IADR Abstract Archives
Alendronate-Modified Multifunctional Envelope-Type Nanoparticle for Craniofacial Bone Repair
Objectives: BMP signaling exerts critical roles in craniofacial bone development and regeneration. Targeting BMP signaling agonists or antagonists can promote endogenous BMP signaling and bone regeneration. While the direct use of BMP morphogens or small molecular agonists/anti-antagonists has shown potentials in bone repair, they are restricted by high dose requirement, low stability and nonspecific targeting. Developing a nanoparticle-based approach with specifically modulating endogenous BMP signaling presents a promising alternative for efficacious bone repair.
Methods: To create a multifunctional envelope-type nanoparticle, cholesterol and palmitic acid were self-assembled and then decorated with hydroxyapatite (HA)-binding alendronate (Alt) and guanidine group. The core of nanoparticle was also assembled with polyethyleneimine/pDNAs encoding both Trb3 (BMP agonist) and Noggin (BMP antagonist) shRNA. The created nanoparticles were further integrated onto an apatite-coated PLGA scaffold. The characterization of multifunctional nanoparticles was analyzed. The osteogenic effect of nanoparticle/scaffold was evaluated in cell level in vitro, and its bone formation capacity was measured in critical-size mouse calvarial defects by microCT image, quantitative analysis, and histologic analysis (n=6/group).
Results: By TEM and NTA, the modified sterosomes displayed spherical nanostructure with the diameter from 100 to 200 nm. Alt-modified sterosomes exhibited high binding capacity to HA. Guanidine-rich sterosomes further showed strong cell penetrating ability with high transfection efficiency. The complex of nanoparticle/scaffold exhibited the increased MSC osteogenesis as detected with elevated ALP activity/mineralization as well as induced osteogenic genes. The implant of nanoparticle/scaffold resulted in robust calvarial healing as visualized by microCT/histological analysis. The mechanistic studies showed that the envelop-type nanoparticles enhance osteogenesis by stimulating endogenous BMP signal.
Conclusions: The molecular and supramolecular engineering of novel nanoparticulate stimulator of BMP signaling can significantly promote calvarial repair. This work offers a promising nanoparticulate alternative and BMP signaling regulation through delivery of BMP agonists and anti-antagonists for high quality of bone repair.
Methods: To create a multifunctional envelope-type nanoparticle, cholesterol and palmitic acid were self-assembled and then decorated with hydroxyapatite (HA)-binding alendronate (Alt) and guanidine group. The core of nanoparticle was also assembled with polyethyleneimine/pDNAs encoding both Trb3 (BMP agonist) and Noggin (BMP antagonist) shRNA. The created nanoparticles were further integrated onto an apatite-coated PLGA scaffold. The characterization of multifunctional nanoparticles was analyzed. The osteogenic effect of nanoparticle/scaffold was evaluated in cell level in vitro, and its bone formation capacity was measured in critical-size mouse calvarial defects by microCT image, quantitative analysis, and histologic analysis (n=6/group).
Results: By TEM and NTA, the modified sterosomes displayed spherical nanostructure with the diameter from 100 to 200 nm. Alt-modified sterosomes exhibited high binding capacity to HA. Guanidine-rich sterosomes further showed strong cell penetrating ability with high transfection efficiency. The complex of nanoparticle/scaffold exhibited the increased MSC osteogenesis as detected with elevated ALP activity/mineralization as well as induced osteogenic genes. The implant of nanoparticle/scaffold resulted in robust calvarial healing as visualized by microCT/histological analysis. The mechanistic studies showed that the envelop-type nanoparticles enhance osteogenesis by stimulating endogenous BMP signal.
Conclusions: The molecular and supramolecular engineering of novel nanoparticulate stimulator of BMP signaling can significantly promote calvarial repair. This work offers a promising nanoparticulate alternative and BMP signaling regulation through delivery of BMP agonists and anti-antagonists for high quality of bone repair.