{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:55:15Z","timestamp":1790916915654,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMAC) have emerged as autologous orthobiologic strategies aimed at modulating inflammation and promoting tissue repair in orthopedic conditions. However, evidence from randomized controlled trials (RCTs) remains heterogeneous, and their clinical role relative to established treatments is still debated. This systematic review aimed to evaluate the efficacy, structural effects, and safety of BMA and BMAC in adults with orthopedic conditions based exclusively on RCT evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, and Web of Science were searched from December 2015 to December 2025. Eligible studies were RCTs comparing BMA or BMAC with placebo, conventional injective therapies, exercise therapy, or standard surgical procedures. Outcomes included pain, functional performance, imaging-based structural healing, treatment failure or revision, and safety. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and results were synthesized narratively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-one RCTs involving knee osteoarthritis, ACL injury or reconstruction, rotator cuff tears, focal cartilage defects, osteonecrosis, discogenic low back pain, and glenohumeral osteoarthritis were included. Across trials, BMA\/BMAC was generally associated with improvements in pain and function, although superiority over comparators was inconsistent and depended on the clinical condition and treatment strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Signals of greater benefit were observed in selected patients with early-stage knee osteoarthritis, focal cartilage pathology, nonsurgical ligament injuries, and rotator cuff disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251241519<\/jats:ext-link>\n                      , identifier CRD420251241519.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fsurg.2026.1932090","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:36:15Z","timestamp":1790915775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of bone marrow aspirate and bone marrow aspirate concentrate in orthopedic conditions: a systematic review of randomized controlled trials"],"prefix":"10.3389","volume":"13","author":[{"given":"Joelington","family":"Dias Batista","sequence":"first","affiliation":[{"name":"Orthopain Pain Institute","place":["An\u00e1polis, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludimila","family":"Dias Silva","sequence":"additional","affiliation":[{"name":"Orthopain Pain Institute","place":["An\u00e1polis, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jobson","family":"Dias Batista","sequence":"additional","affiliation":[{"name":"Orthopain Pain Institute","place":["An\u00e1polis, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielly","family":"Santos Pereira","sequence":"additional","affiliation":[{"name":"Neuropsychobiology and Motor Behavior Laboratory, Faculty of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo \u2013 USP","place":["Ribeir\u00e3o Preto, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Louren\u00e7o","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Neuromodulation and Study of Pain (LANNED), Federal University of Alfenas (UNIFAL-MG)","place":["Alfenas, MG, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e70008","DOI":"10.1002\/jcsm.70008","article-title":"Global burden of musculoskeletal disorders in adults aged 50 and over, 1990\u20132021: risk factors and sociodemographic inequalities","volume":"16","author":"Guan","year":"2025","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100661","DOI":"10.1016\/j.lana.2023.100661","article-title":"Musculoskeletal health: an ecological study assessing disease burden and research funding. Lancet regional health","volume":"29","author":"Nguyen","year":"2024","journal-title":"Americas (Engl ed)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.reth.2020.07.007","article-title":"Degenerative osteoarthritis a reversible chronic disease","volume":"15","author":"Di Nicola","year":"2020","journal-title":"Regener Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"19476035251389049","DOI":"10.1177\/19476035251389049","article-title":"Bone marrow aspirate concentrate to treat ankle osteoarthritis: a narrative review of progress and challenges","author":"Hines","year":"2025","journal-title":"Cartilage"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3390\/pharmaceutics17111457","article-title":"Modern approaches and emerging biological therapies to treat fracture nonunion","volume":"17","author":"Wier","year":"2025","journal-title":"Pharmaceutics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"788","DOI":"10.3390\/biology14070788","article-title":"Injury-driven structural and molecular modifications in nociceptors","volume":"14","author":"Garc\u00eda-Dom\u00ednguez","year":"2025","journal-title":"Biology (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"952375","DOI":"10.1155\/2013\/952375","article-title":"Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson\u2019s disease","volume":"2013","author":"More","year":"2013","journal-title":"Mediat Inflamm"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s44424-025-00005-3","article-title":"Dysregulation of extracellular matrix in diabetic complications: clinical impacts and new molecular targets","volume":"18","author":"Khan","year":"2025","journal-title":"Innov Acupunct Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"627","DOI":"10.14202\/vetworld.2018.627-635","article-title":"The crucial roles of inflammatory mediators in inflammation: a review","volume":"11","author":"Abdulkhaleq","year":"2018","journal-title":"Veterinary World"},{"key":"B10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and central sensitization in chronic and widespread pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/cimb47040247","article-title":"Orthobiologics revisited: a concise perspective on regenerative orthopedics","volume":"47","author":"Costa","year":"2025","journal-title":"Curr Issues Mol Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13620-025-00309-z","article-title":"Regenerative biologics modulating inflammation and promoting tenogenesis in equine superficial digital flexor tendonitis: from molecular pathways to clinical translation","volume":"78","author":"Najeb","year":"2025","journal-title":"Ir Vet J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.3390\/ijms21093224","article-title":"Bone marrow aspirate concentrate: its uses in osteoarthritis","volume":"21","author":"Kim","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1186\/s13287-020-02001-1","article-title":"Mesenchymal stem cells: amazing remedies for bone and cartilage defects","volume":"11","author":"Kangari","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e441","DOI":"10.1016\/j.eats.2016.10.024","article-title":"Bone marrow aspirate concentrate harvesting and processing technique","volume":"6","author":"Chahla","year":"2017","journal-title":"Arthrosc Tech"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1124\/pr.112.007393","article-title":"The pharmacology of regenerative medicine","volume":"65","author":"Christ","year":"2013","journal-title":"Pharmacol Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/medicina61050853","article-title":"Bone marrow aspirate concentrate (BMAC) for knee osteoarthritis: a narrative review of clinical efficacy and future directions","volume":"61","author":"Park","year":"2025","journal-title":"Medicina (Kaunas, Lithuania)"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.91310","article-title":"The rationale of autologously prepared bone marrow aspirate concentrate for use in regenerative medicine applications","volume-title":"Regenerative Medicine","author":"Everts","year":"2020"},{"key":"B19","doi-asserted-by":"publisher","first-page":"901317","DOI":"10.3389\/fbioe.2022.901317","article-title":"Gene therapy in orthopaedics: progress and challenges in pre-clinical development and translation","volume":"10","author":"Watson-Levings","year":"2022","journal-title":"Front Bioeng Biotechnol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1530\/EOR-2025-0069","article-title":"Evidence-based guidelines on orthobiologics","volume":"10","author":"Winkler","year":"2025","journal-title":"EFORT Open Rev"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1016\/j.arthro.2022.01.010","article-title":"Bone marrow aspirate concentrate augmentation may accelerate allograft ligamentization in anterior cruciate ligament reconstruction: a double-blinded randomized controlled trial","volume":"38","author":"Forsythe","year":"2022","journal-title":"Arthroscopy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.1007\/s00167-021-06793-4","article-title":"Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial","volume":"30","author":"Boffa","year":"2022","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"key":"B23","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1177\/0363546516662455","article-title":"A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis","volume":"45","author":"Shapiro","year":"2017","journal-title":"Am J Sports Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1177\/1947603518796142","article-title":"Quantitative T2 MRI mapping and 12-month follow-up in a randomized, blinded, placebo controlled trial of bone marrow aspiration and concentration for osteoarthritis of the knees","volume":"10","author":"Shapiro","year":"2019","journal-title":"Cartilage"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4664","DOI":"10.1016\/j.arthro.2025.05.024","article-title":"Bone marrow aspirate concentrate may decrease reoperation in osteochondral allograft transplantation: a prospective, randomized, double-blind investigation","volume":"41","author":"Yanke","year":"2025","journal-title":"Arthroscopy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13018-023-04512-y","article-title":"Effect of bone marrow aspiration concentrate and platelet-rich plasma combination in anterior cruciate ligament reconstruction: a randomized, prospective, double-blinded study","volume":"19","author":"Lin","year":"2024","journal-title":"J Orthop Surg Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5962354","DOI":"10.1155\/2020\/5962354","article-title":"A randomized controlled trial of the treatment of rotator cuff tears with bone marrow concentrate and platelet products compared to exercise therapy: a midterm analysis","volume":"2020","author":"Centeno","year":"2020","journal-title":"Stem Cells Int"},{"key":"B28","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1177\/03635465211072554","article-title":"Bone marrow aspirate concentrate is equivalent to platelet-rich plasma for the treatment of knee osteoarthritis at 2 years: a prospective randomized trial","volume":"50","author":"Anz","year":"2022","journal-title":"Am J Sports Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1177\/03635465231154601","article-title":"Prospective randomized trial of biologic augmentation with bone marrow aspirate concentrate in patients undergoing arthroscopic rotator cuff repair","volume":"51","author":"Cole","year":"2023","journal-title":"Am J Sports Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3390\/jcm8030392","article-title":"Autologous matrix-induced chondrogenesis (AMIC) and AMIC enhanced by autologous concentrated bone marrow aspirate (BMAC) allow for stable clinical and functional improvements at up to 9 years follow-up: results from a randomized controlled study","volume":"8","author":"de Girolamo","year":"2019","journal-title":"J Clin Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1186\/s12967-018-1736-8","article-title":"A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up","volume":"16","author":"Centeno","year":"2018","journal-title":"J Transl Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1431","DOI":"10.1016\/j.asmr.2021.07.005","article-title":"Injection of bone marrow aspirate for glenohumeral joint osteoarthritis: a pilot randomized control trial","volume":"3","author":"Dwyer","year":"2021","journal-title":"Arthrosc Sports Med Rehabil"},{"key":"B33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00264-020-04571-4","article-title":"Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: a prospective randomized study versus contralateral arthroplasty at a mean fifteen year follow-up","volume":"45","author":"Hernigou","year":"2021","journal-title":"Int Orthop"},{"key":"B34","doi-asserted-by":"publisher","first-page":"s00441800942","DOI":"10.1055\/s-0044-1800942","article-title":"Effects of intra-articular bone marrow aspirate infiltration in the treatment of knee osteoarthritis: a clinical study comparing BMA versus corticosteroid and genicular block","volume":"60","author":"Clazzer","year":"2025","journal-title":"Rev Bras Ortop (Sao Paulo)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1007\/s00264-017-3650-8","article-title":"Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial","volume":"42","author":"Hauzeur","year":"2018","journal-title":"Int Orthop"},{"key":"B36","doi-asserted-by":"publisher","first-page":"E65","DOI":"10.36076\/ppj.2024.27.E65","article-title":"The safety and effectiveness of orthobiologic injections for discogenic chronic low back pain: a multicenter prospective, crossover, randomized controlled trial with 12 months follow-up","volume":"27","author":"Navani","year":"2024","journal-title":"Pain Physician"},{"key":"B37","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1186\/s12891-025-09153-2","article-title":"Non-surgical treatment of anterior cruciate ligament tears with percutaneous bone marrow concentrate and platelet products versus exercise therapy: a randomized-controlled, crossover trial with 2-year follow-up","volume":"26","author":"Centeno","year":"2025","journal-title":"BMC Musculoskelet Disord"},{"key":"B38","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1186\/s12891-024-07519-6","article-title":"Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up","volume":"25","author":"Centeno","year":"2024","journal-title":"BMC Musculoskelet Disord"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2325967119S00275","DOI":"10.1177\/2325967119S00275","article-title":"Prospective randomized trial of biologic augmentation with mesenchymal stem cells in patients undergoing arthroscopic rotator cuff repair","volume":"7","author":"Cole","year":"2019","journal-title":"Orthop J Sports Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"3120","DOI":"10.1038\/s41591-023-02632-w","article-title":"Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial","volume":"29","author":"Mautner","year":"2023","journal-title":"Nat Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"23259671231210035","DOI":"10.1177\/23259671231210035","article-title":"Augmentation of ACL autograft reconstruction with an amnion collagen matrix wrap and bone marrow aspirate concentrate: a pilot randomized controlled trial with 2-year follow-up","volume":"11","author":"Anz","year":"2023","journal-title":"Orthop J Sports Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5447","DOI":"10.26355\/eurrev_202208_29413","article-title":"Injection of biologic agents for treating severe knee osteoarthritis: is there a chance for a good outcome? A systematic review of clinical evidence","volume":"26","author":"Anzillotti","year":"2022","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1177\/1947603517746722","article-title":"Can biologic augmentation improve clinical outcomes following microfracture for symptomatic cartilage defects of the knee? A systematic review","volume":"9","author":"Arshi","year":"2018","journal-title":"Cartilage"},{"key":"B44","doi-asserted-by":"publisher","first-page":"143293","DOI":"10.52965\/001c.143293","article-title":"Comparative efficacy of biologic augmentations in gluteus medius tendon repair is lacking: a systematic review","volume":"17","author":"Liu","year":"2025","journal-title":"Orthop Rev (Pavia)"},{"key":"B45","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s12178-024-09898-8","article-title":"Biologic augmentation of isolated meniscal repair","volume":"17","author":"Chen","year":"2024","journal-title":"Curr Rev Musculoskelet Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1177\/0363546505281938","article-title":"Magnetic resonance imaging of articular cartilage: trauma, degeneration, and repair","volume":"34","author":"Potter","year":"2006","journal-title":"Am J Sports Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/j.neuroimage.2012.02.015","article-title":"The continuing challenge of understanding and modeling hemodynamic variation in fMRI","volume":"62","author":"Handwerker","year":"2012","journal-title":"NeuroImage"},{"key":"B48","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.stem.2011.06.008","article-title":"The MSC: an injury drugstore","volume":"9","author":"Caplan","year":"2011","journal-title":"Cell Stem Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.biocel.2003.11.001","article-title":"Mesenchymal stem cells: clinical applications and biological characterization","volume":"36","author":"Barry","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3390\/gels11070551","article-title":"Recent evidence for orthobiologics combined with hydrogels for joint tissue regeneration: focus on osteoarthritis","volume":"11","author":"Cavallo","year":"2025","journal-title":"Gels"},{"key":"B51","doi-asserted-by":"publisher","first-page":"6959","DOI":"10.3390\/jcm14196959","article-title":"Biologic augmentation in anterior cruciate ligament reconstruction and beyond: a review of PRP and BMAC","volume":"14","author":"Pham","year":"2025","journal-title":"J Clin Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"4","DOI":"10.2106\/JBJS.20.01740","article-title":"Functional outcomes of arthroscopic acetabular labral repair with and without bone marrow aspirate concentrate","volume":"104","author":"Martin","year":"2022","journal-title":"J Bone Joint Surg Am"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1016\/j.arthro.2022.12.012","article-title":"Hip arthroscopy with bone marrow aspirate injection for patients with symptomatic labral tears and early degenerative changes shows similar improvement compared with patients undergoing hip arthroscopy with symptomatic labral tears without arthritis","volume":"39","author":"Day","year":"2023","journal-title":"Arthroscopy"},{"key":"B54","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1177\/11207000251337403","article-title":"Bone marrow aspirate concentrate adjunct for acetabular labral tear repair: a systematic review and meta-analysis","volume":"35","author":"Spicer","year":"2025","journal-title":"Hip Int"}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1932090\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:36:25Z","timestamp":1790915785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2026.1932090\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":54,"alternative-id":["10.3389\/fsurg.2026.1932090"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2026.1932090","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1932090"}}