Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy

Abstract

Rough titanium (Ti) surface microarchitecture and high surface energy have been shown to increase osteoblast differentiation, and this response occurs through signaling via the α2β1 integrin. However, clinical success of implanted materials is dependent not only upon osseointegration but also on neovascularization in the peri-implant bone. Here we tested the hypothesis that Ti surface microtopography and energy interact via α2β1 signaling to regulate the expression of angiogenic growth factors. Primary human osteoblasts (HOB), MG63 cells and MG63 cells silenced for α2 integrin were cultured on Ti disks with different surface microtopographies and energies. Secreted levels of vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (FGF-2), epidermal growth factor (EGF), and angiopoietin-1 (Ang-1) were measured. VEGF-A increased 170% and 250% in MG63 cultures, and 178% and 435% in HOB cultures on SLA and modSLA substrates, respectively. In MG63 cultures, FGF-2 levels increased 20 and 40-fold while EGF increased 4 and 6-fold on SLA and modSLA surfaces. These factors were undetectable in HOB cultures. Ang-1 levels were unchanged on all surfaces. Media from modSLA MG63 cultures induced more rapid differentiation of endothelial cells and this effect was inhibited by anti-VEGF-A antibodies. Treatment of MG63 cells with 1α,25(OH)2D3 enhanced levels of VEGF-A on SLA and modSLA. Silencing the α2 integrin subunit increased VEGF-A levels and decreased FGF-2 levels. These results show that Ti surface microtopography and energy modulate secretion of angiogenic growth factors by osteoblasts and that this regulation is mediated at least partially via α2β1 integrin signaling.

In vitro osteoinduction of human mesenchymal stem cells in biomimetic surface modified titanium alloy implants

“…However, despite the success achieved through surface chemistry modifications in the early host-implant integration, there is a general consensus that the modulation of surface texturing is also an important and desirable variable, regardless of the surface chemistry approach followed in endosseous implants 18,19) . The benefits of topographical surface modifications have been previously described in vitro and in vivo [20][21][22][23] . In vitro studies have shown that surface topography affects different cellular functions such as cell adhesion, proliferation, differentiation and local factor production 24) , but that it also favours appropriate implant-cell interactions on the bone-implant interface [25][26][27] .…”

Titanium surface hydrophilicity enhances platelet activation

“…At the micro-scale, in vitro studies have shown that surface roughness enhances osteoblast differentiation and stimulates the local production of both osteogenic (TGF) and angiogenic (VEGF, FGF, EGF) growth factors 41,42) . Moreover, in vivo studies have shown that a microrough titanium dental implant surface topography increases bone-to-implant contact and improves the clinical rate of wound healing 1) .…”

Effect of enamel matrix derivative on the angiogenic behaviors of human umbilical vein endothelial cells on different titanium surfaces

“…Although there is no direct contact between blood vessels and implant surface in osseointegrated implant, appropriate blood supply plays an important role in healing of both hard and soft tissues. Studies of the last years focus on investigating the role of angiogenesis and the interaction between angiogenesis and osteogenesis in wound healing after implantation [7][8][9] . Endothelial cells (ECs), which underlie the inner surface of the vasculature, play a key role in the angiogenesis, and therefore their interaction with titanium surfaces is an important factor influencing tissue healing.…”