title: Oxidized alginate hydrogels for bone morphogenetic protein-2 delivery in long bone defects.
abstract: Autograft treatment of large bone defects and fracture non-unions is complicated by limited tissue availability and donor site morbidity. Polymeric biomaterials such as alginate hydrogels provide an attractive tissue engineering alternative due to their biocompatibility, injectability, and tunable degradation rates. Irradiated RGD-alginate hydrogels have been used to deliver proteins such as bone morphogenetic protein-2 (BMP-2), to promote bone regeneration and restoration of function in a critically sized rat femoral defect model. However, slow degradation of irradiated alginate hydrogels may impede integration and remodeling of the regenerated bone to its native architecture. Oxidation of alginate has been used to promote degradation of alginate matrices. The objective of this study was to evaluate the effects of alginate oxidation on BMP-2 release and bone regeneration. We hypothesized that oxidized-irradiated alginate hydrogels would elicit an accelerated release of BMP-2, but degrade faster in vivo, facilitating the formation of higher quality, more mature bone compared to irradiated alginate. Indeed, oxidation of irradiated alginate did accelerate in vitro BMP-2 release. Notably, the BMP-2 retained within both constructs was bioactive at 26days, as observed by induction of alkaline phosphatase activity and positive Alizarin Red S staining of MC3T3-E1 cells. From the in vivo study, robust bone regeneration was observed in both groups through 12weeks by radiography, micro-computed tomography analyses, and biomechanical testing. Bone mineral density was significantly greater for the oxidized-irradiated alginate group at 8weeks. Histological analyses of bone defects revealed enhanced degradation of oxidized-irradiated alginate and suggested the presence of more mature bone after 12weeks of healing.
authors: Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, GA 30332, USA.
authors: Lauren B
authors: LB
authors: Priddy
authors: Department of Mechanical Engineering, Stanford University, 496 Lomita Mall, Stanford, CA 94305, USA.
authors: Ovijit
authors: O
authors: Chaudhuri
authors: George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive NW, Atlanta, GA 30332, USA.
authors: Hazel Y
authors: HY
authors: Stevens
authors: Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA.
authors: Laxminarayanan
authors: L
authors: Krishnan
authors: Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive NW, Atlanta, GA 30332, USA.
authors: Brent A
authors: BA
authors: Uhrig
authors: Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive NW, Atlanta, GA 30332, USA.
authors: Nick J
authors: NJ
authors: Willett
authors: Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive NW, Atlanta, GA 30332, USA. Electronic address: robert.guldberg@me.gatech.edu.
authors: Robert E
authors: RE
authors: Guldberg
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D005269:Femur / Q000002:abnormalities / Q000473:pathology; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000464:Alginates; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid
keywords: Alginate; BMP-2 (bone morphogenetic protein-2); Bioactivity; Bone regeneration; Oxidation