Targeting Early Healing Phase with Titania Nanotube Arrays on Tunable Diameters to Accelerate Bone Regeneration and Osseointegration

Abstract

enlarges postoperative complications and morbidity. [1] Implantable materials with the desired surface to stimulate bone formation and prevent prosthesis implant loosening within the host bone remain as unsolved and intractable issues. [2] Manipulating a rapid, stable, and permanent bond between the implant and host bone upon the interface is pivotal for the maintenance of the enduring implant function and integrity. Miscellaneous sophisticated designed implantable materials confer favorable integrity to the implant, but often these materials are focusing on the modulation of osteogenesis and/or angiogenesis through relevant cell-lines. [3-6] This stratagem has achieved incontestable success in the development of the implantable biomaterials; however, persistent discordances between in vitro and in vivo studies connoting the underlying mechanisms pertain to the material-intervened osseointegration is not well-understand hitherto. [7] Osseointegration is a sophisticated process that starts immediately with a blood clot formation upon the implantation. [8] The clot is formed initially by an activated platelet plug that is then reinforced by a 3D fibrin fiber network. [9] Meanwhile, a myriad of growth mediators and cytokines are released by way of the platelet activation, progressively, to the local environment. [10] The thickness and density of the fibrin fiber Blood coagulation and inflammation are the earliest biological responses to implant surfaces. Implant nano-surfaces can significantly impact the osseointegration through the influence on the early phase of bone regeneration. However, the interplay between blood clot property and inflammatory reaction on nanosurfaces is rarely understood. Herein, titania nanotube arrays (TNAs) with different diameters are fabricated on titanium. In vitro evaluation with the whole blood indicates that TNA with a diameter of 15 nm (TNA 15) enables noteworthy platelet activation resulting in distinct clot features compared with that of pure Ti and TNA with a diameter of 120 nm (TNA 120). Further co-culture with macrophages on the clot or in the clot-conditioned medium shows that the clot on TNA 15 downregulates the inflammation and manipulates a favorable osteoimmunomodulatory environment for osteogenesis. In vivo studies further demonstrate that TNA 15 could downregulate the inflammation-related genes while upregulating growth metabolism-related genes in an early healing hematoma. Additionally, TNA 15 promotes de novo bone formation with improved extending of osteocyte dendrites, demonstrating the desired osseointegration. These findings indicate that surface nano-dimensions can significantly influence clot formation and appropriate clot features can manipulate a favorable osteoimmunomodulatory environment for bone regeneration and osseointegration.

Carbon and Neon Ion Bombardment Induced Smoothing and Surface Relaxation of Titania Nanotubes

“…Titanium dioxide (TiO ) nanotube arrays constitute a highly adjustable material that is used for various applications. Recent advances in the development of devices for solar energy conversion [ 1 ], photocatalysis [ 2 ], biomedicine [ 3 ] and biosensors [ 4 , 5 ] have been achieved by specifically modifying the starting material: titania nanotube arrays. These arrays comprise general characteristics of bulk TiO that are enhanced by the enormous surface area.…”

Anodic TiO2 Nanotubes: Tailoring Osteoinduction via Drug Delivery

“…Many previous works demonstrated that various diameter TiO 2 NT structures can also induce the anti-inflammatory response of hosts (Chamberlain et al [21], Smith et al [189], Neacsu et al [20], Yao et al [190], Bai et al [191]). The surface modification induced by the nanotube structures combined with annealing can change the hemocompatibility of TiO 2 NTs, by alleviating platelet activation (Mazare et al [111,150], Junkar et al [15], Huang et al [192], Gong et al [193], Bai et al [191,194]).…”

“…Many previous works demonstrated that various diameter TiO 2 NT structures can also induce the anti-inflammatory response of hosts (Chamberlain et al [21], Smith et al [189], Neacsu et al [20], Yao et al [190], Bai et al [191]). The surface modification induced by the nanotube structures combined with annealing can change the hemocompatibility of TiO 2 NTs, by alleviating platelet activation (Mazare et al [111,150], Junkar et al [15], Huang et al [192], Gong et al [193], Bai et al [191,194]). Several in vivo studies have shown that TiO 2 nanotubular layers could induce successful peri-implant bone formation/osseointegration in various animal models using different diameter NTs: von Wilmowsky et al (30 nm diameter nanotubes) [195], Wang et al (30,70, and 100 nm diameter NTs) in minipigs [174], Alves-Rezende et al (≈ 74 nm diameter NTs) [196], Baker et al (TiO 2 NTs-in vitro and in vivo intramedullary fixation) in rats [197], or the review of Wang et al [198] for the effect of TiO 2 NTs grown on the implants' surface on osseointegration in animal models.…”

Small extracellular vesicles with nanomorphology memory promote osteogenesis

“…For example, Yao et al prepared nanoflake structures through hydrothermal treatment of Ti, and demonstrated that the nanostructure has superior osteogenesis [ 29 ]. Bai et al studied the influence of the nanosurface characteristic on the blood clot property and inflammatory reaction in bone regeneration, and concluded that a titania nanotube with a diameter of 15 nm facilitates bone regeneration by manipulating a favorable osteoimmunomodulatory environment [ 30 ].…”