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Blood compatible materials are required for the development of therapeutic and diagnostic blood contacting devices as blood-material interactions are a key factor dictating device functionality. In this work, we explored biofunctionalization of silk biomaterials with a recombinantly expressed domain V of the human basement membrane proteoglycan perlecan (rDV) towards the development of blood compatible surfaces. Perlecan and rDV are of interest in vascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain, and compared to physisorbed and carbodiimide immobilized rDV. Untreated and treated silk biomaterials were examined for interactions with blood components with varying degrees of complexity, including isolated platelets, platelet rich plasma, blood plasma, and whole blood, both under agitated and flow conditions. rDV-biofunctionalized silk biomaterials were shown to be blood compatible in terms of platelet and whole blood interactions and the PIII treatment was shown to be an effective and efficient means of covalently immobilizing rDV in its bioactive form. These biomimetic silk biomaterials are a promising platform toward development of silk-based blood-contacting devices for therapeutic, diagnostic, and research applications. STATEMENT OF SIGNIFICANCE: Blood compatible materials are required for the development of therapeutic and diagnostic blood contacting devices as blood-material interactions are a key factor dictating device functionality. In this work, we explored biofunctionalization of silk biomaterials with a recombinantly expressed domain V (rDV) of the human basement membrane proteoglycan perlecan towards the development of blood compatible surfaces. Perlecan and rDV are of interest in vascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain. These biomimetic silk biomaterials are a promising platform toward development of silk-based blood-contacting devices for therapeutic, diagnostic, and research applications.

Three-dimensional (3D) bioprinting, where cells, hydrogels, and structural polymers can be printed layer by layer into complex designs, holds great promise for advances in medicine and the biomedical sciences. In principle, this technique enables the creation of highly patient-specific disease models and biomedical implants. However, an ability to tailor surface biocompatibility and interfacial bonding between printed components, such as polymers and hydrogels, is currently lacking. Here we demonstrate that an atmospheric pressure plasma jet (APPJ) can locally activate polymeric surfaces for the reagent-free covalent attachment of proteins and hydrogel in a single-step process at desired locations. Polyethylene and poly-e-caprolactone were used as example polymers. Covalent attachment of the proteins and hydrogel was demonstrated by resistance to removal by rigorous sodium dodecyl sulfate washing. The immobilized protein and hydrogel layers were analyzed using Fourier transform infrared and X-ray photoelectron spectroscopy. Importantly, the APPJ surface activation also rendered the polymer surfaces mildly hydrophilic as required for optimum biocompatibility. Water contact angles were observed to be stable within a range where the conformation of biomolecules is preserved. Single and double electrode designs of APPJs were compared in their characteristics relevant to localized surface functionalization, plume length, and shape. As a proof of efficacy in a biological context, APPJ-treated polyethylene functionalized with fibronectin was used to demonstrate improvements in cell adhesion and proliferation. These results have important implications for the development of a new generation of 3D bioprinters capable of spatially patterned and tailored surface functionalization performed during the 3D printing process in situ.

Hollow-fiber capillary bundles are widely used in the production of medical devices for blood oxygenation and purification purposes such as in cardiopulmonary bypass, hemodialysis, and hemofiltration, but the blood interfacing inner surfaces of these capillaries provide poor hemocompatibility. Here, we present a novel method of packed-bed plasma ion implantation (PBPII) for the modification of the inner surfaces of polymeric hollow-fiber bundles enclosed in a cassette. The method is simple and can be performed on an intact hollow-fiber bundle cassette by the placement of a hollow cylindrical electrode, connected to a negative high-voltage pulse generator, around the cassette. The method does not require the insertion of electrodes inside the capillaries or the cassette. Nitrogen gas is fed into the capillaries inside the cassette by connecting the inlet of the cassette to a gas source. Upon the application of negative high-voltage bias pulses to the electrode, plasma is ignited inside the cassette, achieving the surface modification of both the internal and external surfaces of the capillaries. Fourier transform infrared-attenuated total reflectance spectroscopy of the PBPII-treated capillaries revealed the formation of aromatic C═C bonds, indicating the progressive carbonization of the capillary surfaces. The PBPII treatment was found to be uniform along the capillaries and independent of the radial position in the cassette. Atomic force microscopy of cross sections through the capillaries revealed that the increased stiffness associated with the carbonized layer on the inner surface of the PBPII-treated capillary has a depth (∼40 nm) consistent with that expected for ions accelerated by the applied bias voltage. The modified internal surfaces of the capillary bundle showed a greatly increased wettability and could be biofunctionalized by covalently immobilizing protein directly from the buffer solution. The direct, reagent-free protein immobilization was demonstrated using tropoelastin as an example protein. Covalent binding of the protein was confirmed by its resistance to removal by hot sodium dodecyl sulfate detergent washing, which is known to disrupt physical binding.

The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-l-lactic acid (PLLA)-induced FBR. M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1β luciferase reporter mouse to detect real-time levels of IL-1β expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD68+/CD206+), related cytokines (pro-inflammatory: IL-1β, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-β), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1β activity in M-CSF functionalized scaffolds was ∼50% reduced compared to PLLA-only at day 1 (p 2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-β at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a ∼58% decrease at day 3 in IL-1β; a ∼91% decrease at day 3 and a ∼66% decrease at day 7 in TNF; and a ∼60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment.

Conventional DC magnetron sputter deposition from a carbon target with argon as the sputtering gas is limited by a low deposition rate, and the resultant coatings have low diamond-like sp3 content. Here we study arc-mixed mode high power impulse magnetron sputtering (HiPIMS) of carbon using He, Ne, Ar, Xe and Kr gases and show an increase in deposition rate is achieved by using noble gases heavier than argon. On the other hand, a higher sp3 fraction is achieved by using noble gases lighter than argon. The higher deposition rate of the heavier noble gases is attributed to the higher sputtering yield and an earlier arc onset owing to their lower ionization potential. The higher sp3 fraction achieved by lighter noble gases is attributed to stress generation by knock-on collisions at the surface of the depositing film, in the absence of stress relief created by large thermal spike volumes. When neon was used as the sputtering gas, the inert gas content was higher than for any other noble gas. Our results lead to opportunities for grading the sp3 content with depth simply by changing the gas composition, allowing fabrication of buried conductive channels in ta-C, Metal-Insulator-Metal (MIM) (low sp3/high sp3/low sp3) structures and biosensor films (high sp3/low sp3).

Implant devices containing insulin-secreting β-cells hold great promise for the treatment of diabetes. Using in vitro cell culture, long-term function and viability are enhanced when β-cells are cultured with extracellular matrix (ECM) proteins. Here, our goal is to engineer a favorable environment within implant devices, where ECM proteins are stably immobilized on polymer scaffolds, to better support β-cell adhesion. Four different polymer candidates (low-density polyethylene (LDPE), polystyrene (PS), polyethersulfone (PES) and polysulfone (PSU)) were treated using plasma immersion ion implantation (PIII) to enable the covalent attachment of laminin on their surfaces. Surface characterisation analysis shows the increased hydrophilicity, polar groups and radical density on all polymers after the treatment. Among the four polymers, PIII-treated LDPE has the highest water contact angle and the lowest radical density which correlate well with the non-significant protein binding improvement observed after 2 months of storage. The study found that the radical density created by PIII treatment of aromatic polymers was higher than that created by the treatment of aliphatic polymers. The higher radical density significantly improves laminin attachment to aromatic polymers, making them better substrates for β-cell adhesion.

Current biomaterial-based strategies explored to treat articular cartilage defects have failed to provide adequate physico-chemical cues in order to guide functional tissue regeneration. Here, it is hypothesized that atmospheric-pressure plasma (APPJ) treatment and melt electrowriting (MEW) will produce microfiber support structures with covalently-immobilized transforming growth factor beta-1 (TGFβ1) that can stimulate the generation of functional cartilage tissue. The effect of APPJ operational speeds to activate MEW polycaprolactone meshes for immobilization of TGFβ1 is first investigated and chondrogenic differentiation and neo-cartilage production are assessed in vitro. All APPJ speeds test enhanced hydrophilicity of the meshes, with the slow treatment speed having significantly less C-C/C-H and more COOH than the untreated meshes. APPJ treatment increases TGFβ1 loading efficiency. Additionally, in vitro experiments highlight that APPJ-based TGFβ1 attachment to the scaffolds is more advantageous than direct supplementation within the medium. After 28 days of culture, the group with immobilized TGFβ1 has significantly increased compressive modulus (more than threefold) and higher glycosaminoglycan production (more than fivefold) than when TGFβ1 is supplied through the medium. These results demonstrate that APPJ activation allows reagent-free, covalent immobilization of TGFβ1 on microfiber meshes and, importantly, that the biofunctionalized meshes can stimulate neo-cartilage matrix formation. This opens new perspectives for guided tissue regeneration.

Modification of the surface electronic properties of vertically aligned and randomly distributed carbon nanotubes and the hydrophobic character after exposure to Ar:F 2 and CF 4 plasma are exploited to optimize the sensing characteristics of these materials. The sensing properties of fluorinated carbon nanotubes are disclosed by probing their stability and responsiveness towards the detection of two selected pollutants such as nitrogen dioxide and ammonia (NO 2 and NH 3). The effects of both humidity level and geometry of the sensing layer are assessed. It is demonstrated that fluorination, by increasing the surface hydrophobicity, results in increased response reproducibility and enhanced sensor response towards NH 3 when using vertically aligned carbon nanotubes.

Visual Abstract, Highlights • Electrospun polycaprolactone surfaces were immobilized with a monolayer of the cytokine interleukin-4 to create a “bioactive” immunomodulatory surface capable of influencing the phenotype of macrophages responding to the material surface in vivo. • Bioactive surfaces, evaluated in vitro by using macrophage culture, exhibited upregulation of anti-inflammatory M2 genes and facilitated morphological changes consistent with macrophage activation. • As a subcutaneous implant in a 14-day model of acute inflammation, bioactive surfaces polarized macrophages from their M1 pro-inflammatory to M2 anti-inflammatory phenotypes, leading to a significant reduction in the local immune-driven foreign body response. • As vascular grafts in a 28-day mouse carotid interposition model, bioactive grafts maintained their macrophage polarization and immunomodulatory effects, significantly reducing adventitial encapsulation and neointimal hyperplasia development., Summary Cardiovascular disease is an inflammatory disorder that may benefit from appropriate modulation of inflammation. Systemic treatments lower cardiac events but have serious adverse effects. Localized modulation of inflammation in current standard treatments such as bypass grafting may more effectively treat CAD. The present study investigated a bioactive vascular graft coated with the macrophage polarizing cytokine interleukin-4. These grafts repolarize macrophages to anti-inflammatory phenotypes, leading to modulation of the pro-inflammatory microenvironment and ultimately to a reduction of foreign body encapsulation and inhibition of neointimal hyperplasia development. These resulting functional improvements have significant implications for the next generation of synthetic vascular grafts.

Surface modification of biomaterials is a promising approach to control biofunctionality while retaining the bulk biomaterial properties. Perlecan is the major proteoglycan in the vascular basement membrane that supports low levels of platelet adhesion but not activation. Thus, perlecan is a promising bioactive for blood-contacting applications. This study furthers the mechanistic understanding of platelet interactions with perlecan by establishing that platelets utilize domains III and V of the core protein for adhesion. Polyvinyl chloride (PVC) is functionalized with recombinant human perlecan domain V (rDV) to explore the effect of the tethering method on proteoglycan orientation and bioactivity. Tethering of rDV to PVC is achieved via either physisorption or covalent attachment via plasma immersion ion implantation (PIII) treatment. Both methods of rDV tethering reduce platelet adhesion and activation compared to the pristine PVC, however, the mechanisms are unique for each tethering method. Physisorption of rDV on PVC orientates the molecule to hinder access to the integrin-binding region, which inhibits platelet adhesion. In contrast, PIII treatment orientates rDV to allow access to the integrin-binding region, which is rendered antiadhesive to platelets via the glycosaminoglycan (GAG) chain. These effects demonstrate the potential of rDV biofunctionalization to modulate platelet interactions for blood contacting applications.

Mesenchymal stromal/stem cells (MSCs) typically require significant ex vivo expansion to achieve the high cell numbers required for research and clinical applications. However, conventional MSC culture on planar (2D) plastic surfaces has been shown to induce MSC senescence and decrease cell functionality over long-term proliferation, and usually, it has a high labor requirement, a high usage of reagents, and therefore, a high cost. In this Review, we describe current MSC-based therapeutic strategies and outline the important factors that need to be considered when developing next-generation cell expansion platforms. To retain the functional value of expanded MSCs, ex vivo culture systems should ideally recapitulate the components of the native stem cell microenvironment, which include soluble cues, resident cells, and the extracellular matrix substrate. We review the interplay between these stem cell niche components and their biological roles in governing MSC phenotype and functionality. We discuss current biomimetic strategies of incorporating biochemical and biophysical cues in MSC culture platforms to grow clinically relevant cell numbers while preserving cell potency and stemness. This Review summarizes the current state of MSC expansion technologies and the challenges that still need to be overcome for MSC clinical applications to be feasible and sustainable.

The mechanical strength, durability, corrosion resistance, and biocompatibility of metal alloys based on zirconium (Zr) and titanium (Ti) make them desirable materials for orthopedic implants. However, as bioinert metals, they do not actively promote bone formation and integration. Here we report a plasma coating process for improving integration of such metal implants with local bone tissue. The coating is a stable carbon-based plasma polymer layer that increased surface wettability by 28%, improved surface elasticity to the range exhibited by natural bone, and additionally covalently bound the extracellular matrix protein, tropoelastin, in an active conformation. The thus biofunctionalized material was significantly more resistant to medical-grade sterilization by steam, autoclaving or gamma-ray irradiation, retaining60% of the adhered tropoelastin molecules and preserving full bioactivity. The interface of the coating and metal was robust so as to resist delamination during surgical insertion and in vivo deployment, and the plasma process employed was utilized to also coat the complex 3D geometries typical of orthopedic implants. Osteoblast-like osteosarcoma cells cultured on the biofunctionalized Zr surface exhibited a significant 30% increase in adhesion and up to 70% improvement in proliferation. Cells on these materials also showed significant early stage up-regulation of bone marker expression (alkaline phosphatase, 1.8 fold; osteocalcin, 1.4 fold), and sustained up-regulation of these genes (alkaline phosphatase, 1.3 fold; osteocalcin, 1.2 fold) in osteogenic conditions. In addition, alkaline phosphatase production significantly increased (2-fold) on the functionalized surfaces, whereas bone mineral deposition increased by 30% above background levels compared to bare Zr. These findings have the potential to be readily translated to the development of improved Zr and Ti-based implants for accelerated bone repair.

Amorphous carbon films have many applications that require control over their sp3 fraction to customise the electrical, optical and mechanical properties. Examples of these applications include coatings for machine parts, biomedical and microelectromechanical devices. In this work, we demonstrate the use of a magnetic field with a high-power impulse magnetron sputtering (HiPIMS) source as a simple, new approach to give control over the sp3 fraction. We provide evidence that this strategy enhances the deposition rate by focusing the flux, giving films with high tetrahedral bonding at the centre of the deposition field and lower sp3 fractions further from the centre. Resistive switching appears in films with intermediate sp3 fractions. The production of thin amorphous carbon films with selected properties without the need for electrical bias opens up applications where insulating substrates are required. For example, deposition of sp3 rich films on polymers for wear resistant coatings as well as fabrication of resistive switching devices for neuromorphic technologies that require tuning of the sp3 fraction on insulating substrates are now possible.

Silk-based materials are widely used in biomaterial and tissue engineering applications due to their cytocompatibility and tunable mechanical and biodegradation properties. Aqueous-based processing techniques have enabled the fabrication of silk into a broad range of material formats, making it a highly versatile material platform across multiple industries. Utilizing the full potential of silk in biomedical applications frequently requires modification of silk's surface properties. Dry surface modification techniques, including irradiation and plasma treatment, offer an alternative to the conventional wet chemistry strategies to modify the physical and chemical properties of silk materials without compromising their bulk properties. While dry surface modification techniques are more prevalent in textiles and sterilization applications, the range of modifications available and resultant changes to silk materials all point to the utility of dry surface modification for the development of new, functional silk biomaterials. Dry surface treatment affects the surface chemistry, secondary structure, molecular weight, topography, surface energy, and mechanical properties of silk materials. This Review describes and critically evaluates the effect of physical dry surface modification techniques, including irradiation and plasma processes, on silk materials and discusses their utility in biomedical applications, including recent examples of modulation of cell/protein interactions on silk biomaterials, in vivo performance of implanted biomaterials, and applications in material biofunctionalization and lithographic surface patterning approaches.

Encapsulation devices are an emerging barrier technology designed to prevent the immunorejection of replacement cells in regenerative therapies for intractable diseases. However, traditional polymers used in current devices are poor substrates for cell attachment and induce fibrosis upon implantation, impacting long-term therapeutic cell viability. Bioactivation of polymer surfaces improves local host responses to materials, and here we make the first step toward demonstrating the utility of this approach to improve cell survival within encapsulation implants. Using therapeutic islet cells as an exemplar cell therapy, we show that internal surface coatings improve islet cell attachment and viability, while distinct external coatings modulate local foreign body responses. Using plasma surface functionalization (plasma immersion ion implantation (PIII)), we employ hollow fiber semiporous poly(ether sulfone) (PES) encapsulation membranes and coat the internal surfaces with the extracellular matrix protein fibronectin (FN) to enhance islet cell attachment. Separately, the external fiber surface is coated with the anti-inflammatory cytokine interleukin-4 (IL-4) to polarize local macrophages to an M2 (anti-inflammatory) phenotype, muting the fibrotic response. To demonstrate the power of our approach, bioluminescent murine islet cells were loaded into dual FN/IL-4-coated fibers and evaluated in a mouse back model for 14 days. Dual FN/IL-4 fibers showed striking reductions in immune cell accumulation and elevated levels of the M2 macrophage phenotype, consistent with the suppression of fibrotic encapsulation and enhanced angiogenesis. These changes led to markedly enhanced islet cell survival and importantly to functional integration of the implant with the host vasculature. Dual FN/IL-4 surface coatings drive multifaceted improvements in islet cell survival and function, with significant implications for improving clinical translation of therapeutic cell-containing macroencapsulation implants.

Additive manufacturing has facilitated fabrication of complex and patient-specific metallic meta-biomaterials that offer an unprecedented collection of mechanical, mass transport, and biological properties as well as a fully interconnected porous structure. However, applying meta-biomaterials for addressing unmet clinical needs in orthopedic surgery requires additional surface functionalities that should be induced through tailor-made coatings. Here, we developed multi-functional layer-by-layer coatings to simultaneously prevent implant-associated infections and stimulate bone tissue regeneration. We applied multiple layers of gelatin- and chitosan-based coatings containing either bone morphogenetic protein (BMP)-2 or vancomycin on the surface of selective laser melted porous structures made from commercial pure Titanium (CP Ti) and designed using a triply periodic minimal surface (i.e., sheet gyroid). The additive manufacturing process resulted in a porous structure and met the the design values comparatively. X-ray photoelectron spectroscopy spectra confirmed the presence and composition of the coating layers. The release profiles showed a continued release of both vancomycin and BMP-2 for 2–3 weeks. Furthermore, the developed meta-biomaterials exhibited a very strong antibacterial behavior with up to 8 orders of magnitude reduction in both planktonic and implant-adherent bacteria and no signs of biofilm formation. The osteogenic differentiation of mesenchymal stem cells was enhanced, as shown by two-fold increase in the alkaline phosphatase activity and up to four-fold increase in the mineralization of all experimental groups containing BMP-2. Eight-week subcutaneous implantation in vivo showed no signs of a foreign body response, while connective tissue ingrowth was promoted by the layer-by-layer coating. These results unequivocally confirm the superior multi-functional performance of the developed biomaterials.

Differentiation of stem cells into insulin secreting beta-like cells holds great promise to treat diabetes. Current protocols drive the cells through stages of maturation and produce cells that secrete insulin. However, these cells still lack many of the characteristics of native beta cells. One important influence on native cell responses is the capillary basement membrane. Whether the stem cell-derived spheroids contain basement membrane and whether it plays any role in the cell responses is unknown. Here we show the spheroids do contain basement membrane proteins as a diffuse web-like structure. We demonstrate that the beta-like cells within the spheroid do not respond to this basement membrane and show no evidence for the cell polarization that characterizes native cells. We then isolated cells from the mature spheroids and show that culture on basement membrane protein coated dishes does impose cell polarity and favourably alters glucose dependent insulin secretion. We also show that cells cultured on the inner surface of basement membrane coated polymer devices survive implantation in a mouse and retain their identity. We conclude that the introduction of basement membrane and controlling the environment around stem cell-derived beta cells is a valuable route towards better phenocopying the native responses.

Magnetron sputtering is an established coating process rarely used for carbon films due to low deposition rates and poor adhesion. Substantial ion fluxes with tunable energies can be added by converting the process to high power impulse magnetron sputtering (HiPIMS) using a high voltage pulsed power supply. Here, we use a mixed mode (HiPIMS with transition to arc) process to deposit carbon coatings for applications in blood-contacting devices. Films produced at negative substrate bias in the range 0–350 V covalently bind protein molecules directly from buffer solution, making them biologically functionalisable, unlike coatings deposited with conventional magnetron sputtering. The HiPIMS coatings showed strikingly low thrombogenicity. A proof of principle application was demonstrated by deposition onto a stainless steel cardiovascular stent. Adhesion and toughness sufficient to withstand the extreme deformation, that accompanies surgical insertion, was achieved with negative bias in the range 100–350 V. Covalently immobilized, cell-adhesive extracellular matrix (ECM) proteins, tropoelastin and fibronectin, significantly increased the proliferation of endothelial cells on the HiPIMS coatings. Optimum proliferation was observed in the negative bias range 200–350 V. These results suggest that HiPIMS carbon coatings have great potential for biomedical devices where functionalization with active biomolecules can accelerate tissue integration.

Biomolecule-functionalization, through the presentation of biological motifs that promote optimal cellular responses, has the capacity to improve the tissue integration of biomedical devices and hence patients’ quality of life. Radical-functionalized plasma polymer films (rPPFs) readily immobilize bioactive molecules on exposure to a biomolecule-containing aqueous solution without the need for chemical reagents. However, the potential for damage to cells and tissues due to the high local concentration of radicals in freshly deposited radical-functionalized plasma polymer films is of concern. In this study, we compared a fresh (4 h post-deposition) rPPF with one that had been aged for 11 days to explore the effect of the different radical fluxes on cellular responses. Primary osteoblasts and MG63 bone osteosarcoma cells were used to determine whether rPPFs at early aging times exhibited radical-induced cytotoxicity. The aging behavior of the rPPFs demonstrated a connection between the radical decay kinetics and the surface chemistry and wettability. Significant increases in cell attachment and spreading compared to bare Ti were observed for both cell lineages on the rPPF surfaces. The proliferation assays showed equivalent proliferation rates on both the fresh and aged surfaces, and no evidence of cytotoxicity was observed. Overall, we demonstrated that the high flux of radicals emerging to the surface has minimal influence on the biocompatibility of radical-functionalized plasma polymer films.

In the oral cavity, dental implants are exposed to an environment rich in various microbes that can produce infectious biofilms on the implant surface. Here we report the development of two distinct antimicrobial coatings that prevent biofilm formation by fungi or bacteria. The antimicrobial peptides Mel4 and caspofungin were immobilized on titanium surfaces through reactions with radicals embedded within a mechanically robust, ion-assisted plasma polymerized (PP) film. The immobilization does not require additional chemical reagents and is achieved by simply incubating the surfaces at room temperature in a buffer solution containing the antimicrobial agent. The antibiotic-functionalized surfaces were rigorously washed with hot sodium dodecyl sulphate (SDS) to remove physisorbed molecules, and analyzed by time of flight secondary ion mass spectrometry (ToF-SIMS), which revealed characteristic fragments of the peptides and provided strong evidence for the covalent nature of the binding between the molecules and the PP coating. Both Candida albicans and Staphylococcus aureus pathogens were significantly inhibited in their ability to colonize the surfaces and form biofilms. Our findings suggest that antimicrobial surfaces fabricated using ion-assisted plasma polymerization have great potential for coatings on biomedical devices where activity against fungal and bacterial pathogens is required. Refereed/Peer-reviewed

Silk fibroin isolated from Bombyx mori cocoons is a promising material for a range of biomedical applications, but it has no inherent cell-interactive domains, necessitating functionalization with bioactive molecules. Here we demonstrate significantly enhanced cell interactions with silk fibroin biomaterials in the absence of biofunctionalization following surface modification using plasma immersion ion implantation (PIII). Further, PIII treated silk fibroin biomaterials supported direct covalent immobilization of proteins on the material surface in the absence of chemical cross-linkers. Surface analysis after nitrogen plasma and PIII treatment at 20 kV revealed that the silk macromolecules are significantly fragmented, and at the higher fluences of implanted ions, surface carbonization was observed to depths corresponding to that of the ion penetration. Consistent with the activity of radicals created in the treated surface layer, oxidation was observed on contact with atmospheric oxygen and the PIII treated surfaces were capable of direct covalent immobilization of bioactive macromolecules. Changes in thickness, amide and nitrile groups, refractive index, and extinction coefficient in the wavelength range 400-1000 nm as a function of ion fluence are presented. Reactions responsible for the restructuring of the silk surface under ion beam treatment that facilitate covalent binding of proteins and a significant improvement in cell interactions on the modified surface are proposed.

Multifunctional nanoparticles are increasingly employed to improve biological efficiency in medical imaging, diagnostics, and treatment applications. However, even the most well-established nanoparticle platforms rely on multiple-step wet-chemistry approaches for functionalization often with linkers, substantially increasing complexity and cost, while limiting efficacy. Plasma dust nanoparticles are ubiquitous in space, commonly observed in reactive plasmas, and long regarded as detrimental to many manufacturing processes. As the bulk of research to date has sought to eliminate plasma nanoparticles, their potential in theranostics has been overlooked. Here we show that carbon-activated plasma-polymerized nanoparticles (nanoP3) can be synthesized in dusty plasmas with tailored properties, in a process that is compatible with scale up to high throughput, low-cost commercial production. We demonstrate that nanoP3 have a long active shelf life, containing a reservoir of long-lived radicals embedded during the...

Multiprotein micropatterning allows the creation of complex, controlled microenvironments for single cells that can be used for the study of the localized effects of various proteins and signals on cell survival, development, and functions. To enable analysis of cell interactions with microprinted proteins, the multiprotein micropattern must have low cross-contamination and high long-term stability in a cell culture medium. To achieve this, we employed an optimized plasma ion immersion implantation (PIII) treatment to provide polystyrene (PS) with the ability to covalently immobilize proteins on contact while retaining sufficient transparency and suitable surface properties for contact printing and retention of protein activity. The quality and long-term stability of the micropatterns on untreated and PIII treated PS were compared with those on glass using confocal microscopy. The protein micropattern on the PIII treated PS was more uniform and had a significantly higher contrast that was not affected by long-term incubation in cell culture media because the proteins were covalently bonded to PIII treated PS. The immunostaining of mouse pancreatic β cells interacting with E-cadherin and fibronectin striped surfaces showed phosphorylated paxillin concentrated on cell edges over the fibronectin stripes. This indicates that multiprotein micropatterns printed on PIII treated PS can be used for high-resolution studies of local influence on cell morphology and protein production.

High entropy alloys (HEAs) are considered as advanced materials with excellent properties, such as superior oxidation and corrosion resistance, high hardness and hydrophobicity and excellent thermal stability. The fabrication of thin films of non-metallic compounds such as oxides and nitrides has demonstrated further improvements in various properties of these high entropy-based materials. In this study, AlCoCrCu0.5FeNi high entropy oxide (HEO) thin films were deposited by radio frequency (RF) reactive magnetron sputtering from a custom-made target using three different oxygen flow fractions (RN) of 12.5, 25 and 50%. The microstructure, composition and physical properties of the HEO films were measured using a wide range of characterization methods. X-ray diffraction (XRD) detected a phase transformation from FCC to spinel structure with an increase in RN from 12.5 to 25%, while a further increase in RN from 25 to 50% retained a weak spinel phase as confirmed by transmission electron microscopy (TEM) analysis. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) measured a decrease in both the average agglomerated grain size from 88 to 30 nm and the surface roughness from 6.81 to 1.16 nm with the increase in oxygen fraction from 12.5 to 50%. The film deposited at the highest RN of 50%, had the highest oxygen concentration of 42.7% as determined by energy dispersive spectroscopy (EDS) and 38.4% as determined by X-ray photoelectron spectroscopy (XPS). XPS measurements also indicated a significant presence of surface protective oxides of Al2O3 and Cr2O3 for all the HEO thin films. The film deposited at RN of 25% achieved the highest hardness of 11 GPa, while the film deposited at RN of 50% displayed the highest water contact angle (WCA) of 111°.

We utilized a plasma activated coating (PAC) to covalently bind the active component of high density lipoproteins (HDL), apolipoprotein (apo) A-I, to stainless steel (SS) surfaces. ApoA-I suppresses restenosis and thrombosis and may therefore improve SS stent biocompatibility. PAC-coated SS significantly increased the covalent attachment of apoA-I, compared to SS alone. In static and dynamic flow thrombosis assays, PAC+apoA-I inhibited thrombosis and reduced platelet activation marker p-selectin. PAC+apoA-I reduced smooth muscle cell attachment and proliferation, and augmented EC attachment to PAC. We then coated PAC onto murine SS stents and found it did not peel or delaminate following crimping/expansion. ApoA-I was immobilized onto PAC-SS stents and was retained as a monolayer when exposed to pulsatile flow in vivo in a murine stent model. In conclusion, ApoA-I immobilized on PAC withstands pulsatile flow in vivo and retains its bioactivity, exhibiting anti-thrombotic and anti-restenotic properties, demonstrating the potential to improve stent biocompatibility.

Polyurethane-type shape memory polymers (SMPU) are promising biomedical implant materials due to their ability to recover to a predetermined shape from a temporary shape induced by thermal activation close to human body temperature and their advantageous mechanical properties including large recovery strains and low recovery stresses. Plasma Immersion Ion Implantation (PIII) is a surface modification process using energetic ions that generates radicals in polymer surfaces leading to carbonisation and oxidation and the ability to covalently immobilise proteins without the need for wet chemistry. Here we show that PIII treatment of SMPU significantly enhances its bioactivity making SMPU suitable for applications in permanent implantable biomedical devices. Scanning Electron Microscopy (SEM), contact angle measurements, surface energy measurements, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) were used to characterise the PIII modified surface, including its after treatment aging kinetics and its capability to covalently immobilise protein directly from solution. The results show a substantial improvement in wettability and dramatic changes of surface chemical composition dependent on treatment duration, due to the generation of radicals and subsequent oxidation. The SMPU surface, PIII treated for 200s, achieved a saturated level of covalently immobilized protein indicating that a full monolayer coverage was achieved. We conclude that PIII is a promising and efficient surface modification method to enhance the biocompatibility of SMPU for use in medical applications that demand bioactivity for tissue integration and stability in vivo .

Conducting polymers are good candidates for electronic biomedical devices such as biosensors, artificial nerves, and electrodes for brain tissue. Functionalizing the conducting polymer surface with bioactive molecules can limit adverse immune reactions to the foreign body and direct tissue integration. In this work, we demonstrate a simple one-step method to attach biomolecules covalently to a conductive polymer. Electrochemically synthesized polypyrrole was activated using plasma immersion ion implantation (PIII) in nitrogen. A short treatment with relatively low ion fluence (20 s) was found to enable direct covalent immobilization of protein upon incubation in a protein solution, while the protein is easily removed from untreated polypyrrole by washing in buffer. The covalent nature of the protein immobilization was demonstrated by its resistance to elution when repeatedly washed with SDS detergent. Changes in the surface properties and their evolution with time after PIII activation were studied by a combination of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), cyclic voltammetry, and water contact angle measurements. Notable changes in the chemistry of the modified layer in polypyrrole include the appearance of nitrile groups that gradually disappear with time and oxidation of the surface that increases over time in air. The kinetics of surface energy are consistent with the generation of radicals in the modified layer that are lost predominantly through oxidation. The conductivity of the modified surface layer (64 nm in thickness) decreases for low fluence treatments and is partially restored after high fluence treatment. This simple surface modification process opens up the possibility of creating biologically active interfaces for electro-stimulating biomedical devices and electrical sensing of neurological processes.

Plasma polymerized nanoparticles (PPN) formed in plasma reactors have been considered undesirable in technological applications. More recently however, PPN were proposed as a new class of multifunctional nanocarriers for drug delivery. Therefore, synthesis of PPN requires cost-effective collection strategies that maximize yield and improve reproducibility. This work shows that the collection of PPN in dusty plasmas is modulated by modifying the geometry of substrates from planar to well-shaped collectors. The electric field profile around the wells acts as an electrostatic lens, concentrating nanoparticles and significantly bolstering process yield. The aggregation of PPN is governed by a balance between plasma expansion throughout the wells, inter-particle repulsion, particle size and density. PPN are readily dispersed in aqueous solution yielding monodisperse populations. The use of a disposable well-shape collector provides a cost-effective nanoparticle collection approach that can be adopted in a wide range of plasma polymerization configurations without the need for reactor re-design. Nanoparticle carriers are increasingly used for targeted drug delivery and other medical applications and ideally one would want several functionalities associated with one single nanocarrier. The authors report a method to improve collection and minimize aggregation of plasma polymerized nanoparticles by modifying the substrate design on which they are collected from a typical 2D geometry into a series of well-like structures which increase sample yield as well as inhibiting their fusion with the substrate itself.

Shape memory polyurethanes (SMPU) have been of great interest in biomedical applications because of their unique ability to recover a primary shape by external actuation. This advantage can allow for easy suture and minimum tissue damage caused by surgery. Since SMPU suffer from low stiffness and low strength, carbon fibres have been widely used to reinforce SMPU, and their shape memory properties have been investigated using thermomechanical tensile tests. In reality, however, bending situations are more common than tensile situations, such as human skulls. In this study, carbon fibre reinforced SMPU (CF/SMPU) composites were studied as promising cranial implants that can offer shape memory properties, shape flexibility and high strength. First, the basic properties of pristine SMPU and CF/SMPU composites were characterised, including glass transition temperature (Tg), the viscosity of SMPU, the morphology of CF/SMPU, and their tensile and flexural mechanical properties. Then, a new method using rheometer was developed to study the shape memory behaviours of SMPU and CF/SMPU with three-point bending under relatively small deformations (≤1%), including flexural stress during programming and cooling, and bending recovery force during shape recovery. Finally, due to the invisibility of recovery process that was conducted in an enclosed temperature-controlling chamber of rheometer, the finite element method (FEM) was used to simulate the bending recovery test. The results showed carbon fibres significantly enhanced the mechanical properties (Young's modulus and flexural modulus) of SMPU. In terms of bending shape recovery, compared to pristine SMPU, CF/SMPU composites obtained substantially higher flexural stress during programming and cooling processes, and larger, more stable recovery force during recovery. The FEM results consolidated the peak recovery force of SMPU and the continuously growing recovery force of CF/SMPU as the temperature increased. Our findings on the improved mechanical and shape memory properties can provide a solid foundation for the potential applications of CF/SMPU composites as cranial implants.

The growing applications of electrochromic (EC) devices have generated great interest in bifunctional materials that can serve as both transparent conductive (TC) and EC coatings. WO3/Ag/WO3 (WAW) heterostructures, in principle, facilitate this extension of EC technology without reliance on an indium tin oxide (ITO) substrate. However, these structures synthesized using traditional methods have shown significant performance deficiencies. Thermally evaporated WAW structures show weak adhesion to the substrate with rapid degradation of coloration efficiency. Improved EC durability can be obtained using magnetron sputtering deposition, but this requires the insertion of an extra tungsten (W) sacrificial layer beneath the external WO3 layer to prevent oxidation and associated loss of conductivity of the silver film. Here, we demonstrate for the first time that a new method, known as high-power impulse magnetron sputtering (HiPIMS), can produce trilayer bifunctional EC and TC devices, eliminating the need for ...

As one of the promising smart materials, polyurethane-type shape memory polymers (SMPU) have been extensively investigated as potential biomedical implant materials. However, the hydrophobicity and bio-inertness of SMPU are major problems for biomedical applications. We applied plasma immersion ion implantation (PIII) to increase surface wettability and enable one-step covalent, functionalisation of SMPU with biological molecules to create a tuneable, biocompatible surface. The changes of surface properties due to PIII treatment in nitrogen plasma were determined by measurements of morphology, contact angle, surface energy, and nanoindentation. Collagen attachment on SMPU with and without PIII treatment was measured by Attenuated total reflectance-Fourier transform infrared (ATR-FTIR). To investigate in vivo biocompatibility, SMPU with/without PIII and with/without collagen were subcutaneously implanted in mice. SMPU implants with surrounding tissue were collected at days 1, 3, 7, 14 and 28 to study acute/subacute inflammatory responses at histopathological and immunohistochemical levels. The results show that PIII treatment improves wettability and releases residual stress in the SMPU surfaces substantially. Covalent attachment of collagen on PIII treated SMPU in a single step incubation was demonstrated by its resistance to removal by rigorous Sodium Dodecyl Sulfonate (SDS) washing. The in-vivo results showed significantly lower acute/subacute inflammation in response to SMPU with PIII treatment + collagen coating compared to untreated SMPU, collagen coated untreated SMPU, and PIII treated SMPU, characterised by lower total cell numbers, macrophages, neovascularisation, cellular proliferation, cytokine production, and matrix metalloproteinase production. This comprehensive in vivo study of PIII treatment with protein coating demonstrates that the combination of PIII treatment and collagen coating is a promising approach to enhance the biocompatibility of SMPU, facilitating its application as an implantable biomaterial.

A cassette with uncured preimpregnated based on carbon fibers and epoxy resin was exposed in the stratosphere (40 km altitude) above the ozone layer for over three days. Temperature variations of −76°C to +32.5°C and pressures up to 2.1 Torr were observed during flight. Analyses of the chemical structures of the composites show that the polymer matrix exposed in the stratosphere becomes crosslinked while the epoxy groups remain active, and the ground control polymer matrix reacted through polymerization reaction of epoxy groups. The space radiation exposures are considered to be responsible for crosslinking of the uncured polymers exposed in the stratosphere. The composites were cured on Earth after landing. Analysis of the cured composites showed that the polymer matrix remains active after exposure in the stratosphere. The results can be used for predicting the curing processes of polymer composites in the space environment during an orbital space flight.

Although plasma polymerization is traditionally considered as a substrate-independent process, we present evidence that the propensity of a substrate to form carbide bonds regulates the growth mechanisms of plasma polymer (PP) films. The manner by which the first layers of PP films grow determines the adhesion and robustness of the film. Zirconium, titanium, and silicon substrates were used to study the early stages of PP film formation from a mixture of acetylene, nitrogen, and argon precursor gases. The correlation of initial growth mechanisms with the robustness of the films was evaluated through incubation of coated substrates in simulated body fluid (SBF) at 37° for 2 months. It was demonstrated that the excellent zirconium/titanium-PP film adhesion is linked to the formation of metallic carbide and oxycarbide bonds during the initial stages of film formation, where a 2D-like, layer-by-layer (Frank-van der Merwe) manner of growth was observed. On the contrary, the lower propensity of the silicon surface to form carbides leads to a 3D, island-like (Volmer-Weber) growth mode that creates a sponge-like interphase near the substrate, resulting in inferior adhesion and poor film stability in SBF. Our findings shed light on the growth mechanisms of the first layers of PP films and challenge the property of substrate independence typically attributed to plasma polymerized coatings.

Expanded polytetrafluoroethylene (ePTFE) vascular conduits with less than or equal to 6 mm internal diameter typically occlude due to a combination of thrombus formation and neointimal hyperplasia. We hypothesized that by layering the polymerized elastin precursor, human tropoelastin, in the synthetic vessel lumen we could mimic the internal elastic lamina and so maintain low thrombogenicity while significantly reducing smooth muscle cell proliferation. The luminal surfaces of ePTFE conduits were activated with plasma immersion ion implantation (PIII) treatment to facilitate covalent attachment of tropoelastin. Multilayered tropoelastin vessels (2TE) enhanced endothelial cell attachment and proliferation in vitro and were superior to materials lacking the protein. In an ovine carotid interposition model of graft compatibility, partially tropoelastin coated vessels (1TE) thrombosed at a greater rate than control ePTFE, but 2TE maintained the same patency as controls. 2TE showed a significant reduction in neointimal area down to 9.7 ± 5.2% (p < 0.05) in contrast to 32.3 ± 3.9% for ePTFE alone. This reduction was due to a halving of the number of smooth muscle cells present and a corresponding reduction in their proliferation. 2TE, but not 1TE, enhanced the vascular compatibility of these materials: while both tropoelastin presentations increased in vitro endothelialization, only 2TE displayed the dual benefits of maintained hemocompatibility and simultaneously suppressed neointimal hyperplasia in vivo. We conclude that 2TE surface modification provides a significant improvement over ePTFE vascular conduits in a pilot large animal model study and presents an attractive path toward clinical applications for reduced diameter vessels.

The blend of polysulfone (PSU) and polyvinylpyrrolidone (PVP) is widely used in a production of ultrafiltration membranes and hollow fiber membranes for hemodialysis and tissue engineering. Here we study the effect of plasma immersion ion implantation (PIII) treatment on a two-phase polymer blend. It was found that PIII treatment improves the compatibility between PSU and PVP in the blend in the modified surface layer and results in an increase of wettability and chemical resistance. A synergistic effect in cross-linking and oxidation of PIII treated PSU/PVP blend was observed. The morphology of dichloromethane washed PIII treated films depends on the ion fluence used in the treatment. The wavelength of the periodic wrinkles increases and their amplitude decreases with increasing PIII treatment time. Keywords: Polymer blend, Plasma immersion ion implantation, Wrinkling, Atomic force microscopy

Stoichiometric amorphous HfO2 films have been deposited by reactive High Power Impulse Magnetron Sputtering (HiPIMS) from a Hf target in a 1:1 Ar:O2 atmosphere at pressures 2–4.5 mTorr. An optimum pressure was found for depositing smooth, high refractive index and amorphous films. Stress and refractive index reached a maximum as deposition pressure was increased to 3.5 mTorr. At 3.5 mTorr, HfO2 films were deposited with a refractive index of 2.15 at 500 nm, low leakage currents, moderate fixed charge density and a high dielectric constant of ∼18.3. The intensification of energetic ion bombardment upon the film with increase in HiPIMS pressure plays a dominant role in film properties. Increase in pressure above the optimum relieved the stress in the films and degraded the optical and electrical properties. HiPIMS pressure enables to gain indirect control of ion flux and energy in the plasma and can be used to modify the properties of depositing films.

Graded Ti/C composite films with carbon topcoats are prepared on bendable stainless steel foils by hybrid cathodic arc / glow discharge plasma-assisted chemical vapor deposition to simulate cardiovascular stents. Strong adhesion between the stainless steel substrate and carbon topcoat is achieved due to the graded Ti/C interface and it is further improved by increasing the pulse voltage. Moreover, the graded coating is more hydrophilic than the stainless steel substrate.

A novel plasma treatment method was used to activate a polymer surface for oligonucleotide immobilization. Polypropylene was treated with plasma immersion ion implantation (PIII) to create radicals on its surface and in its subsurface. Treated polypropylene was shown to retain single stranded oligonucleotides after stringent washing whereas they were easily removed from the untreated surface. The attachment is proposed to occur through a covalent binding by reaction between radicals created in the treated surface and the side chains of oligonucleotide bases. The density of attachment depends on the type of nucleobase; for example, adenine was found to be superior to thymine. A demonstration of using 20-thymine and 20-adenine spacers in the capture sequences significantly improved the density of attachment and provided an orientation supporting hybridization with complementary DNA molecules compared to unmodified capture sequences. PIII treatment is a practical and effective method for immobilizing single stranded oligonucleotides on polymers, offering potential for use in DNA and RNA based diagnostic devices, biosensors and microarrays.

Components of many vascular prostheses including endovascular stents, heart valves and ventricular assist devices are made using metal alloys. In these blood contacting applications, metallic devices promote blood clotting, which is managed clinically by profound platelet suppression and/or anticoagulation. Here it is proposed that the localized immobilization of bioactive plasmin, a critical mediator of blood clot stability, may attenuate metallic prosthesis-induced thrombus formation. Previously described approaches to covalently immobilize biomolecules on implantable materials have relied on complex chemical linker chemistry, increasing the possibility of toxic side effects and reducing bioactivity. We utilize a plasma deposited thin film platform to covalently immobilize biologically active plasmin on stainless steel substrates, including stents. A range of in vitro whole blood assays demonstrate striking reductions in thrombus formation. This approach has profound potential to improve the efficacy of a wide range of metallic vascular implants.

Percutaneous coronary intervention has revolutionized the treatment of coronary artery disease. Successive improvements in implantation techniques, stent materials and design, combined with dual antiplatelet therapy have improved stent safety. However, optimal biocompatibility and long-term effectiveness in the absence of pharmaceutical intervention remains elusive. Drug-eluting stents, introduced to combat in-stent restenosis was found to impair endothelial regeneration, increasing thrombotic risk. Innovations in polymer technology and new stent designs have improved, but not solved, these issues. Despite the drawbacks of drug elution it remains a key component of stent platforms, leaving the need for a truly biocompatible platform with lasting clinical efficacy and safety unmet. This review will examine current stent designs and explore proactive approaches to enhance stent biocompatibility.

Thin films of high entropy alloys (HEAs) are of great interest for surface engineering applications due to their exceptional properties including superior hardness, resistance to oxidation and corrosion, high temperature stability and high hydrophobicity. The microstructural and the physical properties of high entropy nitride (HEN) thin films, that are chemically inert and possess superior properties, can be effectively tunned using magnetron sputtering processes in the reactive mode. In this study, high entropy nitride thin films of AlCoCrCu0.5FeNi were deposited using RF reactive magnetron sputtering with three different nitrogen gas flow fractions (RN) of 6.25, 12.5, and 25%. X-ray diffraction technique and transmission electron microscopy revealed that the crystallinity of the HEN films changed from a mixed cubic FCC and BCC to a partially amorphous phase with increasing RN due to the accumulation of more interstitial nitrogen atoms in the film. Modifications of film morphology, such as decreases in grain size and surface roughness, were observed from scanning electron microscopy and atomic force microscopy, respectively. Energy dispersive spectroscopy recorded the highest nitrogen concentration of 10.6% for the film deposited at an intermediate RN of 12.5%. X-ray photoelectron spectroscopy detected significant levels of surface protective oxides (such as Al2O3 and Cr2O3) and nitrides (such as AlN and CrN) for the HEN thin films deposited at higher gas fractions of 12.5 and 25%. According to nanoindentation results, the film deposited at the RN of 25% attained a hardness of 9.8 GPa. The highest hardness, significant oxidation resistance and the highest hydrophobicity with a WCA of 112° were achieved for the HEN film deposited using the highest RN of 25%. Such high entropy nitride films deposited by reactive magnetron sputtering have important implications as protective coatings for a wide range of applications including turbines, engine blades and aircraft bodies used in aerospace industries.

High entropy alloy (HEA) thin films are extensively studied recently due to their propensity to display a combination of excellent properties such as high hardness, hydrophobicity, superior oxidation and corrosion resistance. Sputter deposition of thin films comprised of several elements typically requires the use of targets containing multiple elements, making both the stoichiometry and microstructure of the resulting films strongly dependent on the process parameters. In this study, HEA thin films of AlCoCrCu0.5FeNi were deposited at various radio frequency (RF) powers, from 200 to 300 W, to reveal how the power affects composition, microstructure and physical properties. X-ray diffraction (XRD) indicated a mixed phase of FCC and BCC and transmission electron microscopy (TEM) data revealed the presence of amorphous phases between the grain boundaries. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) respectively showed an increase in grain size and surface roughness with increasing RF power. X-ray photoelectron spectroscopy (XPS) confirmed the presence of Al2O3 and Cr2O3 protective oxide layers on the surface of all the HEA films. The highest concentration of Al (19.7%) was detected by energy dispersive spectroscopy (EDS) in the film deposited at the lowest power, which also had the highest nanoindentation hardness of 13 GPa. The hardness dropped to 4.5 GPa as power increased due to a reduction in Al concentration and an increase in average grain size. The film deposited at the highest power showed the highest hydrophobicity with a contact angle of 129°, while the lowest resistivity of 414 μΩ-cm was recorded for the sample deposited with the lowest power. This study shows the influence of deposition power on the microstructure and composition of the HEA thin films, demonstrating that the power can be an effective processing parameter to control various properties of AlCoCrCu0.5FeNi films. An understanding of how key process parameters affect the resulting thin film properties will enable application specific process optimization.

Covalent immobilization of biomolecules to surfaces is desirable in applications in biomedicine and biotechnology, such as biosensors, protein microarrays and implantable biomedical devices. Surface-embedded radicals in polymers, produced by plasma immersion ion implantation, are known to covalently immobilize biomolecules directly from buffer without additional reagents. Here we explore the prospects for creating a surface activated for direct covalent immobilization using a dielectric barrier discharge in air at atmospheric pressure, eliminating the need for vacuum and gas feed systems. We find that a surface activation process at atmospheric pressure in air can activate polytetrafluoroethylene (PTFE) in order to achieve reagent-free covalent immobilization of biomolecules. The presence of surface immobilized protein was verified by X-ray photoelectron spectroscopy (XPS), and its covalent immobilization was demonstrated by resilience to rigorous SDS washing at elevated temperature. Time course immobilization studies show that the covalent coupling capability of the activated surfaces is retained for several days. Proof-of-concept cell assays with immobilized tropoelastin demonstrate the technique’s ability to present functional cell binding molecules for the production of truly bioactive surfaces.

Orthopedic implants are increasing in global prevalence, with hundreds of thousands of operations performed annually. However, a significant proportion of these operations experiences failure due to poor bone integration. Many avenues of investigation have been explored to address this issue and improve the biocompatibility of orthopedic devices by modifying the biological response to the implant surface. Biomimetic functionalization of orthopedic surfaces enables control over the biological response by signaling through immobilized proteins and other biomolecules. This approach seeks to promote osteoblast differentiation and bone formation at the implant surface, leading to integration between the orthopedic surface and the local bone tissue. This review commences by highlighting the need for biomimetic functionalization from a materials and biological perspective. The surface properties that govern protein-surface interactions are subsequently explained. Progress in biomolecule functionalization of orthopedic surfaces performed via adsorption, chemical covalent immobilization, and physical covalent immobilization are discussed and reviewed. The immobilization mechanisms for each approach are examined and the strategies are evaluated according to their complexity, efficacy, reproducibility, and scalability. Emerging and prospective avenues for the transition from 2D to 3D substrates and the multi-functionalization of biomimetic surfaces are then explored.