res. 2014; 472 (12):

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