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Rational Design of a Stable, Effective, and Sustainable Dexamethasone Delivery Platform on Ti Implant- An Innovative Application of Metal Organic Framework in Bone implants
EAO Online Library. ZENG H. Oct 9, 2018; 232572; P-BR-26
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Tissue-engineered bone regeneration and osseointegration in extreme conditions still requires the regulation of additional growth factors or osteogenic drugs. Endowing Ti implants controlled growth factors osteogenic drugs delivery capability to stimulate specific cell gene responses at the molecular level and therefore promoting osteointegration and osteogenesis has become an emerging filed and has drawn tremendous attention. Metal-organic frameworks (MOFs) are good nanocarriers.In this work, we constructed a stable, effective, and sustainable DEX delivery platform on Ti disc by immobilizing DEX@zeolitic imidazolate framework-8 (DEX@ZIF-8) nanoparticles into the micrometer-scale artificial etch pits on Ti substrate.The morphology and particle size of the as-prepared DEX@ZIF-8 nanoparticles were investigated and the DEX loading encapsulation efficiency was determined, as well. Then, the surface morphology and DEX release behavior of the as-prepared Ti disc as well as the bonding strength of the SF membrane with the Ti substrate were investigated in detail. Besides, we also researched the barrier effect of the pit walls on the deposited drug carriers under the condition of simulated mechanical wear. The in vitro cell culture assay was performed by cultivating MC3T3-E1 cells on the Ti disc. Briefly, we investigated the adhesion, proliferation, differentiation, calcium deposition, osteogenic genes expressions of the adherent cells.Owing to the synergistic barrier effect of the ZIF-8 shell and the SF membrane, the SF-DEX@ZIF-8-Ti demonstrated controlled DEX release behavior over the following 30 days in phosphate buffer solution (PBS). In addition, the pit walls together with the SF membrane protected the DEX@ZIF-8 nanoparticles from detaching from the Ti substrate in the case of mechanical wear. The covalent interaction between the SF membrane and the Ti substrate prevented the SF membrane from self-peeling from the Ti substrate in moisture environment. In vitro cell culture indicated that the SF-DEX@ZIF-8-Ti had good cytocompatibility with MC3T3-E1 cells. Furthermore, the cells cultured on the SF-DEX@ZIF-8-Ti demonstrated higher differentiation, calcium deposition, and osteogenic genes expressions than the cells cultured on the SF-ZIF-8-Ti and pristine Ti.In this work, ZIF-8, an emerging nano-sized drug carrier, found a novel application in bone implants. DEX was utilized as a drug model and could be replaced by other osteogenic drugs or growth factors. Thus, we believed that our design philosophy could inspire future research work in developing Ti implants for dental care and bone defect repair.
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