title: Salicylic Acid-Based Polymers for Guided Bone Regeneration Using Bone Morphogenetic Protein-2.
abstract: Bone morphogenetic protein-2 (BMP-2) is used clinically to promote spinal fusion, treat complex tibia fractures, and to promote bone formation in craniomaxillofacial surgery. Excessive bone formation at sites where BMP-2 has been applied is an established complication and one that could be corrected by guided tissue regeneration methods. In this study, anti-inflammatory polymers containing salicylic acid [salicylic acid-based poly(anhydride-ester), SAPAE] were electrospun with polycaprolactone (PCL) to create thin flexible matrices for use as guided bone regeneration membranes. SAPAE polymers hydrolyze to release salicylic acid, which is a nonsteroidal anti-inflammatory drug. PCL was used to enhance the mechanical integrity of the matrices. Two different SAPAE-containing membranes were produced and compared: fast-degrading (FD-SAPAE) and slow-degrading (SD-SAPAE) membranes that release salicylic acid at a faster and slower rate, respectively. Rat femur defects were treated with BMP-2 and wrapped with FD-SAPAE, SD-SAPAE, or PCL membrane or were left unwrapped. The effects of different membranes on bone formation within and outside of the femur defects were measured by histomorphometry and microcomputed tomography. Bone formation within the defect was not affected by membrane wrapping at BMP-2 doses of 12 μg or more. In contrast, the FD-SAPAE membrane significantly reduced bone formation outside the defect compared with all other treatments. The rapid release of salicylic acid from the FD-SAPAE membrane suggests that localized salicylic acid treatment during the first few days of BMP-2 treatment can limit ectopic bone formation. The data support development of SAPAE polymer membranes for guided bone regeneration applications as well as barriers to excessive bone formation.
authors: 1 Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, New Jersey.
authors: Sangeeta
authors: S
authors: Subramanian
authors: 1 Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, New Jersey.
authors: Ashley
authors: A
authors: Mitchell
authors: 2 Department of Biomedical Engineering, School of Engineering, Rutgers, The State University of New Jersey , Piscataway, New Jersey.
authors: Weiling
authors: W
authors: Yu
authors: 2 Department of Biomedical Engineering, School of Engineering, Rutgers, The State University of New Jersey , Piscataway, New Jersey.
authors: Sabrina
authors: S
authors: Snyder
authors: 3 Department of Chemistry and Chemical Biology, School of Arts and Sciences, Rutgers, The State University of New Jersey , Piscataway, New Jersey.
authors: Kathryn
authors: K
authors: Uhrich
authors: 1 Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, New Jersey.
authors: J Patrick
authors: JP
authors: O'Connor
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D020156:Salicylic Acid / Q000737:chemistry / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D008567:Membranes, Artificial; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C016240:polycaprolactone; D020156:Salicylic Acid