{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:32:27Z","timestamp":1791379947572,"version":"4.3.3"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T00:00:00Z","timestamp":1547164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Titanium particles\/ions detected in peri\u2010implant tissues have been considered as a potential etiologic factor for crestal bone loss around oral implants. However, the definite impact of titanium wear particles on the health of surrounding structures remains undetermined. The purpose of this study was to investigate the effects of titanium particles\u2010induced foreign body reaction on peri\u2010implant bone level and the related mechanism by using clodronate liposomes to deplete macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>\n                      Sprague Dawley rats with custom\u2010made titanium screw implanted in bilateral maxillary first molar area for 4\u00a0weeks to obtain osseointegration were randomly divided into four groups. Twenty microgram titanium particles were introduced into the peri\u2010implant tissue to induce aseptic foreign body reaction, and macrophages were depleted by the local injection of 100\u00a0\u03bcL clodronate liposome immediately and re\u2010injection every 3\u00a0days until the sacrifice of the rats (Ti + LipClod group). Titanium\u2010injected rats also treated with phosphate buffer solution (Ti + PBS) or empty liposome (Ti + Lip) as well as rats injected with\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      alone (Control) were included as controls. Eight weeks later, animals were sacrificed and samples containing implants were collected. Half of the samples were analyzed radiologically to measure bone level change, and macrophage markers (\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      68,\n                      <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n                      7,\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      163) was also characterized by immunofluorescence to evaluate macrophage number, density, and phenotype distribution (\n                      <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n                      7+M1\/\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      163+M2). The rest of the samples were used to determine the relative\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      expression levels of\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      \u2010\u03b1,\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20101\u03b2,\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20106, and\n                      <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                      with real\u2010time PCR analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No obvious bacterial contamination was found in all titanium\u2010injected areas, and the implant survival rate was 100% with no implant loss. Compared with Ti\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      and Ti\u00a0+\u00a0Lip group, macrophage density (1.64\u00a0\u00b1\u00a00.86%) infiltrated into peri\u2010implant tissue and bone loss (0.17\u00a0\u00b1\u00a00.03\u00a0mm) around implant decreased significantly in the Ti\u00a0+\u00a0LipClod group. Immunofluorescence analysis showed that more macrophage infiltrated into peri\u2010implant tissue in the Ti\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      and Ti + Lip groups, predominantly with M1 phenotype. In contrast, the macrophage density was lower and M2 phenotype was dominant in the Control group, while macrophages density was significantly reduced and the M1 type macrophages were slightly more than M2 type in the Ti + LipClod group. Accordingly,\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      \u2010\u03b1,\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20101\u03b2,\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      6, and\n                      <jats:styled-content style=\"fixed-case\">RANKL mRNA<\/jats:styled-content>\n                      expression increased significantly in the Ti\u00a0+\u00a0\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      and Ti\u00a0+\u00a0Lip groups compared with Control and Ti\u00a0+\u00a0LipClod groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Titanium particles had a negative effect on peri\u2010implant tissue by activating macrophages which induced an M1 macrophage phenotype promoting local secretion of inflammatory cytokines. It was found that clodronate liposome treatment attenuated the severity of inflammation and bone loss by depletion of macrophages. Therefore, the present study revealed the marked impact of macrophage polarization with respect to peri\u2010implant bone loss caused by titanium particles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.12633","type":"journal-article","created":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T01:40:37Z","timestamp":1547257237000},"page":"329-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Macrophage polarization in aseptic bone resorption around dental implants induced by Ti particles in a murine model"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-8103","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology &amp;National Clinical Research Center for Oral Diseases &amp; Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture 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