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1.
Cell Mol Life Sci ; 80(5): 118, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37022488

RESUMO

Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1+ stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and atherosclerosis. Using genetic lineage tracing mice and veingraft mice surgery model, we found that suppression of lncRNA Malat1 promoted Sca1+ cells to differentiate into SMCs in vivo, resulting in excess SMC accumulation in neointima and vessel stenosis. Genetic ablation of Sca1+ cells attenuated venous arterialization and impaired vascular structure normalization, and thus, resulting in less Malat1 down-regulation. Single cell sequencing further revealed a fibroblast-like phenotype of Sca1+ SPCs-derived SMCs. Protein array sequencing and in vitro assays revealed that SMC regeneration from Sca1+ SPCs was regulated by Malat1 through miR125a-5p/Stat3 signaling pathway. These findings delineate the critical role of Sca1+ SPCs in vascular remodeling and reveal that lncRNA Malat1 is a key regulator and might serve as a novel biomarker or potential therapeutic target for vascular diseases.


Assuntos
RNA Longo não Codificante , Ataxias Espinocerebelares , Doenças Vasculares , Animais , Camundongos , Células Cultivadas , Modelos Animais de Doenças , Músculo Liso Vascular , Miócitos de Músculo Liso/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ataxias Espinocerebelares/metabolismo , Células-Tronco/metabolismo , Doenças Vasculares/metabolismo , Remodelação Vascular/genética
2.
J Am Chem Soc ; 145(24): 13195-13203, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37305923

RESUMO

Polymer/metal-organic framework (MOF) composites have been widely studied for their favorable combination of polymer flexibility and MOF crystallinity. While traditional polymer-coated MOFs maximize the polymer properties at the surface, the dramatic loss of MOF porosity due to blockage by the nonporous polymeric coating remains a problem. Herein, we introduce intrinsically microporous synthetic allomelanin (AM) as a porous coating on the zirconium-based MOF (Zr-MOF) UiO-66 via an in situ surface-constrained oxidative polymerization of the AM precursor, 1,8-dihydroxynaphthalene (1,8-DHN). Transmission electron microscopy images verify the formation of well-defined nanoparticles with a core-shell morphology (AM@UiO-66), and nitrogen sorption isotherms indicate the porosity of the UiO-66 core remains constant and is not disturbed by the AM coating. Notably, such a strategy could be adapted to MOFs with larger pores, such as MOF-808 by generating porous AM polymer coatings from bulkier DHN oligomers, highlighting the versatility of this method. Finally, we showed that by tuning the AM coating thickness on UiO-66, the hierarchically porous structures of these AM@UiO-66 composites engender excellent hexane isomer separation selectivity and storage capacity.

3.
Cell Mol Life Sci ; 79(11): 576, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36315271

RESUMO

RATIONALE: CD34+ cells are believed being progenitors that may be used to treat cardiovascular disease. However, the exact identity and the role of CD34+ cells in physiological and pathological conditions remain unclear. METHODS: We performed single-cell RNA sequencing analysis to provide a cell atlas of normal tissue/organ and pathological conditions. Furthermore, a genetic lineage tracing mouse model was used to investigate the role of CD34+ cells in angiogenesis and organ fibrosis. RESULTS: Single-cell RNA sequencing analysis revealed a heterogeneous population of CD34+ cells in both physiological and pathological conditions. Using a genetic lineage tracing mouse model, we showed that CD34+ cells not only acquired endothelial cell fate involved in angiogenesis, but also, CD34+ cells expressing Pi16 may transform into myofibroblast and thus participate in organ fibrosis. CONCLUSION: A heterogeneous CD34+ cells serve as a contributor not only to endothelial regeneration but also a wound healing response that may provide therapeutic insights into fibrosis.


Assuntos
Células Endoteliais , Miofibroblastos , Camundongos , Animais , Fibrose , Diferenciação Celular , Células Endoteliais/patologia , Miofibroblastos/patologia , Cicatrização/fisiologia , Antígenos CD34
4.
J Am Chem Soc ; 143(7): 2622-2637, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33560127

RESUMO

Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five types-eumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelanin-based on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melanin-based materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure-function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.


Assuntos
Melaninas/química , Espectroscopia de Ressonância de Spin Eletrônica , Indóis/química , Indóis/metabolismo , Espectroscopia de Ressonância Magnética , Melaninas/biossíntese , Conformação Molecular , Polímeros/química , Polímeros/metabolismo
5.
J Am Chem Soc ; 143(10): 4005-4016, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33673734

RESUMO

Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m2/g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.


Assuntos
Biopolímeros/química , Melaninas/química , Adsorção , Biopolímeros/metabolismo , Fungos/metabolismo , Melaninas/metabolismo , Nanopartículas/química , Naftóis/química , Naftóis/metabolismo , Paraoxon/química , Paraoxon/metabolismo , Porosidade , Espalhamento a Baixo Ângulo , Difração de Raios X
6.
Angew Chem Int Ed Engl ; 60(32): 17464-17471, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33913253

RESUMO

Melanosomes in nature have diverse morphologies, including spheres, rods, and platelets. By contrast, shapes of synthetic melanins have been almost entirely limited to spherical nanoparticles with few exceptions produced by complex templated synthetic methods. Here, we report a non-templated method to access synthetic melanins with a variety of architectures including spheres, sheets, and platelets. Three 1,8-dihydroxynaphthalene dimers (4-4', 2-4' and 2-2') were used as self-assembling synthons. These dimers pack to form well-defined structures of varying morphologies depending on the isomer. Specifically, distinctive ellipsoidal platelets can be obtained using 4-4' dimers. Solid-state polymerization of the preorganized dimers generates polymeric synthetic melanins while maintaining the initial particle morphologies. This work provides a new route to anisotropic synthetic melanins, where the building blocks are preorganized into specific shapes, followed by solid-state polymerization.


Assuntos
Corantes/química , Naftóis/química , Polímeros/química , Anisotropia , Corantes/síntese química , Naftóis/síntese química , Polimerização , Polímeros/síntese química
7.
J Am Chem Soc ; 142(29): 12802-12810, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32638590

RESUMO

Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.


Assuntos
Melaninas/química , Compostos Organosselênicos/química , Selênio/química , Humanos , Queratinócitos/efeitos dos fármacos , Melaninas/farmacologia , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/farmacologia , Tamanho da Partícula , Selênio/farmacologia , Propriedades de Superfície , Raios X
8.
Proc Natl Acad Sci U S A ; 114(34): E7045-E7053, 2017 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-28784782

RESUMO

A three-component system of Janus dendrimers (JDs) including hydrogenated, fluorinated, and hybrid hydrogenated-fluorinated JDs are reported to coassemble by film hydration at specific ratios into an unprecedented class of supramolecular Janus particles (JPs) denoted Janus dendrimersomes (JDSs). They consist of a dumbbell-shaped structure composed of an onion-like hydrogenated vesicle and an onion-like fluorinated vesicle tethered together. The synthesis of dye-tagged analogs of each JD component enabled characterization of JDS architectures with confocal fluorescence microscopy. Additionally, a simple injection method was used to prepare submicron JDSs, which were imaged with cryogenic transmission electron microscopy (cryo-TEM). As reported previously, different ratios of the same three-component system yielded a variety of structures including homogenous onion-like vesicles, core-shell structures, and completely self-sorted hydrogenated and fluorinated vesicles. Taken together with the JDSs reported herein, a self-sorting pathway is revealed as a function of the relative concentration of the hybrid JD, which may serve to stabilize the interface between hydrogenated and fluorinated bilayers. The fission-like pathway suggests the possibility of fusion and fission processes in biological systems that do not require the assistance of proteins but instead may result from alterations in the ratios of membrane composition.


Assuntos
Fusão Celular , Dendrímeros/química , Hidrogênio/química , Dendrímeros/síntese química , Modelos Biológicos , Estrutura Molecular
9.
Angew Chem Int Ed Engl ; 59(43): 19136-19142, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32659039

RESUMO

Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL-1 ) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.


Assuntos
Apoptose , Luz , Nanopartículas/química , Peptídeos/química , Polímeros/química , Sequência de Aminoácidos , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Micelas , Polimerização
10.
J Am Chem Soc ; 141(12): 4928-4935, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30892027

RESUMO

The sustainable production of chemically recyclable polymers presents a significant opportunity to polymer scientists to tackle the growing environmental and energy problems of current petroleum-based plastics. Despite recent advances, however, there are still pressing needs for an expanded horizon of chemically recyclable polymers. Herein, we introduce a new paradigm of biosourced polythioesters (PTEs) with high polymerizability and complete recyclability under mild and economical conditions. The thiolactone monomers with a high ring strain can be easily prepared in a two-step process from 4-hydroxyproline. Controlled ring-opening polymerizations (ROP) using inexpensive and weak bases afford PTEs with high molar masses ( Mn) up to 259 kg mol-1 and narrow dispersities generally below 1.15. The properties of PTEs can be readily adjusted by copolymerization and/or pre/post-functionalization on the side chains. Selective and complete depolymerizations of the PTEs in dilute solution at ambient to modest temperatures recycle clean monomers. Density functional theory (DFT) calculation of model reactions provides mechanistic insights and highlights the importance of judicious molecular design. Taken together, the unique ROP/depolymerization chemistry of such PTEs may offer a sustainable solution for creating and manufacturing high-value materials such as optical/photochemical plastics, self-immolative polymers, and degradable biomaterials under situations where recycle and reuse are indispensable.

11.
Angew Chem Int Ed Engl ; 58(48): 17359-17364, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31595626

RESUMO

Harnessing metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme-responsive and pro-apoptotic peptide brush polymers. Thermolysin-responsive peptide-based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm-like micelles upon enzyme-triggered cleavage of coronal peptide sidechains. Moreover, pro-apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro-apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo-RDRP, make it possible to access well-defined peptide-based polymer bioconjugate structures with tunable bioactivity.


Assuntos
Micelas , Nanopartículas/química , Peptídeos/química , Polímeros/química , Termolisina/química , Acrilatos/química , Aminoácidos/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/química , Células HeLa , Humanos , Conformação Molecular , Processos Fotoquímicos , Polimerização , Polimetil Metacrilato/química , Solventes/química , Relação Estrutura-Atividade
12.
Angew Chem Int Ed Engl ; 56(46): 14677-14681, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-28940633

RESUMO

Chemical and biological tools are harnessed to investigate the impact of spatial factors for functional pairing of human lectins with counterreceptors. The homodimeric adhesion/growth-regulatory galectin-1 and a set of covalently linked homo-oligomers from di- to tetramers serve as proof-of-principle test cases. Glycodendrimersomes provide a versatile and sensitive diagnostic platform to reveal thresholds for ligand density and protein concentration in aggregation assays (trans-activity), irrespective of linker length between lectin domains. Monitoring the affinity of cell binding and ensuing tumor growth inhibition reveal the linker length to be a bidirectional switch for cis-activity. The discovery that two aspects of lectin functionality (trans- versus cis-activity) respond non-uniformly to a structural change underscores the power of combining synthetic and biological tools to advance understanding of the sugar functionality of the cell surface.


Assuntos
Lectinas/química , Polissacarídeos/química , Açúcares/química , Membrana Celular/química , Humanos
13.
J Vis Exp ; (204)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38372398

RESUMO

Cell patterning, allowing precise control of cell positioning, presents a unique advantage in the study of cell behavior. In this protocol, a cell patterning strategy based on the Magnetic-Archimedes (Mag-Arch) effect is introduced. This approach enables precise control of cell distribution without the use of ink materials or labeling particles. By introducing a paramagnetic reagent to enhance the magnetic susceptibility of the cell culture medium, cells are repelled by magnets and arrange themselves into a pattern complementary to the magnet sets positioned beneath the microfluidic substrate. In this article, detailed procedures for cell patterning using the Mag-Arch-based strategy are provided. Methods for patterning single-cell types as well as multiple cell types for co-culture experiments are offered. Additionally, comprehensive instructions for fabricating microfluidic devices containing channels for cell patterning are provided. Achieving this feature using parallel methods is challenging but can be done in a simplified and cost-effective manner. Employing Mag-Arch-based cell patterning equips researchers with a powerful tool for in vitro research.


Assuntos
Magnetismo , Microfluídica , Técnicas de Cocultura , Indicadores e Reagentes , Fenômenos Magnéticos
14.
Adv Sci (Weinh) ; 11(35): e2401527, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39007192

RESUMO

Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu2+ carrier through molecular-docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.


Assuntos
Cobre , Modelos Animais de Doenças , Homeostase , Infarto do Miocárdio , Animais , Infarto do Miocárdio/metabolismo , Cobre/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Masculino , Miocárdio/metabolismo , Géis , Proteínas do Leite/metabolismo , Proteínas do Leite/genética , Proteínas do Leite/farmacologia
15.
Nat Commun ; 15(1): 557, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38228638

RESUMO

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.


Assuntos
Estenose da Valva Aórtica , Calcinose , Camundongos , Animais , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/tratamento farmacológico , Osteogênese , Calcinose/tratamento farmacológico , Calcinose/metabolismo , Células Cultivadas , Fenômenos Magnéticos
16.
Sci Adv ; 10(16): eadj0268, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640247

RESUMO

Continuous monitoring of biomarkers at locations adjacent to targeted internal organs can provide actionable information about postoperative status beyond conventional diagnostic methods. As an example, changes in pH in the intra-abdominal space after gastric surgeries can serve as direct indicators of potentially life-threatening leakage events, in contrast to symptomatic reactions that may delay treatment. Here, we report a bioresorbable, wireless, passive sensor that addresses this clinical need, designed to locally monitor pH for early detection of gastric leakage. A pH-responsive hydrogel serves as a transducer that couples to a mechanically optimized inductor-capacitor circuit for wireless readout. This platform enables real-time monitoring of pH with fast response time (within 1 hour) over a clinically relevant period (up to 7 days) and timely detection of simulated gastric leaks in animal models. These concepts have broad potential applications for temporary sensing of relevant biomarkers during critical risk periods following diverse types of surgeries.


Assuntos
Implantes Absorvíveis , Transdutores , Animais , Tecnologia sem Fio , Concentração de Íons de Hidrogênio , Biomarcadores
17.
Lab Chip ; 23(22): 4901-4908, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37874569

RESUMO

Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.


Assuntos
Nanofibras , Nanopartículas , Microfluídica , Poliestirenos
18.
Biomater Adv ; 145: 213244, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36549150

RESUMO

Infection can disturb the wound healing process and lead to poor skin regeneration, chronic wound, septicemia and even death. To combat the multi-drug resistance bacteria or fungi, it is urgent and necessary to develop advanced antimicrobial wound dressings. In this study, a composite hydrogel dressing composed of polyvinyl alcohol (PVA), agarose, glycerol and antibacterial hyperbranched polylysine (HBPL) was prepared by a freeze-thawing method. The hydrogel showed robust mechanical properties, and the HBPL in the hydrogel displayed effective and broad-spectrum antimicrobial properties to bacteria and fungi as well as biofilms. The composite hydrogel exhibited good biocompatibility with respect to the levels of cells, blood, tissue and main organs. In an animal experiment of an infected wound model, the hydrogel significantly eliminated the infection and accelerated the wound regeneration with better tissue morphology and angiogenesis. The hydrogel also successfully achieved scalable production of over 600 g with a yield over 90 %, suggesting the great potential for the application in practice.


Assuntos
Anti-Infecciosos , Hidrogéis , Animais , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bandagens , Anti-Infecciosos/farmacologia
19.
Biomater Res ; 27(1): 6, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737833

RESUMO

BACKGROUND: Post-traumatic massive hemorrhage demands immediately available first-aid supplies with reduced operation time and good surgical compliance. In-situ crosslinking gels that are flexibly adapting to the wound shape have a promising potential, but it is still hard to achieve fast gelation, on-demand adhesion, and wide feasibility at the same time. METHODS: A white-light crosslinkable natural milk-derived casein hydrogel bioadhesive is presented for the first time. Benefiting from abundant tyrosine residues, casein hydrogel bioadhesive was synthesized by forming di-tyrosine bonds under white light with a ruthenium-based catalyst. We firstly optimized the concentration of proteins and initiators to achieve faster gelation and higher mechanical strength. Then, we examined the degradation, cytotoxicity, tissue adhesion, hemostasis, and wound healing ability of the casein hydrogels to study their potential to be used as bioadhesives. RESULT: Rapid gelation of casein hydrogel is initiated with an outdoor flashlight, a cellphone flashlight, or an endoscopy lamp, which facilitates its usage during first-aid and minimally invasive operations. The rapid gelation enables 3D printing of the casein hydrogel and excellent hemostasis even during liver hemorrhage due to section injury. The covalent binding between casein and tissue enables robust adhesion which can withstand more than 180 mmHg blood pressure. Moreover, the casein-based hydrogel can facilitate post-traumatic wound healing caused by trauma due to its biocompatibility. CONCLUSION: Casein-based bioadhesives developed in this study pave a way for broad and practical application in emergency wound management.

20.
Chem Sci ; 14(15): 4183-4192, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37063797

RESUMO

Herein, we investigate synthetic routes to a close mimic of natural pheomelanin. Three different oxidative polymerization routes were attempted to generate synthetic pheomelanin, each giving rise to structurally dissimilar materials. Among them, the route employing 5-cysteinyl-dihydroxyphenylalanine (5-CD) as a monomer was verified as a close analogue of extracted pheomelanin from humans and birds. The resulting biomimetic and natural pheomelanins were compared via various techniques, including solid-state Nuclear Magnetic Resonance (ssNMR) and Electron Paramagnetic Resonance (EPR). This synthetic pheomelanin closely mimics the structure of natural pheomelanin as determined by parallel characterization of pheomelanin extracted from multiple biological sources. With a good synthetic biomimetic material in hand, we describe cation-π interactions as an important driving force for pheomelanogenesis, further advancing our fundamental understanding of this important biological pigment.

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