Programmable polymer materials empowered by DNA nanotechnology

Over the past century, synthetic polymers have had a transformative impact on human life, replacing nature-derived materials in many areas. Yet, despite their many advantages, the structure and function of synthetic polymers still appear rudimentary compared to biological matter: cells use dynamic self-assembly to construct complex materials and operate sophisticated macromolecular devices. The field of DNA nanotechnology has demonstrated that synthetic DNA molecules can be programmed to undergo predictable self-assembly, offering unparalleled control over the formation and dynamic properties of artificial nanostructures. Intriguingly, the principles of DNA nanotechnology can be applied to the engineering of soft programmable materials, bringing the abilities of synthetic polymers closer to their biological counterparts. In this perspective, we discuss the unique features of DNA-functionalized polymer materials. We describe design principles that allow researchers to build complex supramolecular architectures with predictable and dynamically adjustable material properties. Finally, we highlight two key application areas where this biologically inspired material class offers particularly promising opportunities: (1) as dynamic matrices for 3D cell and organoid culture and (2) as smart materials for nucleic acid sequencing and pathogen detection.

Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine.

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS-CoV-2 vaccines require an initial two-shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations-scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune-escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, a single immunization SARS-CoV-2 subunit vaccine is developed that can rapidly generate potent, broad, and durable humoral immunity. Injectable polymer-nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND-NP) displaying multiple copies of the SARS-CoV-2 receptor-binding domain (RBD) and potent adjuvants including CpG and 3M-052. Compared to a clinically relevant prime-boost regimen with soluble vaccines formulated with CpG/alum or 3M-052/alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single-immunization hydrogel-based vaccines elicit potent and consistent neutralizing responses. Overall, it is shown that PNP hydrogels elicit improved anti-COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness.

Biodegradable Microrobots for DNA Vaccine Delivery.

The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two-photon polymerization of gelatin methacryloyl (GelMA) and their proof-of-concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrated the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.

Double-Network Protein Hydrogels as Flexible Pressure Sensors for Contactless Delivery

To meet the growing demand for sustainable development and ecofriendliness, hydrogels based on biopolymers have attracted widespread attention for developing flexible pressure sensors. Natural globular proteins exhibit great potential for developing biobased pressure sensors owing to their advantages of high water solubility, easy gelation, biocompatibility, and low production cost. However, realizing globular protein hydrogel-based sensors with interfacial and bulk toughness for pressure sensing and use in wearable devices remains a challenge. This study focuses on developing a high-performance flexible pressure sensor based on a biobased protein hydrogel. Consequently, a flexible protein/polyacrylamide (PAM) hydrogel with a featured double-network (DN) structure linked covalently with hydrogen bonds was first synthesized via a one-pot method based on natural ovalbumin (OVA). The unique DN structure of the as-synthesized OVA/PAM hydrogel affords excellent mechanical performance, flexibility, and adhesion properties. The mechanical properties of the DN hydrogel were enhanced after further cross-linking with Fe3+ and treatment with glycerol. Subsequently, the flexible pressure sensor was constructed by sandwiching a microstructured OVA/PAM dielectric layer between two flexible silver nanowire electrodes. The obtained sensor exhibits a high sensitivity of 2.9 kPa-1 and a short response time of 18 ms, ensuring the ability to monitor physiological signals. Based on its excellent performance, the fabricated sensor was used for monitoring the signals obtained using practical applications such as wrist bending, finger knocking, stretching, international Morse code, and pressure distribution. Particularly, we implemented a contactless delivery system using the fabricated OVA-based pressure sensors linked to unmanned vehicles and global positioning systems, providing a solution for low-risk commodity distribution during Coronavirus disease 2019 (COVID-19).

Double-Network Protein Hydrogels as Flexible Pressure Sensors for Contactless Delivery

To meet the growing demand for sustainable development and ecofriendliness, hydrogels based on biopolymers have attracted widespread attention for developing flexible pressure sensors. Natural globular proteins exhibit great potential for developing biobased pressure sensors owing to their advantages of high water solubility, easy gelation, biocompatibility, and low production cost. However, realizing globular protein hydrogel-based sensors with interfacial and bulk toughness for pressure sensing and use in wearable devices remains a challenge. This study focuses on developing a high-performance flexible pressure sensor based on a biobased protein hydrogel. Consequently, a flexible protein/polyacrylamide (PAM) hydrogel with a featured double-network (DN) structure linked covalently with hydrogen bonds was first synthesized via a one-pot method based on natural ovalbumin (OVA). The unique DN structure of the as-synthesized OVA/PAM hydrogel affords excellent mechanical performance, flexibility, and adhesion properties. The mechanical properties of the DN hydrogel were enhanced after further cross-linking with Fe3+ and treatment with glycerol. Subsequently, the flexible pressure sensor was constructed by sandwiching a microstructured OVA/PAM dielectric layer between two flexible silver nanowire electrodes. The obtained sensor exhibits a high sensitivity of 2.9 kPa-1 and a short response time of 18 ms, ensuring the ability to monitor physiological signals. Based on its excellent performance, the fabricated sensor was used for monitoring the signals obtained using practical applications such as wrist bending, finger knocking, stretching, international Morse code, and pressure distribution. Particularly, we implemented a contactless delivery system using the fabricated OVA-based pressure sensors linked to unmanned vehicles and global positioning systems, providing a solution for low-risk commodity distribution during Coronavirus disease 2019 (COVID-19). © 2023 American Chemical Society.

Hybrid Peptide–Agarose Hydrogels for 3D Immunoassays

Recent advances in biosensing analytical platforms have brought relevant outcomes for novel diagnostic and therapy-oriented applications. In this context, 3D droplet microarrays, where hydrogels are used as matrices to stably entrap biomolecules onto analytical surfaces, potentially provide relevant advantages over conventional 2D assays, such as increased loading capacity, lower nonspecific binding, and enhanced signal-to-noise ratio. Here, we describe a hybrid hydrogel composed of a self-assembling peptide and commercial agarose (AG) as a suitable matrix for 3D microarray bioassays. The hybrid hydrogel is printable and self-adhesive and allows analyte diffusion. As a showcase example, we describe its application in a diagnostic immunoassay for the detection of SARS-CoV-2 infection. © 2023, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Stretchable, self‐healable, and breathable biomimetic iontronics with superior humidity‐sensing performance for wireless respiration monitoring

Stretchable, self‐healing, and breathable skin‐biomimetic‐sensing iontronics play an important role in human physiological signal monitoring and human–computer interaction. However, previous studies have focused on the mimicking of skin tactile sensing (pressure, strain, and temperature), and the development of more functionalities is necessary. To this end, a superior humidity‐sensitive ionic skin is developed based on a self‐healing, stretchable, breathable, and biocompatible polyvinyl alcohol–cellulose nanofibers organohydrogel film, showing a pronounced thickness‐dependent humidity‐sensing performance. The as‐prepared 62.47‐μm‐thick organohydrogel film exhibits a high response (25,000%) to 98% RH, excellent repeatability, and long‐term stability (120 days). Moreover, this ionic skin has excellent resistance to large mechanical deformation and damage, and the worn‐out material can still retain its humidity‐sensing capabilities after self‐repair. Humidity‐sensing mechanism studies show that the induced response is mainly related to the increase of proton mobility and interfacial charge transport efficiency after water adsorption. The superior humidity responsiveness is attributed to the reduced thickness and the increased specific surface area of the organohydrogel film, allowing real‐time recording of physiological signals. Notably, by combining with a self‐designed printed circuit board, a continuous and wireless respiration monitoring system is developed, presenting its great potential in wearable and biomedical electronics.

Double Hydrogen-bonding Reinforced High-Performance Supramolecular Hydrogel Thermocell for Self-powered Sensing Remote-Controlled by Light

Non-contact human-machine interaction is the future trend for wearable technologies. This demand is recently highlighted by the pandemic of coronavirus disease (COVID-19). Herein, an anti-fatigue and highly conductive hydrogel thermocell with photo-thermal conversion ability for non-contact self-powering applications is designed. Double hydrogen-bonding enhanced supramolecular hydrogel is obtained with N-acryloyl glycinamide (NAGA) and diacrylate capped Pluronic F68 (F68-DA) via one-step photo-initiated polymerization. The supramolecular hydrogel can accommodate saturated electrolytes to fulfill the triple function of ionic crosslinking, heat-to-electricity conversion, and light response of thermocell. Eminently, the thermocell stands out by virtue of its high seebeck coefficient (-2.17 mV K−1) and extraordinary toughness (Fatigue threshold ≈ 3120 J m−2). The self-powering ability under the control of light heating is explored, and a model of a non-contact "light-remoted” sensor with self-powered and sensing integrated performance remote-controlled by light is constructed. It is believed that this study will pave the way for the non-contact energy supply of wearable devices. © 2023 Wiley-VCH GmbH.

Biologically Inspired: Fighting Germs Using HCIO Hydrogels with Smectites

Hypochlorous acid (HClO) is formed in the white blood cells of all mammals [1]. As part of a mechanism that developed several millions of years ago, it also helps the human body to protect against pathogens that enter it. This makes the weak acid a nature-based option for disinfection. Despite this, a disadvantage of water-thin solutions of hypochlorous acid is that they have significantly limited anti-microbial potential due to the reduced contact time. Hydrogels overcome this limitation and lead to improved and more sustainable use. Due to the high reactivity of hypochlorous acid, common additives such as polymer thickeners and natural clays are not suitable. Synthetic smectite clays -- of which the presented PURABYK-R 5500 is one example -- are very similar in structure to natural clays. However, due to their subsequent technical development, synthetic smectite clays exhibit better stability and are therefore very well suited to forming these hydrogels. They stabilize the hypochlorous acid in the required pH value range and are free from components that impair the activity of HClO. These unique additives are produced under controlled conditions from naturally occurring inorganic mineral sources. They offer the possibility of using structures from nature, paired with a very high purity and consistent quality. Their great potential is presented here using PURABYK-R 5500 as an example. [ FROM AUTHOR]

Synthetic Mucin Gels with Self-Healing Properties Augment Lubricity and Inhibit HIV-1 and HSV-2 Transmission.

Mucus is a self-healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel's mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%-5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature's example, bovine submaxillary mucins (BSMs) are assembled into "mucus-like" gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self-healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV-1) and genital herpes virus type 2 (HSV-2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV-1 significantly less and do not inhibit HSV-2. Mechanistically, the prophylaxis of HIV-1 infection by BSM gels is found to be that the gels trap HIV-1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission.

Hybrid Peptide-Agarose Hydrogels for 3D Immunoassays

Recent advances in biosensing analytical platforms have brought relevant outcomes for novel diagnostic and therapy-oriented applications. In this context, 3D droplet microarrays, where hydrogels are used as matrices to stably entrap biomolecules onto analytical surfaces, potentially provide relevant advantages over conventional 2D assays, such as increased loading capacity, lower nonspecific binding, and enhanced signal-to-noise ratio. Here, we describe a hybrid hydrogel composed of a self-assembling peptide and commercial agarose (AG) as a suitable matrix for 3D microarray bioassays. The hybrid hydrogel is printable and self-adhesive and allows analyte diffusion. As a showcase example, we describe its application in a diagnostic immunoassay for the detection of SARS-CoV-2 infection.

Impact of Surface Area on Sensitivity in Autonomously Reporting Sensing Hydrogel Nanomaterials for the Detection of Bacterial Enzymes

The rapid and selective detection of bacterial contaminations and bacterial infections in a non-laboratory setting using advanced sensing materials holds the promise to enable robust point-of-care tests and rapid diagnostics for applications in the medical field as well as food safety. Among the various possible analytes, bacterial enzymes have been targeted successfully in various sensing formats. In this current work, we focus on the systematic investigation of the role of surface area on the sensitivity in micro- and nanostructured autonomously reporting sensing hydrogel materials for the detection of bacterial enzymes. The colorimetric sensing materials for the detection of β-glucuronidase (ß-GUS) from Escherichia coli (E. coli) were fabricated by template replication of crosslinked pullulan acetoacetate (PUAA) and by electrospinning chitosan/polyethylene oxide nanofibers (CS/PEO NFs), both equipped with the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-D-glucuronide. The investigation of the dependence of the initial reaction rates on surface area unveiled a linear relationship of rate and thereby time to observe a signal for a given concentration of bacterial enzyme. This knowledge was exploited in nanoscale sensing materials made of CS/PEO NFs with diameters of 295 ± 100 nm. Compared to bulk hydrogel slabs, the rate of hydrolysis was significantly enhanced in NFs when exposed to bacteria suspension cultures and thus ensuring a rapid detection of living E. coli that produces the enzyme β-GUS. The findings afford generalized design principles for the improvement of known and novel sensing materials towards rapid detection of bacteria by nanostructuring in medical and food related settings.

COLLAGEN-PEPTIDE-BASED DRUG DELIVERY STRATEGIES

Collagen-targeting strategies have proven to be an effective method for targeting drugs to pathological tissues for treatment of disease. The use of collagen-like peptides for controlling the assembly of drug delivery vehicles, as well as their integration into collagen-containing matrices, offers significant advantages for tuning the morphologies of assembled structures, their thermoresponsiveness, and the loading and release of both small-molecule and macromolecular cargo. In this contribution, we summarize the design and development of collagen-peptide-based drug delivery systems introduced by the Kiick group and detail the expansion of our understanding and the application of these unique molecules through collaborations with experts in computational simulations (Jayaraman), osteoarthritis (Price), and gene delivery (Sullivan). Kiick was inducted as a Fellow of the National Academy of Inventors in 2019 and was to deliver an address describing the innovations of her research. Given the cancellation of the NAI Annual Meeting as a result of coronavirus travel restrictions, her work based on collagen-peptide-mediated assembly is instead summarized in this contribution.

LIGNIN VALORIZATION PROBLEMS

The review considers two directions of lignin valorization: valorization of technical lignins, as such, without preliminary depolymerization, and valorization through monomeric compounds formed as a result of their selective destruction. The first area includes the production of lignin hydrogels, the use of lignin in medicine and pharmacology, 3D printing, as well as in the production of carbon fibers and biofuels. Lignin hydrogels are distinguished by a high sorption capacity with respect to heavy metals such as lead, iron and copper, which, depending on the content of acidic groups in lignin and the molar mass of sorbate, is ~ 25-50% of the mass of lignin, and therefore they can be used for the purification of waste waters of chemical enterprises. Lignin has high biological activity against various pathogens, including viruses, which makes research in this area very relevant, especially against the backdrop of the COVID-19 pandemic. The use of lignin in some composites for 3D printing can increase the mechanical strength of finished products. The industrial implementation of the technology for the production of carbon fibers from lignin will ensure a twofold reduction in the mass of vehicles. The second direction of lignin valorization - hydrogenolysis and selective oxidation - allows one to obtain monomeric compounds with a yield close to the theoretical one. The economic aspects of valorization are also considered. In addition, based on a comparison of the results of valorization of coniferous and deciduous lignins, a hypothesis on the structure of native lignin was proposed. © 2022 Altai State University. All rights reserved.

A Review on Current Designation of Metallic Nanocomposite Hydrogel in Biomedical Applications

In the past few decades, nanotechnology has been receiving significant attention globally and is being continuously developed in various innovations for diverse applications, such as tissue engineering, biotechnology, biomedicine, textile, and food technology. Nanotechnological materials reportedly lack cell-interactive properties and are easily degraded into unfavourable products due to the presence of synthetic polymers in their structures. This is a major drawback of nanomaterials and is a cause of concern in the biomedicine field. Meanwhile, particulate systems, such as metallic nanoparticles (NPs), have captured the interest of the medical field due to their potential to inhibit the growth of microorganisms (bacteria, fungi, and viruses). Lately, researchers have shown a great interest in hydrogels in the biomedicine field due to their ability to retain and release drugs as well as to offer a moist environment. Hence, the development and innovation of hydrogel-incorporated metallic NPs from natural sources has become one of the alternative pathways for elevating the efficiency of therapeutic systems to make them highly effective and with fewer undesirable side effects. The objective of this review article is to provide insights into the latest fabricated metallic nanocomposite hydrogels and their current applications in the biomedicine field using nanotechnology and to discuss the limitations of this technology for future exploration. This article gives an overview of recent metallic nanocomposite hydrogels fabricated from bioresources, and it reviews their antimicrobial activities in facilitating the demands for their application in biomedicine. The work underlines the fabrication of various metallic nanocomposite hydrogels through the utilization of natural sources in the production of biomedical innovations, including wound healing treatment, drug delivery, scaffolds, etc. The potential of these nanocomposites in relation to their mechanical strength, antimicrobial activities, cytotoxicity, and optical properties has brought this technology into a new dimension in the biomedicine field. Finally, the limitations of metallic nanocomposite hydrogels in terms of their methods of synthesis, properties, and outlook for biomedical applications are further discussed.

Recent Advances in Mucoadhesive Interface Materials, Mucoadhesion Characterization, and Technologies

Mucoadhesion is an extremely important field of adhesion science and the comprehensive understanding and modulation of mucoadhesion can lead to lifesaving materials and technologies. For instance, deadly cases of COVID-19 (SARS-CoV-2) cytokine storm are associated with viral adhesion and overproduction of mucus, which obstructs the airways. Mucin is the key polymeric compound that is known as a family of high molecular weight, heavily glycosylated proteins in epithelial tissues. Mucoadhesion can occur in many different ways such as receptor specific and charge interactions, covalent or noncovalent bonds. New mucin-mimic polymers that replicate its beneficial traits can prevent biofilm formation and biofouling not only in biotechnology but also in membrane technologies. This review addresses the latest understandings related to mucin's role in wet adhesion considering different physiological conditions and shows how this translates into interfacial polymer adhesion. Advances in mucoadhesion measurement techniques including the rheological aspects of polymer-mucin adhesive interactions are presented. Specific mucoadhesive systems are discussed such as hydrogel mucoadhesion, catechol/dopamine functionalization, and polymeric nanoparticles. This overview may expand the current understanding of mucoadhesion between soft materials but also contributes to elastocapillary phenomena in soft materials design and applications such as new membranes, drugs, pharmaceutical devices, and lubricated surfaces.

Biocompatible Conductive Hydrogels: Applications in the Field of Biomedicine.

The impact of COVID-19 has rendered medical technology an important factor to maintain social stability and economic increase, where biomedicine has experienced rapid development and played a crucial part in fighting off the pandemic. Conductive hydrogels (CHs) are three-dimensional (3D) structured gels with excellent electrical conductivity and biocompatibility, which are very suitable for biomedical applications. CHs can mimic innate tissue's physical, chemical, and biological properties, which allows them to provide environmental conditions and structural stability for cell growth and serve as efficient delivery substrates for bioactive molecules. The customizability of CHs also allows additional functionality to be designed for different requirements in biomedical applications. This review introduces the basic functional characteristics and materials for preparing CHs and elaborates on their synthetic techniques. The development and applications of CHs in the field of biomedicine are highlighted, including regenerative medicine, artificial organs, biosensors, drug delivery systems, and some other application scenarios. Finally, this review discusses the future applications of CHs in the field of biomedicine. In summary, the current design and development of CHs extend their prospects for functioning as an intelligent and complex system in diverse biomedical applications.

Biocompatible Films of Calcium Alginate Inactivate Enveloped Viruses Such as SARS-CoV-2.

The current pandemic is urgently demanding the development of alternative materials capable of inactivating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus 2019 (COVID-19) disease. Calcium alginate is a crosslinked hydrophilic biopolymer with an immense range of biomedical applications due to its excellent chemical, physical, and biological properties. In this study, the cytotoxicity and antiviral activity of calcium alginate in the form of films were studied. The results showed that these films, prepared by solvent casting and subsequent crosslinking with calcium cations, are biocompatible in human keratinocytes and are capable of inactivating enveloped viruses such as bacteriophage phi 6 with a 1.43-log reduction (94.92% viral inactivation) and SARS-CoV-2 Delta variant with a 1.64-log reduction (96.94% viral inactivation) in virus titers. The antiviral activity of these calcium alginate films can be attributed to its compacted negative charges that may bind to viral envelopes inactivating membrane receptors.