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Investigation of Sustained BMP Delivery in the Prevention of Medication‐Related Osteonecrosis of the Jaw (MRONJ) in a Rat Model
Author(s) -
Brierly Gary I.,
Ren Jiongyu,
Baldwin Jeremy,
Saifzadeh Siamak,
Theodoropoulos Christina,
Tsurkan Mikhail V.,
Lynham Anthony,
Hsu Edward,
Nikolarakos Dimitrios,
Werner Carsten,
Woodruff Maria A.,
Hutmacher Dietmar W.,
Bray Laura J.
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201900226
Subject(s) - osteonecrosis of the jaw , medicine , zoledronic acid , dentistry , bisphosphonate , bone morphogenetic protein 2 , bisphosphonate associated osteonecrosis of the jaw , bone morphogenetic protein , surgery , osteoporosis , pathology , chemistry , biochemistry , in vitro , gene
Medication‐related osteonecrosis of the jaw (MRONJ) poses an ongoing challenge for clinicians and researchers. Currently, there is a lack of preventative measures available for at‐risk patients undergoing tooth extractions, especially those with prior bisphosphonate treatment due to osteoporosis or bone metastasis diagnoses. Here, these issues are addressed using a preventative tissue engineering strategy against MRONJ development. This study evaluates the efficacy of a poly(ethylene glycol)‐heparin hydrogel as a tool for the delivery of arginylglycylaspartic acid (RGD) and recombinant human bone morphogenic protein‐2 (rhBMP‐2). Three groups of skeletally mature rats each receive two doses of intravenous zoledronic acid prior to surgery and undergo extraction of the right first mandibular molar with gingival closure. Experimental groups either have the sockets left empty, filled with hydrogel minus rhBMP‐2, or filled with hydrogel plus rhBMP‐2. Eight weeks postoperatively specimens are analyzed using radiological, histological, and scanning electron microscopy (SEM) techniques. µCT analysis shows increased bone formation with hydrogel/rhBMP‐2 delivery compared to the empty socket. Hydrogel‐treated groups display increased presence of osteocytes and increased osteoclastic action compared to the empty sockets. These results represent the first step toward improved delivery of rhBMP‐2 and a potential MRONJ preventative for patients undergoing bisphosphonate treatment.