title: In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering.
abstract: Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10-7-10-4M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.
authors.affiliation: Bonecell Biotech. Inc., Dunsan-dong, Seo-gu, Daejeon 602-830, Republic of Korea; Wonkwang Bone Regeneration Institute, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Beom Su
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Oral & Maxillofacial and Surgery, Wonkwang University Daejeon Dental Hospital, Seo-gu, Daejeon 302-120, Republic of Korea.
authors.forename: Feride
authors.initials: F
authors.lastname: Shkembi
authors.affiliation: Wonkwang Bone Regeneration Institute, Wonkwang University, Iksan 570-749, Republic of Korea; Department of Oral & Maxillofacial and Surgery, Wonkwang University Daejeon Dental Hospital, Seo-gu, Daejeon 302-120, Republic of Korea.
authors.forename: Jun
authors.identifier: 0000-0001-6398-8122
authors.initials: J
authors.lastname: Lee
mesh_terms: D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005337:Fibrin / Q000627:therapeutic use; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D010024:Osteoporosis / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D015718:Fibrin Tissue Adhesive; D020100:Hydrogels; D005337:Fibrin; D019386:Alendronate