Showing papers in "Advanced Healthcare Materials in 2018"

Antibacterial Activity of Silver Nanoparticles: Structural Effects

Abstract: The increase of antibiotic resistance in bacteria has become a major concern for successful diagnosis and treatment of infectious diseases. Over the past few decades, significant progress has been achieved on the development of nanotechnology-based medicines for combating multidrug resistance in microorganisms. Among this, silver nanoparticles (AgNPs) hold great promise in addressing this challenge due to their broad-spectrum and robust antimicrobial properties. This review illustrates the antibacterial mechanisms of silver nanoparticles and further elucidates how different structural factors including surface chemistry, size, and shape, impact their antibacterial activities, which are expected to promote the future development of more potent silver nanoparticle-based antibacterial agents.

Enzyme-Based Glucose Sensor: From Invasive to Wearable Device.

Abstract: Blood glucose concentration is a key indicator of patients' health, particularly for symptoms associated with diabetes mellitus. Because of the large number of diabetic patients, many approaches for glucose measurement have been studied to enable continuous and accurate glucose level monitoring. Among them, electrochemical analysis is prominent because it is simple and quantitative. This technology has been incorporated into commercialized and research-level devices from simple test strips to wearable devices and implantable systems. Although directly monitoring blood glucose assures accurate information, the invasive needle-pinching step to collect blood often results in patients (particularly young patients) being reluctant to adopt the process. An implantable glucose sensor may avoid the burden of repeated blood collections, but it is quite invasive and requires periodic replacement of the sensor owing to biofouling and its short lifetime. Therefore, noninvasive methods to estimate blood glucose levels from tears, saliva, interstitial fluid (ISF), and sweat are currently being studied. This review discusses the evolution of enzyme-based electrochemical glucose sensors, including materials, device structures, fabrication processes, and system engineering. Furthermore, invasive and noninvasive blood glucose monitoring methods using various biofluids or blood are described, highlighting the recent progress in the development of enzyme-based glucose sensors and their integrated systems.

Advances in Magnetic Nanoparticles for Biomedical Applications.

Abstract: V.F.C. and A.F. contributed equally to this work. The authors thank the FCT—Fundacao para a Ciencia e Tecnologia—for financial support under framework of the Strategic Funding UID/FIS/04650/2013, project PTDC/ EEI-SII/5582/2014 and project UID/EEA/04436/2013 by FEDER funds through the COMPETE 2020—Programa Operacional Competitividade e Internacionalizacao (POCI). Funds provided by FCT in the framework of EuroNanoMed 2016 call, Project LungChek ENMed/0049/2016 are also gratefully acknowledged. V.F.C., A.F., C.R., and P.M. also thank the FCT for the grants SFRH/BPD/98109/2013, SFRH/BPD/104204/2014, SFRH/ BPD/90870/2012 and SFRH/BPD/96227/2013, respectively. Finally, the authors acknowledge funding by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2016-76039C4-3-R (AEI/FEDER, UE) and from the Basque Government Industry Department under the ELKARTEK program.

Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications.

Abstract: Predetermining the physico-chemical properties, biosafety, and stimuli-responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico-chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica-based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer's disease therapy.

Nanomaterial-Enabled Wearable Sensors for Healthcare.

Abstract: Highly sensitive wearable sensors that can be conformably attached to human skin or integrated with textiles to monitor the physiological parameters of human body or the surrounding environment have garnered tremendous interest. Owing to the large surface area and outstanding material properties, nanomaterials are promising building blocks for wearable sensors. Recent advances in the nanomaterial-enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review. Integration of multiple sensors for multimodal sensing and integration with other components into wearable systems are summarized. Representative applications of nanomaterial-enabled wearable sensors for healthcare, including continuous health monitoring, daily and sports activity tracking, and multifunctional electronic skin are highlighted. Finally, challenges, opportunities, and future perspectives in the field of nanomaterial-enabled wearable sensors are discussed.

2D Ultrathin MXene-Based Drug-Delivery Nanoplatform for Synergistic Photothermal Ablation and Chemotherapy of Cancer.

Abstract: Two-dimensional (2D) MXenes, as a new 2D functional material nanosystem, have been extensively explored for broad applications. However, their specific performance and applications in theranostic nanomedicine have still rarely been explored. This work reports on the drug-delivery performance and synergistic therapeutic efficiency of Ti3 C2 MXenes for highly efficient tumor eradication. These Ti3 C2 MXenes not only possess high drug-loading capability of as high as 211.8%, but also exhibit both pH-responsive and near infrared laser-triggered on-demand drug release. Especially, based on the high photothermal-conversion capability of Ti3 C2 MXenes, they have been further explored for efficient tumor eradication by synergistic photothermal ablation and chemotherapy, which has been systematically demonstrated both in vitro and in vivo. These Ti3 C2 MXenes have also been demonstrated as the desirable contrast agents for photoacoustic imaging, showing the potential for diagnostic-imaging guidance and monitoring during therapy. The high in vivo histocompatibility of Ti3 C2 and their easy excretion out of the body have been evaluated and demonstrated, showing the potential high biosafety for further clinical translation. This work paves a new way for broadening biomedical applications of MXenes in nanomedicine where they can exert the high performance and functionality for synergistic therapy, especially on combating cancer.

Recent Advances in Extrusion-Based 3D Printing for Biomedical Applications.

Abstract: Additive manufacturing, or 3D printing, has become significantly more commonplace in tissue engineering over the past decade, as a variety of new printing materials have been developed. In extrusion-based printing, materials are used for applications that range from cell free printing to cell-laden bioinks that mimic natural tissues. Beyond single tissue applications, multi-material extrusion based printing has recently been developed to manufacture scaffolds that mimic tissue interfaces. Despite these advances, some material limitations prevent wider adoption of the extrusion-based 3D printers currently available. This progress report provides an overview of this commonly used printing strategy, as well as insight into how this technique can be improved. As such, it is hoped that the prospective report guides the inclusion of more rigorous material characterization prior to printing, thereby facilitating cross-platform utilization and reproducibility.

Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies.

Abstract: Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological applications. A variety of biomaterials are used in tissue fabrication providing multiple biological, structural, and mechanical cues in the regulation of cell behavior and tissue morphogenesis. Cells derived from humans enable the fabrication of personalized OOC platforms. Microscale technologies are specifically helpful in providing physiological microenvironments for tissues and organs. In this review, biomaterials, cells, and microscale technologies are described as essential components to construct OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as functional tools in simulating human physiology and metabolism. Future perspectives and major challenges in the development of OOC platforms toward accelerating clinical studies of drug discovery are finally highlighted.

Conceptually Novel Black Phosphorus/Cellulose Hydrogels as Promising Photothermal Agents for Effective Cancer Therapy.

Abstract: Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short-term therapeutic and inhomogeneous photothermal effect. Development of BP-based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP-polymer-based photothermal agents in the form of hydrogels for biomedical-related clinic applications.

Current Advances in Immunomodulatory Biomaterials for Bone Regeneration.

Abstract: Biomaterials with suitable surface modification strategies are contributing significantly to the rapid development of the field of bone tissue engineering. Despite these encouraging results, utilization of biomaterials is poorly translated to human clinical trials potentially due to lack of knowledge about the interaction between biomaterials and the body defense mechanism, the "immune system". The highly complex immune system involves the coordinated action of many immune cells that can produce various inflammatory and anti-inflammatory cytokines. Besides, bone fracture healing initiates with acute inflammation and may later transform to a regenerative or degenerative phase mainly due to the cross-talk between immune cells and other cells in the bone regeneration process. Among various immune cells, macrophages possess a significant role in the immune defense, where their polarization state plays a key role in the wound healing process. Growing evidence shows that the macrophage polarization state is highly sensitive to the biomaterial's physiochemical properties, and advances in biomaterial research now allow well controlled surface properties. This review provides an overview of biomaterial-mediated modulation of the immune response for regulating key bone regeneration events, such as osteogenesis, osteoclastogenesis, and inflammation, and it discusses how these strategies can be utilized for future bone tissue engineering applications.

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications.

Abstract: Poly(lactic-co-glycolic) acid (PLGA) is one of the most versatile biomedical polymers, already approved by regulatory authorities to be used in human research and clinics. Due to its valuable characteristics, PLGA can be tailored to acquire desirable features for control bioactive payload or scaffold matrix. Moreover, its chemical modification with other polymers or bioconjugation with molecules may render PLGA with functional properties that make it the Holy Grail among the synthetic polymers to be applied in the biomedical field. In this review, the physical-chemical properties of PLGA, its synthesis, degradation, and conjugation with other polymers or molecules are revised in detail, as well as its applications in drug delivery and regeneration fields. A particular focus is given to successful examples of products already on the market or at the late stages of trials, reinforcing the potential of this polymer in the biomedical field.

Graphene Materials in Antimicrobial Nanomedicine: Current Status and Future Perspectives

Abstract: Graphene materials (GMs), such as graphene, graphene oxide (GO), reduced GO (rGO), and graphene quantum dots (GQDs), are rapidly emerging as a new class of broad-spectrum antimicrobial agents. This report describes their state-of-the-art and potential future covering both fundamental aspects and biomedical applications. First, the current understanding of the antimicrobial mechanisms of GMs is illustrated, and the complex picture of underlying structure-property-activity relationships is sketched. Next, the different modes of utilization of antimicrobial GMs are explained, which include their use as colloidal dispersions, surface coatings, and photothermal/photodynamic therapy agents. Due to their practical relevance, the examples where GMs function as synergistic agents or release platforms for metal ions and/or antibiotic drugs are also discussed. Later, the applicability of GMs in the design of wound dressings, infection-protective coatings, and antibiotic-like formulations ("nanoantibiotics") is assessed. Notably, to support our assessments, the existing clinical applications of conventional carbon materials are also evaluated. Finally, the key hurdles of the field are highlighted, and several possible directions for future investigations are proposed. We hope that the roadmap provided here will encourage researchers to tackle remaining challenges toward clinical translation of promising research findings and help realize the potential of GMs in antimicrobial nanomedicine.

3D Bioprinting of Self‐Standing Silk‐Based Bioink

Abstract: Silk/polyethylene glycol (PEG) hydrogels are studied as self-standing bioinks for 3D printing for tissue engineering. The two components of the bioink, silk fibroin protein (silk) and PEG, are both Food and Drug Administration approved materials in drug and medical device products. Mixing PEG with silk induces silk β-sheet structure formation and thus gelation and water insolubility due to physical crosslinking. A variety of constructs with high resolution, high shape fidelity, and homogeneous gel matrices are printed. When human bone marrow mesenchymal stem cells are premixed with the silk solution prior to printing and the constructs are cultured in this medium, the cell-loaded constructs maintain their shape over at least 12 weeks. Interestingly, the cells grow faster in the higher silk concentration (10%, w/v) gel than in lower ones (7.5 and 5%, w/v), likely due to the difference in material stiffness and the amount of residual PEG remaining in the gel related to material hydrophobicity. Subcutaneous implantation of 7.5% (w/v) bioink gels with and without printed fibroblast cells in mice reveals that the cells survive and proliferate in the gel matrix for at least 6 week postimplantation. The results suggest that these silk/PEG bioink gels may provide suitable scaffold environments for cell printing and function.

A Bioprinted Cardiac Patch Composed of Cardiac-Specific Extracellular Matrix and Progenitor Cells for Heart Repair.

Abstract: Congenital heart defects are present in 8 of 1000 newborns and palliative surgical therapy has increased survival. Despite improved outcomes, many children develop reduced cardiac function and heart failure requiring transplantation. Human cardiac progenitor cell (hCPC) therapy has potential to repair the pediatric myocardium through release of reparative factors, but therapy suffers from limited hCPC retention and functionality. Decellularized cardiac extracellular matrix hydrogel (cECM) improves heart function in animals, and human trials are ongoing. In the present study, a 3D bioprinted patch containing cECM for delivery of pediatric hCPCs is developed. Cardiac patches are printed with bioinks composed of cECM, hCPCs, and gelatin methacrylate (GelMA). GelMA-cECM bioinks print uniformly with a homogeneous distribution of cECM and hCPCs. hCPCs maintain >75% viability and incorporation of cECM within patches results in a 30-fold increase in cardiogenic gene expression of hCPCs compared to hCPCs grown in pure GelMA patches. Conditioned media from GelMA-cECM patches show increased angiogenic potential (>2-fold) over GelMA alone as seen by improved endothelial cell tube formation. Finally, patches are retained on rat hearts and show vascularization over 14 days in vivo. This work shows the successful bioprinting and implementation of cECM-hCPC patches for potential use in repairing damaged myocardium.

Tissue Engineering at the Blood-Contacting Surface: A Review of Challenges and Strategies in Vascular Graft Development.

Abstract: Tissue engineered vascular grafts (TEVGs) are beginning to achieve clinical success and hold promise as a source of grafting material when donor grafts are unsuitable or unavailable. Significant technological advances have generated small-diameter TEVGs that are mechanically stable and promote functional remodeling by regenerating host cells. However, developing a biocompatible blood-contacting surface remains a major challenge. The TEVG luminal surface must avoid negative inflammatory responses and thrombogenesis immediately upon implantation and promote endothelialization. The surface has therefore become a primary focus for research and development efforts. The current state of TEVGs is herein reviewed with an emphasis on the blood-contacting surface. General vascular physiology and developmental challenges and strategies are briefly described, followed by an overview of the materials currently employed in TEVGs. The use of biodegradable materials and stem cells requires careful control of graft composition, degradation behavior, and cell recruitment ability to ensure that a physiologically relevant vessel structure is ultimately achieved. The establishment of a stable monolayer of endothelial cells (ECs) and the quiescence of smooth muscle cells (SMCs) are critical to the maintenance of patency. Several strategies to modify blood-contacting surfaces to resist thrombosis and control cellular recruitment are reviewed, including coatings of biomimetic peptides and heparin.

Progress in Applications of Prussian Blue Nanoparticles in Biomedicine.

Abstract: Prussian blue nanoparticles (PBNPs) with favorable biocompatibility and unique properties have captured the attention of extensive biomedical researchers. A great progress is made in the application of PBNPs as therapy and diagnostics agents in biomedicine. This review begins with the recent synthetic strategies of PBNPs and the regulatory approaches for their size, shape, and uniformity. Then, according to the different properties of PBNPs, their application in biomedicine is summarized in detail. With modifiable features, PBNPs can be used as drug carriers to improve the therapeutic efficacy. Moreover, the exchangeable protons and adsorbability enable PBNPs to decontaminate the radioactive ions from the body. For biomedical imaging, photoacoustic and magnetic resonance imaging based on PBNPs are summarized, as well as the strategies to improve the diagnostic effectiveness. The applications related to the photothermal effects and nanoenzyme activities of PBNPs are described. The challenges and critical factors for the clinical translation of PBNPs as multifunctional theranostic agents are also discussed. Finally, the future prospects for the application of PBNPs are considered. The aim of this review is to provide a better understanding and key consideration for rational design of this increasingly important new paradigm of PBNPs as theranostics.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities.

Abstract: Structured macroporous hydrogels that have controllable porosities on both the nanoscale and the microscale offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of "hard" macroporous materials. While a variety of techniques such as solvent casting, freeze drying, gas foaming, and phase separation have been developed to fabricate structured macroporous hydrogels, the typically weak mechanics and isotropic pore structures achieved as well as the required use of solvent/additives in the preparation process all limit the potential applications of these materials, particularly in biomedical contexts. This review highlights recent developments in the field of structured macroporous hydrogels aiming to increase network strength, create anisotropy and directionality within the networks, and utilize solvent-free or additive-free fabrication methods. Such functional materials are well suited for not only biomedical applications like tissue engineering and drug delivery but also selective filtration, environmental sorption, and the physical templating of secondary networks.

Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings

Abstract: Preparation-free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super-soft and self-adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin-contact impedance of 50 kΩ cm2 at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm-2 without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high-fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long-term biopotential recordings with clinical-grade signal performance.

Freestanding, Fiber-Based, Wearable Temperature Sensor with Tunable Thermal Index for Healthcare Monitoring.

Abstract: Fiber-based sensors integrated on textiles or clothing systems are required for the next generation of wearable electronic platforms. Fiber-based physical sensors are developed, but the development of fiber-based temperature sensors is still limited. Herein, a new approach to develop wearable temperature sensors that use freestanding single reduction graphene oxide (rGO) fiber is proposed. A freestanding and wearable temperature-responsive rGO fiber with tunable thermal index is obtained using simple wet spinning and a controlled graphene oxide reduction time. The freestanding fiber-based temperature sensor shows high responsivity, fast response time (7 s), and good recovery time (20 s) to temperature. It also maintains its response under an applied mechanical deformation. The fiber device fabricated by means of a simple process is easily integrated into fabric such as socks or undershirts and can be worn by a person to monitor the temperature of the environment and skin temperature without interference during movement and various activities. These results demonstrate that the freestanding fiber-based temperature sensor has great potential for fiber-based wearable electronic platforms. It is also promising for applications in healthcare and biomedical monitoring.

Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma Screening

Abstract: Wearable bendable bandage-based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level. The flexible epidermal bandage sensor relies on printing stress-enduring inks which display good resiliency against mechanical deformations, whereas the hollow microneedle device is filled with catechol-coated carbon paste for assessing tissue TYR levels. The bandage sensor can thus be used directly on the skin whereas microneedle device can reach melanoma tissues under the skin. Both wearable sensors are interfaced to an ultralight flexible electronic board, which transmits data wirelessly to a mobile device. The analytical performance of the resulting bandage and microneedle sensing systems are evaluated using TYR-containing agarose phantom gel and porcine skin. The new integrated conformal portable sensing platforms hold considerable promise for decentralized melanoma screening, and can be extended to the screening of other key biomarkers in skin moles.

Carbon-Based Nanomaterials for Cancer Therapy via Targeting Tumor Microenvironment.

Abstract: Cancer remains one of the major health problems all over the world and conventional therapeutic approaches have failed to attain an effective cure. Tumor microenvironments (TME) present a unique challenge in tumor therapy due to their complex structures and multiple components, which also serve as the soil for tumor growth, development, invasion, and migration. The complex TME includes immune cells, fibrous collagen structures, and tortuous blood vessels, in which conventional therapeutic approaches are rendered useless. State-of-the-art nanotechnologies have potential to cope with the threats of malignant tumors. With unique physiochemical properties, carbon nanomaterials (CNMs), including graphene, fullerenes, carbon nanotubes, and carbon quantum dots, offer opportunities to resolve the hurdles, by targeting not only cancer cells but also the TME. This review summarizes the progress about CNM-based cancer therapy strategies, which mainly focuses on both the treatment for cancer cells and TME-targeted modulation. In the last, the challenges for TME-based therapy via CNMs are discussed, which will be important in guiding current basic research to clinical translation in the future.

Nanocellulose-Based Antibacterial Materials

Abstract: In recent years, nanocellulose-based antimicrobial materials have attracted a great deal of attention due to their unique and potentially useful features. In this review, several representative types of nanocellulose and modification methods for antimicrobial applications are mainly focused on. Recent literature related with the preparation and applications of nanocellulose-based antimicrobial materials is reviewed. The fabrication of nanocellulose-based antimicrobial materials for wound dressings, drug carriers, and packaging materials is the focus of the research. The most important additives employed in the preparation of nanocellulose-based antimicrobial materials are presented, such as antibiotics, metal, and metal oxide nanoparticles, as well as chitosan. These nanocellulose-based antimicrobial materials can benefit many applications including wound dressings, drug carriers, and packaging materials. Finally, the challenges of industrial production and potentials for development of nanocellulose-based antimicrobial materials are discussed.

Soy Protein/Cellulose Nanofiber Scaffolds Mimicking Skin Extracellular Matrix for Enhanced Wound Healing.

Abstract: Historically, soy protein and extracts have been used extensively in foods due to their high protein and mineral content. More recently, soy protein has received attention for a variety of its potential health benefits, including enhanced skin regeneration. It has been reported that soy protein possesses bioactive molecules similar to extracellular matrix (ECM) proteins and estrogen. In wound healing, oral and topical soy has been heralded as a safe and cost-effective alternative to animal protein and endogenous estrogen. However, engineering soy protein-based fibrous dressings, while recapitulating ECM microenvironment and maintaining a moist environment, remains a challenge. Here, the development of an entirely plant-based nanofibrous dressing comprised of cellulose acetate (CA) and soy protein hydrolysate (SPH) using rotary jet spinning is described. The spun nanofibers successfully mimic physicochemical properties of the native skin ECM and exhibit a high water retaining capability. In vitro, CA/SPH nanofibers promote fibroblast proliferation, migration, infiltration, and integrin β1 expression. In vivo, CA/SPH scaffolds accelerate re-epithelialization and epidermal thinning as well as reduce scar formation and collagen anisotropy in a similar fashion to other fibrous scaffolds, but without the use of animal proteins or synthetic polymers. These results affirm the potential of CA/SPH nanofibers as a novel wound dressing.

Nanogenerator for Biomedical Applications.

Abstract: In the past 10 years, the development of nanogenerators (NG) has enabled different systems to operate without external power supply. NG have the ability to harvest the mechanical energies in different forms. Human body motions and activities can also serve as the energy source to drive NG and enable self-powered healthcare system. In this review, a summary of several major actual applications of NG in the biomedical fields is made including the circulatory system, the neural system, cell modulation, microbe disinfection, and biodegradable electronics. Nevertheless, there are still many challenges for NG to be actually adopted in clinical applications, including the miniaturization, duration, encapsulation, and output performance. It is also very important to further combine the NG development more precisely with the medical principles. In future, NG can serve as highly promising complementary or even alternative power suppliers to traditional batteries for the healthcare electronics.

Tumor Microenvironment-Enabled Nanotherapy.

Abstract: Cancer is now one of the world's leading threats to human health. With the development of oncology in both biology and biomedicine, it has been demonstrated that abnormal physiochemical conditions and dysregulated biosynthetic intermediates in tumor microenvironment (TME) play a pivotal role in enabling tumor cells to defend or evade the damage by traditional clinical tumor therapeutics including surgery, chemotherapy, radiotherapy, etc. The fast advances of TME-enabled theranostic nanomedicine have offered promising perspectives, strategies, and approaches for combating cancer based on the novel concept of TME-enabled nanotherapy. In this comprehensive review, the origins of TME (e.g., enhanced permeability and retention effect, overexpressed biosynthetic intermediates, mild acidic nature, redox potentials, hypoxia) are initially introduced and discussed, followed by detailed discussion and overview on the state-of-the-art progresses in TME-enabled antitumor nanotherapies (e.g., chemo/chemodynamic therapy, photodynamic therapy, radiotherapy). Finally, the obstacles and challenges of future development on TME-enabled nanotherapies for further clinical translation are outlooked.

Biomaterials for Skin Substitutes.

Abstract: Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.

Silk-Based Bioinks for 3D Bioprinting.

Abstract: Despite fascinating potential, 3D bioprinting of clinically relevant 3D-engineered tissues is still a challenging proposition Several variables such as replicating the complex tissue architecture, choice of bioink, and optimization of the physicochemical, biomechanical, and topographical functionality of printed scaffolds with encapsulated cells and morphogens offer major complications Silk fibroin has emerged as a promising material suitable for bioink preparation as it possesses unique features required for optimum ink preparation including shear-thinning behavior, self-supporting filamentous extrusion, cytocompatible gelation strategy, and mechanical strength In this chapter, we will discuss and summarize the recent advancements in silk fibroin processing for 3D bioprinting applications, focusing on their rheology, current gelation strategies, and blends with other polymers We will further discuss the potential areas for future research, challenges faced by current methods, and gaps in knowledge required for pushing the field further towards the creation of clinical-sized functional 3D tissues

2D MoS2 Nanostructures for Biomedical Applications.

Abstract: MoS2 nanosheets, a typical kind of layered transition metal dichalcogenides with the 2D structure and many unique physical and chemical properties, have attracted a lot of research interests in various fields. Typically, MoS2 nanosheets present similarities to graphene in terms of their large surface area and strong absorbance in near-infrared region, which in combination with their easily functionalized surface make them promising nanoplatforms in biomedical applications. Herein, the progress of MoS2 nanosheets and their composites in the area of nanomedicine, with the emphasis on their synthesis and modification strategies, their biomedical applications in biosensing, imaging and therapy, as well as evaluations of their in vivo behaviors and toxicology profiles are summarized. Finally, the challenges and opportunities of applying MoS2 -based nanomaterials in the biomedicine areas will be discussed.

Reducing Bacterial Infections and Biofilm Formation Using Nanoparticles and Nanostructured Antibacterial Surfaces.

Abstract: With the rapid spreading of resistance among common bacterial pathogens, bacterial infections, especially antibiotic-resistant bacterial infections, have drawn much attention worldwide. In light of this, nanoparticles, including metal and metal oxide nanoparticles, liposomes, polymersomes, and solid lipid nanoparticles, have been increasingly exploited as both efficient antimicrobials themselves or as delivery platforms to enhance the effectiveness of existing antibiotics. In addition to the emergence of widespread antibiotic resistance, of equal concern are implantable device-associated infections, which result from bacterial adhesion and subsequent biofilm formation at the site of implantation. The ineffectiveness of conventional antibiotics against these biofilms often leads to revision surgery, which is both debilitating to the patient and expensive. Toward this end, micro- and nanotopographies, especially those that resemble natural surfaces, and nonfouling chemistries represent a promising combination for long-term antibacterial activity. Collectively, the use of nanoparticles and nanostructured surfaces to combat bacterial growth and infections is a promising solution to the growing problem of antibiotic resistance and biofilm-related device infections.

In Situ Forming Injectable Silk Fibroin Hydrogel Promotes Skin Regeneration in Full Thickness Burn Wounds.

Abstract: Full-thickness skin wounds, associated with deep burns or chronic wounds pose a major clinical problem. Herein, the development of in situ forming hydrogel using a natural silk fibroin (SF) biomaterial for treating burn wounds is reported. Blends of SF solutions isolated from Bombyx mori and Antheraea assama show inherent self-assembly between silk proteins and lead to irreversible gelation at body temperature. Investigation of the gelation mechanism reveals crosslinking due to formation of β-sheet structures as examined by X-ray diffraction and Fourier transform infrared spectroscopy. The SF hydrogel supports proliferation of primary human dermal fibroblasts and migration of keratinocytes comparable to collagen gel (Col) as examined under in vitro conditions. The SF hydrogel also provides an instructive and supportive matrix to the full-thickness third-degree burn wounds in vivo. A 3-week comparative study with Col indicates that SF hydrogel not only promotes wound healing but also shows transitions from inflammation to proliferation stage as observed through the expression of TNF-α and CD163 genes. Further, deposition and remodeling of collagen type I and III fibers suggests an enhanced overall tissue regeneration. Comparable results with Col demonstrate the SF hydrogel as an effective and inexpensive formulation toward a potential therapeutic approach for burn wound treatment.