Effects of Surface Nanotopography and Calcium Chemistry of Titanium Bone Implants on Early Blood Platelet and Macrophage Cell Function

Abstract

Early responses of blood platelets and immunoinflammatory cells (macrophages) to titanium (Ti) bone implants affect the subsequent biological healing of implants by modulating early tissue healing-microenvironments via the formation of temporary fibrin matrix scaffolds for stem cell migration and production of growth factors and cytokines. This study investigated the effects of nanoscale surface topography and calcium ion (Ca2+) modification of Ti surfaces on biocompatibility regulated by blood platelets and macrophages, for the future surface design of Ti bone implants with enhanced early osteogenic capacity. A nanostructured Ti surface with or without Ca2+ enrichment was prepared using the hydrothermal treatment. Immediate and early functions of platelets and macrophages modulated by modified Ti surfaces were investigated by morphological observation of platelet spreading and fibrin matrix formation, platelet growth factor release, immunostaining of macrophage phenotypes, and macrophage inflammatory cytokine production. The results showed that surface nanoscale topographical modification of Ti promotes blood platelet activation and suppresses the inflammatory response of macrophages. In addition, surface chemistry modifications with Ca2+ enhanced the platelet response-modulating function of the nanostructured Ti surface, which accelerated immediate fibrin matrix formation and platelet-derived growth factor-AB release. Thus, nanotopographical and Ca2+ modifications of implant surfaces are expected to be effective approaches that favor the initial phase of wound healing around the Ti bone implants through positive modulation of immediate blood platelet function and early macrophage immunoinflammatory response.

Biological efficacy of perpendicular type-I collagen protruded from TiO2-nanotubes

“…The post-anodization treatment with H 2 O 2 and subsequent Col-I binding with the EPF method rendered the surface hydrophilic. A study published by Park et al 36 showed that nano-topography positively modulated the immediate blood platelet function and early macrophage immunoinflammatory response. Our results indicated that the nano-topography has a marked effect on the release of TGF-β and a slight stimulatory effect on PDGF-AB, which was masked by the greater influence of Col-I coatings.…”

Nanotubular TiO₂ regulates macrophage M2 polarization and increases macrophage secretion of VEGF to accelerate endothelialization via the ERK1/2 and PI3K/AKT pathways

“…To date, many studies have addressed the key roles of Ti implants in anti-inflammatory responses and have emphasized the important role of nanostructured surfaces. 44,[51][52][53][54] However, most of these studies have focused on the proliferation, adhesion, and secretion of pro-inflammatory cytokines from macrophages on the material. [53][54][55] Yao et al similarly used different voltages to fabricate nanotube surfaces and found that larger nanotubular surfaces (120 nm) could inhibit the expression and secretion of pro-inflammatory cytokines in macrophages.…”

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

“…A second approach is through application of in situ forming drug carriers, where they undergo a sol-gel transition from a low viscous liquid and into a gel (Figure 1.3) (Hossen et al 2019). Third option for regional therapies is the implantation of solid materials that have surface-altered calcium or titanium modifications, carried out in treatment for bone cancer at present (Park et al 2018).…”

“…Use of both natural and synthetic polymers for local drug delivery has been observed in cancer therapeutics. Natural polymers have been based on polysaccharides, such as chitosan, alginate dextran etc, or polypeptides using gelatine, albumin, collagen, or silk (Kim et al 2015;Newland et al 2018;Park et al 2018). Synthetic polymers are usually preferred to natural-based ones due to the ability to easily modify specific properties like degradation, biocompatibility, mechanical properties, and drug release etc.…”

“…Synthetic polymers are usually preferred to natural-based ones due to the ability to easily modify specific properties like degradation, biocompatibility, mechanical properties, and drug release etc. Although natural polymers offer high in vivo tolerance and can easily form hydrogels, the requirement of tailoring aforementioned properties of these polymers is a difficult task in the process involving delivery of several drugs (Kim et al 2015;Park et al 2018).…”