{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:44:42Z","timestamp":1771465482790,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T00:00:00Z","timestamp":1301443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low\u2010dose bone morphogenetic protein 2 (BMP\u20102).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Combined delivery of EP4A and BMP\u20102 was carried out with a nanogel\u2010based scaffold in the shape of a disc, to repair critical\u2010size circle\u2010shaped bone defects in calvariae that otherwise did not heal spontaneously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combination treatment with EP4A and low\u2010dose BMP\u20102 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low\u2010dose BMP\u20102\u2013induced cell differentiation and activation of transcription events in osteoblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data indicate that combined delivery of EP4A and low\u2010dose BMP\u20102 via nanogel\u2010based hydrogel provides a new system for bone repair.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30151","type":"journal-article","created":{"date-parts":[[2010,12,28]],"date-time":"2010-12-28T18:15:18Z","timestamp":1293560118000},"page":"1021-1033","source":"Crossref","is-referenced-by-count":48,"title":["Nanogel\u2010based scaffold delivery of prostaglandin E<sub>2<\/sub> receptor\u2013specific agonist in combination with a low dose of growth factor heals critical\u2010size bone defects in 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