title: Sequestration of rhBMP-2 into self-assembled polyelectrolyte complexes promotes anatomic localization of new bone in a porcine model of spinal reconstructive surgery.
abstract: Efficient and therapeutically safe delivery of recombinant human bone morphogenetic protein 2 (rhBMP-2) continues to be a central issue in bone tissue engineering. Recent evidence indicates that layer-by-layer self-assembly of polyelectrolyte complexes (PECs) can be used to recreate synthetic matrix environments that would act as tuneable reservoirs for delicate biomolecules and cells. Although preliminary in vitro as well as small-animal in vivo studies support this premise, translation into clinically relevant bone defect volumes in larger animal models remains unreported. Here we explored the use of native heparin-based PEC, deposited on a hydrated alginate gel template, to load bioactive rhBMP-2 and to facilitate lumbar interbody spinal fusion in pigs. We observed that triple PEC deposits with the highest protein sequestration efficiency and immobilization capacity promoted higher volume of new bone formation when compared with single PEC with low sequestration efficiency and immobilization capacity. This also resulted in a significantly enhanced biomechanical stability of the fused spinal segment when compared with PEC carriers with relatively low protein sequestration and immobilization capacities (p<0.05). Most importantly, PEC carriers showed a more orderly pattern of new bone deposition and superior containment of bone tissue within implant site when compared to collagen sponge carriers. We conclude that this growth factor sequestration platform is effective in the healing of clinically relevant bone defect volume and could overcome some of the safety concerns and limitations currently associated with rhBMP-2 therapy such as excessive heterotopic ossification.
authors.affiliation: 1 Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .
authors.forename: Sunny-Akogwu
authors.initials: SA
authors.lastname: Abbah
authors.forename: Wing Moon Raymond
authors.initials: WM
authors.lastname: Lam
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.forename: James
authors.initials: J
authors.lastname: Goh
authors.forename: Hee-Kit
authors.initials: HK
authors.lastname: Wong
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D004195:Disease Models, Animal; D004573:Electrolytes / Q000494:pharmacology*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008863:Microspheres; D019637:Orthopedic Procedures; D016348:Osseointegration / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D019651:Plastic Surgery Procedures; D017550:Spectroscopy, Fourier Transform Infrared; D013131:Spine / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D034421:Sus scrofa; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D004573:Electrolytes; D006603:Hexuronic Acids; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D020723:Glucuronic Acid