{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:31:30Z","timestamp":1787063490183,"version":"build-2736575974"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"ALF"},{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Topical application of antibiotics in the treatment of orthopaedic implant-related infections can be achieved by using hyaluronic acid (HA)-based hydrogels as carriers. Our aim was to investigate potential toxic effects of a novel antibiotic-loaded hydrogel on osteogenic cells and its antibacterial effect against staphylococci. A covalently cross-linked hyaluronic acid (HA)-based hydrogel was loaded with increasing concentrations of cefuroxime and vancomycin and their release was examined by UV spectrometry. Primary human (HoBs), mouse (MoBs) osteoblasts, or SaoS-2 cells were either exposed to the drug-loaded hydrogel or to antibiotics alone, followed by assessment of cell metabolism and proliferation. Antibacterial effects were evaluated against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ) and\n                    <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                    (\n                    <jats:italic>S. epidermidis<\/jats:italic>\n                    ). Increasing concentrations of antibiotics did not affect cell metabolism in any osteogenic cell type, whereas cell proliferation remained unaltered in MoBs, was significantly reduced in SaoS-2, and was stimulated in HoBs. Cultures of MoBs and HoBs tolerated higher concentrations of vancomycin than SaoS-2. Antibiotic-loaded hydrogels did not exert toxic effects on HoBs. After 24\u00a0h, 16.8% of vancomycin and 70.8% of cefuroxime were released from the hydrogel. Cefuroxime-loaded hydrogels significantly inhibited growth of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    but not of\n                    <jats:italic>S. epidermidis<\/jats:italic>\n                    , while vancomycin-loaded hydrogel had scarce effects on\n                    <jats:italic>S. epidermidis<\/jats:italic>\n                    . Loading HA-based hydrogel with antibiotics does not harm osteoblasts at clinically relevant concentrations but inhibits bacterial growth. Higher loading of vancomycin may be required due to its slow release while cefuroxime is released more rapidly. A resorbable, antibiotic-loaded hydrogel may be used for implant-related infections in orthopaedics.\n                  <\/jats:p>","DOI":"10.1007\/s00441-026-04053-w","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:17:21Z","timestamp":1770794241000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of antibiotics encapsulated in hyaluronic acid hydrogels on different osteogenic cells and bacteria"],"prefix":"10.1007","volume":"403","author":[{"given":"Dimitrios","family":"Argyrakis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh N.","family":"Nawale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oommen P.","family":"Varghese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Mourkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef D.","family":"J\u00e4rhult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils P.","family":"Hailer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Schizas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"4053_CR1","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1007\/s00264-021-05056-8","volume":"45","author":"C Acosta-Olivo","year":"2021","unstructured":"Acosta-Olivo C, Vilchez-Cavazos F, Bl\u00e1zquez-Salda\u00f1a J et al (2021) Comparison of open arthrotomy versus arthroscopic surgery for the treatment of septic arthritis in adults: a systematic review and meta-analysis. International Orthopaedics (SICOT) 45:1947\u20131959. https:\/\/doi.org\/10.1007\/s00264-021-05056-8","journal-title":"International Orthopaedics (SICOT)"},{"key":"4053_CR2","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2013.0038","volume":"4","author":"M Ahearne","year":"2014","unstructured":"Ahearne M (2014) Introduction to cell\u2013hydrogel mechanosensing. Interface Focus 4:20130038. https:\/\/doi.org\/10.1098\/rsfs.2013.0038","journal-title":"Interface Focus"},{"key":"4053_CR3","doi-asserted-by":"publisher","first-page":"E52","DOI":"10.1503\/cjs.004219","volume":"63","author":"J Akindolire","year":"2020","unstructured":"Akindolire J, Morcos MW, Marsh JD et al (2020) The economic impact of periprosthetic infection in total hip arthroplasty. CJS 63:E52\u2013E56. https:\/\/doi.org\/10.1503\/cjs.004219","journal-title":"CJS"},{"key":"4053_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/jac\/48.suppl_1.5","volume":"48","author":"JM Andrews","year":"2001","unstructured":"Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 48:5\u201316. https:\/\/doi.org\/10.1093\/jac\/48.suppl_1.5","journal-title":"J Antimicrob Chemother"},{"key":"4053_CR5","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1097\/BLO.0b013e31811ff866","volume":"462","author":"V Antoci","year":"2007","unstructured":"Antoci V, Adams CS, Hickok NJ et al (2007) Antibiotics for local delivery systems cause skeletal cell toxicity in vitro. Clin Orthop Relat Res 462:200\u2013206. https:\/\/doi.org\/10.1097\/BLO.0b013e31811ff866","journal-title":"Clin Orthop Relat Res"},{"key":"4053_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jhin.2017.03.004","volume":"96","author":"JM Badia","year":"2017","unstructured":"Badia JM, Casey AL, Petrosillo N et al (2017) Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries. J Hosp Infect 96:1\u201315. https:\/\/doi.org\/10.1016\/j.jhin.2017.03.004","journal-title":"J Hosp Infect"},{"key":"4053_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-021-04843-z","volume":"22","author":"G Balato","year":"2021","unstructured":"Balato G, De Matteo V, Ascione T et al (2021) Management of septic arthritis of the hip joint in adults. A systematic review of the literature. BMC Musculoskelet Disord 22:1006. https:\/\/doi.org\/10.1186\/s12891-021-04843-z","journal-title":"BMC Musculoskelet Disord"},{"key":"4053_CR8","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/236314a0","volume":"236","author":"DR Bard","year":"1972","unstructured":"Bard DR, Dickens MJ, Smith AU, Zarek JM (1972) Isolation of living cells from mature mammalian bone. Nature 236:314\u2013315. https:\/\/doi.org\/10.1038\/236314a0","journal-title":"Nature"},{"key":"4053_CR9","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00018-007-7360-z","volume":"65","author":"ER Bastow","year":"2008","unstructured":"Bastow ER, Byers S, Golub SB et al (2008) Hyaluronan synthesis and degradation in cartilage and bone. Cell Mol Life Sci 65:395\u2013413. https:\/\/doi.org\/10.1007\/s00018-007-7360-z","journal-title":"Cell Mol Life Sci"},{"key":"4053_CR10","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1080\/000164700317362280","volume":"71","author":"HVD Belt","year":"2000","unstructured":"Belt HVD, Neut D, Schenk W et al (2000) Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand 71:625\u2013629. https:\/\/doi.org\/10.1080\/000164700317362280","journal-title":"Acta Orthop Scand"},{"key":"4053_CR11","doi-asserted-by":"publisher","unstructured":"Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23. https:\/\/doi.org\/10.1002\/adma.201003963","DOI":"10.1002\/adma.201003963"},{"key":"4053_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.ocl.2015.06.010","volume":"46","author":"JM Cancienne","year":"2015","unstructured":"Cancienne JM, Burrus MT, Weiss DB, Yarboro SR (2015) Applications of local antibiotics in orthopedic trauma. Orthop Clin North Am 46:495\u2013510. https:\/\/doi.org\/10.1016\/j.ocl.2015.06.010","journal-title":"Orthop Clin North Am"},{"key":"4053_CR13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1369\/0022155420929772","volume":"69","author":"I Caon","year":"2021","unstructured":"Caon I, Parnigoni A, Viola M et al (2021) Cell energy metabolism and hyaluronan synthesis. J Histochem Cytochem 69:35\u201347. https:\/\/doi.org\/10.1369\/0022155420929772","journal-title":"J Histochem Cytochem"},{"key":"4053_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/gels8020070","volume":"8","author":"R Carpa","year":"2022","unstructured":"Carpa R, Remizovschi A, Culda CA, Butiuc-Keul AL (2022) Inherent and composite hydrogels as promising materials to limit antimicrobial resistance. Gels 8:70. https:\/\/doi.org\/10.3390\/gels8020070","journal-title":"Gels"},{"key":"4053_CR15","doi-asserted-by":"publisher","first-page":"100452","DOI":"10.1016\/j.xpro.2021.100452","volume":"2","author":"C Chevalier","year":"2021","unstructured":"Chevalier C, \u00c7olako\u011flu M, Brun J et al (2021) Primary mouse osteoblast and osteoclast culturing and analysis. STAR Protoc 2:100452. https:\/\/doi.org\/10.1016\/j.xpro.2021.100452","journal-title":"STAR Protoc"},{"key":"4053_CR16","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.carbpol.2012.10.028","volume":"92","author":"MN Collins","year":"2013","unstructured":"Collins MN, Birkinshaw C (2013) Hyaluronic acid based scaffolds for tissue engineering\u2014a review. Carbohydr Polym 92:1262\u20131279. https:\/\/doi.org\/10.1016\/j.carbpol.2012.10.028","journal-title":"Carbohydr Polym"},{"key":"4053_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22203\/eCM.v024a01","volume":"24","author":"E Czekanska","year":"2012","unstructured":"Czekanska E, Stoddart M et al (2012) In search of an osteoblast cell model for in vitro research. eCM 24:1\u201317. https:\/\/doi.org\/10.22203\/eCM.v024a01","journal-title":"eCM"},{"key":"4053_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/gels7030126","volume":"7","author":"D De Meo","year":"2021","unstructured":"De Meo D, Ceccarelli G, Iaiani G et al (2021) Clinical application of antibacterial hydrogel and coating in orthopaedic and traumatology surgery. Gels 7:126. https:\/\/doi.org\/10.3390\/gels7030126","journal-title":"Gels"},{"key":"4053_CR19","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S0142-9612(03)00580-5","volume":"25","author":"H Declercq","year":"2004","unstructured":"Declercq H (2004) Isolation, proliferation and differentiation of osteoblastic cells to study cell\/biomaterial interactions: comparison of different isolation techniques and source. Biomaterials 25:757\u2013768. https:\/\/doi.org\/10.1016\/S0142-9612(03)00580-5","journal-title":"Biomaterials"},{"key":"4053_CR20","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1007\/s11999-014-3558-1","volume":"472","author":"L Drago","year":"2014","unstructured":"Drago L, Boot W, Dimas K et al (2014) Does implant coating with antibacterial-loaded hydrogel reduce bacterial colonization and biofilm formation in vitro? Clin Orthop Relat Res 472:3311\u20133323. https:\/\/doi.org\/10.1007\/s11999-014-3558-1","journal-title":"Clin Orthop Relat Res"},{"key":"4053_CR21","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1136\/ard.61.3.267","volume":"61","author":"JJ Dubost","year":"2002","unstructured":"Dubost JJ, Soubrier M, De Champs C et al (2002) No changes in the distribution of organisms responsible for septic arthritis over a 20 year period. Ann Rheum Dis 61:267\u2013269. https:\/\/doi.org\/10.1136\/ard.61.3.267","journal-title":"Ann Rheum Dis"},{"key":"4053_CR22","doi-asserted-by":"publisher","unstructured":"Edin ML, Miclau T, Lester GE et al (1996) Effect of cefazolin and vancomycin on osteoblasts in vitro. Clin Orthop Relat Res:245\u2013251. https:\/\/doi.org\/10.1097\/00003086-199612000-00027","DOI":"10.1097\/00003086-199612000-00027"},{"key":"4053_CR23","doi-asserted-by":"publisher","first-page":"7081","DOI":"10.1016\/j.actbio.2013.03.005","volume":"9","author":"A Fakhari","year":"2013","unstructured":"Fakhari A, Berkland C (2013) Applications and emerging trends of hyaluronic acid in tissue engineering, as a dermal filler and in osteoarthritis treatment. Acta Biomater 9:7081\u20137092. https:\/\/doi.org\/10.1016\/j.actbio.2013.03.005","journal-title":"Acta Biomater"},{"key":"4053_CR24","volume-title":"Hydrogels","author":"G Gaetano","year":"2018","unstructured":"Gaetano G, Giuseppe P, Salvatore PF et al (2018) Hyaluronic-based antibacterial hydrogel coating for implantable biomaterials in orthopedics and trauma: from basic research to clinical applications. In: Haider S, Haider A (eds) Hydrogels. InTech"},{"key":"4053_CR25","first-page":"1024","volume":"12","author":"A Ghallab","year":"2013","unstructured":"Ghallab A (2013) In vitro test systems and their limitations. EXCLI J 12:1024\u20131026","journal-title":"EXCLI J"},{"key":"4053_CR26","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1007\/s00264-013-2237-2","volume":"38","author":"G Giavaresi","year":"2014","unstructured":"Giavaresi G, Meani E, Sartori M et al (2014) Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant. International Orthopaedics (SICOT) 38:1505\u20131512. https:\/\/doi.org\/10.1007\/s00264-013-2237-2","journal-title":"International Orthopaedics (SICOT)"},{"key":"4053_CR27","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1007\/BF03354640","volume":"56","author":"R Gundle","year":"1995","unstructured":"Gundle R, Beresford JN (1995) The isolation and culture of cells from explants of human trabecular bone. Calcif Tissue Int 56:S8\u2013S10. https:\/\/doi.org\/10.1007\/BF03354640","journal-title":"Calcif Tissue Int"},{"key":"4053_CR28","doi-asserted-by":"crossref","unstructured":"Gundle R, Stewart K, Screen J, Beresrord JN (1998) Isolation and culture of human bone-derived cells. In: Beresford JN, Owen ME (eds) Marrow stromal cell culture, 1st edn. Cambridge University Press, pp 43\u201366. ISBN: 978-0521621055","DOI":"10.1017\/CBO9780511623219.006"},{"key":"4053_CR29","doi-asserted-by":"publisher","first-page":"297","DOI":"10.5966\/sctm.2012-0111","volume":"2","author":"D Hanjaya-Putra","year":"2013","unstructured":"Hanjaya-Putra D, Shen Y-I, Wilson A et al (2013) Integration and regression of implanted engineered human vascular networks during deep wound healing. Stem Cells Transl Med 2:297\u2013306. https:\/\/doi.org\/10.5966\/sctm.2012-0111","journal-title":"Stem Cells Transl Med"},{"key":"4053_CR30","doi-asserted-by":"publisher","first-page":"931","DOI":"10.3171\/2020.10.SPINE201511","volume":"34","author":"K Hanson","year":"2021","unstructured":"Hanson K, Isder C, Shogren K et al (2021) The inhibitory effects of vancomycin on rat bone marrow\u2013derived mesenchymal stem cell differentiation. J Neurosurg Spine 34:931\u2013935. https:\/\/doi.org\/10.3171\/2020.10.SPINE201511","journal-title":"J Neurosurg Spine"},{"key":"4053_CR31","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.copbio.2016.02.008","volume":"40","author":"CB Highley","year":"2016","unstructured":"Highley CB, Prestwich GD, Burdick JA (2016) Recent advances in hyaluronic acid hydrogels for biomedical applications. Curr Opin Biotechnol 40:35\u201340. https:\/\/doi.org\/10.1016\/j.copbio.2016.02.008","journal-title":"Curr Opin Biotechnol"},{"key":"4053_CR32","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/wnan.91","volume":"3","author":"J Hilborn","year":"2011","unstructured":"Hilborn J (2011) In vivo injectable gels for tissue repair. Wires Nanomed Nanobiotechnol 3:589\u2013606. https:\/\/doi.org\/10.1002\/wnan.91","journal-title":"Wires Nanomed Nanobiotechnol"},{"key":"4053_CR33","doi-asserted-by":"publisher","unstructured":"Jones SJ, Boyde A (1977) Some morphological observations on osteoclasts. Cell Tissue Res 185. https:\/\/doi.org\/10.1007\/BF00220298","DOI":"10.1007\/BF00220298"},{"key":"4053_CR34","doi-asserted-by":"publisher","first-page":"e28","DOI":"10.1097\/BOT.0000000000002487","volume":"37","author":"C Kruse","year":"2023","unstructured":"Kruse C, Axelrod D, Al-Mohrej OA et al (2023) Effect of local antibiotic prophylaxis on postoperative deep infection in fracture surgery: a systematic review and meta-analysis. J Orthop Trauma 37:e28\u2013e35. https:\/\/doi.org\/10.1097\/BOT.0000000000002487","journal-title":"J Orthop Trauma"},{"key":"4053_CR35","doi-asserted-by":"publisher","unstructured":"Kurapatti M, Oakley C, Singh V, Aggarwal VK (2022) Antibiotic therapy in 2-stage revision for periprosthetic joint infection: a systematic review. JBJS Rev 10. https:\/\/doi.org\/10.2106\/JBJS.RVW.21.00143","DOI":"10.2106\/JBJS.RVW.21.00143"},{"key":"4053_CR36","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1016\/j.actbio.2013.07.025","volume":"10","author":"J Lam","year":"2014","unstructured":"Lam J, Truong NF, Segura T (2014) Design of cell\u2013matrix interactions in hyaluronic acid hydrogel scaffolds. Acta Biomater 10:1571\u20131580. https:\/\/doi.org\/10.1016\/j.actbio.2013.07.025","journal-title":"Acta Biomater"},{"key":"4053_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-024-05357-9","volume":"19","author":"X Li","year":"2024","unstructured":"Li X, Lai J, Yang X et al (2024) Intra-articular injection of vancomycin after arthrotomy closure following gentamicin-impregnated bone cementation in primary total knee arthroplasty provides a high intra-articular concentration while avoiding systemic toxicity: a prospective study. J Orthop Surg Res 19:856. https:\/\/doi.org\/10.1186\/s13018-024-05357-9","journal-title":"J Orthop Surg Res"},{"key":"4053_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02850-3","volume":"17","author":"S Linke","year":"2022","unstructured":"Linke S, Th\u00fcrmer A, Bienger K et al (2022) Microbiological pathogen analysis in native versus periprosthetic joint infections: a retrospective study. J Orthop Surg Res 17:9. https:\/\/doi.org\/10.1186\/s13018-021-02850-3","journal-title":"J Orthop Surg Res"},{"key":"4053_CR39","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jor.2018.01.032","volume":"15","author":"JX Liu","year":"2018","unstructured":"Liu JX, Bravo D, Buza J et al (2018) Topical vancomycin and its effect on survival and migration of osteoblasts, fibroblasts, and myoblasts: an in vitro study. J Orthop 15:53\u201358. https:\/\/doi.org\/10.1016\/j.jor.2018.01.032","journal-title":"J Orthop"},{"key":"4053_CR40","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s10195-017-0442-2","volume":"18","author":"K Malizos","year":"2017","unstructured":"Malizos K, Blauth M, Danita A et al (2017) Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: a multicenter randomized controlled trial. J Orthop Traumatol 18:159\u2013169. https:\/\/doi.org\/10.1007\/s10195-017-0442-2","journal-title":"J Orthop Traumatol"},{"key":"4053_CR41","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1002\/jor.1100110503","volume":"11","author":"T Miclau","year":"1993","unstructured":"Miclau T, Dahners LE, Lindsey RW (1993) In vitro pharmacokinetics of antibiotic release from locally implantable materials. J Orthop Res 11:627\u2013632. https:\/\/doi.org\/10.1002\/jor.1100110503","journal-title":"J Orthop Res"},{"key":"4053_CR42","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1002\/adfm.201201698","volume":"23","author":"OP Oommen","year":"2013","unstructured":"Oommen OP, Wang S, Kisiel M et al (2013) Smart design of stable extracellular matrix mimetic hydrogel: synthesis, characterization, and in vitro and in vivo evaluation for tissue engineering. Adv Funct Materials 23:1273\u20131280. https:\/\/doi.org\/10.1002\/adfm.201201698","journal-title":"Adv Funct Materials"},{"key":"4053_CR43","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.colsurfb.2014.10.025","volume":"123","author":"X Pang","year":"2014","unstructured":"Pang X, Lu Z, Du H et al (2014) Hyaluronic acid-quercetin conjugate micelles: synthesis, characterization, in vitro and in vivo evaluation. Colloids Surf B Biointerfaces 123:778\u2013786. https:\/\/doi.org\/10.1016\/j.colsurfb.2014.10.025","journal-title":"Colloids Surf B Biointerfaces"},{"key":"4053_CR44","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1007\/s11999-017-5333-6","volume":"475","author":"TJ Parisi","year":"2017","unstructured":"Parisi TJ, Konopka JF, Bedair HS (2017) What is the long-term economic societal effect of periprosthetic infections after THA? A Markov analysis. Clin Orthop Relat Res 475:1891\u20131900. https:\/\/doi.org\/10.1007\/s11999-017-5333-6","journal-title":"Clin Orthop Relat Res"},{"key":"4053_CR45","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1089\/sur.2016.186","volume":"18","author":"H Patel","year":"2017","unstructured":"Patel H, Khoury H, Girgenti D et al (2017) Burden of surgical site infections associated with select spine operations and involvement of Staphylococcus aureus. Surg Infect 18:461\u2013473. https:\/\/doi.org\/10.1089\/sur.2016.186","journal-title":"Surg Infect"},{"key":"4053_CR46","doi-asserted-by":"publisher","first-page":"6772","DOI":"10.1016\/j.biomaterials.2010.05.047","volume":"31","author":"J Patterson","year":"2010","unstructured":"Patterson J, Siew R, Herring SW et al (2010) Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration. Biomaterials 31:6772\u20136781. https:\/\/doi.org\/10.1016\/j.biomaterials.2010.05.047","journal-title":"Biomaterials"},{"key":"4053_CR47","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1126\/science.146.3650.1476","volume":"146","author":"WA Peck","year":"1964","unstructured":"Peck WA, Birge SJ, Fedak SA (1964) Bone cells: biochemical and biological studies after enzymatic isolation. Science 146:1476\u20131477. https:\/\/doi.org\/10.1126\/science.146.3650.1476","journal-title":"Science"},{"key":"4053_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.otsr.2020.09.006","volume":"107","author":"Z Peng","year":"2021","unstructured":"Peng Z, Lin X, Kuang X et al (2021) The application of topical vancomycin powder for the prevention of surgical site infections in primary total hip and knee arthroplasty: a meta-analysis. Orthop Traumatol Surg Res 107:102741. https:\/\/doi.org\/10.1016\/j.otsr.2020.09.006","journal-title":"Orthop Traumatol Surg Res"},{"key":"4053_CR49","doi-asserted-by":"publisher","unstructured":"Perp\u00e9tuo IP, Bourne LE, Orriss IR (2019) Isolation and generation of osteoblasts. In: Idris AI (ed) Bone research protocols. Springer New York, New York, NY, pp 21\u201338. https:\/\/doi.org\/10.1007\/978-1-4939-8997-3_2","DOI":"10.1007\/978-1-4939-8997-3_2"},{"key":"4053_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2021.712461","volume":"9","author":"E Piednoir","year":"2021","unstructured":"Piednoir E, Robert-Yap J, Baillet P et al (2021) The socioeconomic impact of surgical site infections. Front Public Health 9:712461. https:\/\/doi.org\/10.3389\/fpubh.2021.712461","journal-title":"Front Public Health"},{"key":"4053_CR51","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1002\/jor.21343","volume":"29","author":"CR Rathbone","year":"2011","unstructured":"Rathbone CR, Cross JD, Brown KV et al (2011) Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthop Res 29:1070\u20131074. https:\/\/doi.org\/10.1002\/jor.21343","journal-title":"J Orthop Res"},{"key":"4053_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-015-0294-5","volume":"10","author":"CL Roman\u00f2","year":"2015","unstructured":"Roman\u00f2 CL, Scarponi S, Gallazzi E et al (2015) Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama. J Orthop Surg Res 10:157. https:\/\/doi.org\/10.1186\/s13018-015-0294-5","journal-title":"J Orthop Surg Res"},{"key":"4053_CR53","doi-asserted-by":"publisher","first-page":"34","DOI":"10.7150\/jbji.15986","volume":"1","author":"CL Roman\u00f2","year":"2016","unstructured":"Roman\u00f2 CL, Malizos K, Capuano N et al (2016) Does an antibiotic-loaded hydrogel coating reduce early post-surgical infection after joint arthroplasty? J Bone Joint Infect 1:34\u201341. https:\/\/doi.org\/10.7150\/jbji.15986","journal-title":"J Bone Joint Infect"},{"key":"4053_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcot.2021.101720","volume":"24","author":"A Russo","year":"2022","unstructured":"Russo A, Cavagnaro L, Alessio-Mazzola M et al (2022) Two-stage arthroplasty for septic arthritis of the hip and knee: a systematic review on infection control and clinical functional outcomes. Journal of Clinical Orthopaedics and Trauma 24:101720. https:\/\/doi.org\/10.1016\/j.jcot.2021.101720","journal-title":"Journal of Clinical Orthopaedics and Trauma"},{"key":"4053_CR55","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/jbm.a.31158","volume":"82A","author":"GM Salzmann","year":"2007","unstructured":"Salzmann GM, Naal FD, Von Knoch F et al (2007) Effects of cefuroxime on human osteoblasts in vitro. J Biomed Mater Res 82A:462\u2013468. https:\/\/doi.org\/10.1002\/jbm.a.31158","journal-title":"J Biomed Mater Res"},{"key":"4053_CR56","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00992-17","volume":"61","author":"R Schwameis","year":"2017","unstructured":"Schwameis R, Syr\u00e9 S, Marhofer D et al (2017) Pharmacokinetics of cefuroxime in synovial fluid. Antimicrob Agents Chemother 61:e00992-17. https:\/\/doi.org\/10.1128\/AAC.00992-17","journal-title":"Antimicrob Agents Chemother"},{"key":"4053_CR57","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/BF02546595","volume":"11","author":"DM Smith","year":"1973","unstructured":"Smith DM, Johnston CC, Severson AR (1973) Studies of the metabolism of separated bone cells: i. Techniques of separation and identification. Calcif Tissue Res 11:56\u201369. https:\/\/doi.org\/10.1007\/BF02546595","journal-title":"Calcif Tissue Res"},{"key":"4053_CR58","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202307040","volume":"34","author":"S Tavakoli","year":"2024","unstructured":"Tavakoli S, Krishnan N, Mokhtari H et al (2024) Fine\u2010tuning dynamic cross\u2013linking for enhanced 3D bioprinting of hyaluronic acid hydrogels. Adv Funct Mater 34:2307040. https:\/\/doi.org\/10.1002\/adfm.202307040","journal-title":"Adv Funct Mater"},{"key":"4053_CR59","doi-asserted-by":"publisher","unstructured":"Taylor SEB, Shah M, Orriss IR (2014) Generation of rodent and human osteoblasts. BoneKEy Rep 3. https:\/\/doi.org\/10.1038\/bonekey.2014.80","DOI":"10.1038\/bonekey.2014.80"},{"key":"4053_CR60","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1177\/1460408620978142","volume":"24","author":"J Vaida","year":"2022","unstructured":"Vaida J, Conti AD, Ray JJ et al (2022) Evaluating the efficacy of topical vancomycin powder in the treatment of open lower extremity fractures. Trauma 24:147\u2013153. https:\/\/doi.org\/10.1177\/1460408620978142","journal-title":"Trauma"},{"key":"4053_CR61","first-page":"3575","volume":"20","author":"TJ Voegele","year":"2000","unstructured":"Voegele TJ, Voegele-Kadletz M, Esposito V et al (2000) The effect of different isolation techniques on human osteoblast-like cell growth. Anticancer Res 20:3575\u20133581","journal-title":"Anticancer Res"},{"key":"4053_CR62","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1007\/s00132-021-04148-y","volume":"51","author":"N Walter","year":"2022","unstructured":"Walter N, Deng L, Brochhausen C et al (2022) Behandlung von Knochen- und Protheseninfektionen mit Bakteriophagen: Ein systematisches Review. Orthop\u00e4de 51:138\u2013145. https:\/\/doi.org\/10.1007\/s00132-021-04148-y","journal-title":"Orthop\u00e4de"},{"key":"4053_CR63","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1021\/bm400612h","volume":"14","author":"S Wang","year":"2013","unstructured":"Wang S, Oommen OP, Yan H, Varghese OP (2013) Mild and efficient strategy for site-selective aldehyde modification of glycosaminoglycans: tailoring hydrogels with tunable release of growth factor. Biomacromol 14:2427\u20132432. https:\/\/doi.org\/10.1021\/bm400612h","journal-title":"Biomacromol"},{"key":"4053_CR64","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1097\/corr.0000000000001777","volume":"479","author":"MT Wong","year":"2021","unstructured":"Wong MT, Sridharan SS, Davison EM et al (2021) Can topical vancomycin prevent periprosthetic joint infection in hip and knee arthroplasty? A systematic review. Clin Orthop Relat Res 479:1655\u20131664. https:\/\/doi.org\/10.1097\/corr.0000000000001777","journal-title":"Clin Orthop Relat Res"},{"key":"4053_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.mser.2021.100641","volume":"146","author":"Q Xu","year":"2021","unstructured":"Xu Q, Torres JE, Hakim M et al (2021) Collagen- and hyaluronic acid-based hydrogels and their biomedical applications. Mater Sci Eng R Rep 146:100641. https:\/\/doi.org\/10.1016\/j.mser.2021.100641","journal-title":"Mater Sci Eng R Rep"},{"key":"4053_CR66","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.biomaterials.2018.01.041","volume":"161","author":"HJ Yan","year":"2018","unstructured":"Yan HJ, Casalini T, Hulsart-Billstr\u00f6m G et al (2018) Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. Biomaterials 161:190\u2013202. https:\/\/doi.org\/10.1016\/j.biomaterials.2018.01.041","journal-title":"Biomaterials"},{"key":"4053_CR67","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1007\/s00590-021-02884-7","volume":"31","author":"C Zoccali","year":"2021","unstructured":"Zoccali C, Scoccianti G, Biagini R et al (2021) Antibacterial hydrogel coating in joint mega-prosthesis: results of a comparative series. Eur J Orthop Surg Traumatol 31:1647\u20131655. https:\/\/doi.org\/10.1007\/s00590-021-028","journal-title":"Eur J Orthop Surg Traumatol"},{"key":"4053_CR68","doi-asserted-by":"publisher","unstructured":"Zustiak SP, Wei Y, Leach JB (2013) Protein\u2013hydrogel interactions in tissue engineering: mechanisms and applications. Tissue Eng Part B Rev 19:160\u2013171. https:\/\/doi.org\/10.1089\/ten.teb.2012.0458","DOI":"10.1089\/ten.teb.2012.0458"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-026-04053-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-026-04053-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-026-04053-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T19:02:43Z","timestamp":1772564563000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-026-04053-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":68,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4053"],"URL":"https:\/\/doi.org\/10.1007\/s00441-026-04053-w","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"22 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were conducted after approval from the local committee for research and ethics and the local committee for animal welfare (dnr: 2020\u201304462, 5.8.18\u201300683\/2017 and 5.8.18\u201316672\/2019).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18"}}