title: An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects.
abstract: The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal μ-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. μ-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA 30332, USA. yash.kolambkar@gmail.com
authors.forename: Yash M
authors.initials: YM
authors.lastname: Kolambkar
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Dupont
authors.forename: Joel D
authors.initials: JD
authors.lastname: Boerckel
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.forename: Robert E
authors.initials: RE
authors.lastname: Guldberg
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000792:Angiography; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D020007:Implants, Experimental; D007700:Kinetics; D057139:Nanofibers / Q000648:ultrastructure; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D006603:Hexuronic Acids; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D020723:Glucuronic Acid