Date of this Version
Journal of Controlled Release
Diabetes mellitus (DM) involves metabolic changes that can impair bone repair, including a prolonged inflammatory response. A salicylic acid-based poly(anhydride-ester) (SA-PAE) provides controlled and sustained release of salicylic acid (SA) that locally resolves inflammation. This study investigates the effect of polymer-controlled SA release on bone regeneration in diabetic rats where enhanced inflammation is expected. Fifty-six Sprague–Dawley rats were randomly assigned to two groups: diabetic group induced by streptozotocin (STZ) injection or normoglycemic controls injected with citrate buffer alone. Three weeks after hyperglycemia development or vehicle injection, 5 mm critical sized defects were created at the rat mandibular angle and treated with SA-PAE/bone graft mixture or bone graft alone. Rats were euthanized 4 and 12 weeks after surgery, then bone fill percentage in the defect region was assessed by micro-computed tomography (CT) and histomorphometry. It was observed that bone fill increased significantly at 4 and 12 weeks in SA-PAE/bone graft-treated diabetic rats compared to diabetic rats receiving bone graft alone. Accelerated bone formation in normoglycemic rats caused by SA-PAE/bone graft treatment was observed at 4 weeks but not at 12 weeks. This study shows that treatment with SA-PAE enhances bone regeneration in diabetic rats and accelerates bone regeneration in normoglycemic animals.
NOTICE: This is the author’s version of a work that was accepted for publication in Journal of Controlled Release. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Controlled Release, Volume 171, Issue 1, 10 October 2013, DOI: 10.1016/j.jconrel.2013.06.024.
poly(anhydride-ester, salicylic acid, diabetes, bone regeneration
Wada, K., Yu, W., Elaziz, M., Barakat, S., Ouimet, M. A., Rosario-Meléndez, R., Fiorellini, J. P., Graves, D. T., & Uhrich, K. E. (2013). Locally Delivered Salicylic Acid From a Poly(anhydride-ester): Impact on Diabetic Bone Regeneration. Journal of Controlled Release, 171 (1), 33-37. http://dx.doi.org/10.1016/j.jconrel.2013.06.024
Date Posted: 02 April 2015
This document has been peer reviewed.