Surface Modification by Divalent Main-Group-Elemental Ions for Improved Bone Remodeling To Instruct Implant Biofabrication

Abstract

Divalent main-group-elemental ions are widely used to improve osteogenic capacity of implants biofabricated from Ti and its alloys. However, the conclusions regarding their osseointegration and immunogenicity are always inconsistent because of the multiple bone remodeling processes as well as the distinct material surface features arising from processing. Here we successfully manufactured the porous micro/nanostructured surface topography with divalent main-group-elemental ions (Mg2+, Ca2+, Sr2+, Ba2+) on substrates through hydrothermal treatment and comprehensively evaluated the complex bone remodeling processes, including osseointegration, immunogenicity, and fibrosis of substrates and implants. We found that Sr-modified implants not only upregulated the adhesion and proliferation of mesenchymal stem cells but also the differentiation of osteogenic markers compared with those modified by other divalent main-group-elemental ions (Mg2+, Ca2+, Ba2+). More importantly, the osteoclastogenesis, immunogenicity, and fibrosis of Sr-modified implants were also significantly downregulated. In vivo, evaluations of new bone formation and histological morphology at the interface of implant and host as well as the removal torque similarly indicated the improved osseointegration of Sr-modified implants as well as the absence of immunogenicity, fibrosis, or necrosis. Our results suggested that among various divalent main-group-elemental ions, Sr2+ might be a promising one for enhancing bone remodeling, which can be used to instruct functionalization of the surfaces of biofabricated Ti-based orthopedic and dental implants in the future.

3D Cell Culture—Can It Be As Popular as 2D Cell Culture?

“…[66] Modification of biological coating on its surface can increase its biological activity. [67] Bioceramics (phosphate, silicate, and bioactive glass) have good biological activity, especially for bone mineralization. [68,69] CNTs/carbon fibers can conduct electricity and regulate cell electrophysiological signals, and can be used in heart, [70] muscle, [71] and nerve tissue.…”

Biofunctional Elements Incorporated Nano/Microstructured Coatings on Titanium Implants with Enhanced Osteogenic and Antibacterial Performance

“…Some researchers believe that Sr does not affect the number of initial adherent cell [83] but Gong et al have found that Sr-modified im-plants upregulate adhesion of MSCs. [75] Cell migration is closely associated with the effect of osteogenesis, especially for BMSCs. The GFP-labeled BMSCs migrated quickly on Sr-incorporated NTs surface than that on NTs.…”

“…Not reported [ 168] Ag-Ti alloy Reproduced with permission. [75] Copyright 2019, American Chemical Society.…”

“…[ 74 ] A comparison between Sr 2+ and other divalent ions (Mg 2+ , Ca 2+ , Ba 2+ ) demonstrates that Sr‐doped coating shows more significant upregulation of osteogenesis and downregulation of osteoclastogenesis, immunogenicity, and fibrosis ( Figure ). [ 75 ] Various kinds of Sr‐incorporated coatings on Ti implants have been fabricated, including Sr‐nanosheets, [ 28 ] Sr‐nanotubes, [ 76 ] Sr‐bioactive glass, [ 77 ] GO/PDA/Sr 2+ nanosheets, [ 78 ] Sr‐nano/microrough surface, [ 79 ] and Sr‐SLA. [ 80,81 ] The concentration controlling of Sr 2+ ions is crucial and it has been observed that 0.1 × 10 −3 –1 × 10 −3 m (8.76–87.62 ppm) is the physiologically active range of Sr 2+ ions in vitro.…”

Immunomodulation and osseointegration activities of Na2TiO3 nanorods-arrayed coatings doped with different Sr content

“…Besides nanotopographical cue, studies have also highlighted the significance of inorganic ions (such as Sr 2+ [ 22 , 23 ], Mg 2+ [ 24 , 25 ] and Zn 2+ [ 26 ]) in controlling polarization behavior of macrophages. Among these ions, Sr 2+ exhibits great potential in accelerating phenotypic transition of macorphages towards M2 compared to other inorganic ions [ 27 ]. For instance, Sr contained silica-based bioactive materials facilitated phenotypic transformation of macrophages towards M2 by the released Sr 2+ to secrete abundant platelet-derived growth factor-BB (PDGF-BB), enhancing angiogenesis and thus osseointegration [ 28 , 29 ].…”