{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:53:39Z","timestamp":1784886819323,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"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. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening. Periprosthetic osteolysis is often treated with revision surgery because of the lack of effective therapeutic agents. As key messengers of intercellular interactions, exosomes can be independently used as therapeutic agents to promote tissue repair and regeneration. In this study, we fabricated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that carry exosomes derived from human urine stem cells (USC-Exos) and explored their effects on polyethylene-induced osteolysis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> USCs were identified by multipotent differentiation and flow cytometry analyses. USC-Exos were isolated and identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. PLGA microspheres containing USC-Exos were fabricated to synthesize NPs using the mechanical double-emulsion method. The obtained NPs were characterized in terms of stability, toxicity, exosome release, and cell uptake. Then, these NPs were implanted into the murine air pouch model, and their effects on polyethylene-induced osteolysis were evaluated by microcomputed tomography (micro-CT) and histological analyses.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The average NP diameter was ~282 \u00b1 0.4 nm, and the zeta potential was \u22122.02 \u00b1 0.03 mV. After long-term storage at room temperature and 4\u00b0C, the NP solution was stable without significant coaggregation. <jats:italic>In vitro<\/jats:italic> release profiles indicated sustained release of exosomes for 12 days. <jats:italic>In vivo<\/jats:italic>, injection of NPs into the murine air pouch caused less osteolysis than that of USC-Exos, and NPs significantly reduced bone absorption, as indicated by histology and micro-CT scanning.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings suggest that USC-Exo-based PLGA NPs can prevent particulate polyethylene-induced osteolysis and bone loss.<\/jats:p>","DOI":"10.3389\/fmed.2021.781449","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T05:07:42Z","timestamp":1638767262000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Exosomes From Human Urine-Derived Stem Cells Encapsulated Into PLGA Nanoparticles for Therapy in Mice With Particulate Polyethylene-Induced Osteolysis"],"prefix":"10.3389","volume":"8","author":[{"given":"Hui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1157\/13125355","article-title":"Cost-outcome analysis of joint replacement: evidence from a Spanish public hospital","volume":"22","author":"Navarro Espigares","year":"2008","journal-title":"Gac Sanit."},{"key":"B2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cger.2012.05.006","article-title":"Perioperative complications following total joint replacement","volume":"28","author":"Talmo","year":"2012","journal-title":"Clin Geriatr Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"204","DOI":"10.5507\/bp.2012.063","article-title":"Advantages and disadvantages of ceramic on ceramic total hip arthroplasty: a review","volume":"156","author":"Gallo","year":"2012","journal-title":"Biomed Pap Olomouc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"715","DOI":"10.2106\/JBJS.M.01534","article-title":"Current failure mechanisms after knee arthroplasty have changed: polyethylene wear is less common in revision surgery","volume":"97","author":"Thiele","year":"2015","journal-title":"J Bone Joint Surg Am."},{"key":"B5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00264-010-1143-0","article-title":"New animal models of wear-particle osteolysis","volume":"35","author":"Langlois","year":"2011","journal-title":"Int Orthop."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1007\/s11999-014-3786-4","article-title":"Do genetic susceptibility, Toll-like receptors, and pathogenassociated molecular patterns modulate the effects of wear?","volume":"472","author":"Greenfield","year":"2014","journal-title":"Clin Orthop Relat Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1002\/jbm.a.34599","article-title":"Macrophages-key cells in the response to wear debris from joint replacements","volume":"101","author":"Nich","year":"2013","journal-title":"J Biomed Mater Res A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/ncprheum0428","article-title":"Mechanisms of disease: molecular insights into aseptic loosening of orthopedic implants","volume":"3","author":"Drees","year":"2007","journal-title":"Nat Clin Pract Rheumatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by extracellular vesicles: where we are and where we need to go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell."},{"key":"B10","doi-asserted-by":"publisher","first-page":"11150","DOI":"10.1038\/ncomms11150","article-title":"Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1","volume":"7","author":"Au Yeung","year":"2016","journal-title":"Nat Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.gendis.2014.07.001","article-title":"Urine-derived stem cells: a novel and versatile progenitor source for cell-based therapy and regenerative medicine","volume":"1","author":"Zhang","year":"2014","journal-title":"Genes Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.7150\/thno.39238","article-title":"Human umbilical cord mesenchymal stromal cells-derived extracellular vesicles exert potent bone protective effects by CLEC11A-mediated regulation of bone metabolism","volume":"10","author":"Hu","year":"2020","journal-title":"Theranostics."},{"key":"B13","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.actbio.2020.05.020","article-title":"Extracellular vesicles from human urine-derived stem cells inhibit glucocorticoid-induced osteonecrosis of the femoral head by transporting and releasing pro-angiogenic DMBT1 and anti-apoptotic TIMP1","volume":"111","author":"Chen","year":"2020","journal-title":"Acta Biomater."},{"key":"B14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41413-019-0056-9","article-title":"Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG","volume":"7","author":"Chen","year":"2019","journal-title":"Bone Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.jconrel.2015.07.030","article-title":"Using exosomes, naturally-equipped nanocarriers, for drug delivery","volume":"219","author":"Batrakova","year":"2015","journal-title":"J Control Release."},{"key":"B16","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1586\/erm.09.15","article-title":"Current advances in research and clinical applications of PLGA-based nanotechnology","volume":"9","author":"Lu","year":"2009","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1109\/TNANO.2013.2279532","article-title":"Salt-leaching synthesis of porous PLGA nanoparticles","volume":"12","author":"Ilyas","year":"2013","journal-title":"IEEE Trans. Nanotechnol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2013006475","article-title":"Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights","volume":"30","author":"Hines","year":"2013","journal-title":"Crit Rev Ther Drug Carrier Syst."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1706759","DOI":"10.1002\/adma.201706759","article-title":"Cell membrane coating nanotechnology","volume":"30","author":"Fang","year":"2018","journal-title":"Adv Mater."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1038\/nprot.2012.115","article-title":"Generation of human induced pluripotent stem cells from urine samples","volume":"7","author":"Zhou","year":"2012","journal-title":"Nat Protoc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"6536","DOI":"10.1021\/acsnano.8b00553","article-title":"Mesenchymal stem cell\/red blood cell-inspired nanoparticle therapy in mice with carbon tetrachloride-induced acute liver failure","volume":"12","author":"Liang","year":"2018","journal-title":"ACS Nano."},{"key":"B22","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.jconrel.2020.06.006","article-title":"Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy","volume":"324","author":"Swanson","year":"2020","journal-title":"J Control Release"},{"key":"B23","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/03009740410005944","article-title":"A novel murine model of orthopaedic wear-debris associated osteolysis","volume":"33","author":"Ren","year":"2004","journal-title":"Scand J Rheumatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.2106\/JBJS.K.01045","article-title":"Comparison of the norwegian knee arthroplasty register and a United States arthroplasty registry","volume":"93","author":"Paxton","year":"2011","journal-title":"J Bone Joint Surg Am."},{"key":"B25","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1097\/00003086-200112000-00008","article-title":"Osteolysis: basic science","volume":"393","author":"Jacobs","year":"2001","journal-title":"Clin Orthop Relat Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3572","DOI":"10.1002\/jbm.a.35484","article-title":"Parthenolide reduces empty lacunae and osteoclastic bone surface resorption induced by polyethylene particles in a murine calvarial model of peri-implant osteolysis","volume":"103","author":"Zawawi","year":"2015","journal-title":"J Biomed Mater Res A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.11.039","article-title":"Mutant CCL2 protein coating mitigates wear particle-induced bone loss in a murine continuous polyethylene infusion model","volume":"117","author":"Nabeshima","year":"2017","journal-title":"Biomaterials."},{"key":"B28","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.actbio.2016.01.016","article-title":"Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis","volume":"33","author":"Ormsby","year":"2016","journal-title":"Acta Biomater."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.1016\/j.arth.2017.03.066","article-title":"Current epidemiology of revision total knee arthroplasty in the United States","volume":"32","author":"Delanois","year":"2017","journal-title":"J Arthroplasty."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1016\/j.arth.2017.02.046","article-title":"Current epidemiology of revision total hip arthroplasty in the United States: National inpatient sample 2009 to 2013","volume":"32","author":"Gwam","year":"2017","journal-title":"J Arthroplasty."},{"key":"B31","doi-asserted-by":"publisher","first-page":"20884","DOI":"10.1039\/C9NR02791B","article-title":"Aptamer-functionalized exosomes from bone marrow stromal cells target bone to promote bone regeneration","volume":"11","author":"Luo","year":"2019","journal-title":"Nanoscale."},{"key":"B32","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.biomaterials.2016.07.003","article-title":"Efficient production and enhanced tumor delivery of engineered extracellular vesicles","volume":"105","author":"Watson","year":"2016","journal-title":"Biomaterials."},{"key":"B33","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.actbio.2020.09.052","article-title":"Scaffolds with controlled release of pro-mineralization exosomes to promote craniofacial bone healing without cell transplantation","volume":"118","author":"Swanson","year":"2020","journal-title":"Acta Biomater"},{"key":"B34","doi-asserted-by":"publisher","first-page":"736","DOI":"10.5966\/sctm.2016-0275","article-title":"Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model","volume":"6","author":"Tao","year":"2017","journal-title":"Stem Cells Transl Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"10279","DOI":"10.1021\/acsnano.9b03656","article-title":"Efficient angiogenesis-based diabetic wound healing\/skin reconstruction through bioactive antibacterial adhesive ultra-violet shielding nanodressing with exosome release","volume":"13","author":"Wang","year":"2019","journal-title":"ACS Nano."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1778883","DOI":"10.1080\/20013078.2020.1778883","article-title":"miR-23a-3p-abundant small extracellular vesicles released from Gelma\/nanoclay hydrogel for cartilage regeneration","volume":"9","author":"Hu","year":"2020","journal-title":"J Extracell Vesicles."},{"key":"B37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.7150\/thno.29766","article-title":"Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics."},{"key":"B38","doi-asserted-by":"publisher","first-page":"5542241","DOI":"10.1155\/2021\/5542241","article-title":"Exosomal MATN3 of urine-derived stem cells ameliorates intervertebral disc degeneration by antisenescence effects and promotes NPC proliferation and ECM synthesis by activating TGF-\u03b2","volume":"2021","author":"Guo","year":"2021","journal-title":"Oxid Med Cell Longev."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6697577","DOI":"10.1155\/2020\/6697577","article-title":"Exosomes derived from human urine-derived stem cells inhibit intervertebral disc degeneration by ameliorating endoplasmic reticulum stress","volume":"2020","author":"Xiang","year":"2020","journal-title":"Oxid Med Cell Longev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.esxm.2019.02.001","article-title":"Extracellular vesicles from human urine-derived stem cells ameliorate erectile dysfunction in a diabetic rat model by delivering proangiogenic microRNA","volume":"7","author":"Ouyang","year":"2019","journal-title":"Sex Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1089\/scd.2019.0026","article-title":"Urine-derived stem cells facilitate endogenous spermatogenesis restoration of busulfan-induced non-obstructive azoospermic mice by paracrine exosomes","volume":"28","author":"Deng","year":"2019","journal-title":"Stem Cells Dev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"7613","DOI":"10.1021\/acsnano.7b07643","article-title":"Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving beta-cell destruction","volume":"12","author":"Sun","year":"2018","journal-title":"ACS Nano."},{"key":"B43","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1021\/acsnano.6b07607","article-title":"Re-engineering extracellular vesicles as smart nanoscale therapeutics","volume":"11","author":"Armstrong","year":"2017","journal-title":"ACS Nano."},{"key":"B44","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jconrel.2016.02.037","article-title":"Exosomes as therapeutics: the implications of molecular composition and exosomal heterogeneity","volume":"228","author":"Ferguson","year":"2016","journal-title":"J Controlled Release."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1703074","DOI":"10.1002\/adfm.201703074","article-title":"Exosome as a vehicle for delivery of membrane protein therapeutics, PH20, for enhanced tumor penetration and antitumor efficacy","volume":"28","author":"Hong","year":"2018","journal-title":"Adv Funct Mater."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1900105","DOI":"10.1002\/ppsc.201900105","article-title":"Monodisperse branched molybdenum-based bioactive nanoparticles significantly promote osteogenic differentiation of adipose-derived stem cells","volume":"36","author":"Niu","year":"2019","journal-title":"Part Part Syst Charact."},{"key":"B47","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fchem.2019.00186","article-title":"Micro-nano bioactive glass particles incorporated porous scaffold for promoting osteogenesis and angiogenesis in vitro","volume":"7","author":"Tian","year":"2019","journal-title":"Front Chem."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.781449\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T05:07:45Z","timestamp":1638767265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.781449\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,6]]},"references-count":47,"alternative-id":["10.3389\/fmed.2021.781449"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.781449","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,6]]},"article-number":"781449"}}