Tuning Chemistry and Topography of Nanoengineered Surfaces to Manipulate Immune Response for Bone Regeneration Applications

Abstract

Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.

Zinc‐Modified Sulfonated Polyetheretherketone Surface with Immunomodulatory Function for Guiding Cell Fate and Bone Regeneration

“…Specifically, it was reported that cytokine‐ or drug‐loaded biomaterials can harness macrophage polarization and generate an osteogenic immune microenvironment. [[qv: 7b,16]] Moreover, some studies suggested that tuning the chemistry and topography of surfaces can manipulate the response of macrophages to biomaterials 17. In the present study, we investigated the osteoimmunomodulatory ability of the active ion zinc and its immunomodulatory and osteogenic effects on osteointegration.…”

“…Immunofluorescence staining and flow cytometry results validated the higher proportion of M2 macrophages on Zn‐coated SPEEK (Figure 4). As to the higher proportion of the M2 phenotype on SPEEK than on PEEK (Figure 4), reasons may be as follow: it is reported that porous structure can facilitate the attachment and spread of macrophages, then the physical and mechanical signals of porous surface can be translated into biological signals, and subsequently modulate local microenvironment and macrophage polarization 17, 28. As revealed in Figure 1A, porous structure with pore size about 0.5–1 µm can be observed on the surface of SPEEK, which may provide some biological signals for the polarization of macrophages.…”

Heparinization of Beta Tricalcium Phosphate: Osteo‐immunomodulatory Effects

“…Nevertheless, the main focus of many investigations has been their osteogenic potential, while their interaction with the immune system has often been overlooked. Chen et al have recently made a step forward toward unraveling the tight link between osteogenesis and immunology on ceramic substrates, mainly β‐TCP or porous alumina. However, the studies performed were limited to the evaluation of the effect of β‐TCP extracts rather than involving direct cell seeding on the material.…”

Current Advances in Immunomodulatory Biomaterials for Bone Regeneration

“…Furthermore, effects of nanoroughness on osteoimmunity were also investigated. For example, the different size of gold nanoparticles (16–68 nm) on allylamine surface balanced secretion of cytokines in nanoroughness groups to enhance osteogenesis . Ma et al modified surface of TiO 2 with UV irradiation to give different roughness (6–12 nm).…”