{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T23:46:28Z","timestamp":1788047188186,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T00:00:00Z","timestamp":1253664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic\/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP\u20107) derived peptide (DIF\u20107c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano\u2010HA) by either covalent chemical attachment or physical adsorption. These drug\u2010carrying nano\u2010HA particles were then dispersed into a degradable polymer (poly\u2010lactide\u2010<jats:italic>co<\/jats:italic>\u2010glycolide or PLGA) matrix to create an implantable system capable of long\u2010term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite\u2010based drug delivery systems were then characterized for drug loading efficiency and<jats:italic>in vitro<\/jats:italic>drug release. Results demonstrated that DIF\u20107c was successfully immobilized onto nano\u2010HA placed in PLGA. Moreover, a greater prolonged two\u2010phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano\u2010HA particles. Since previous studies have demonstrated greater<jats:italic>in vivo<\/jats:italic>bone growth on nano\u2010 compared with micron\u2010HA particles placed in rat calvaria, this study continued to demonstrate that ceramic\/polymer nanocomposites are promising candidates as novel orthopedic materials to promote bone regeneration. \u00a9 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010<\/jats:p>","DOI":"10.1002\/jbm.a.32614","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T17:38:43Z","timestamp":1253727523000},"page":"1180-1192","source":"Crossref","is-referenced-by-count":41,"title":["Ceramic\/polymer nanocomposites with tunable drug delivery capability at specific disease sites"],"prefix":"10.1002","volume":"93A","author":[{"given":"Huinan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,23]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"Bone Health and Osteoporosis: A Report of the Surgeon General","author":"U.S. Department of Health and Human Services","year":"2004"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.1787"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16727-5"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.09.040"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015842108772"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1208\/pt030101"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31151"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.07.003"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30734"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30923"},{"key":"e_1_2_6_12_2","unstructured":"LiuH.Design fabrication and evaluation of 2D to 3D nanostructured ceramic\/polymer composites for orthopedic regeneration and controlled drug delivery Ph.D. Dissertation. Providence RI: Brown University;2008."},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(00)00075-2"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.10519"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.08.049"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.2217\/17435889.1.2.169"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(19980905)41:3<359::AID-JBM3>3.0.CO;2-B"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(00)00322-7"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.6.2220"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.3.681"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199274050-00005"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199101000-00014"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1991.01870220049009"},{"key":"e_1_2_6_25_2","first-page":"317","article-title":"Healing of segmental femoral defects in sheep using recombinant human bone morphogenetic protein","volume":"293","author":"Gerhart TN","year":"1993","journal-title":"Clin Orthop Relat Res"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30299"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30523"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2004.02.010"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199810001-00018"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200104150-00017"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.11.028"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-007-0424-8"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-007-0422-x"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-007-0423-9"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-2197.2007.04175.x"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002640100262"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.32246"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.10.041"},{"key":"e_1_2_6_39_2","first-page":"15","article-title":"Stoichiometric apatite fine single crystals by hydrothermal synthesis","volume":"1","author":"Ioku K","year":"1991","journal-title":"Phosphorus Res Bull"},{"key":"e_1_2_6_40_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4028\/www.scientific.net\/MSF.34-36.371","article-title":"Hydrothermal synthesis and characterization of fine apatite crystals","volume":"34","author":"Somiya S","year":"1988","journal-title":"Mater Sci Forum"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/la00013a023"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.12.008"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac00005a005"},{"key":"e_1_2_6_44_2","unstructured":"Instructions for Micro BCA\u2122 Protein Assay Kit. Pierce. Also available athttp:\/\/www.piercenet.com\/files\/0412dh5.pdf."},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.2147\/nano.2006.1.4.541"},{"key":"e_1_2_6_46_2","first-page":"1618","article-title":"Degradation behavior of porous poly (\u03b1\u2010hydroxy acid)\/hydroxyapatite composite scaffolds","volume":"41","author":"Zhang R","year":"2000","journal-title":"Polym Prepr"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03218355"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.05.025"},{"key":"e_1_2_6_49_2","unstructured":"GeninFY LuoP DashAK. Hydroxyapatite Based Drug Delivery Implant for Cancer Treatment. U.S. Pat. 6 767 550 2004."},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2007.02.018"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31151"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbm.a.32614","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.32614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T09:27:06Z","timestamp":1739352426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.32614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,23]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,6]]}},"alternative-id":["10.1002\/jbm.a.32614"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.32614","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9,23]]}}}