E-cardiac patch to sense and repair infarcted myocardium.

Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.

Early infiltrating NKT lymphocytes attenuate bone regeneration through secretion of CXCL2.

Trauma rapidly mobilizes the immune response of surrounding tissues and activates regeneration program. Manipulating immune response to promote tissue regeneration shows a broad application prospect. However, the understanding of bone healing dynamics at cellular level remains limited. Here, we characterize the landscape of immune cells after alveolar bone injury and reveal a pivotal role of infiltrating natural killer T (NKT) cells. We observe a rapid increase in NKT cells after injury, which inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and impair alveolar bone healing. Cxcl2 is up-regulated in NKT cells after injury. Systemic administration of CXCL2-neutralizing antibody or genetic deletion of Cxcl2 improves the bone healing process. In addition, we fabricate a gelatin-based porous hydrogel to deliver NK1.1 depletion antibody, which successfully promotes alveolar bone healing. In summary, our study highlights the importance of NKT cells in the early stage of bone healing and provides a potential therapeutic strategy for accelerating bone regeneration.

Ultra-Hydrophobic Gauze Driving Super-Haemostasis.

Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, we develop a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of about 160°. We demonstrate that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs were combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peel-able, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, our gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. Our work presents promising applications in terms of prehospital first aid. This article is protected by copyright. All rights reserved.

Plant mucus-derived microgels: Blood-triggered gelation and strong hemostatic adhesion.

Arrest of bleeding usually applies clotting agents to trigger coagulation procedures or adhesives to interrupt blood flow through sealing the vessel; however, the efficiency is compromised. Here, we propose a concept of integration of hemostasis and adhesion via yam mucus's microgels. The mucus microgels exhibit attractive attributes of hydrogel with uniform size and shape. Their shear-thinning, self-healing and strong adhesion make them feasible as injectable bioadhesion. Exceptionally, the blood can trigger the microgels' gelation with the outcome of super extensibility, which leads to the microgels a strong hemostatic agent. We also found a tight gel adhesive layer formed upon microgels' contacting the blood on the tissue, where there is the coagulation factor XIII triggered to form a dense three-dimensional fibrin meshwork. The generated structures show that the microgels look like hard balls in the dispersed phase into the blood-produced fibrin mesh of a soft net phase. Both phases work together for a super-extension gel. We demonstrated the microgels' fast adhesion and hemostasis in the livers and hearts of rabbits and mini pigs. The microgels also promoted wound healing with good biocompatibility and biodegradability.

Analyzing Mushroom Structural Patterns of a Highly Compressible and Expandable Hemostatic Foam for Gastric Perforation Repair.

Nature presents the most beautiful patterns through evolving. Here, a layered porous pattern in golden ratio (0.618) is reported from a type of mushroom -Dictyophora Rubrovalvata stipe (DRS). The hierarchical structure shows a mathematical correlation with the golden ratio. This unique structure leads to superior mechanical properties. The gradient porous structure from outside to innermost endows it with asymmetrical hydrophilicity. A mathematical model is then developed to predict and apply to 3D printed structures. The mushroom is then explored to repair gastric perforation because the stomach is a continuous peristaltic organ, and the perforated site is subject to repeated mechanical movements and pressure changes. At present, endoscopic clipping is ineffective in treating ulcerative perforation with fragile surrounding tissues. Although endoscopic implant occlusion provides a new direction for the treatment of gastric ulcers, but the metal or plastic occluder needs to be removed, requiring a second intervention. Decellularized DRS (DDRS) is found with asymmetric water absorption rate, super-compressive elasticity, shape memory, and biocompatibility, making it a suitable occluder for the gastric perforation. The efficacy in blocking gastric perforation and promoting healing is confirmed by endoscopic observation and tissue analysis during a 2-month study.

Highly efficient semiconductor modules making controllable parallel microchannels for non-compressible hemorrhages.

Nature makes the most beautiful solution to involuted problems. Among them, the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems, which demonstrate an ingenious evolutionary design. This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels. The modules decrease quickly the temperature of polymer solution from 20 °C to -20 °C within 5 min. In addition to the exceptional liquid absorption rate, the foams exhibited shape memory mechanics. Our mini device universally makes the inspired structure in such as chitosan, gelatin, alginate and polyvinyl alcohol. Non-compressible hemorrhages are the primary cause of death in emergency. The rapid liquid absorption leads to fast activation of coagulation, which provides an efficient strategy for hemostasis management. We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity (96.43%) and rapid expansion rate (2934%). They absorb liquid with 37.25 times of the own weight, show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams. These superior properties lead to strong hemostatic performance in vitro and in vivo.

Platelet Vesicles Synergetic with Biosynthetic Cellulose Aerogels for Ultra-Fast Hemostasis and Wound Healing.

Achieving hemostasis in penetrating and irregular wounds is challenging because the hemostasis factor cannot arrive at the bleeding site, and substantial bleeding will wash away the blood clot. Since the inherently gradual nature of blood clot formation takes time, a physical barrier is needed before blood clot formation. Herein, an ultra-light and shape memory hemostatic aerogel consisting of oxidized bacterial cellulose (OBC) and platelet extracellular vesicles (pVEs) is reported. The OBC-pVEs aerogel provides a physical barrier for the bleeding site by self-expansion, absorbing the liquid from blood to concentrate platelets and clotting factors and accelerating the clot formation by activating platelets and transforming fibrinogen into fibrin. In the rat liver and tail injury models, the blood loss decreases by 73% and 59%, and the bleeding times are reduced by 55% and 62%, respectively. OBC-pVEs aerogel has also been shown to accelerate wound healing. In conclusion, this work introduces an effective tool for treating deep, non-compressible, and irregular wounds and offers valuable strategies for trauma bleeding and wound treatment.

Two way workable microchanneled hydrogel suture to diagnose, treat and monitor the infarcted heart.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

Duo-role Platelet-rich Plasma: temperature-induced fibrin gel and growth factors' reservoir for microneedles to promote hair regrowth.

INTRODUCTION: Alopecia concerns more than half our adult population. Platelet-rich plasma (PRP) has been applied in skin rejuvenation and hair loss treatment. However, the pain and bleeding during injection and the troublesome for fresh preparation of each action limit PRP's in-depth applying dedication to clinics. OBJECTIVES: We report a temperature-sensitive PRP induced fibrin gel included in a detachable transdermal microneedle (MN) for hair growth. RESULTS: PRP gel interpenetrated with the photocrosslinkable gelatin methacryloyl (GelMA) to realize sustained release of growth factors (GFs) and led to 14% growth in mechanical strength of a single microneedle whose strength reached 1.21 N which is sufficient to penetrate the stratum corneum. PRP-MNs' release of VEGF, PDGF, and TGF-ß were characterized and quantitatively around the hair follicles (HFs) for 4-6 days consecutively. PRP-MNs promoted hair regrowth in mice models. From transcriptome sequencing, PRP-MNs induced hair regrowth through angiogenesis and proliferation. The mechanical and TGF-ß sensitive gene Ankrd1 was significantly upregulated by PRP-MNs treatment. CONCLUSION: PRP-MNs show convenient, minimally invasive, painless, inexpensive manufacture, storable and sustained effects in boosting hair regeneration.

Extracellular Matrices as Bioactive Materials for In Situ Tissue Regeneration.

Bioactive materials based on a nature-derived extracellular matrix (NECM) represent a category of biomedical devices with versatile therapeutic applications in the realms of tissue repair and engineering. With advancements in decellularization technique, the inherent bioactive molecules and the innate nano-structural and mechanical properties are preserved in three-dimensional scaffolds mainly composed of collagens. Techniques such as electrospinning, three-dimensional printing, and the intricate fabrication of hydrogels are developed to mimic the physical structures, biosignalling and mechanical cues of ECM. Until now, there has been no approach that can fully account for the multifaceted properties and diverse applications of NECM. In this review, we introduce the main proteins composing NECMs and explicate the importance of them when used as therapeutic devices in tissue repair. Nano-structural features of NECM and their applications regarding tissue repair are summarized. The origins, degradability, and mechanical property of and immune responses to NECM are also introduced. Furthermore, we review their applications, and clinical features thereof, in the repair of acute and chronic wounds, abdominal hernia, breast deformity, etc. Some typical marketed devices based on NECM, their indications, and clinical relevance are summarized.

Bioactive and electrically conductive GelMA-BG-MWCNT nanocomposite hydrogel bone biomaterials.

Natural bone is a complex organic-inorganic composite tissue that possesses endogenous electrically conductive properties in response to mechanical forces. Mimicking these unique properties collectively in a single synthetic biomaterial has so far remained a formidable task. In this study, we report a synthesis strategy that comprised gelatin methacryloyl (GelMA), sol-gel derived tertiary bioactive glass (BG), and uniformly dispersed multiwall carbon nanotubes (MWCNTs) to create nanocomposite hydrogels that mimic the organic-inorganic composition of bone. Using this strategy, biomaterials that are electrically conductive and possess electro-mechanical properties similar to endogenous bone were prepared without affecting their biocompatibility. Nanocomposite hydrogel biomaterials were biodegradable and promoted biomineralization, and supported multipotent mesenchymal progenitor cell (10T1/2) cell interactions and differentiation into an osteogenic lineage. To the best of our knowledge, this work presents the first study to functionally characterize suitable electro-mechanical responses in nanocomposite hydrogels, a key process that occurs in the natural bone to drive its repair and regeneration. Overall, the results demonstrated GelMA-BG-MWCNT nanocomposite hydrogels have the potential to become promising bioactive biomaterials for use in bone repair and regeneration.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Development of Organs-on-Chips and Their Impact on Precision Medicine and Advanced System Simulation.

Drugs may undergo costly preclinical studies but still fail to demonstrate their efficacy in clinical trials, which makes it challenging to discover new drugs. Both in vitro and in vivo models are essential for disease research and therapeutic development. However, these models cannot simulate the physiological and pathological environment in the human body, resulting in limited drug detection and inaccurate disease modelling, failing to provide valid guidance for clinical application. Organs-on-chips (OCs) are devices that serve as a micro-physiological system or a tissue-on-a-chip; they provide accurate insights into certain functions and the pathophysiology of organs to precisely predict the safety and efficiency of drugs in the body. OCs are faster, more economical, and more precise. Thus, they are projected to become a crucial addition to, and a long-term replacement for, traditional preclinical cell cultures, animal studies, and even human clinical trials. This paper first outlines the nature of OCs and their significance, and then details their manufacturing-related materials and methodology. It also discusses applications of OCs in drug screening and disease modelling and treatment, and presents the future perspective of OCs.

Biosynthetic Plastics as Tunable Elastic and Visible Stent with Shape-Memory to Treat Biliary Stricture.

Common biliary tract is ≈4 mm in diameter to deliver bile from liver to small intestine to help digestion. The abnormal narrowing leads to severe symptoms such as pain and nausea. Stents are an effective treatment. Compared with non-degradable stents which require repeated removal, biodegradable stents have the advantage of reducing secondary injury related to endoscopic operation and patient burden. However, current biodegradable materials may cause tissue hyperplasia and the treatment method does not target etiology of stricture. So recurrence rates after biodegradable stent implantation are still high. Here, a biodegradable helical stent fabricated from biosynthetic P(3HB-co-4HB) is reported. Tunable properties can be acquired through altering culture substrates. Stent shows shape memory in various solvents. The stent has an optimized design with helical structure and outer track. The self-expanding of helical structure and double drainage realized by outer track greatly improve drainage of bile. Importantly, stent-loading triamcinolone acetonide can inhibit proliferation of fibroblasts and reduce incidence of restricture. Therapeutic effect is also demonstrated in minipigs with biliary stricture. The results of minipig experiments show that biliary duct in treatment group is unobstructed and tissue hyperplasia is effectively inhibited.

Hydrophobic Polystyrene-Modified Gelatin Enhances Fast Hemostasis and Tissue Regeneration in Traumatic Brain Injury.

Hemostatic sealant is required to deal with blood loss, especially in the scenario of traumatic brain injury (TBI), which presents high rates of morbidity and disability. Hemostasis in surgery with traditional gelatin-based sealants often leads to blood loss and other issues in brain because of the hydrophilic gelatin swelling. Herein, hydrophobic effects on the hemostasis in TBI surgery are studied by tuning the chain length of polystyrene (PS) onto methylacrylated gelatin (Gel-MA). The hydrophobicity and hemostatic efficiency can be tuned by controlling the length of PS groups. The platelet activation of modified sealants Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P is as much as 17.5, 9.1, and 2.1 times higher than Gel-MA in vitro. The hemostatic time of Gel-MA-2P, Gel-MA-P, and Gel-MA-0.5P groups is 2.0-, 1.6-, and 1.1-folds faster than that in Gel-MA group in TBI mice. Increased formation of fibrins and platelet aggregation can also be observed in vitro by scanning electron microscopy. Animal's mortality is lowered by 46%, neurologic deficiency is reduced by 1.5 times, and brain edema is attenuated by 10%. Protein expression is further investigated to exhibit toxic iron-related processes caused by delayed hemostasis and activation of platelets via PI3K/PKC-α signaling. The hydrophobic Gel-MA has the potential in hemostatic TBI and promotes nervous system recovery in brain with the potentials in clinics.

Mussel-Derived Bioadaptive Artificial Tendon Facilitates the Cell Proliferation and Tenogenesis to Promote Tendon Functional Reconstruction.

Tendon injuries range from acute-related trauma to chronic-related injuries are prevalent and bring substantial pain, functional loss, and even disability to the patients. The management of tendon injuries is tricky due to the innate limited regenerative capability of the tendon. Currently, surgical intervention of tendon injuries with artificial tendons remains the standard of care. However, most of artificial tendons are manufactured with synthetic materials, which possess relatively poor biomimetic characteristics and inadequate inherent biodegradability, hence rendering limited cell proliferation and migration for tendon healing. To address these limitations, this work develops a mussel-derived artificial tendon based on double-cross-linked chitosan modification. In this design, decellularized artificial tendon serves as a natural biomimetic scaffold to facilitate the migration and adhesion of tendon repair cells. Additionally, as the cells proliferate, the artificial tendon can be degraded to facilitate tendon regeneration. Moreover, the chitosan cross-linking further enhances the mechanical strength of artificial tendon and offers a controllable degradation. The in vitro and in vivo experimental results demonstrate that mussel-derived artificial tendon not only accelerate the tendon functional reconstruction but also enable harmless clearance at postimplantation. The finding provides a promising alternative to conventional artificial tendons and spurs a new frontier to explore nature-derived artificial tendons.

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology.

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail.

Chemical Synthesis of Innovative Silver Nanohybrids with Synergistically Improved Antimicrobial Properties.

Background: The wide use of antibiotics has created challenges related to antibiotic-resistant bacteria, which have been increasingly found in recent decades. Antibiotic resistance has led to limited choices of antibiotics. Multiple old antimicrobial agents have high antimicrobial properties toward bacteria, but they unfortunately also possess high toxicity toward humans. For instance, silver (Ag) compounds were frequently used to treat tetanus and rheumatism in the 19th century and to treat colds and gonorrhea in the early 20th century. However, the high toxicity of Ag has limited its clinical use. Purpose: We aimed to reformulate Ag to reduce its toxicity toward human cells like osteoblasts and to optimize its antimicrobial properties. Results: Ag, an old antimicrobial agent, was reformulated by hybriding nanomaterials of different dimensions, and silver nanoparticles (AgNPs) of controllable sizes (95-200 nm) and varying shapes (cube, snowflake, and sphere) were synthesized on carbon nanotubes (CNTs). The obtained AgNP-CNT nanohybrids presented significantly higher killing efficacy against Staphylococcus aureus (S. aureus) compared to AgNPs at the same molar concentration and showed synergism in killing S. aureus at 0.2 and 0.4 mM. AgNPs presented significant osteoblast toxicity; in contrast, AgNP-CNT nanohybrids demonstrated significantly enhanced osteoblast viability at 0.04-0.8 mM. The killing of S. aureus by AgNP-CNT nanohybrids was fast, occurring within 15 min. Conclusion: Ag was successfully reformulated and Ag nanohybrids with various AgNP shapes on CNTs were synthesized. The nanohybrids presented significantly enhanced antimicrobial properties and significantly higher osteoblast cell viability compared to AgNPs, showing promise as an innovative antimicrobial nanomaterial for a broad range of biomedical applications.

Reversible adhesives with controlled wrinkling patterns for programmable integration and discharging.

Switchable and minimally invasive tissue adhesives have great potential for medical applications. However, on-demand adherence to and detachment from tissue surfaces remain difficult. We fabricated a switchable hydrogel film adhesive by designing pattern-tunable wrinkles to control adhesion. When adhered to a substrate, the compressive stress generated from the bilayer system leads to self-similar wrinkling patterns at short and long wavelengths, regulating the interfacial adhesion. To verify the concept and explore its application, we established a random skin flap model, which is a crucial strategy for repairing severe or large-scale wounds. Our hydrogel adhesive provides sufficient adhesion for tissue sealing and promotes neovascularization at the first stage, and then gradually detaches from the tissue while a dynamic wrinkling pattern transition happens. The gel film can be progressively ejected out from the side margins after host-guest integration. Our findings provide insights into tunable bioadhesion by manipulating the wrinkling pattern transition.