Icariin/Aspirin Composite Coating on TiO2 Nanotubes Surface Induce Immunomodulatory Effect of Macrophage and Improve Osteoblast Activity

Abstract

Surface coating modification of titanium-based alloys is an efficient way to accelerate early osseointegration in dental implant fields. Icariin (ICA) is a traditional Chinese medicine that has bone activating functions, while aspirin (ASP) is a classical non-steroidal anti-inflammatory drug with good antipyretic and analgesic capabilities. Moreover, poly(lactic–co–glycolic acid) (PLGA) has attracted great attention due to its excellent biocompatibility and biodegradability. We superimposed an ASP/PLGA coating onto ICA loaded TiO2 nanotubes structure so as to establish an icariin/aspirin composite coating on TiO2 nanotubes surface. Scanning electron microscopy, X-ray photoelectron spectroscopy, a contact angle test and a drug release test confirmed the successful preparation of the NT–ICA–ASP/PLGA substrate, with a sustained release pattern of both ICA and ASP. Compared to those cultured on the Ti surface, macrophage cells on the NT-ICA-ASP/PLGA substrate displayed decreased M1 proinflammatory and enhanced M2 proregenerative genes and proteins expression, which implied activated immunomodulatory effect. Moreover, when cultured with conditioned medium from macrophages, osteoblast cells on the NT-ICA-ASP/PLGA substrate revealed improved cell proliferation, adhesion and osteogenic genes and proteins expression, compared with those on the Ti surface. The abovementioned results suggest that the established NT-ICA-ASP/PLGA substrate is a promising candidate for functionalized coating material in Ti implant surface modification.

TiO2 Nanotubes Functionalized with Icariin for an Attenuated In Vitro Immune Response and Improved In Vivo Osseointegration

“…The choice of Ica can be easily explained by its low cost and anti-inflammatory and anticancer capabilities [ 23 ]. In addition, Ica can promote osteoblast proliferation and the inhibition of osteoclast activity [ 63 ], with studies in the literature demonstrating not only its beneficial effects on bone forming cells but also on the immune system [ 64 ]. Moreover, recent studies have used Ica as a functional coating for various Ti surfaces, which led to an increase in the osteogenic ability of the implants [ 44 , 65 ].…”

A state-of-the-art review of the fabrication and characteristics of titanium and its alloys for biomedical applications

“…Recent advancements in nanomedicine have facilitated the development of new immunomodulatory agents that include immunosuppressive agents or immunologically active components. In conjunction with an immunosuppressive agent, the unique surface structure of TNA enables the effective reduction of compromising immune responses that would contribute to unsuccessful transplants as a result of localized autoimmune or allergic reactions [ 205 , 215 ]. Such applications have the potential to significantly enhance clinical outcomes for a range of infectious and non-infectious diseases.…”

Dental Implant Nano-Engineering: Advances, Limitations and Future Directions

“…These drugs have been loaded inside TNTs for the purpose of local release. Briefly, Ibuprofen [98], Indomethacin [99], Dexamethasone [100], Aspirin [101], Sodium naproxen [102], Quercetin [103], Enrofloxacin [104], Propolis [105] and immunomodulatory cytokines [106] have been successfully loaded and locally eluted from TNTs in vitro. Further, to achieve substantial loading and the delayed/controlled release of anti-inflammatory drugs, approaches including biopolymer coating on drug-loaded TNTs [107,108], polymeric micelle encapsulation of drugs prior to loading [109], the periodic tailoring of TNTs [110], the chemical intercalation of drugs inside TNTs [111] and trigger-based release [112,113] have been reported for TNT-based Ti implants.…”