Mapping the microcarrier design pathway to modernise clinical mesenchymal stromal cell expansion.

Microcarrier expansion systems show exciting potential to revolutionise mesenchymal stromal cell (MSC)-based clinical therapies by providing an opportunity for economical large-scale expansion of donor- and patient-derived cells. The poor reproducibility and efficiency of cell expansion on commercial polystyrene microcarriers have driven the development of novel microcarriers with tuneable physical, mechanical, and cell-instructive properties. These new microcarriers show innovation toward improving cell expansion outcomes, although their limited biological characterisation and compatibility with dynamic culture systems suggest the need to realign the microcarrier design pathway. Clear headway has been made toward developing infrastructure necessary for scaling up these technologies; however, key challenges remain in characterising the wholistic effects of microcarrier properties on the biological fate and function of expanded MSCs.

Recombinant perlecan domain V covalently immobilized on silk biomaterials via plasma immersion ion implantation supports the formation of functional endothelium.

Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials with recombinantly expressed domain V of human perlecan (rDV) to promote endothelial cell interactions and the formation of functional endothelium. Perlecan is essential in vascular development and homeostasis and rDV has been shown to uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions, both key contributors of vascular graft failure. rDV was covalently immobilized on silk using plasma immersion ion implantation (PIII), a simple one-step surface treatment process which enables strong immobilization in the absence of chemical cross-linkers. rDV immobilization on surface-modified silk was assessed for amount, orientation, and bio-functionality in terms of endothelial cell interactions and functional endothelial layer formation. rDV immobilized on PIII-treated silk (rDV-PIII-silk) supported rapid endothelial cell adhesion, spreading, and proliferation to form functional endothelium, as evidenced by the expression of vinculin and VE-cadherin markers. Taken together, the results provide evidence for the potential of rDV-PIII-silk as a biomimetic vascular graft material.

Osteo-Immunomodulatory Role of Interleukin-4-Immobilized Plasma Immersion Ion Implantation Membranes for Bone Regeneration.

Barrier membranes for guided tissue regeneration are essential for bone repair and regeneration. The implanted membranes may trigger early inflammatory responses as a foreign material, which can affect the recruitment and differentiation of bone cells during tissue regeneration. The purpose of this study was to determine whether immobilizing interleukin 4 (IL4) on plasma immersion ion implantation (PIII)-activated surfaces may alter the osteo-immunoregulatory characteristics of the membranes and produce pro-osteogenic effects. In order to immobilize IL4, polycaprolactone surfaces were modified using the PIII technology. No discernible alterations were found between the morphology before and after PIII treatment or IL4 immobilization. IL4-immobilized PIII surfaces polarized macrophages to an M2 phenotype and mitigated inflammatory cytokine production under lipopolysaccharide stimulation. Interestingly, the co-culture of macrophages (on IL4-immobilized PIII surfaces) and bone marrow-derived mesenchymal stromal cells enhanced the production of angiogenic and osteogenic factors and triggered autophagy activation. Exosomes produced by PIII + IL4-stimulated macrophages were also found to play a role in osteoblast differentiation. In conclusion, the osteo-immunoregulatory properties of bone materials can be modified by PIII-assisted IL4 immobilization, creating a favorable osteoimmune milieu for bone regeneration.

Development of tropoelastin-functionalized anisotropic PCL scaffolds for musculoskeletal tissue engineering.

The highly organized extracellular matrix (ECM) of musculoskeletal tissues, encompassing tendons, ligaments and muscles, is structurally anisotropic, hierarchical and multi-compartmental. These features collectively contribute to their unique function. Previous studies have investigated the effect of tissue-engineered scaffold anisotropy on cell morphology and organization for musculoskeletal tissue repair and regeneration, but the hierarchical arrangement of ECM and compartmentalization are not typically replicated. Here, we present a method for multi-compartmental scaffold design that allows for physical mimicry of the spatial architecture of musculoskeletal tissue in regenerative medicine. This design is based on an ECM-inspired macromolecule scaffold. Polycaprolactone (PCL) scaffolds were fabricated with aligned fibers by electrospinning and mechanical stretching, and then surface-functionalized with the cell-supporting ECM protein molecule, tropoelastin (TE). TE was attached using two alternative methods that allowed for either physisorption or covalent attachment, where the latter was achieved by plasma ion immersion implantation (PIII). Aligned fibers stimulated cell elongation and improved cell alignment, in contrast to randomly oriented fibers. TE coatings bound by physisorption or covalently following 200 s PIII treatment promoted fibroblast proliferation. This represents the first cytocompatibility assessment of novel PIII-treated TE-coated PCL scaffolds. To demonstrate their versatility, these 2D anisotropic PCL scaffolds were assembled into 3D hierarchical constructs with an internally compartmentalized structure to mimic the structure of musculoskeletal tissue.

The fabrication and growth mechanism of AlCrFeCoNiCu0.5 HEA thin films by substrate-biased cathodic arc deposition.

AlCrFeCoNiCu0.5 thin films were fabricated by cathodic arc deposition under different substrate biases. Detailed characterization of the chemistry and structure of the film, from the substrate interface to the film surface, was achieved by combining high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. Computer simulations using the transport of ions in matter model were applied to understand the ion surface interactions that revealed the key mechanism of the film growth. The final compositions of the films are significantly different from that of the target used. A trend of elemental segregation, which was more pronounced with higher ion kinetic energy, was observed. The XPS results reveal the formation of [Formula: see text] and [Formula: see text] on the thin film surface. The grain size is shown to increase with the increasing of the ion kinetic energy. The growth of equiaxed grains contributed to the formation of a flat surface with a relatively low surface roughness as shown by atomic force microscopy.

Plasma Activation of Microplates Optimized for One-Step Reagent-Free Immobilization of DNA and Protein.

Activated microplates are widely used in biological assays and cell culture to immobilize biomolecules, either through passive physical adsorption or covalent cross-linking. Covalent attachment gives greater stability in complex biological mixtures. However, current multistep chemical activation methods add complexity and cost, require specific functional groups, and can introduce cytotoxic chemicals that affect downstream cellular applications. Here, we show a method for one-step linker-free activation of microplates by energetic ions from plasma for covalent immobilization of DNA and protein. Two types of energetic ion plasma treatment were shown to be effective: plasma immersion ion implantation (PIII) and plasma-activated coating (PAC). This is the first time that PIII and PAC have been reported in microwell plates with nonflat geometry. We confirm that the plasma treatment generates radical-activated surfaces at the bottom of wells despite potential shadowing from the walls. Comprehensive surface characterization studies were used to compare the PIII and PAC microplate surface composition, wettability, radical density, optical properties, stability, and biomolecule immobilization density. PAC plates were found to have more nitrogen and lower radical density and were more hydrophobic and more stable over 3 months than PIII plates. Optimal conditions were obtained for high-density DNA (PAC, 0 or 21% nitrogen, pH 3-4) and streptavidin (PAC, 21% nitrogen, pH 5-7) binding while retaining optical properties required for typical high-throughput biochemical microplate assays, such as low autofluorescence and high transparency. DNA hybridization and protein activity of immobilized molecules were confirmed. We show that PAC activation allows for high-density covalent immobilization of functional DNA and protein in a single step on both 96- and 384-well plates without specific linker chemistry. These microplates could be used in the future to bind other user-selected ligands in a wide range of applications, for example, for solid phase polymerase chain reaction and stem cell culture and differentiation.

Biomimetic Culture Strategies for the Clinical Expansion of Mesenchymal Stromal Cells.

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.

Effect of Recombinant Human Perlecan Domain V Tethering Method on Protein Orientation and Blood Contacting Activity on Polyvinyl Chloride.

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.

Biomimetic silk biomaterials: Perlecan-functionalized silk fibroin for use in blood-contacting devices.

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.

Dry Surface Treatments of Silk Biomaterials and Their Utility in Biomedical Applications.

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.

Bioactivation of Encapsulation Membranes Reduces Fibrosis and Enhances Cell Survival.

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.

Atmospheric Pressure Plasma Jet Treatment of Polymers Enables Reagent-Free Covalent Attachment of Biomolecules for Bioprinting.

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-ε-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.

Covalent Biofunctionalization of the Inner Surfaces of a Hollow-Fiber Capillary Bundle Using Packed-Bed Plasma Ion Implantation.

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.

A multifaceted biomimetic interface to improve the longevity of orthopedic implants.

The rise of additive manufacturing has provided a paradigm shift in the fabrication of precise, patient-specific implants that replicate the physical properties of native bone. However, eliciting an optimal biological response from such materials for rapid bone integration remains a challenge. Here we propose for the first time a one-step ion-assisted plasma polymerization process to create bio-functional 3D printed titanium (Ti) implants that offer rapid bone integration. Using selective laser melting, porous Ti implants with enhanced bone-mimicking mechanical properties were fabricated. The implants were functionalized uniformly with a highly reactive, radical-rich polymeric coating generated using a unique combination of plasma polymerization and plasma immersion ion implantation. We demonstrated the performance of such activated Ti implants with a focus on the coating's homogeneity, stability, and biological functionality. It was shown that the optimized coating was highly robust and possessed superb physico-chemical stability in a corrosive physiological solution. The plasma activated coating was cytocompatible and non-immunogenic; and through its high reactivity, it allowed for easy, one-step covalent immobilization of functional biomolecules in the absence of solvents or chemicals. The activated Ti implants bio-functionalized with bone morphogenetic protein 2 (BMP-2) showed a reduced protein desorption and a more sustained osteoblast response both in vitro and in vivo compared to implants modified through conventional physisorption of BMP-2. The versatile new approach presented here will enable the development of bio-functionalized additively manufactured implants that are patient-specific and offer improved integration with host tissue. STATEMENT OF SIGNIFICANCE: Additive manufacturing has revolutionized the fabrication of patient-specific orthopedic implants. Although such 3D printed implants can show desirable mechanical and mass transport properties, they often require surface bio-functionalities to enable control over the biological response. Surface covalent immobilization of bioactive molecules is a viable approach to achieve this. Here we report the development of additively manufactured titanium implants that precisely replicate the physical properties of native bone and are bio-functionalized in a simple, reagent-free step. Our results show that covalent attachment of bone-related growth factors through ion-assisted plasma polymerized interlayers circumvents their desorption in physiological solution and significantly improves the bone induction by the implants both in vitro and in vivo.

Immobilized Macrophage Colony-Stimulating Factor (M-CSF) Regulates the Foreign Body Response to Implanted Materials.

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-1ß luciferase reporter mouse to detect real-time levels of IL-1ß 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-1ß, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-ß), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1ß activity in M-CSF functionalized scaffolds was ∼50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post-implantation. There were >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-ß 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-1ß; 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.

Bending shape memory behaviours of carbon fibre reinforced polyurethane-type shape memory polymer composites under relatively small deformation: Characterisation and computational simulation.

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.

Transparent Conductive Dielectric-Metal-Dielectric Structures for Electrochromic Applications Fabricated by High-Power Impulse Magnetron Sputtering.

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 the additional protective layer. X-ray photoelectron spectroscopy and X-ray diffraction data provided evidence that oxidation of the silver layer can be avoided, whilst stoichiometric WO3 structures are achieved. To achieve optimum WAW structures, we tuned the partial pressure of oxygen in the HiPIMS atmosphere applied for the deposition of WO3 layers. Our optimized WO3 (30 nm)/Ag (10 nm)/WO3 (50 nm) structure had a sheet resistance of 23.0 ± 0.4 Ω/□ and a luminous transmittance of 80.33 ± 0.07%. The HiPIMS coatings exhibited excellent long-term cycling stability for at least 2500 cycles, decent switching times (bleaching: 22.4 s, coloring: 15 s), and luminescence transmittance modulation (Δ T) of 34.5%. The HiPIMS strategy for the fabrication of ITO-free EC coatings for smart windows holds great promise to be extended to producing other metal-dielectric composite coatings for modern applications such as organic light-emitting diodes (OLEDs), liquid crystals, and wearable displays.

Enhanced biocompatibility of polyurethane-type shape memory polymers modified by plasma immersion ion implantation treatment and collagen coating: An in vivo study.

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 plasma ion bombardment process enabling reagent-free covalent binding of multiple functional molecules onto magnetic particles.

We report a plasma immersion ion implantation process for functionalizing polymer coated magnetic particles, converting them into a universal covalent binding platform for the simultaneous binding of multiple molecular agents without the need for specialised chemical linking groups. As an example, we demonstrate the improvement of wettability and the control of surface charge of polystyrene coated magnetic particles, enhancing biomolecule attachment density with strong covalent binding. We demonstrate the preparation of multifunctional magnetic particles where two or more types of molecule are co-immobilized. This enables a platform technology with simultaneous multiple covalent binding of molecules drawn from oligonucleotides, antibodies and enzymes suitable for targeted nanoparticle diagnostic and therapies.

Bioactive Materials Facilitating Targeted Local Modulation of Inflammation.

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.