title: Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects.
abstract: Osteogenic growth factors that promote endogenous repair mechanisms hold considerable potential for repairing challenging bone defects. The local delivery of one such growth factor, bone morphogenetic protein (BMP), has been successfully translated to clinical practice for spinal fusion and bone fractures. However, improvements are needed in the spatial and temporal control of BMP delivery to avoid the currently used supraphysiologic doses and the concomitant adverse effects. We have recently introduced a hybrid protein delivery system comprised of two parts: a perforated nanofibrous mesh that spatially confines the defect region and a functionalized alginate hydrogel that provides temporal growth factor release kinetics. Using this unique spatiotemporal delivery system, we previously demonstrated BMP-mediated functional restoration of challenging 8mm femoral defects in a rat model. In this study, we compared the efficacy of the hybrid system in repairing segmental bone defects to that of the current clinical standard, collagen sponge, at the same dose of recombinant human BMP-2. In addition, we investigated the specific role of the nanofibrous mesh tube on bone regeneration. Our results indicate that the hybrid delivery system significantly increased bone regeneration and improved biomechanical function compared to collagen sponge delivery. Furthermore, we observed that presence of the nanofiber mesh tube was essential to promote maximal mineralized matrix synthesis, prevent extra-anatomical mineralization, and guide an integrated pattern of bone formation. Together, these results suggest that spatiotemporal strategies for osteogenic protein delivery may enhance clinical outcomes by improving localized protein retention.
authors.affiliation: Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA 30332, USA. yashk@gatech.edu
authors.forename: Yash M
authors.initials: YM
authors.lastname: Kolambkar
authors.forename: Joel D
authors.initials: JD
authors.lastname: Boerckel
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Dupont
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bajin
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: D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology; D006801:Humans; D057139:Nanofibers; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2