Advanced healthcare materials

A wound dressing is a sterile pad or compress that is used in direct contact with a wound to help it heal and prevent further issues or complications. Though wound healing is an intricate dynamic process that involves multiple biomolecular species, conventional wound dressings have a limited ability to provide timely information of abnormal conditions, missing the best time for early treatment. The current perspective presents and discusses the design and development of smart wound dressings that are integrated with multifunctional materials, wearable sensors and drug delivery systems as well as their application ranging from wound monitoring to timely application of therapeutics. The perspective also discusses the ongoing challenges and exciting opportunities associated with the development of wearable sensor-based smart wound dressing and provide critical insights into wound healing monitoring and management.

خرید پکیج و مشاهده آنلاین مقاله

Extracellular Matrix-Mimetic Hydrogels for Treating Neural Tissue Injury: A Focus on Fibrin, Hyaluronic Acid, and Elastin-Like Polypeptide Hydrogels

Derek W. Nelson,Ryan J. Gilbert

doi : 10.1002/adhm.202101329

Volume 10, Issue 22 2101329

Neurological and functional recovery is limited following central nervous system injury and severe injury to the peripheral nervous system. Extracellular matrix (ECM)-mimetic hydrogels are of particular interest as regenerative scaffolds for the injured nervous system as they provide 3D bioactive interfaces that modulate cellular response to the injury environment and provide naturally degradable scaffolding for effective tissue remodeling. In this review, three unique ECM-mimetic hydrogels used in models of neural injury are reviewed: fibrin hydrogels, which rely on a naturally occurring enzymatic gelation, hyaluronic acid hydrogels, which require chemical modification prior to chemical crosslinking, and elastin-like polypeptide (ELP) hydrogels, which exhibit a temperature-sensitive gelation. The hydrogels are reviewed by summarizing their unique biological properties, their use as drug depots, and their combination with other biomaterials, such as electrospun fibers and nanoparticles. This review is the first to focus on these three ECM-mimetic hydrogels for their use in neural tissue engineering. Additionally, this is the first review to summarize the use of ELP hydrogels for nervous system applications. ECM-mimetic hydrogels have shown great promise in preclinical models of neural injury and future advancements in their design and use can likely lead to viable treatments for patients with neural injury.

خرید پکیج و مشاهده آنلاین مقاله

Advances in Microsensors and Wearable Bioelectronics for Digital Stethoscopes in Health Monitoring and Disease Diagnosis

Sung Hoon Lee,Yun-Soung Kim,Woon-Hong Yeo

doi : 10.1002/adhm.202101400

Volume 10, Issue 22 2101400

Acoustic stethoscopes have demonstrated beneficial factors aiding diagnosis from the doctors with accurate body sounds. Still, the conventional acoustic stethoscopes require a substantial amount of clinical experience and hearing skills for the physicians to accurately diagnose symptoms from abnormal sounds. Especially for cardiopulmonary systems, it is crucial to collect sounds with precision since they contain valuable information in specific frequency ranges for various sounds. This review paper summarizes recent advances and technical developments in microsensors, circuits, chips, and integrated electronics for fabricating different digital stethoscopes that offer portable detection of body sounds. They solve the limitations of conventional stethoscopes, aiming for wireless auscultation in digitized medicine. Overall, this comprehensive review will help researchers design and develop new wearable electronics and digital stethoscopes for advancing human healthcare, continuous monitoring, and better diagnosis.

خرید پکیج و مشاهده آنلاین مقاله

Converging 2D Nanomaterials and 3D Bioprinting Technology: State-of-the-Art, Challenges, and Potential Outlook in Biomedical Applications

Hadi Rastin,Negar Mansouri,Tran Thanh Tung,Kamrul Hassan,Arash Mazinani,Mahnaz Ramezanpour,Pei Lay Yap,Le Yu,Sarah Vreugde,Dusan Losic

doi : 10.1002/adhm.202101439

Volume 10, Issue 22 2101439

The development of next-generation of bioinks aims to fabricate anatomical size 3D scaffold with high printability and biocompatibility. Along with the progress in 3D bioprinting, 2D nanomaterials (2D NMs) prove to be emerging frontiers in the development of advanced materials owing to their extraordinary properties. Harnessing the properties of 2D NMs in 3D bioprinting technologies can revolutionize the development of bioinks by endowing new functionalities to the current bioinks. First the main contributions of 2D NMS in 3D bioprinting technologies are categorized here into six main classes: 1) reinforcement effect, 2) delivery of bioactive molecules, 3) improved electrical conductivity, 4) enhanced tissue formation, 5) photothermal effect, 6) and stronger antibacterial properties. Next, the recent advances in the use of each certain 2D NMs (1) graphene, 2) nanosilicate, 3) black phosphorus, 4) MXene, 5) transition metal dichalcogenides, 6) hexagonal boron nitride, and 7) metal–organic frameworks) in 3D bioprinting technology are critically summarized and evaluated thoroughly. Third, the role of physicochemical properties of 2D NMSs on their cytotoxicity is uncovered, with several representative examples of each studied 2D NMs. Finally, current challenges, opportunities, and outlook for the development of nanocomposite bioinks are discussed thoroughly.

خرید پکیج و مشاهده آنلاین مقاله

Ultrathin 2D Titanium Carbide MXene (Ti3C2Tx) Nanoflakes Activate WNT/HIF-1?-Mediated Metabolism Reprogramming for Periodontal Regeneration

Di Cui,Na Kong,Liang Ding,Yachong Guo,Wenrong Yang,Fuhua Yan

doi : 10.1002/adhm.202101215

Volume 10, Issue 22 2101215

Periodontal defect regeneration in severe periodontitis relies on the differentiation and proliferation of periodontal ligament cells (PDLCs). Recently, an emerging 2D nanomaterial, MXene (Ti3C2Tx), has gained more and more attention due to the extensive antibacterial and anticancer activity, while its potential biomedical application on tissue regeneration remains unclear. Through a combination of experimental and multiscale simulation schemes, Ti3C2Tx has exhibited satisfactory biocompatibility and induced distinguish osteogenic differentiation of human PDLCs (hPDLCs), with upregulated osteogenesis-related genes. Ti3C2Tx manages to activate the Wnt/?-catenin signaling pathway by enhancing the Wnt-Frizzled complex binding, thus stabilizing HIF-1? and altering metabolic reprogramming into glycolysis. In vivo, hPDLCs pretreated by Ti3C2Tx display excellent performance in new bone formation and osteoclast inhibition with enhanced RUNX2, HIF-1?, and ?-catenin in an experimental rat model of periodontal fenestration defects, indicating that this material has high efficiency of periodontal regeneration promotion. It is demonstrated in this work that Ti3C2Tx has highly efficient therapeutic effects in osteogenic differentiation and periodontal defect repairment.

خرید پکیج و مشاهده آنلاین مقاله

Dual Ultrasound and Photoacoustic Tracking of Magnetically Driven Micromotors: From In Vitro to In Vivo

Azaam Aziz,Joost Holthof,Sandra Meyer,Oliver G. Schmidt,Mariana Medina-Sánchez

doi : 10.1002/adhm.202101077

Volume 10, Issue 22 2101077

The fast evolution of medical micro- and nanorobots in the endeavor to perform non-invasive medical operations in living organisms has boosted the use of diverse medical imaging techniques in the last years. Among those techniques, photoacoustic imaging (PAI), considered a functional technique, has shown to be promising for the visualization of micromotors in deep tissue with high spatiotemporal resolution as it possesses the molecular specificity of optical methods and the penetration depth of ultrasound. However, the precise maneuvering and function's control of medical micromotors, in particular in living organisms, require both anatomical and functional imaging feedback. Therefore, herein, the use of high-frequency ultrasound and PAI is reported to obtain anatomical and molecular information, respectively, of magnetically-driven micromotors in vitro and under ex vivo tissues. Furthermore, the steerability of the micromotors is demonstrated by the action of an external magnetic field into the uterus and bladder of living mice in real-time, being able to discriminate the micromotors’ signal from one of the endogenous chromophores by multispectral analysis. Finally, the successful loading and release of a model cargo by the micromotors toward non-invasive in vivo medical interventions is demonstrated.

خرید پکیج و مشاهده آنلاین مقاله

Rapid and Label-Free Detection of 5-Hydroxymethylcytosine in Genomic DNA Using an Au/ZnO Nanorods Hybrid Nanostructure-Based Electrochemical Sensor

Kiesar Sideeq Bhat,Hyejin Kim,Asrar Alam,Myunggon Ko,Jungeun An,Sooman Lim

doi : 10.1002/adhm.202101193

Volume 10, Issue 22 2101193

Ten-eleven-translocation (TET) proteins modify DNA methylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Loss of 5hmC, a widely accepted epigenetic hallmark of cancers, is proposed as a biomarker for early cancer diagnosis and prognosis. Thus, precise quantification of 5hmC holds great potential for diverse clinical applications. DNAs containing 5mC or 5hmC display different adsorption affinity toward the gold surface, thus producing different electrochemical responses. Here a novel, label-free electrochemical sensor based on gold nanoparticles (Au NPs)/zinc oxide nanorods (ZnO NRs) nanostructure for the facile and real-time detection of 5hmC-enriched DNAs is reported. The hybrid structure is fabricated by the vertical hydrothermal growth of ZnO NRs onto indium tin oxide glass substrate, followed by the decoration of ZnO NRs with Au NPs via sputtering. Successful fabrication is confirmed by analyzing the morphology and chemical composition of the sensor. By coupling the fabricated sensor with cyclic voltammetry, its functionality in distinguishing genomic DNAs containing different levels of 5hmC is validated. Notably, the sensor device successfully and consistently detects 5hmC loss in primary hepatocellular carcinoma, compared to the normal tissues. Thus, the novel sensing strategy to assess DNA hydroxymethylation will likely find broad applications in early cancer diagnosis and prognosis evaluation.

خرید پکیج و مشاهده آنلاین مقاله

Conjugation-Free Multilamellar Protein-Lipid Hybrid Vesicles for Multifaceted Immune Responses

Bon Il Koo,Seon-Mi Jin,Hayeon Kim,Dong Jae Lee,Eunji Lee,Yoon Sung Nam

doi : 10.1002/adhm.202101239

Volume 10, Issue 22 2101239

Various lipid-based nanocarriers have been developed for the co-delivery of protein antigens with immunological adjuvants. However, their in vivo potency in vaccine delivery is limited by structural instability, which causes off-target delivery and low cross-presentation efficacies. Recent works employ covalent cross-linking to stabilize the lipid nanostructures, though the immunogenicity and side effects of chemically modified protein antigens and lipids can cause a long-lasting safety issue. Here robust “conjugation-free” multilamellar protein antigen-lipid hybrid nanovesicles (MPLVs) are introduced through the antigen-mediated self-assembly of unilamellar lipid vesicles for the co-delivery of protein antigens and immunologic adjuvants. The nanocarriers coated with monophosphoryl lipid A and hyaluronic acids elicit highly increase antigen-specific immune responses in vitro and in vivo. The MPLVs increase the generation of immunological surface markers and cytokines in mouse-derived bone-marrow dendritic cells compared to soluble antigens with adjuvants. Besides, the vaccination of mice with the MPLVs significantly increase the production of anti-antigen antibody and interferon-gamma via the activation of CD4+ and CD8+ T cells, respectively. These findings suggest that MPLVs can serve as a promising nanovaccine delivery platform for efficient antigen cross-presentation through the efficient co-delivery of protein antigens with adjuvants.

خرید پکیج و مشاهده آنلاین مقاله

Synthetic Mimics of Antimicrobial Peptides for the Targeted Therapy of Multidrug-Resistant Bacterial Infection

Chenyu Gong,Junjie Sun,Yan Xiao,Xue Qu,Meidong Lang

doi : 10.1002/adhm.202101244

Volume 10, Issue 22 2101244

Antibacterial materials are highly demanded in treatment of bacterial infection, especially severe ones with multidrug-resistance. Herein, pH-responsive polypeptide, i.e., poly-L-lysine modified by 1-(propylthio)acetic acid-3-octylimidazolium and citraconic anhydride (PLL-POIM-CA), is synthesized by post-polymerization modification of poly-L-lysine (PLL) with 1-(propylthio)acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA). It is observed that PLL-POIM-CA is stable under normal physiological condition, while CA cleaves rapidly at weakly acidic environment like bacterial infectious sites. The hydrolyzed PLL-POIM-CA exhibits excellent broad-spectrum antibacterial activities against Gram-negative bacteria of Escherichia coli and Gram-positive bacteria of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). In particular, the minimum inhibitory concentration (MIC) against multidrug-resistant bacteria like MRSA is as low as 7.8 µg mL?1. Moreover, PLL-POIM-CA exhibits good biocompatibility with mouse fibroblast cells (L929) in vitro and improved hemocompatibility with an HC50 exceeding 5000 µg mL?1. Therefore, PLL-POIM-CA displays an excellent bacteria versus cells selectivity (HC50/MIC) over 534, which is 53 times higher than natural antimicrobial peptide of indolicidin. It is further demonstrated in vivo that the antimicrobial polypeptide effectively accelerates MRSA-infected wound healing by relieving local inflammatory response. Therefore, this targeted antimicrobial polypeptide has broad application prospects for the treatment of multidrug-resistant bacterial infection.

خرید پکیج و مشاهده آنلاین مقاله

Polymer Composite Sponges with Inherent Antibacterial, Hemostatic, Inflammation-Modulating and Proregenerative Performances for Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing

Wenshuai Liu,Chunfang Yang,Rui Gao,Chao Zhang,Wenbin Ou-Yang,Zujian Feng,Chuangnian Zhang,Xiangbin Pan,Pingsheng Huang,Deling Kong,Weiwei Wang

doi : 10.1002/adhm.202101247

Volume 10, Issue 22 2101247

Clinical wound management remains a major challenge due to massive bleeding, bacterial infection, and difficult wound healing after tissue trauma. To simultaneously address these issues, composite polymer sponges for accelerating drug-resistant bacterial infected wound healing are fabricated by facilely mixing sodium polyacrylate (PAAS), double quaternary ammonium salts-conjugated chitosan (QAS-CS), and collagen (COL) in aqueous solution, followed by lyophilization. Composite sponges (PAAS/QAS-CS/COL, PQC) show highly porous microstructures (porosity ?90%) with moderate compress modulus (?0.3 MPa), tensile strength (0.004 MPa), and high swelling ratio (?3500%). Importantly, PQC sponge demonstrates superior hemostasis ability over commercially available CS sponge by inducing rapid hemagglutination, and exhibits significantly better antibacterial activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli by destroying cell membrane and causing the leakage of bioactive components such as potassium ion and ?-galactosidase from treated bacterial. Furthermore, PQC sponge can efficiently promote cell proliferation. Significantly, the sponge greatly expedites the regeneration of MRSA-infected full-thickness skin wound in rabbit by successfully eradicating bacterial infection, and reducing inflammation. PQC sponge also improves both early angiogenesis and blood vessel maturation at the wound site. Overall, this multifunctional sponge is a promising wound dressing for clinical use and holds great potential for rapid clinical translation.

خرید پکیج و مشاهده آنلاین مقاله

Bionanoscale Recognition Underlies Cell Fate and Therapy

Shan Sun,Peng Deng,Li Mu,Xiangang Hu,Shuqing Guo

doi : 10.1002/adhm.202101260

Volume 10, Issue 22 2101260

Understanding the bionanoscale recognition of nanostructured architectures is critical to the design and application of nanomaterials, but the related information is not well understood. In this study, it is found that bionanoscale recognition underlies cell fate and therapy. For example, 1T phase (octahedral coordination) monolayer MoS2 exhibits a markedly stronger affinity for fibronectin than the 2H structure (triangular prism coordination) and promotes cell spreading and differentiation. The van der Waals energy and increased turn components contribute to the high adhesion of fibronectin onto the 1T-MoS2 structure. 1T-MoS2 exhibits a significantly stronger affinity (KD, 6.59 × 10?7 m) for liposomes than 2H-MoS2 (1.21 × 10?6 m) due to strong hydrophobic interactions. The existence of octahedrally coordinated atomic structures that improve cell viability by enhancing the neurite length is first proven by random forest and structural equation models. Consequently, octahedral coordination disaggregates ?-synuclein (e.g., by decreasing ?-sheets and increasing coil structures) and protects cells and hosts against Parkinson's disease. As a proof-of-principle demonstration, these findings indicate that bionanoscale recognition underlies the design of biomaterials and cell therapeutics.

خرید پکیج و مشاهده آنلاین مقاله

Spherical Nucleic Acid Vaccine Structure Markedly Influences Adaptive Immune Responses of Clinically Utilized Prostate Cancer Targets

Michelle H. Teplensky,Jasper W. Dittmar,Lei Qin,Shuya Wang,Michael Evangelopoulos,Bin Zhang,Chad A. Mirkin

doi : 10.1002/adhm.202101262

Volume 10, Issue 22 2101262

Cancer vaccines, which activate the immune system against a target antigen, are attractive for prostate cancer, where multiple upregulated protein targets are identified. However, many clinical trials implementing peptides targeting these proteins have yielded suboptimal results. Using spherical nucleic acids (SNAs), we explore how precise architectural control of vaccine components can activate a robust antigen-specific immune response in comparison to clinical formulations of the same targets. The SNA vaccines incorporate peptides for human prostate-specific membrane antigen (PSMA) or T-cell receptor ? alternate reading frame protein (TARP) into an optimized architecture, resulting in high rates of immune activation and cytolytic ability in humanized mice and human peripheral blood mononuclear cells (hPBMCs). Specifically, administered SNAs elevate the production and secretion of cytokines and increase polyfunctional cytotoxic T cells and effector memory. Importantly, T cells raised from immunized mice potently kill targets, including clinically relevant cells expressing the whole PSMA protein. Treatment of hPBMCs increases costimulatory markers and cytolytically active T cells. This work demonstrates the importance of vaccine structure and its ability to reformulate and elevate clinical targets. Moreover, it encourages the field to reinvestigate ineffective peptide targets and repackage them into optimally structured vaccines to harness antigen potency and enhance clinical outcomes.

خرید پکیج و مشاهده آنلاین مقاله

Small Intestinal Submucosa Membrane Modified by Fusion Peptide-Mediated Extracellular Vesicles to Promote Tissue Regeneration

Lei Zhang,Shiqing Ma,Pengfei Wei,Yifan Zhao,Yuzhu Mu,Jinzhe Wu,Wei Jing,Bo Zhao,Jiayin Deng,Zihao Liu

doi : 10.1002/adhm.202101298

Volume 10, Issue 22 2101298

Tissue injury, which often occurs in daily life, remains challenging in clinical medicine. Developing a novel biomaterial with the capability to provide an ideal microenvironment and homeostasis around the wound is highly desirable for effective tissue regenerative medicine. The small intestinal submucosa (SIS) membrane possesses a precise spatial structure with excellent biocompatibility. Extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells can achieve rapid cell proliferation and migration with little immune response by creating a satisfactory microenvironment. In this study, fusion peptide-mediated EVs are able to modify the surface of the SIS membrane via specific combination. In vitro studies prove that modified SIS membranes can promote cell migration and spreading. This phenomenon may be because of the activation of TEADs, which regulate cell behavior. By constructing a rat abdominal wall defect model, it is further demonstrated that the modified SIS membrane is more conducive to tissue regeneration. Collectively, these results suggest that SIS membranes modified by fusion peptide-mediated EVs achieve excellent biofunction and provide promising prospects for tissue regeneration.

خرید پکیج و مشاهده آنلاین مقاله

Acoustic Droplet Printing Tumor Organoids for Modeling Bladder Tumor Immune Microenvironment within a Week

Zhiyi Gong,Lanxiang Huang,Xuan Tang,Keke Chen,Zhuhao Wu,Lingling Zhang,Yue Sun,Yu Xia,Hui Chen,Yongchang Wei,Fubing Wang,Shishang Guo

doi : 10.1002/adhm.202101312

Volume 10, Issue 22 2101312

Current organoid models are limited by the incapability of rapidly fabricating organoids that can mimic the immune microenvironment for a short term. Here, an acoustic droplet-based platform is presented to facilitate the rapid formation of tumor organoids, which retains the original tumor immune microenvironment and establishes a personalized bladder cancer tumor immunotherapy model. In combination with a hydrophobic substrate, the acoustic droplet printer can yield a large number of homogeneous and highly viable bladder tumor organoids in vitro within a week. The generated organoids consist of all components of bladder tumor, including diverse immune elements and tumor cells. By coculturing tumor organoids with autologous immune cells for 2 days, tumor reactive T cells are induced in vitro. Furthermore, it is also demonstrated that these tumor-reactive T cells can also enhance the killing efficiency of matched organoids. Because of the easy operation, repeatability, and stability, the proposed acoustic droplet platform will provide a reliable approach for personalized tumor immunotherapy.

خرید پکیج و مشاهده آنلاین مقاله

Stem/Proliferative and Differentiated Cells within Primary Murine Colonic Epithelium Display Distinct Intracellular Free Ca2+ Signal Codes

Sebastian Mestril,Raehyun Kim,Samuel S. Hinman,Shawn M. Gomez,Nancy L. Allbritton

doi : 10.1002/adhm.202101318

Volume 10, Issue 22 2101318

The second messenger, intracellular free calcium (Ca2+), acts to transduce mitogenic and differentiation signals incoming to the colonic epithelium. A self-renewing monolayer of primary murine colonic epithelial cells is formed over a soft, transparent hydrogel matrix for the scalable analysis of intracellular Ca2+ transients. Cultures that are enriched for stem/proliferative cells exhibit repetitive, high frequency (?25 peaks h?1), and short pulse width (?25 s) Ca2+ transients. Upon cell differentiation the transient frequency declines by 50% and pulse width widens by 200%. Metabolites and growth factors that are known to modulate stem cell proliferation and differentiation through Wnt and Notch signaling pathways, including CHIR-99021, N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT), bone morphogenetic proteins (BMPs), and butyrate, also modulate Ca2+ oscillation patterns in a consistent manner. Increasing the stiffness of the supportive matrix from 200 Pa to 3 GPa shifts Ca2+ transient patterns toward those resembling differentiated cells. The ability to monitor Ca2+ oscillations with the spatial and temporal resolution offered by this platform, combined with its amenability to high-content screens, provides a powerful tool for investigating real-time communication within a wide range of primary tissues in addition to the colonic epithelium.

خرید پکیج و مشاهده آنلاین مقاله

Poly(2-alkyl-2-oxazoline)-Heparin Hydrogels—Expanding the Physicochemical Parameter Space of Biohybrid Materials

Dominik Hahn,Jannick M. Sonntag,Steffen Lück,Manfred F. Maitz,Uwe Freudenberg,Rainer Jordan,Carsten Werner

doi : 10.1002/adhm.202101327

Volume 10, Issue 22 2101327

Poly(ethylene glycol) (PEG)-glycosaminoglycan (GAG) hydrogel networks are established as very versatile biomaterials. Herein, the synthetic gel component of the biohybrid materials is systematically varied by combining different poly(2-alkyl-2-oxazolines) (POx) with heparin applying a Michael-type addition crosslinking scheme: POx of gradated hydrophilicity and temperature-responsiveness provides polymer networks of distinctly different stiffness and swelling. Adjusting the mechanical properties and the GAG concentration of the gels to similar values allows for modulating the release of GAG-binding growth factors (VEGF165 and PDGF-BB) by the choice of the POx and its temperature-dependent conformation. Adsorption of fibronectin, growth of fibroblasts, and bacterial adhesion scale with the hydrophobicity of the gel-incorporated POx. In vitro hemocompatibility tests with freshly drawn human whole blood show advantages of POx-based gels compared to the PEG-based reference materials. Biohybrid POx hydrogels can therefore enable biomedical technologies requiring GAG-based materials with customized and switchable physicochemical characteristics.

خرید پکیج و مشاهده آنلاین مقاله

A Modular Biomaterial Scaffold-Based Vaccine Elicits Durable Adaptive Immunity to Subunit SARS-CoV-2 Antigens

Fernanda Langellotto,Maxence O. Dellacherie,Chyenne Yeager,Hamza Ijaz,Jingyou Yu,Chi-An Cheng,Nikolaos Dimitrakakis,Benjamin T. Seiler,Makda S. Gebre,Tal Gilboa,Rebecca Johnson,Nadia Storm,Sarai Bardales,Amanda Graveline,Des White,Christina M. Tringides,Mark J. Cartwright,Edward J. Doherty,Anna Honko,Anthony Griffiths,Dan H. Barouch,David R. Walt,David J. Mooney

doi : 10.1002/adhm.202101370

Volume 10, Issue 22 2101370

The coronavirus disease 2019 (COVID-19) pandemic demonstrates the importance of generating safe and efficacious vaccines that can be rapidly deployed against emerging pathogens. Subunit vaccines are considered among the safest, but proteins used in these typically lack strong immunogenicity, leading to poor immune responses. Here, a biomaterial COVID-19 vaccine based on a mesoporous silica rods (MSRs) platform is described. MSRs loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF), the toll-like receptor 4 (TLR-4) agonist monophosphoryl lipid A (MPLA), and SARS-CoV-2 viral protein antigens slowly release their cargo and form subcutaneous scaffolds that locally recruit and activate antigen-presenting cells (APCs) for the generation of adaptive immunity. MSR-based vaccines generate robust and durable cellular and humoral responses against SARS-CoV-2 antigens, including the poorly immunogenic receptor binding domain (RBD) of the spike (S) protein. Persistent antibodies over the course of 8 months are found in all vaccine configurations tested and robust in vitro viral neutralization is observed both in a prime-boost and a single-dose regimen. These vaccines can be fully formulated ahead of time or stored lyophilized and reconstituted with an antigen mixture moments before injection, which can facilitate its rapid deployment against emerging SARS-CoV-2 variants or new pathogens. Together, the data show a promising COVID-19 vaccine candidate and a generally adaptable vaccine platform against infectious pathogens.

خرید پکیج و مشاهده آنلاین مقاله

A Biofilm Microenvironment-Activated Single-Atom Iron Nanozyme with NIR-Controllable Nanocatalytic Activities for Synergetic Bacteria-Infected Wound Therapy

Qiqi Xu,Yusheng Hua,Yuetong Zhang,Mingzhu Lv,Huan Wang,Yang Pi,Jiani Xie,Chengyan Wang,Yuan Yong

doi : 10.1002/adhm.202101374

Volume 10, Issue 22 2101374

Biofilm microenvironment (BME)-activated antimicrobial agents display great potential for improved biofilm-related infection therapy because of their superior specificities and sensitivities, effective eliminations, and minimal side effects. Herein, BME-activated Fe-doped polydiaminopyridine nanofusiform-mediated single-atom nanozyme (FePN SAzyme) is presented for photothermal/chemodynamic synergetic bacteria-infected wound therapy. The photothermal therapy (PTT) function of SAzyme can be specifically initiated by the high level of H2O2 and further accelerated through mild acid within the inflammatory environment through “two-step rocket launching-like” process. Additionally, the enhanced chemodynamic therapy (CDT) for the FePN SAzyme can also be endowed by producing hydroxyl radicals through reacting with H2O2 and consuming glutathione (GSH) of the BME, thereby contributing to more efficient synergistic therapeutic effect. Meanwhile, FePN SAzyme could catalyze biofilm-overexpressed H2O2 decomposing into O2 and overcome the hypoxia of biofilm, which significantly enhances the susceptibility of biofilm and increases the synergistic efficacy. Most importantly, the synergistic therapy of bacterial-induced infection diseases can be switched on by the internal and external stimuli simultaneously, resulting in minimal nonspecific damage to healthy tissue. These remarkable characteristics of FePN SAzyme not only develop an innovative strategy for the BME-activated combination therapy but also open a new avenue to explore other nanozyme-involved nanoplatforms for bacterial biofilm infections.

خرید پکیج و مشاهده آنلاین مقاله

Polymyxin B-Triggered Assembly of Peptide Hydrogels for Localized and Sustained Release of Combined Antimicrobial Therapy

Yejiao Shi,David W. Wareham,Yichen Yuan,Xinru Deng,Alvaro Mata,Helena S. Azevedo

doi : 10.1002/adhm.202101465

Volume 10, Issue 22 2101465

Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade-old antibiotic with increasing clinical utility for treating multidrug-resistant Gram-negative bacterial infections. The hydrogel is assembled by additing PMB solution into a rationally designed peptide amphiphile (PA) solution and its mechanical properties can be adjusted through the addition of counterions, envisioning its application in diverse infection scenarios. Sustained release of PMB from the hydrogel over a 5-day period and prolonged antimicrobial activities against Gram-negative bacteria are observed. The localized release of active PMB from the hydrogel is shown to be effective in vivo for treating Pseudomonas aeruginosa infection in the Galleria mellonella burn wound infection model, dramatically reducing the mortality from 93% to 13%. Complementary antimicrobial activity against Gram-positive Staphylococcus aureus and enhanced antimicrobial effect against the Gram-negative Acinetobacter baumannii are observed when an additional antibiotic fusidic acid is incorporated into the hydrogen network. These results demonstrate the potential of the PMB-triggered PA hydrogel as a versatile platform for the localized and sustained delivery of combined antimicrobial therapies.

خرید پکیج و مشاهده آنلاین مقاله

Antibacterial Zeolite Imidazole Frameworks with Manganese Doping for Immunomodulation to Accelerate Infected Wound Healing

Yao Wan,Jiao Fang,Yu Wang,Jiao Sun,Yue Sun,Xiaolin Sun,Manlin Qi,Wen Li,Chunyan Li,Yanmin Zhou,Lin Xu,Biao Dong,Lin Wang

doi : 10.1002/adhm.202101515

Volume 10, Issue 22 2101515

Numerous nanomedicines currently emerge to reduce the dramatic threat in antibiotics resistance for antibacterial application against severe bacterial infections, while it is restricted by over-reacted immune response to pathogenic bacteria. Herein, enzymatic activity is introduced into the zeolitic imidazolate framework-8 (ZIF-8) to achieve sterilization by releasing Zn ions, as well as inflammation regulation through the variable valence of Mn ions that are uniformly doped into its framework. Within this simple metal organic framework (MOF) structure design, Mn-ZIF-8 possesses the co-existence of Mn2+/Mn4+ to endow the nanocomposite with the anti-inflammatory capabilities, which can be adjusted through the redox environment. The enzymatic activity of Mn ions and superiority of pore structure of ZIF-8 are effectively combined to realize the substrate selection via reactant molecular size and high-efficiency internal catalytic performance. By such design, this nanocomposite would not only exhibit an excellent antibacterial performance against pathogenic bacteria, but also reshape the inflammatory immunity by regulating macrophage polarization to suppress over-reacted inflammation, leading to a favorably therapeutic efficiency on bacteria-infected wound healing in animal models. Taken together, this nanoplatform provides effective approach for accelerating infected wound healing via bacteria killing and inflammation modulation, and may be extended for the therapy of other severe bacteria-induced infections.

خرید پکیج و مشاهده آنلاین مقاله