Self-Adhesive and Self-Sustainable Bioelectronic Patch for Physiological Feedback Electronic Modulation of Soft Organs.

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.

Stability Study of Synthetic Diamond Using a Thermally Controlled Biological Environment: Application towards Long-Lasting Neural Prostheses.

This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode's enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.

Dynamic Regulation of Cell Mechanotransduction through Sequentially Controlled Mobile Surfaces.

The physical properties of nanoscale cell-extracellular matrix (ECM) ligands profoundly impact biological processes, such as adhesion, motility, and differentiation. While the mechanoresponse of cells to static ligands is well-studied, the effect of dynamic ligand presentation with "adaptive" properties on cell mechanotransduction remains less understood. Utilizing a controllable diffusible ligand interface, we demonstrated that cells on surfaces with rapid ligand mobility could recruit ligands through activating integrin α5ß1, leading to faster focal adhesion growth and spreading at the early adhesion stage. By leveraging UV-light-sensitive anchor molecules to trigger a "dynamic to static" transformation of ligands, we sequentially activated α5ß1 and αvß3 integrins, significantly promoting osteogenic differentiation of mesenchymal stem cells. This study illustrates how manipulating molecular dynamics can directly influence stem cell fate, suggesting the potential of "sequentially" controlled mobile surfaces as adaptable platforms for engineering smart biomaterial coatings.

Liquid Metal-Enabled Epidermal Interfaces.

Soft materials are crucial for epidermal interfaces in biomedical devices due to their capability to conform to the body compared to rigid inorganic materials. Gels, liquids, and polymers have been extensively explored, but they lack sufficient electrical and thermal conductivity required for many application settings. Gallium-based alloys are molten metals at room temperature with exceptional electrical and thermal conductivity. These liquid metals and their composites can be directly applied onto the skin as interface materials. In this Spotlight on Applications, we focus on the rapidly evolving field of liquid metal-enabled epidermal interfaces featuring unique physical properties beyond traditional gels and polymers. We delve into the role of liquid metal in electrical and thermal biointerfaces in various epidermal applications. Current challenges and future directions in this active area are also discussed.

Piercing of the Human Parainfluenza Virus by Nanostructured Surfaces.

This paper presents a comprehensive experimental and theoretical investigation into the antiviral properties of nanostructured surfaces and explains the underlying virucidal mechanism. We used reactive ion etching to fabricate silicon (Si) surfaces featuring an array of sharp nanospikes with an approximate tip diameter of 2 nm and a height of 290 nm. The nanospike surfaces exhibited a 1.5 log reduction in infectivity of human parainfluenza virus type 3 (hPIV-3) after 6 h, a substantially enhanced efficiency, compared to that of smooth Si. Theoretical modeling of the virus-nanospike interactions determined the virucidal action of the nanostructured substrata to be associated with the ability of the sharp nanofeatures to effectively penetrate the viral envelope, resulting in the loss of viral infectivity. Our research highlights the significance of the potential application of nanostructured surfaces in combating the spread of viruses and bacteria. Notably, our study provides valuable insights into the design and optimization of antiviral surfaces with a particular emphasis on the crucial role played by sharp nanofeatures in maximizing their effectiveness.

Nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) with repercussions toward apoptosis, necrosis, and cancer necrosis factor (TNF-α) at nano-biointerfaces.

Introduction: Apoptosis, necrosis, and cancer necrosis factor (TNF-a) are all impacted by the nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) at nano-biointerfaces. The creation of multi-functional nanoparticles has had a considerable impact on the transport of drugs and genes, nanotheranostics (in-vivo imaging, concurrent diagnostics), interventions for external healing, the creation of nano-bio interfaces, and the instigation of desired changes in nanotherapeutics. Objectives: The quantitative structure-activity relationships, chemical transformations, biological interactions as well as toxicological analyses are considered as main objectives. Discrete dimensions of SCoNPs-cell interaction interfaces, their characteristic physical features (size, shape, shell structure, and surface chemistry), impact on cell proliferation and differentiation are the key factors responsible for nanotoxicity. Methods: The development of multi-functional nanoparticles has been significant in drug/gene delivery, nanotheranostics (in-vivo imaging, coinciding diagnostics), and external healing interventions, designing a nano-bio interface, as well as inciting desired alterations in nanotherapeutics. Every so often, the cellular uptake of multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoONPs) influences cellular mechanics and initiates numerous repercussions (oxidative stress, DNA damage, cytogenotoxicity, and chromosomal damage) in pathways, including the generation of dysregulating factors involved in biochemical transformations. Results: The concerns and influences of multifunctional SCoNPs on different cell mechanisms (mitochondria impermeability, hydrolysis of ATP, the concentration of Ca2+, impaired calcium clearance, defective autophagy, apoptosis, and necrosis), and interlinked properties (adhesion, motility, and internalization dynamics, role in toxicity, surface hydrophilic and hydrophobicity, biokinetics and biomimetic behaviors of biochemical reactions) have also been summarized. SCoONPs have received a lot of interest among the nanocarriers family because of its advantageous qualities such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity. Conclusion: Various applications, such as bio-imaging, cell labeling, gene delivery, enhanced chemical stability, and increased biocompatibility, concerning apoptosis, necrosis, and nano-bio interfaces, along with suitable examples. In this analysis, the multi-functional cobalt [Co, CoO, Co2(CO)8 and Co3O4] nanoparticles (SCoNPs) intricacies (cytogenotoxicity, clastogenicity, and immunomodulatory), nanotoxicity, and associated repercussions have been highlighted and explained.

Metallic Micro-Nano Network-Based Soft Transparent Electrodes: Materials, Processes, and Applications.

Soft transparent electrodes (TEs) have received tremendous interest from academia and industry due to the rapid development of lightweight, transparent soft electronics. Metallic micro-nano networks (MMNNs) are a class of promising soft TEs that exhibit excellent optical and electrical properties, including low sheet resistance and high optical transmittance, as well as superior mechanical properties such as softness, robustness, and desirable stability. They are genuinely interesting alternatives to conventional conductive metal oxides, which are expensive to fabricate and have limited flexibility on soft surfaces. This review summarizes state-of-the-art research developments in MMNN-based soft TEs in terms of performance specifications, fabrication methods, and application areas. The review describes the implementation of MMNN-based soft TEs in optoelectronics, bioelectronics, tactile sensors, energy storage devices, and other applications. Finally, it presents a perspective on the technical difficulties and potential future possibilities for MMNN-based TE development.

Intratumor delivery of amino-modified graphene oxide as a multifunctional photothermal agent for efficient antitumor phototherapy.

Due to the high selectivity and non-invasive property, phototherapy has attracted increasing attention in the treatment of cancer. Targeted delivery and retention of photoactive agents in tumor tissue is of great significance and importance for safe and efficient phototherapy. Herein, we report a multifunctional nanomaterial photothermal agent, namely amino-modified graphene oxide (AGO) for anti-oral cancer photothermal therapy (PTT). Compared to the parental graphene oxide (GO) which has a negative charge and weak photothermal effect, AGO possesses a positive charge (∼+50 mV) and the significantly enhanced photothermal effect. Positive charge allows AGO to efficiently interact with tumor cells and retain in tumor tissue after intratumor injection. The enhanced photothermal effect allows AGO to achieve the tunable and efficient PTT. In vitro results show that AGO (15 µg/mL) reduces the viability of HSC-3 cells (oral squamous cell carcinoma cell line) to 5% under near infrared (NIR) irradiation (temperature increased to 58.4 °C). In vivo antitumor study shows that intratumor delivery of AGO (200 µg/mouse) has no inhibition effects on tumor growth (454% of initial tumor size) without NIR. With a single dose of NIR irradiation, however, AGO significantly reduces the tumor size to 25% of initial size in 1 of 4 mice, and even induces the complete tumor ablation in 3 of 4 mice. Furthermore, the injected AGO falls off along with the scab after PTT. Our findings indicate that AGO is a potential nano-photothermal agent for tunable, convenient and efficient anticancer PTT.

Development of Mesoporous Silica Nanoparticle-Based Films with Tunable Arginine-Glycine-Aspartate Peptide Global Density and Clustering Levels to Study Stem Cell Adhesion and Differentiation.

Stem cell adhesion is mediated via the binding of integrin receptors to adhesion motifs present in the extracellular matrix (ECM). The spatial organization of adhesion ligands plays an important role in stem cell integrin-mediated adhesion. In this study, we developed a series of biointerfaces using arginine-glycine-aspartate (RGD)-functionalized mesoporous silica nanoparticles (MSN-RGD) to study the effect of RGD adhesion ligand global density (ligand coverage over the surface), spacing, and RGD clustering levels on stem cell adhesion and differentiation. To prepare the biointerface, MSNs were chemically functionalized with RGD peptides via an antifouling poly(ethylene glycol) (PEG) linker. The RGD surface functionalization ratio could be controlled to create MSNs with high and low RGD ligand clustering levels. MSN films with varying RGD global densities could be created by blending different ratios of MSN-RGD and non-RGD-functionalized MSNs together. A computational simulation study was performed to analyze nanoparticle distribution and RGD spacing on the resulting surfaces to determine experimental conditions. Enhanced cell adhesion and spreading were observed when RGD global density increased from 1.06 to 5.32 nmol cm-2 using highly clustered RGD-MSN-based films. Higher RGD ligand clustering levels led to larger cell spreading and increased formation of focal adhesions. Moreover, a higher RGD ligand clustering level promoted the expression of alkaline phosphatase in hMSCs. Overall, these findings indicate that both RGD global density and clustering levels are crucial variables in regulating stem cell behaviors. This study provides important information about ligand-integrin interactions, which could be implemented into biomaterial design to achieve optimal performance of adhesive functional peptides.

Adsorption of Ferritin at Nanofaceted Al2O3 Surfaces.

The influence of nanoscale surface topography on protein adsorption is highly important for numerous applications in medicine and technology. Herein, ferritin adsorption at flat and nanofaceted, single-crystalline Al2O3 surfaces is investigated using atomic force microscopy and X-ray photoelectron spectroscopy. The nanofaceted surfaces are generated by the thermal annealing of Al2O3 wafers at temperatures above 1000 °C, which leads to the formation of faceted saw-tooth-like surface topographies with periodicities of about 160 nm and amplitudes of about 15 nm. Ferritin adsorption at these nanofaceted surfaces is notably suppressed compared to the flat surface at a concentration of 10 mg/mL, which is attributed to lower adsorption affinities of the newly formed facets. Consequently, adsorption is restricted mostly to the pattern grooves, where the proteins can maximize their contact area with the surface. However, this effect depends on the protein concentration, with an inverse trend being observed at 30 mg/mL. Furthermore, different ferritin adsorption behavior is observed at topographically similar nanofacet patterns fabricated at different annealing temperatures and attributed to different step and kink densities. These results demonstrate that while protein adsorption at solid surfaces can be notably affected by nanofacet patterns, fine-tuning protein adsorption in this way requires the precise control of facet properties.

Multiprotein Adsorption from Human Serum at Gold and Oxidized Iron Surfaces Studied by Atomic Force Microscopy and Polarization-Modulation Infrared Reflection Absorption Spectroscopy.

Multiprotein adsorption from complex body fluids represents a highly important and complicated phenomenon in medicine. In this work, multiprotein adsorption from diluted human serum at gold and oxidized iron surfaces is investigated at different serum concentrations and pH values. Adsorption-induced changes in surface topography and the total amount of adsorbed proteins are quantified by atomic force microscopy (AFM) and polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS), respectively. For both surfaces, stronger protein adsorption is observed at pH 6 compared to pH 7 and pH 8. PM-IRRAS furthermore provides some qualitative insights into the pH-dependent alterations in the composition of the adsorbed multiprotein films. Changes in the amide II/amide I band area ratio and in particular side-chain IR absorption suggest that the increased adsorption at pH 6 is accompanied by a change in protein film composition. Presumably, this is mostly driven by the adsorption of human serum albumin, which at pH 6 adsorbs more readily and thereby replaces other proteins with lower surface affinities in the resulting multiprotein film.

Polyglycerol-Based Biomedical Matrix for Immunomagnetic Circulating Tumor Cell Isolation and Their Expansion into Tumor Spheroids for Drug Screening.

Circulating tumor cells (CTCs) are established as distinct cancer biomarkers for diagnosis, as preclinical models, and therapeutic targets. Their use as preclinical models is limited owing to low purity after isolation and the lack of effective techniques to create 3D cultures that accurately mimic in vivo conditions. Herein, a two-component system for detecting, isolating, and expanding CTCs to generate multicellular tumor spheroids that mimic the physiology and microenvironment of the diseased organ is proposed. First, an antifouling biointerface on magnetic beads is fabricated by adding a bioinert polymer layer and conjugation of biospecific ligands to isolate cancer cells, dramatically enhancing the selectivity and purity of the isolated cancer cells. Next, the isolated cells are encapsulated into self-degradable hydrogels synthesized using a thiol-click approach. The hydrogels are mechanochemically tuned to enable tumor spheroid growth to a size greater than 300 µm and to further release the grown spheroids while retaining their tumor-like characteristics. In addition, drug treatment highlights the need for 3D culture environments rather than conventional 2D culture. The designed biomedical matrix shows potential as a universal method to ensure mimicry of in vivo tumor characteristics in individual patients and to improve the predictability of preclinical screening of personalized therapeutics.

Mechanically-Compliant Bioelectronic Interfaces through Fatigue-Resistant Conducting Polymer Hydrogel Coating.

Because of their distinct electrochemical and mechanical properties, conducting polymer hydrogels have been widely exploited as soft, wet, and conducting coatings for conventional metallic electrodes, providing mechanically compliant interfaces and mitigating foreign body responses. However, the long-term viability of these hydrogel coatings is hindered by concerns regarding fatigue crack propagation and/or delamination caused by repetitive volumetric expansion/shrinkage during long-term electrical interfacing. This study reports a general yet reliable approach to achieving a fatigue-resistant conducting polymer hydrogel coating on conventional metallic bioelectrodes by engineering nanocrystalline domains at the interface between the hydrogel and metallic substrates. It demonstrates the efficacy of this robust, biocompatible, and fatigue-resistant conducting hydrogel coating in cardiac pacing, showcasing its ability to effectively reduce the pacing threshold voltage and enhance the long-term reliability of electric stimulation. This study findings highlight the potential of its approach as a promising design and fabrication strategy for the next generation of seamless bioelectronic interfaces.

Specific Clearance of Lipopolysaccharide from Blood Based on Peptide Bottlebrush Polymer for Sepsis Therapy.

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.

Fluorescence-Based Measurements of Two-Dimensional Affinity in Membrane Interfaces.

Binding between ligands and receptors across cell contacts influences a range of biological processes including the formation of the immune synapse. The dissociation constant (Kd = 1/affinity) of the interaction corresponds to the concentration of ligands where half of the receptors in the contact have bound a ligand. In this chapter, we outline how to measure this two-dimensional affinity using model cell membranes called supported lipid bilayers (SLBs) functionalized with fluorescently labeled ligands that bind to cells containing the corresponding receptor. The affinity is calculated from the accumulation of ligands at the cell-SLB interface, while the use of different fluorescent tags, and/or unlabeled molecules, makes it possible to include various binding pairs in the contact to better mimic the conditions of binding in vivo.

Perfusable Biohybrid Designs for Bioprinted Skeletal Muscle Tissue.

Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival, and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately coprinted with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that i) coprinted synthetic structures display highly coherent interfaces with the living tissue, ii) perfusable designs preserve cells from hypoxia all over the scaffold volume, iii) constructs can undergo passive mechanical tension during matrix remodeling, and iv) the constructs can be used to study the distribution of drugs. Extrusion-based multimaterial bioprinting with the inks and design realizes in vitro matured biohybrid SMT for biomedical applications.

The Year 2022 in biomaterials research: A perspective from the editors of six leading journals.

The field of biomaterials science is highly active, with a steadily increasing number of publications and new journals being founded. This article brings together contributions from the editors of six leading journals in the area of biomaterials science and engineering. Each contributor highlights specific advances, topics, and trends that have emerged through the publications in their respective journal in the calendar year 2022. It presents a global perspective on a wide range of material types, functionalities, and applications. The highlighted topics include a diversity of biomaterials; from proteins, polysaccharides, and lipids to ceramics, metals, advanced composites, and a variety of new forms of these materials. Important advances in dynamically functional materials are presented, including a range of fabrication techniques such as bioassembly, 3D bioprinting and microgel formation. Similarly, several applications are highlighted in drug and gene delivery, biological sensing, cell guidance, immunoengineering, electroconductivity, wound healing, infection resistance, tissue engineering, and treatment of cancer. The goal of this paper is to provide the reader with both a broad view of recent biomaterials research, as well as expert commentary on some of the key advances that will shape the future of biomaterials science and engineering.

Functionalization of 3D Printed Scaffolds Using Polydopamine and Silver Nanoparticles for Bone-Interfacing Applications.

The prevention of bacterial colonization and the stimulation of osseointegration are two major requirements for bone-interfacing materials to reduce the incidence of complications and promote the restoration of the patient's health. The present investigation developed an effective, two-step functionalization of 3D printed scaffolds intended for bone-interfacing applications using a simple polydopamine (PDA) dip-coating method followed by the formation of silver nanoparticles (AgNPs) after a second coating step in silver nitrate. 3D printed polymeric substrates coated with a ∼20 nm PDA layer and 70 nm diameter AgNPs proved effective in hindering Staphylococcus aureus biofilm formation, with a 3000-8000-fold reduction in the number of bacterial colonies formed. The implementation of porous geometries significantly accelerated osteoblast-like cell growth. Microscopy characterization further elucidated homogeneity, features, and penetration of the coating inside the scaffold. A proof-of-concept coating on titanium substrates attests to the transferability of the method to other materials, broadening the range of applications both in and outside the medical sector. The antibacterial efficiency of the coating is likely to lead to a decrease in the number of bacterial infections developed after surgery in the presence of these coatings on prosthetics, thus translating to a reduction in revision surgeries and improved health outcomes.

Real-Time Monitoring and Early Warning of a Cytokine Storm In Vivo Using a Wearable Noninvasive Skin Microneedle Patch.

A cytokine storm may be the last attack of various diseases, such as sepsis, cancer, and coronavirus disease 2019, that can be life threatening. Real-time monitoring of cytokines in vivo is helpful for assessing the immune status of patients and providing an early warning of a cytokine storm. In this study, a functional carbon nanotube biointerface-based wearable microneedle patches for real-time monitoring of a cytokine storm in vivo via electrochemical analysis are reported. This wearable system has sensitivity with a detection limit of 0.54 pg mL-1 , high specificity, and 5 days of stability with a coefficient of variation of 4.0%. The system also has a quick response of several hours (1-4 h) to increasing cytokines. This wearable microneedle patch may offer a promising route for real-time biomolecule wearables construction. The patch is also the first reported integrated capture and monitoring system that is capable of real-time measurement of protein markers in interstitial fluid.