{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:26:41Z","timestamp":1788848801327,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Local antibiotic delivery has gained a central role as an adjunct to radical debridement in chronic osteomyelitis, allowing high antimicrobial concentrations at the infection site while reducing systemic toxicity. This narrative review summarizes the current clinical evidence on commercially available antibiotic-loadable bone substitutes, with particular focus on calcium sulfate (CaSO4)-based systems and biphasic calcium sulfate\/hydroxyapatite (CaS\/HA) composites. Nineteen studies were included. Differences in formulation, resorption kinetics, antibiotic elution profile and osteoconductive behavior are discussed, alongside clinical outcomes including recurrence of infection, reoperation rates and complication patterns. Finally, based on the currently available evidence and expert recommendations, practical guidance is proposed to support carrier selection in different clinical scenarios (cavitary vs. corticomedullary defects; high-risk soft tissue; polymicrobial or resistant infections). Across published series, although heterogeneous, infection eradication rates are generally high when local carriers are integrated into structured surgical protocols. Calcium sulfate carriers provide rapid resorption and robust early antibiotic release but are associated with higher rates of sterile wound drainage. In contrast, CaS\/HA biocomposites demonstrate more gradual remodeling and radiographic integration, potentially improving defect consolidation and reducing wound-related morbidity, although leakage and cost considerations remain relevant.<\/jats:p>","DOI":"10.3390\/bioengineering13040436","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:41:18Z","timestamp":1775648478000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Local Antibiotic-Loadable Carriers for the Treatment of Chronic Osteomyelitis: A Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-8547","authenticated-orcid":false,"given":"Andrea","family":"Sambri","sequence":"first","affiliation":[{"name":"Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bruschi","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7984-7614","authenticated-orcid":false,"given":"Cristina","family":"Scollo","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-9870","authenticated-orcid":false,"given":"Massimiliano","family":"De Paolis","sequence":"additional","affiliation":[{"name":"Orthopedic and Traumatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","first-page":"195","article-title":"Chronic osteomyelitis: Results obtained by an integrated team approach to management","volume":"69","author":"Salvana","year":"2005","journal-title":"Conn. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1302\/2058-5241.1.000017","article-title":"Chronic osteomyelitis: What the surgeon needs to know","volume":"1","author":"Panteli","year":"2016","journal-title":"EFORT Open Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.surge.2015.12.005","article-title":"The management of osteomyelitis in the adult","volume":"14","author":"Maffulli","year":"2016","journal-title":"Surgeon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(04)16727-5","article-title":"Osteomyelitis","volume":"364","author":"Lew","year":"2004","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/01.blo.0000087320.60612.86","article-title":"A dedicated team approach enhances outcomes of osteomyelitis treatment","volume":"414","author":"Ziran","year":"2003","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sambri, A., Fiore, M., Tedeschi, S., and De Paolis, M. (2022). The Need for Multidisciplinarity in Modern Medicine: An Insight into Orthopaedic Infections. Microorganisms, 10.","DOI":"10.3390\/microorganisms10040756"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1302\/0301-620X.81B6.0811046","article-title":"A comparison of short- and long-term intravenous antibiotic therapy in the postoperative management of adult osteomyelitis","volume":"81","author":"Swiontkowski","year":"1999","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1302\/0301-620X.75B3.8496203","article-title":"Two-stage management of chronic osteomyelitis of the long bones. The Belfast technique","volume":"75","author":"McNally","year":"1993","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0002-9610(03)00292-7","article-title":"Surgical management of chronic osteomyelitis","volume":"188","author":"Parsons","year":"2004","journal-title":"Am. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1055\/s-0039-1687920","article-title":"Management of Post-Traumatic Osteomyelitis in the Lower Limb: Current State of the Art","volume":"52","author":"Chan","year":"2019","journal-title":"Indian J. Plast. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1302\/0301-620X.99B11.BJJ-2016-0298.R3","article-title":"The levels of vancomycin in the blood and the wound after the local treatment of bone and soft-tissue infection with antibiotic-loaded calcium sulphate as carrier material","volume":"99","author":"Wahl","year":"2017","journal-title":"Bone Jt. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00264-007-0342-9","article-title":"Cierny-Mader Type III chronic osteomyelitis: The results of patients treated with debridement, irrigation, vancomycin beads and systemic antibiotics","volume":"32","author":"Kinik","year":"2008","journal-title":"Int. Orthop."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1302\/2058-5241.6.200136","article-title":"Management of chronic osteomyelitis of the femur and tibia: A scoping review","volume":"6","author":"Arshad","year":"2021","journal-title":"EFORT Open Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1186\/s13063-019-3832-3","article-title":"Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): A randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy","volume":"20","author":"Dudareva","year":"2019","journal-title":"Trials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.2106\/JBJS.OA.25.00157","article-title":"Local Antibiotic Delivery Systems and Their Applications in Orthopaedic Surgery","volume":"10","author":"Hoveidaei","year":"2025","journal-title":"JBJS Open Access"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2174\/1874325001509010372","article-title":"The Effectiveness of Local Antibiotics in Treating Chronic Osteomyelitis in a Cohort of 50 Patients with an Average of 4 Years Follow-Up","volume":"9","author":"Leung","year":"2015","journal-title":"Open Orthop. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"38","DOI":"10.7150\/jbji.17234","article-title":"Ceramic Biocomposites as Biodegradable Antibiotic Carriers in the Treatment of Bone Infections","volume":"2","author":"Ferguson","year":"2017","journal-title":"J. Bone Jt. Infect."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Alegrete, N., Sousa, S.R., Peleteiro, B., Monteiro, F.J., and Gutierres, M. (2023). Local Antibiotic Delivery Ceramic Bone Substitutes for the Treatment of Infected Bone Cavities and Bone Regeneration: A Systematic Review on What We Have Learned from Animal Models. Materials, 16.","DOI":"10.3390\/ma16062387"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1375266","DOI":"10.3389\/fbioe.2024.1375266","article-title":"Current application and future perspectives of antimicrobial degradable bone substitutes for chronic osteomyelitis","volume":"12","author":"Jiang","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1302\/2058-5241.6.200083","article-title":"Review of calcium-sulphate-based ceramics and synthetic bone substitutes used for antibiotic delivery in PJI and osteomyelitis treatment","volume":"6","author":"Ene","year":"2021","journal-title":"EFORT Open Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1177\/230949900201000110","article-title":"The treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant","volume":"10","author":"Gitelis","year":"2002","journal-title":"J. Orthop. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1302\/0301-620X.96B6.33014","article-title":"A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: A retrospective comparative study","volume":"96","author":"Romano","year":"2014","journal-title":"Bone Jt. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1302\/0301-620X.98B9.38057","article-title":"Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate\/hydroxyapatite biocomposite: A prospective series of 100 cases","volume":"98","author":"McNally","year":"2016","journal-title":"Bone Jt. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11751-014-0206-y","article-title":"Adjuvant treatment of chronic osteomyelitis of the tibia following exogenous trauma using OSTEOSET((R))-T: A review of 21 patients in a regional trauma centre","volume":"9","author":"Humm","year":"2014","journal-title":"Strateg. Trauma Limb Reconstr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1302\/0301-620X.96B6.32756","article-title":"The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of chronic osteomyelitis: A series of 195 cases","volume":"96","author":"Ferguson","year":"2014","journal-title":"Bone Jt. J."},{"key":"ref_26","first-page":"238","article-title":"Adult osteomyelitis: Debridement versus debridement plus Osteoset T pellets","volume":"73","author":"Chang","year":"2007","journal-title":"Acta Orthop. Belg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1097\/00005131-200210000-00002","article-title":"The use of an antibiotic-impregnated, osteoconductive, bioabsorbable bone substitute in the treatment of infected long bone defects: Early results of a prospective trial","volume":"16","author":"McKee","year":"2002","journal-title":"J. Orthop. Trauma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1302\/0301-620X.104B9.BJJ-2022-0396.R1","article-title":"Mid- to long-term results of single-stage surgery for patients with chronic osteomyelitis using a bioabsorbable gentamicin-loaded ceramic carrier","volume":"104","author":"McNally","year":"2022","journal-title":"Bone Jt. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.7150\/jbji.31592","article-title":"Radiographic and Histological Analysis of a Synthetic Bone Graft Substitute Eluting Gentamicin in the Treatment of Chronic Osteomyelitis","volume":"4","author":"Ferguson","year":"2019","journal-title":"J. Bone Jt. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jor.2019.08.017","article-title":"Augmented debridement for implant related chronic osteomyelitis with an absorbable, gentamycin loaded calcium sulfate\/hydroxyapatite biocomposite","volume":"17","author":"Drampalos","year":"2020","journal-title":"J. Orthop."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hoveidaei, A.H., Shahul, S., Esmaeili, S., Pirahesh, K., Ghaseminejad-Raeini, A., Annasamudram, A., Shrestha, R.K., and Janet, D. (2024). Conway The Efficacy of Calcium Sulfate\/Hydroxyapatite (CaS\/HA) Gentamicin in Osteomyelitis Treatment: A Case Series. Antibiotics, 13.","DOI":"10.3390\/antibiotics13111068"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Niemann, M., Graef, F., Ahmad, S.S., Braun, K.F., Stockle, U., Trampuz, A., and Meller, S. (2022). Outcome Analysis of the Use of Cerament((R)) in Patients with Chronic Osteomyelitis and Corticomedullary Defects. Diagnostics, 12.","DOI":"10.3390\/diagnostics12051207"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sambri, A., Cevolani, L., Passarino, V., Bortoli, M., Parisi, S.C., Fiore, M., Campanacci, L., Staals, E., Donati, D.M., and De Paolis, M. (2023). Mid-Term Results of Single-Stage Surgery for Patients with Chronic Osteomyelitis Using Antibiotic-Loaded Resorbable PerOssal((R)) Beads. Microorganisms, 11.","DOI":"10.3390\/microorganisms11071623"},{"key":"ref_34","first-page":"25","article-title":"Treatment of chronic osteomyelitis with antibiotic-loaded bone void filler systems: An experience with hydroxyapatites calcium-sulfate biomaterials","volume":"84","author":"Visani","year":"2018","journal-title":"Acta Orthop. Belg."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Armbruster, J., Bussmann, F., Freischmidt, H., Reiter, G., Gruetzner, P.A., and El Barbari, J.S. (2024). Treatment of High-Grade Chronic Osteomyelitis and Nonunions with PerOssal((R)): A Retrospective Analysis of Clinical Efficacy and Patient Perspectives. J. Clin. Med., 13.","DOI":"10.20944\/preprints202411.2159.v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102426","DOI":"10.1016\/j.jcot.2024.102426","article-title":"Role of STIMULAN in chronic osteomyelitis-A randomised blinded study on 95 patients comparing 3 antibiotic compositions, bead quality, forming & absorption time","volume":"52","author":"Palo","year":"2024","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00264-018-4063-z","article-title":"One-stage surgery for adult chronic osteomyelitis: Concomitant use of antibiotic-loaded calcium sulphate and bone marrow aspirate","volume":"43","author":"Badie","year":"2019","journal-title":"Int. Orthop."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"194","DOI":"10.7150\/jbji.20404","article-title":"Treatment of Cavitary Bone Defects in Chronic Osteomyelitis: Biogactive glass S53P4 vs. Calcium Sulphate Antibiotic Beads","volume":"2","author":"Ferrando","year":"2017","journal-title":"J. Bone Jt. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s13018-020-01721-7","article-title":"Single-stage treatment of chronic localized tibial osteomyelitis with local debridement and antibiotic-loaded calcium sulfate implantation: A retrospective study of 42 patients","volume":"15","author":"Zhou","year":"2020","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_40","first-page":"320","article-title":"The Use of Calcium Sulphate Beads in the Management of Osteomyelitis of Femur and Tibia: A Systematic Review","volume":"10","author":"Thahir","year":"2022","journal-title":"Arch. Bone Jt. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sambri, A., Pignatti, M., Tedeschi, S., Lozano Miralles, M.E., Giannini, C., Fiore, M., Filippini, M., Cipriani, R., Viale, P., and De Paolis, M. (2022). Combined Orthoplastic Approach in Fracture-Related Infections of the Distal Tibia. Microorganisms, 10.","DOI":"10.3390\/microorganisms10081640"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"49135","DOI":"10.1021\/acsami.4c10385","article-title":"NIR-Responsive Deployable and Self-Fitting 4D-Printed Bone Tissue Scaffold","volume":"16","author":"Choudhury","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.2106\/JBJS.19.00062","article-title":"Definition of Successful Infection Management and Guidelines for Reporting of Outcomes After Surgical Treatment of Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society (MSIS)","volume":"101","author":"Fillingham","year":"2019","journal-title":"J. Bone Jt. Surg. Am."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/4\/436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T12:08:30Z","timestamp":1775650110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/4\/436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["bioengineering13040436"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13040436","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]}}}