title: Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration.
abstract: We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03μg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78±6.84%) than the groups implanted with the plates without drug (23.6±3.81%) (p<0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair.
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Plastic and Reconstructive Surgery, Institute of Human-Environment Interface Biology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Woojune
authors.initials: W
authors.lastname: Hur
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Se-Na
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, Graduate School of Public Health, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Plastic and Reconstructive Surgery, Institute of Human-Environment Interface Biology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Min
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chai
authors.affiliation: Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Sang Jeong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Human-Environment Interface Biology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Sukwha
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Human-Environment Interface Biology, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: psthchoi@snu.ac.kr.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea; Institute of Medical & Biological Engineering, Medical Research Center, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D020341:Absorbable Implants; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001860:Bone Plates; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D006801:Humans; D008297:Male; D051379:Mice; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D048271:Chitosan; D019386:Alendronate
keywords: Alendronate; Bioabsorbable bone plate; Bone regeneration; Drug delivery