Showing papers in "Advanced Healthcare Materials in 2021"

Wound Healing: From Passive to Smart Dressings.

Abstract: The universal increase in the number of patients with nonhealing skin wounds imposes a huge social and economic burden on the patients and healthcare systems. Although, the application of traditional wound dressings contributes to an effective wound healing outcome, yet, the complexity of the healing process remains a major health challenge. Recent advances in materials and fabrication technologies have led to the fabrication of dressings that provide proper conditions for effective wound healing. The 3D-printed wound dressings, biomolecule-loaded dressings, as well as smart and flexible bandages are among the recent alternatives that have been developed to accelerate wound healing. Additionally, the new generation of wound dressings contains a variety of microelectronic sensors for real-time monitoring of the wound environment and is able to apply required actions to support the healing progress. Moreover, advances in manufacturing flexible microelectronic sensors enable the development of the next generation of wound dressing substrates, known as electronic skin, for real-time monitoring of the whole physiochemical markers in the wound environment in a single platform. The current study reviews the importance of smart wound dressings as an emerging strategy for wound care management and highlights different types of smart dressings for promoting the wound healing process.

A Hydrogen-Bonded Extracellular Matrix-Mimicking Bactericidal Hydrogel with Radical Scavenging and Hemostatic Function for pH-Responsive Wound Healing Acceleration.

Abstract: Generation of reactive oxygen species, delayed blood clotting, prolonged inflammation, bacterial infection, and slow cell proliferation are the main challenges of effective wound repair. Herein, a multifunctional extracellular matrix-mimicking hydrogel is fabricated through abundant hydrogen bonding among the functional groups of gelatin and tannic acid (TA) as a green chemistry approach. The hydrogel shows adjustable physicochemical properties by altering the concentration of TA and it represents high safety features both in vitro and in vivo on fibroblasts, red blood cells, and mice organs. In addition to the merit of facile encapsulation of cell proliferation-inducing hydrophilic drugs, accelerated healing of skin injury is obtained through pH-dependent release of TA and its multifaceted mechanisms as an antibacterial, antioxidant, hemostatic, and anti-inflammatory moiety. The developed gelatin-TA (GelTA) hydrogel also shows an outstanding effect on the formation of extracellular matrix and wound closure in vivo via offered cell adhesion sites in the backbone of gelatin that provide increased re-epithelialization and better collagen deposition. These results suggest that the multifunctional GelTA hydrogel is a promising candidate for the clinical treatment of full-thickness wounds and further development of wound dressing materials that releases active agents in the neutral or slightly basic environment of infected nonhealing wounds.

Noble Metal Nanomaterials for NIR-Triggered Photothermal Therapy in Cancer

Abstract: It is of great significance to develop anticancer therapeutic agents or technologies with high degree of specificity and patient compliance, while low toxicity. The emerging photothermal therapy (PTT) has become a new and powerful therapeutic technology due to its noninvasiveness, high specificity, low side effects to normal tissues and strong anticancer efficacy. Noble metal nanomaterials possess strong surface plasmon resonance (SPR) effect and synthetic tunability, which make them facile and effective PTT agents with superior optical and photothermal characteristics, such as high absorption cross-section, incomparable optical-thermal conversion efficiency in the near infrared (NIR) region, as well as the potential of bioimaging. By incorporating with various functional reagents such as antibodies, peptides, biocompatible polymers, chemo-drug and immune factors, noble metal nanomaterials have presented strong potential in multifunctional cancer therapy. Herein, the recent development regarding the application of noble metal nanomaterials for NIR-triggered PTT in cancer treatment is summarized. A variety of studies with good therapeutic effects against cancer from impressive photothermal efficacy of noble metal nanomaterials are concluded. Intelligent nanoplatforms through ingenious fabrication showing potential of multifunctional PTT, combined with chemo-therapy, immunotherapy, photodynamic therapy (PDT), as well as simultaneous imaging modality are also demonstrated.

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

Abstract: Injectable hydrogels have received considerable interest in the biomedical field due to their potential applications in minimally invasive local drug delivery, more precise implantation, and site-specific drug delivery into poorly reachable tissue sites and into interface tissues, where wound healing takes a long time. Injectable hydrogels, such as in situ forming and/or shear-thinning hydrogels, can be generated using chemically and/or physically crosslinked hydrogels. Yet, for controlled and local drug delivery applications, the ideal injectable hydrogel should be able to provide controlled and sustained release of drug molecules to the target site when needed and should limit nonspecific drug molecule distribution in healthy tissues. Thus, such hydrogels should sense the environmental changes that arise in disease states and be able to release the optimal amount of drug over the necessary time period to the target region. To address this, researchers have designed stimuli-responsive injectable hydrogels. Stimuli-responsive hydrogels change their shape or volume when they sense environmental stimuli, e.g., pH, temperature, light, electrical signals, or enzymatic changes, and deliver an optimal concentration of drugs to the target site without affecting healthy tissues.

Polymers for Melt Electrowriting

Abstract: Melt electrowriting (MEW) is an emerging high-resolution additive manufacturing technique based on the electrohydrodynamic processing of polymers. MEW is predominantly used to fabricate scaffolds for biomedical applications, where the microscale fiber positioning has substantial implications in its macroscopic mechanical properties. This review gives an update on the increasing number of polymers processed via MEW and different commercial sources of the gold standard poly(e-caprolactone) (PCL). A description of MEW-processed polymers beyond PCL is introduced, including blends and coated fibers to provide specific advantages in biomedical applications. Furthermore, a perspective on printer designs and developments is highlighted, to keep expanding the variety of processable polymers for MEW.

Selenium Nanoparticles for Biomedical Applications: From Development and Characterization to Therapeutics.

Abstract: Selenium (Se) is an essential element to human health that can be obtained in nature through several sources. In the human body, it is incorporated into selenocysteine, an amino acid used to synthesize several selenoproteins, which have an active center usually dependent on the presence of Se. Although Se shows several beneficial properties in human health, it has also a narrow therapeutic window, and therefore the excessive intake of inorganic and organic Se-based compounds often leads to toxicity. Nanoparticles based on Se (SeNPs) are less toxic than inorganic and organic Se. They are both biocompatible and capable of effectively delivering combinations of payloads to specific cells following their functionalization with active targeting ligands. Herein, the main origin of Se intake, its role on the human body, and its primary biomedical applications are revised. Particular focus will be given to the main therapeutic targets that are explored for SeNPs in cancer therapies, discussing the different functionalization methodologies used to improve SeNPs stability, while enabling the extensive delivery of drug-loaded SeNP to tumor sites, thus avoiding off-target effects.

Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery.

Abstract: Nucleic acid vaccines are a method of immunization aiming to elicit immune responses akin to live attenuated vaccines. In this method, DNA or messenger RNA (mRNA) sequences are delivered to the body to generate proteins, which mimic disease antigens to stimulate the immune response. Advantages of nucleic acid vaccines include stimulation of both cell-mediated and humoral immunity, ease of design, rapid adaptability to changing pathogen strains, and customizable multiantigen vaccines. To combat the SARS-CoV-2 pandemic, and many other diseases, nucleic acid vaccines appear to be a promising method. However, aid is needed in delivering the fragile DNA/mRNA payload. Many delivery strategies have been developed to elicit effective immune stimulation, yet no nucleic acid vaccine has been FDA-approved for human use. Nanoparticles (NPs) are one of the top candidates to mediate successful DNA/mRNA vaccine delivery due to their unique properties, including unlimited possibilities for formulations, protective capacity, simultaneous loading, and delivery potential of multiple DNA/mRNA vaccines. This review will summarize the many varieties of novel NP formulations for DNA and mRNA vaccine delivery as well as give the reader a brief synopsis of NP vaccine clinical trials. Finally, the future perspectives and challenges for NP-mediated nucleic acid vaccines will be explored.

Combination Therapy of Killing Diseases by Injectable Hydrogels: From Concept to Medical Applications

Abstract: The complexity of hard-to-treat diseases strongly undermines the therapeutic potential of available treatment options. Therefore, a paradigm shift from monotherapy toward combination therapy has been observed in clinical research to improve the efficiency of available treatment options. The advantages of combination therapy include the possibility of synchronous alteration of different biological pathways, reducing the required effective therapeutic dose, reducing drug resistance, and lowering the overall costs of treatment. The tunable physical properties, excellent biocompatibility, facile preparation, and ease of administration with minimal invasiveness of injectable hydrogels (IHs) have made them excellent candidates to solve the clinical and pharmacological limitations of present systems for multitherapy by direct delivery of therapeutic payloads and improving therapeutic responses through the formation of depots containing drugs, genes, cells, or a combination of them in the body after a single injection. In this review, currently available methods for the design and fabrication of IHs are systematically discussed in the first section. Next, as a step toward establishing IHs for future multimodal synergistic therapies, recent advances in cancer combination therapy, wound healing, and tissue engineering are addressed in detail in the following sections. Finally, opportunities and challenges associated with IHs for multitherapy are listed and further discussed.

Accelerated Skin Wound Healing by Electrical Stimulation.

Abstract: When the integrity of the skin got damaged, an endogenous electric field will be generated in the wound and a series of physiological reactions will be initiated to close the wound. The existence of the endogenous electric field of the wound has a promoting effect on all stages of wound healing. For wounds that cannot heal on their own, the exogenous electric field can assist the treatment. In this review, the effects of exogenous electrical stimulation on wound healing, such as the inflammation phase, blood flow, cell proliferation and migration, and the wound scarring is overviewed. This article also reviews the new electrical stimulation methods that have emerged in recent years, such as small power supplies, nanogenerators (NGs), and other physical, chemical or biological strategies. These new electrical stimulation methods and devices are safe, low-cost, stable, and small in size. The challenge and perspective are discussed for the future trends of the electrical stimulation treatment in accelerating skin wound healing.

Hydrogels and Their Role in Biosensing Applications

Abstract: Hydrogels play an important role in the field of biomedical research and diagnostic medicine. They are emerging as a powerful tool in the context of bioanalytical assays and biosensing. In this context, this review gives an overview of different hydrogels and the role they adopt in a range of applications. Not only are hydrogels beneficial for the immobilization and embedding of biomolecules, but they are also used as responsive material, as wearable devices, or as functional material. In particular, the scientific and technical progress during the last decade is discussed. The newest hydrogel types, their synthesis, and many applications are presented. Advantages and performance improvements are described, along with their limitations.

In Situ Synthesized Selenium Nanoparticles-Decorated Bacterial Cellulose/Gelatin Hydrogel with Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Capabilities for Facilitating Skin Wound Healing.

Abstract: Bacterial-associated wound infection and antibiotic resistance have posed a major burden on patients and health care systems. Thus, developing a novel multifunctional antibiotic-free wound dressing that cannot only effectively prevent wound infection, but also facilitate wound healing is urgently desired. Herein, a series of multifunctional nanocomposite hydrogels with remarkable antibacterial, antioxidant, and anti-inflammatory capabilities, based on bacterial cellulose (BC), gelatin (Gel), and selenium nanoparticles (SeNPs), are constructed for wound healing application. The BC/Gel/SeNPs nanocomposite hydrogels exhibit excellent mechanical properties, good swelling ability, flexibility and biodegradability, and favorable biocompatibility, as well as slow and sustainable release profiles of SeNPs. The decoration of SeNPs endows the hydrogels with superior antioxidant and anti-inflammatory capability, and outstanding antibacterial activity against both common bacteria (E. coli and S. aureus) and their multidrug-resistant counterparts. Furthermore, the BC/Gel/SeNPs hydrogels show an excellent skin wound healing performance in a rat full-thickness defect model, as evidenced by the significantly reduced inflammation, and the notably enhanced wound closure, granulation tissue formation, collagen deposition, angiogenesis, and fibroblast activation and differentiation. This study suggests that the developed multifunctional BC/Gel/SeNPs nanocomposite hydrogel holds a great promise as a wound dressing for preventing wound infection and accelerating skin regeneration in clinic.

Lab under the Skin: Microneedle Based Wearable Devices.

Abstract: While the current smartwatches and cellphones can readily track mobility and vital signs, a new generation of wearable devices is rapidly developing to enable users to monitor their health parameters at the molecular level. Within this emerging class of wearables, microneedle-based transdermal sensors are in a prime position to play a key role in synergizing the significant advantages of dermal interstitial fluid (ISF) as a rich source of clinical indicators and painless skin pricking to allow the collection of real-time diagnostic information. While initial efforts of microneedle sensing focused on ISF extraction coupled with either on-chip analysis or off-chip instrumentation, the latest trend has been oriented toward assembling electrochemical biosensors on the tip of microneedles to allow direct continuous chemical measurements. In this context, significant advances have recently been made in exploiting microneedle-based devices for real-time monitoring of various metabolites, electrolytes, and therapeutics and toward the simultaneous multiplexed detection of key chemical markers; yet, there are several grand challenges that still exist. In this review, we outline current progress, recent trends, and new capabilities of microneedle-empowered sensors, along with the current unmet challenges and a future roadmap toward transforming the latest innovations in the field to commercial products.

Liposomes and Extracellular Vesicles as Drug Delivery Systems: A Comparison of Composition, Pharmacokinetics, and Functionalization.

Abstract: Over the past decades, lipid-based nanoparticle drug delivery systems (DDS) have caught the attention of researchers worldwide, encouraging the field to rapidly develop improved ways for effective drug delivery. One of the most prominent examples is liposomes, which are spherical shaped artificial vesicles composed of lipid bilayers and able to encapsulate both hydrophilic and hydrophobic materials. At the same time, biological nanoparticles naturally secreted by cells, called extracellular vesicles (EVs), have emerged as promising more complex biocompatible DDS. In this review paper, the differences and similarities in the composition of both vesicles are evaluated, and critical mediators that affect their pharmacokinetics are elucidate. Different strategies that have been assessed to tweak the pharmacokinetics of both liposomes and EVs are explored, detailing the effects on circulation time, targeting capacity, and cytoplasmic delivery of therapeutic cargo. Finally, whether a hybrid system, consisting of a combination of only the critical constituents of both vesicles, could offer the best of both worlds is discussed. Through these topics, novel leads for further research are provided and, more importantly, gain insight in what the liposome field and the EV field can learn from each other.

Flexible Wearable Sensors for Cardiovascular Health Monitoring.

Abstract: Cardiovascular diseases account for the highest mortality globally, but recent advances in wearable technologies may potentially change how these illnesses are diagnosed and managed. In particular, continuous monitoring of cardiovascular vital signs for early intervention is highly desired. To this end, flexible wearable sensors that can be comfortably worn over long durations are gaining significant attention. In this review, advanced flexible wearable sensors for monitoring cardiovascular vital signals are outlined and discussed. Specifically, the functional materials, configurations, mechanisms, and recent advances of these flexible sensors for heart rate, blood pressure, blood oxygen saturation, and blood glucose monitoring are highlighted. Different mechanisms in bioelectric, mechano-electric, optoelectric, and ultrasonic wearable sensors are presented to monitor cardiovascular vital signs from different body locations. Present challenges, possible strategies, and future directions of these wearable sensors are also discussed. With rapid development, these flexible wearable sensors will potentially be applicable for both medical diagnosis and daily healthcare use in tackling cardiovascular diseases.

Cell-Free Bilayered Porous Scaffolds for Osteochondral Regeneration Fabricated by Continuous 3D-Printing Using Nascent Physical Hydrogel as Ink.

Abstract: Cartilage is difficult to self-repair and it is more challenging to repair an osteochondral defects concerning both cartilage and subchondral bone. Herein, it is hypothesized that a bilayered porous scaffold composed of a biomimetic gelatin hydrogel may, despite no external seeding cells, induce osteochondral regeneration in vivo after being implanted into mammal joints. This idea is confirmed based on the successful continuous 3D-printing of the bilayered scaffolds combined with the sol-gel transition of the aqueous solution of a gelatin derivative (physical gelation) and photocrosslinking of the gelatin methacryloyl (gelMA) macromonomers (chemical gelation). At the direct printing step, a nascent physical hydrogel is extruded, taking advantage of non-Newtonian and thermoresponsive rheological properties of this 3D-printing ink. In particular, a series of crosslinked gelMA (GelMA) and GelMA-hydroxyapatite bilayered hydrogel scaffolds are fabricated to evaluate the influence of the spacing of 3D-printed filaments on osteochondral regeneration in a rabbit model. The moderately spaced scaffolds output excellent regeneration of cartilage with cartilaginous lacunae and formation of subchondral bone. Thus, tricky rheological behaviors of soft matter can be employed to improve 3D-printing, and the bilayered hybrid scaffold resulting from the continuous 3D-printing is promising as a biomaterial to regenerate articular cartilage.

Zn-MOF Encapsulated Antibacterial and Degradable Microneedles Array for Promoting Wound Healing

Abstract: An infected skin wound caused by external injury remains a serious challenge in clinical practice. Wound dressings with the properties of antibacterial activity and potent regeneration capacity are highly desirable for wound healing. In this paper, a degradable, ductile, and wound-friendly Zn-MOF encapsulated methacrylated hyaluronic acid (MeHA) microneedles (MNs) array is fabricated through the molding method for promoting wound healing. Due to the damage capability against the bacteria capsule and oxidative stress of the zinc ion released from the Zn-MOF, such MNs array presents excellent antibacterial activity, as well as considerable biocompatibility. Besides, the degradable MNs array composed of photo-crosslinked MeHA possesses the superior capabilities to continuously and steadily release the loaded active ingredients and avoid secondary damage to the wound. Moreover, the low molecular weight hyaluronic acid (HA) generated by hydrolysis of MeHA is also conducive to tissue regeneration. Benefiting from these features, it has been demonstrated that the Zn-MOF encapsulated degradable MNs array can dramatically accelerate epithelial regeneration and neovascularization. These results indicate that the combination of MOFs and degradable MNs array is of great value for promoting wound healing.

Conductive Materials for Healing Wounds: Their Incorporation in Electroactive Wound Dressings, Characterization, and Perspectives.

Abstract: The use of conductive materials to promote the activity of electrically responsive cells is an effective means of accelerating wound healing. This article focuses on recent advancements in conductive materials, with emphasis on overviewing their incorporation with non-conducting polymers to fabricate electroactive wound dressings. The characteristics of these electroactive dressings are deliberated, and the mechanisms on how they accelerate the wound healing process are discussed. Potential directions for the future development of electroactive wound dressings and their potential in monitoring the course of wound healing in vivo concomitantly are also proposed.

A Smart Nanoplatform with Photothermal Antibacterial Capability and Antioxidant Activity for Chronic Wound Healing.

Abstract: Chronic wounds, such as the diabetic ulcer wounds have serious effect on people's lives, and can even lead to death. Diabetic ulcer wounds are different from normal wounds and much easier to be infected and induce oxidative stress due to the special surrounding microenvironment, which makes it necessary to prepare materials with antibacterial property and antioxidant activity simultaneously. The molybdenum disulfide-ceria (MoS2 -CeO2 ) nanocomposite possesses both the photo-thermal therapy (PTT) antibacterial capability of polyethylene glycol modified molybdenum disulfide nanosheets and the antioxidant activity of cerium dioxide nanoparticles (CeO2 NPs). By combining the inherent antibacterial activity of CeO2 NPs, the MoS2 -CeO2 nanocomposite exhibits excellent PTT antibacterial capability against both gram-positive and gram-negative bacteria through 808 nm laser treatment, thereby reducing the risk of wound infection. Owing to the abundant oxygen vacancies in CeO2 NPs, Ce3+ and Ce4+ can transform reversibly which endows MoS2 -CeO2 nanocomposite with remarkable antioxidant ability to clear away the excessive reactive oxygen species around the diabetic ulcer wounds and promote wound healing. The results demonstrate that MoS2 -CeO2 nanocomposite is a promising class for the clinical treatment of chronic wounds especially the diabetic ulcer wounds, and 808 nm laser can be used as a PTT antibacterial switch.

Covalent Organic Frameworks for Biomedical Applications.

Abstract: Covalent organic frameworks (COFs) are porous organic polymeric materials that are composed of organic elements and linked together by the thermodynamically stable covalent bonds. The applications of COFs in energy sector and drug delivery are afforded because of the desirable properties of COFs, such as high stability, low density, large surface area, multidimensionality, porosity, and high-ordered crystalline structure expanded. In this review COFs are reviewed, from the perspective of different types of reported COFs, different methods for their synthesis, and their potential applications in the biomedical field. The main goal of this review is to introduce COFs as a biomaterial and to identify specific advantages of different types of COFs that can be exploited for specialized biomedical applications, such as immune engineering.

Stimuli-Responsive Biomaterials: Scaffolds for Stem Cell Control

Abstract: Stem cell fate is closely intertwined with microenvironmental and endogenous cues within the body. Recapitulating this dynamic environment ex vivo can be achieved through engineered biomaterials which can respond to exogenous stimulation (including light, electrical stimulation, ultrasound, and magnetic fields) to deliver temporal and spatial cues to stem cells. These stimuli-responsive biomaterials can be integrated into scaffolds to investigate stem cell response in vitro and in vivo, and offer many pathways of cellular manipulation: biochemical cues, scaffold property changes, drug release, mechanical stress, and electrical signaling. The aim of this review is to assess and discuss the current state of exogenous stimuli-responsive biomaterials, and their application in multipotent stem cell control. Future perspectives in utilizing these biomaterials for personalized tissue engineering and directing organoid models are also discussed.

Conductive Composite Fiber with Optimized Alignment Guides Neural Regeneration under Electrical Stimulation

Abstract: Conductivity and alignment of scaffolds are two primary factors influencing the efficacy of nerve repair. Herein, conductive composite fibers composed of poly(ɛ-caprolactone) (PCL) and carbon nanotubes (CNTs) with different orientation degrees are prepared by electrospinning at various rotational speeds (0, 500, 1000, and 2000 rpm), and meanwhile the synergistic promotion mechanism of aligned topography and electrical stimulation on neural regeneration is fully demonstrated. Under an optimized rotational speed of 1000 rpm, the electrospun PCL fiber exhibits orientated structure at macroscopic (mean deviation angle = 2.78°) or microscopic crystal scale (orientation degree = 0.73), decreased contact angle of 99.2° ± 4.9°, and sufficient tensile strength in both perpendicular and parallel directions to fiber axis (1.13 ± 0.15 and 5.06 ± 0.98 MPa). CNTs are introduced into the aligned fiber for further improving conductivity (15.69-178.63 S m-1 ), which is beneficial to the oriented growth of neural cells in vitro as well as the regeneration of injured sciatic nerves in vivo. On the basis of robust cell induction behavior, optimum sciatic nerve function index, and enhanced remyelination/axonal regeneration, such conductive PCL/CNTs composite fiber with optimized fiber alignment may serve as instructive candidates for promoting the scaffold- and cell-based strategies for neural repair.

Liquid Metal-Based Soft Electronics for Wearable Healthcare.

Abstract: Wearable healthcare devices have garnered substantial interest for the realization of personal health management by monitoring the physiological parameters of individuals. Attaining the integrity between the devices and the biological interfaces is one of the greatest challenges to achieving high-quality body information in dynamic conditions. Liquid metals, which exist in the liquid phase at room temperatures, are advanced intensively as conductors for deformable devices because of their excellent stretchability and self-healing ability. The unique surface chemistry of liquid metals allows the development of various sensors and devices in wearable form. Also, the biocompatibility of liquid metals, which is verified through numerous biomedical applications, holds immense potential in uses on the surface and inside of a living body. Here, the recent progress of liquid metal-based wearable electronic devices for healthcare with respect to the featured properties and the processing technologies is discussed. Representative examples of applications such as biosensors, neural interfaces, and a soft interconnection for devices are reviewed. The current challenges and prospects for further development are also discussed, and the future directions of advances in the latest research are explored.

2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges

Abstract: Regenerative medicine has become one of the hottest research topics in medical science that provides a promising way for repairing tissue defects in the human body. Due to their excellent physicochemical properties, the application of 2D nanomaterials in regenerative medicine has gradually developed and has been attracting a wide range of research interests in recent years. In particular, graphene and its derivatives, black phosphorus, and transition metal dichalcogenides are applied in all the aspects of tissue engineering to replace or restore tissues. This review focuses on the latest advances in the application of 2D-nanomaterial-based hydrogels, nanosheets, or scaffolds that are engineered to repair skin, bone, and cartilage tissues. Reviews on other applications, including cardiac muscle regeneration, skeletal muscle repair, nerve regeneration, brain disease treatment, and spinal cord healing are also provided. The challenges and prospects of applications of 2D nanomaterials in regenerative medicine are discussed.

Nanocatalyst-Mediated Chemodynamic Tumor Therapy.

Abstract: Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, have been developed and used to treat different types of cancer. Recently, chemodynamic therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton-like reaction to generate highly cytotoxic hydroxyl radicals (·OH) from endogenous hydrogen peroxide (H2 O2 ) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off-target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies have been implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H2 O2 level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst-mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed. This article is protected by copyright. All rights reserved.

Recent Advances in Cell Membrane-Derived Biomimetic Nanotechnology for Cancer Immunotherapy.

Abstract: Immunotherapy will significantly impact the standard of care in cancer treatment. Recent advances in nanotechnology can improve the efficacy of cancer immunotherapy. However, concerns regarding efficiency of cancer nanomedicine, complex tumor microenvironment, patient heterogeneity, and systemic immunotoxicity drive interest in more novel approaches to be developed. For this purpose, biomimetic nanoparticles are developed to make innovative changes in the delivery and biodistribution of immunotherapeutics. Biomimetic nanoparticles have several advantages that can advance the clinical efficacy of cancer immunotherapy. Thus there is a greater push toward the utilization of biomimetic nanotechnology for developing effective cancer immunotherapeutics that demonstrate increased specificity and potency. The recent works and state-of-the-art strategies for anti-tumor immunotherapeutics are highlighted here, and particular emphasis has been given to the applications of cell-derived biomimetic nanotechnology for cancer immunotherapy.

PEDOT:PSS-Based Bioelectronic Devices for Recording and Modulation of Electrophysiological and Biochemical Cell Signals

Abstract: To understand the physiology and pathology of electrogenic cells and the corresponding tissue in their full complexity, the quantitative investigation of the transmission of ions as well as the release of chemical signals is important. Organic (semi-) conducting materials and in particular organic electrochemical transistor are gaining in importance for the investigation of electrophysiological and recently biochemical signals due to their synthetic nature and thus chemical diversity and modifiability, their biocompatible and compliant properties, as well as their mixed electronic and ionic conductivity featuring ion-to-electron conversion. Here, the aim is to summarize recent progress on the development of bioelectronic devices utilizing polymer polyethylenedioxythiophene: poly(styrene sulfonate) (PEDOT:PSS) to interface electronics and biological matter including microelectrode arrays, neural cuff electrodes, organic electrochemical transistors, PEDOT:PSS-based biosensors, and organic electronic ion pumps. Finally, progress in the material development is summarized for the improvement of polymer conductivity, stretchability, higher transistor transconductance, or to extend their field of application such as cation sensing or metabolite recognition. This survey of recent trends in PEDOT:PSS electrophysiological sensors highlights the potential of this multifunctional material to revolve current technology and to enable long-lasting, multichannel polymer probes for simultaneous recordings of electrophysiological and biochemical signals from electrogenic cells.

Effects of Mesenchymal Stem Cell-Derived Paracrine Signals and Their Delivery Strategies.

Abstract: Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion of angiogenesis, and reduction in fibrosis. This review focuses on profiling the effects of paracrine signals of MSCs, commonly referred to as the secretome, and highlighting the various engineering approaches to tune the MSC secretome. Recent advances in biomaterials-based therapeutic strategies for delivery of MSCs and MSC-derived secretome in the form of extracellular vesicles are discussed, along with their advantages and challenges.

Designing Hydrogels for 3D Cell Culture Using Dynamic Covalent Crosslinking.

Abstract: Designing simple biomaterials to replicate the biochemical and mechanical properties of tissues is an ongoing challenge in tissue engineering. For several decades, new biomaterials have been engineered using cytocompatible chemical reactions and spontaneous ligations via click chemistries to generate scaffolds and water swollen polymer networks, known as hydrogels, with tunable properties. However, most of these materials are static in nature, providing only macroscopic tunability of the scaffold mechanics, and do not reflect the dynamic environment of natural extracellular microenvironment. For more complex applications such as organoids or co-culture systems, there remain opportunities to investigate cells that locally remodel and change the physicochemical properties within the matrices. In this review, advanced biomaterials where dynamic covalent chemistry is used to produce stable 3D cell culture models and high-resolution constructs for both in vitro and in vivo applications, are discussed. The implications of dynamic covalent chemistry on viscoelastic properties of in vitro models are summarized, case studies in 3D cell culture are critically analyzed, and opportunities to further improve the performance of biomaterials for 3D tissue engineering are discussed.

Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering

Abstract: Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.

Advances in Magnetic Nanoparticle-Mediated Cancer Immune-Theranostics.

Abstract: Cancer immunotherapy is a cutting-edge strategy that eliminates cancer cells by amplifying the host's immune system. However, the low response rate and risks of inducing systemic toxicity have raised uncertainty in the treatment. Magnetic nanoparticles (MNPs) as a versatile theranostic tool can be used to target delivery of multiple immunotherapeutics and monitor cell/tissue responses. These capabilities enable the real-time characterization of the factors that contribute to immunoactivity so that future treatments can be optimized. The magnetic properties of MNPs further allow the implementation of magnetic navigation and magnetic hyperthermia for boosting the efficacy of immunotherapy. The multimodal approach opens an avenue to induce robust immune responses, minimize safety issues, and monitor immune activities simultaneously. Thus, the object of this review is to provide an overview of the burgeoning fields and to highlight novel technologies for next-generation immunotherapy. The review further correlates the properties of MNPs with the latest treatment strategies to explore the crosstalk between magnetic nanomaterials and the immune system. This comprehensive review of MNP-derived immunotherapy covers the obstacles and opportunities for future development and clinical translation.