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.

Synthetic materials employed for enhancing, replacing, or restoring biological functionality may be compromised by the host immune responses that they evoke. Surface modification has attracted substantial attention as a tool to modulate the host response to synthetic materials; however, how surface nanotopography combined with chemistry affects immune effector cell responses is still poorly understood. To address this open question, a unique set of model surfaces with controlled surface nanotopography in the range of 16, 38, and 68 nm has been generated. Tailored outermost surface chemistry that was amine, carboxyl, or methyl group rich has been provided. The combinations of these properties yield 12 surface types that are subject to functional assays assessing key immune effector cells, namely, primary neutrophil and macrophage responses in vitro. The data demonstrate that surface nanotopography leads to enhanced matrix metalloproteinase-9 production from primary neutrophils, and a decrease in pro-inflammatory cytokine secretion from primary macrophages. Together, these results are the first to directly compare the immunomodulatory effects of the cooperative interplay between surface nanotopography and chemistry.

Immune cells play vital roles in regulating bone dynamics. Successful bone regeneration requires a favourable osteo-immune environment. The high plasticity and diversity of immune cells make it possible to manipulate the osteo-immune response of immune cells, thus modulating the osteoimmune environment and regulating bone regeneration. With the advancement in nanotechnology, nanotopographies with different controlled surface properties can be fabricated. On tuning the surface properties, the osteo-immune response can be precisely modulated. This highly tunable characteristic and immunomodulatory effects make nanotopography a promising strategy to precisely manipulate osteoimmunomdulation for bone tissue engineering applications. This review first summarises the effects of the immune response during bone healing to show the importance of regulating the immune response for the bone response. The plasticity of immune cells is then reviewed to provide rationales for manipulation of the osteoimmune response. Subsequently, we highlight the current types of nanotopographies applied in bone biomaterials and their fabrication techniques, and explain how these nanotopographies modulate the immune response and the possible underlying mechanisms. The effects of immune cells on nanotopography-mediated osteogenesis are emphasized, and we propose the concept of "nano-osteoimmunomodulation" to provide a valuable strategy for the development of nanotopographies with osteoimmunomodulatory properties that can precisely regulate bone dynamics.

Tuning the material properties in order to control the cellular behavior is an important issue in tissue engineering. It is now well-established that the surface chemistry can affect cell adhesion, proliferation, and differentiation. In this study, plasma polymerization, which is an appealing method for surface modification, was employed to generate surfaces with different chemical compositions. Allylamine (AAm), acrylic acid (AAc), 1,7-octadiene (OD), and ethanol (ET) were used as precursors for plasma polymerization in order to generate thin films rich in amine (-NH2), carboxyl (-COOH), methyl (-CH3), and hydroxyl (-OH) functional groups, respectively. The surface chemistry was characterized by X-ray photoelectron spectroscopy (XPS), the wettability was determined by measuring the water contact angles (WCA) and the surface topography was imaged by atomic force microscopy (AFM). The effects of surface chemical compositions on the behavior of human adipose-derive stem cells (hASCs) were evaluated in vitro: Cell Count Kit-8 (CCK-8) analysis for cell proliferation, F-actin staining for cell morphology, alkaline phosphatase (ALP) activity analysis, and Alizarin Red S staining for osteogenic differentiation. The results show that AAm-based plasma-polymerized coatings can promote the attachment, spreading, and, in turn, proliferation of hASCs, as well as promote the osteogenic differentiation of hASCs, suggesting that plasma polymerization is an appealing method for the surface modification of scaffolds used in bone tissue engineering.

Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body response: an acute sterile inflammatory reaction which overlaps with tissue vascularisation and remodelling and ultimately fibrotic encapsulation of the biomaterial to prevent further interaction with host tissue. Severity and clinical manifestation of the biomaterial-induced foreign body response are different for each biomaterial, with cases of incompatibility often associated with loss of function. However, unravelling the mechanisms that progress to the formation of the fibrotic capsule highlights the tightly intertwined nature of immunological responses to a seemingly noncanonical “antigen.” In this review, we detail the pathways associated with the foreign body response and describe possible mechanisms of immune involvement that can be targeted. We also discuss methods of modulating the immune response by altering the physiochemical surface properties of the biomaterial prior to implantation. Developments in these areas are reliant on reproducible and effective animal models and may allow a “combined” immunomodulatory approach of adapting surface properties of biomaterials, as well as treating key immune pathways to ultimately reduce the negative consequences of biomaterial implantation.

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The importance of nanostructured surfaces in a range of technological and biological processes is welldocumented within literature, yet often ill-understood. Simple and reliable methods for the preparation of nanotextured surfaces are required to advance both fundamental understandings of nanoscale phenomena and our capacity to design nano-engineered materials for specific applications. Nanoengineered surfaces are, for instance, needed to shed light on the effect of nanostructures' size and density on immune cells cytokine production. In applied bioengineering, nanostructured artificial surfaces could be specifically tailored to enhance the osteo-integration of implants. This study presents a versatile, plasma polymer enabled method for the generation of surfaces with well-defined nanotopography and tailored outermost surface chemistry. This was achieved by finely controlling the covalent bonding of gold nanoparticles of desired size to plasma-deposited poly(methyloxazoline) interlayer deposited on the material substrate. An additional 5 nm thin polymer was deposited over the nanostructures providing a uniformly tailored outermost surface chemistry while preserving the topography. This rapid, versatile, substrate independent, and scalable strategy for the preparation of a well-defined nanotopography surface has promising prospects in many fields relying on surface engineering, including food and membrane technologies, biomaterial and environmental engineering, sensing, marine sciences, and even pollution control.