title: Sustained, localized salicylic acid delivery enhances diabetic bone regeneration via prolonged mitigation of inflammation.
abstract: Diabetes is a metabolic disorder caused by insulin resistance and/or deficiency and impairs bone quality and bone healing due to altered gene expression, reduced vascularization, and prolonged inflammation. No effective treatments for diabetic bone healing are currently available, and most existing treatments do not directly address the diabetic complications that impair bone healing. We recently demonstrated that sustained and localized delivery of salicylic acid (SA) via an SA-based polymer provides a low-cost approach to enhance diabetic bone regeneration. Herein, we report mechanistic studies that delve into the biological action and local pharmacokinetics of SA-releasing polymers shown to enhance diabetic bone regeneration. The results suggest that low SA concentrations were locally maintained at the bone defect site for more than 1 month. As a result of the sustained SA release, a significantly reduced inflammation was observed in diabetic animals, which in turn, yielded reduced osteoclast density and activity, as well as increased osteoblastogenesis. Based upon these results, localized and sustained SA delivery from the SA-based polymer effectively improved bone regeneration in diabetic animals by affecting both osteoclasts and osteoblasts, thereby providing a positive basis for clinical treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2595-2603, 2016.
authors.affiliation: Department of Biomedical Engineering, Rutgers, the State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey.
authors.forename: Weiling
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, the State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bien-Aime
authors.affiliation: Department of Periodontics, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, Pennsylvania.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Mattos
authors.affiliation: Department of Periodontics, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, Pennsylvania.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alsadun
authors.affiliation: Department of Periodontics, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, Pennsylvania.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogado
authors.affiliation: Department of Periodontics, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, Pennsylvania.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fiorellini
authors.affiliation: Department of Periodontics, University of Pennsylvania School of Dental Medicine, 240 South 40th Street, Philadelphia, Pennsylvania.
authors.forename: Dana
authors.initials: D
authors.lastname: Graves
authors.affiliation: Department of Biomedical Engineering, Rutgers, the State University of New Jersey, 599 Taylor Road, Piscataway, New Jersey.|Department of Chemistry and Chemical Biology, Rutgers, the State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Uhrich
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001862:Bone Resorption / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations / Q000737:chemistry; D048909:Diabetes Complications / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D053582:Interleukin-1alpha / Q000032:analysis; D008297:Male; D008338:Mandibular Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D011108:Polymers / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D053582:Interleukin-1alpha; D011108:Polymers; D020156:Salicylic Acid
keywords: control inflammation; controlled and sustained drug delivery; diabetic bone healing; histology; salicylic acid