Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis

Abstract

Implant surface properties are a key factor in bone responses to metallic bone implants. In view of the emerging evidence on the important role of osteoclasts in bone regeneration, we here studied how surface roughness affects osteoclastic differentiation and to what extent these osteoclasts have stimulatory effects on osteogenic differentiation of osteoprogenitor cells. For this, we induced osteoclasts derived from RAW264.7 cell line and primary mouse macrophages on titanium surfaces with different roughness (Ra 0.02–3.63 μm) and analyzed osteoclast behavior in terms of cell number, morphology, differentiation, and further anabolic effect on osteoblastic cells. Surfaces with different roughness induced the formation of osteoclasts with distinct phenotypes, based on total osteoclast numbers, morphology, size, cytoskeletal organization, nuclearity, and osteoclastic features. Furthermore, these different osteoclast phenotypes displayed differential anabolic effects toward the osteogenic differentiation of osteoblastic cells, for which the clastokine CTHRC1 was identified as a causative factor. Morphologically, osteoclast potency to stimulate osteogenic differentiation of osteoblastic cells was found to logarithmically correlate with the nuclei number per osteoclast. Our results demonstrate the existence of a combinatorial effect of surface roughness, osteoclastogenesis, and osteogenic differentiation. These insights open up a new dimension for designing and producing metallic implants by considering the implant roughness to locally regulate osseointegration through coupling osteoclastogenesis with osteogenesis.

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

“…55,56 The results of the studies reported herein demonstrate that osteogenesis may be partially due to the rough topography of LOG nanoparticles, further supported by published studies. [57][58][59][60][61][62]…”

Biological responses to physicochemical properties of biomaterial surface

“…[209][210][211] When we evaluate host responses to biomaterials in tissues containing different cell types, the differences between responses of various cells to surface roughness can pose many challenges. 212,213 (v) On the other hand, there is a considerable contradiction between the literature outcomes when it comes to one particular cell type response to surface roughness. These contradictions could arise from the current misuse of biocompatibility definition by ignoring critical biochemical signal transduction pathways, which indeed might play vital roles in determining cell responses.…”

Use of Impedance Spectroscopy for the Characterization of In-Vitro Osteoblast Cell Response in Porous Titanium Bone Implants

“…On the other hand, the inherent roughness to pore wall (increase of surface contact) and surface free energy, are both considered key factors for cell adhesion, migration and differentiation [32] while inhibiting the bacterial attachment and biofilm formation [33,34]. In this context, many reports have shown the interaction between roughness and cellular response and how the microstructure and nanostructure [35] can interfere and modulate cellular adhesion, spreading and differentiation of mesenchymal stem cells [36], osteoblasts [37,38], macrophages [39,40] and osteoclast [41]. The vast majority of surface modification treatments are based on the micro and submicron scale roughness development but recently the nanotopography architecture has shown an important role for guiding bone regeneration [35].…”