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1.
Nat Commun ; 11(1): 4907, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999289

RESUMO

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.


Assuntos
Materiais Biomiméticos/administração & dosagem , Matriz Extracelular/química , Neoplasias/terapia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/química , Fibrinogênio/efeitos da radiação , Géis , Humanos , Injeções Intravenosas , Metabolômica , Camundongos , Neoplasias/metabolismo , Trombina/administração & dosagem , Trombina/química , Trombina/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
2.
Phys Rev Lett ; 125(9): 098101, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32915604

RESUMO

Programmable valves and actuators are widely used in man-made systems to provide sophisticated control of fluid flows. In nature, however, this process is frequently achieved using passive soft materials. Here we study how elastic deformations of cylindrical pores embedded in a flexible membrane enable passive flow control. We develop biomimetic valves with variable pore radius, membrane radius, and thickness. Our experiments reveal a mechanism where small deformations bend the membrane and constrict the pore-thus reducing flow-while larger deformations stretch the membrane, expand the pore, and enhance flow. We develop a theory capturing this highly nonmonotonic behavior, and validate the scaling across a broad range of material and geometric parameters. Our results suggest that intercompartmental flow control in living systems can be encoded entirely in the physical attributes of soft materials. Moreover, this design could enable autonomous flow control in man-made systems.


Assuntos
Materiais Biomiméticos/química , Modelos Biológicos , Modelos Químicos , Animais , Membranas/química
3.
Nat Commun ; 11(1): 4502, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908136

RESUMO

Biological tissues, such as muscle, can increase their mechanical strength after swelling due to the existence of many biological membrane barriers that can regulate the transmembrane transport of water molecules and ions. Oppositely, typical synthetic materials show a swelling-weakening behavior, which always suffers from a sharp decline in mechanical strength after swelling, because of the dilution of the network. Here, we describe a swelling-strengthening phenomenon of polymer materials achieved by a bioinspired strategy. Liposomal membrane nanobarriers are covalently embedded in a crosslinked network to regulate transmembrane transport. After swelling, the stretched network deforms the liposomes and subsequently initiates the transmembrane diffusion of the encapsulated molecules that can trigger the formation of a new network from the preloaded precursor. Thanks to the tough nature of the double-network structure, the swelling-strengthening phenomenon is achieved to polymer hydrogels successfully. Swelling-triggered self-strengthening enables the development of various dynamic materials.


Assuntos
Materiais Biomiméticos/química , Hidrogéis/química , Lipossomos/química , Nanoestruturas/química , Força Compressiva , Reagentes para Ligações Cruzadas/química , Lipossomos/ultraestrutura , Teste de Materiais , Microscopia Eletrônica de Transmissão , Nanoestruturas/ultraestrutura , Resistência à Tração
4.
Science ; 369(6506): 993-999, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820126

RESUMO

Stimulator of interferon genes (STING) links innate immunity to biological processes ranging from antitumor immunity to microbiome homeostasis. Mechanistic understanding of the anticancer potential for STING receptor activation is currently limited by metabolic instability of the natural cyclic dinucleotide (CDN) ligands. From a pathway-targeted cell-based screen, we identified a non-nucleotide, small-molecule STING agonist, termed SR-717, that demonstrates broad interspecies and interallelic specificity. A 1.8-angstrom cocrystal structure revealed that SR-717 functions as a direct cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) mimetic that induces the same "closed" conformation of STING. SR-717 displayed antitumor activity; promoted the activation of CD8+ T, natural killer, and dendritic cells in relevant tissues; and facilitated antigen cross-priming. SR-717 also induced the expression of clinically relevant targets, including programmed cell death 1 ligand 1 (PD-L1), in a STING-dependent manner.


Assuntos
Antineoplásicos/farmacologia , Materiais Biomiméticos/farmacologia , Proteínas de Membrana/metabolismo , Nucleotídeos Cíclicos/farmacologia , Animais , Antígeno B7-H1/metabolismo , Materiais Biomiméticos/química , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Cristalografia por Raios X , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Nucleotídeos Cíclicos/química , Conformação Proteica/efeitos dos fármacos
5.
PLoS One ; 15(8): e0237116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857787

RESUMO

Bone metastases are a frequent complication in prostate cancer, and several studies have shown that vitamin D deficiency promotes bone metastases. However, while many studies focus on vitamin D's role in cell metabolism, the effect of chronically low vitamin D levels on bone tissue, i.e. insufficient mineralization of the tissue, has largely been ignored. To investigate, whether poor tissue mineralization promotes cancer cell attachment, we used a fluorescence based adhesion assay and single cell force spectroscopy to quantify the adhesion of two prostate cancer cell lines to well-mineralized and demineralized dentin, serving as biomimetic bone model system. Adhesion rates of bone metastases-derived PC3 cells increased significantly on demineralized dentin. Additionally, on mineralized dentin, PC3 cells adhered mainly via membrane anchored surface receptors, while on demineralized dentin, they adhered via cytoskeleton-anchored transmembrane receptors, pointing to an interaction via exposed collagen fibrils. The adhesion rate of lymph node derived LNCaP cells on the other hand is significantly lower than that of PC3 and not predominately mediated by cytoskeleton-linked receptors. This indicates that poor tissue mineralization facilitates the adhesion of invasive cancer cells by the exposure of collagen and emphasizes the disease modifying effect of sufficient vitamin D for cancer patients.


Assuntos
Calcificação Fisiológica , Adesão Celular , Neoplasias da Próstata/metabolismo , Animais , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Colágeno/metabolismo , Citoesqueleto/metabolismo , Dentina/química , Elefantes , Humanos , Masculino , Receptores de Superfície Celular/metabolismo , Tecidos Suporte/química , Vitamina D/metabolismo
6.
Nat Commun ; 11(1): 3362, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620794

RESUMO

Intrinsically and fully stretchable active-matrix-driven displays are an important element to skin electronics that can be applied to many emerging fields, such as wearable electronics, consumer electronics and biomedical devices. Here, we show for the first time a fully stretchable active-matrix-driven organic light-emitting electrochemical cell array. Briefly, it is comprised of a stretchable light-emitting electrochemical cell array driven by a solution-processed, vertically integrated stretchable organic thin-film transistor active-matrix, which is enabled by the development of chemically-orthogonal and intrinsically stretchable dielectric materials. Our resulting active-matrix-driven organic light-emitting electrochemical cell array can be readily bent, twisted and stretched without affecting its device performance. When mounted on skin, the array can tolerate to repeated cycles at 30% strain. This work demonstrates the feasibility of skin-applicable displays and lays the foundation for further materials development.


Assuntos
Materiais Biomiméticos/química , Elastômeros/química , Transistores Eletrônicos , Dispositivos Eletrônicos Vestíveis , Eletroquímica , Éteres/química , Estudos de Viabilidade , Fluorcarbonetos/química , Luminescência , Teste de Materiais , Ácidos Polimetacrílicos/química , Pele
7.
Proc Natl Acad Sci U S A ; 117(28): 16127-16137, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601214

RESUMO

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.


Assuntos
Adesivos/química , Materiais Revestidos Biocompatíveis/química , Peptídeos/química , Stents , Adesivos/síntese química , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Adesão Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Química Click , Células Progenitoras Endoteliais/citologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Miócitos de Músculo Liso/citologia , Óxido Nítrico/química , Compostos Organosselênicos/química , Peptídeos/síntese química , Proteínas/química , Coelhos , Stents/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle
8.
Proc Natl Acad Sci U S A ; 117(29): 16743-16748, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32611809

RESUMO

Mammalian nervous systems, as natural ionic circuitries, stand out in environmental perception and sophisticated information transmission, relying on protein ionic channels and additional necessary structures. Prosperously emerged ionic regulated biomimetic nanochannels exhibit great potentialities in various application scenarios, especially signal transduction. Most reported direct current systems possess deficiencies in informational density and variability, which are superiorities of alternating current (AC) systems and necessities in bioinspired nervous signal transmission. Here, inspired by myelinated saltatory conduction, alternating electrostatic potential controlled nanofluidics are constructed with a noncontact application pattern and MXene nanosheets. Under time-variant external stimuli, ions confined in the interlaminar space obtain the capability of carriers for the AC ionic circuit. The transmitted information is accessible from typical sine to a frequency-modulated binary signal. This work demonstrates the potentiality of the bioinspired nervous signal transmission between electronics and ionic nanofluidics, which might push one step forward to the avenue of AC ionics.


Assuntos
Potenciais de Ação , Materiais Biomiméticos/química , Condutividade Elétrica , Microfluídica/métodos , Modelos Neurológicos , Nanoestruturas/química , Dimetilpolisiloxanos/química , Equipamentos e Provisões Elétricas , Transporte de Íons , Microfluídica/instrumentação
9.
Proc Natl Acad Sci U S A ; 117(25): 14602-14608, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32522869

RESUMO

Bioinspired actuators with stimuli-responsive and deformable properties are being pursued in fields such as artificial tissues, medical devices and diagnostics, and intelligent biosensors. These applications require that actuator systems have biocompatibility, controlled deformability, biodegradability, mechanical durability, and stable reversibility. Herein, we report a bionic actuator system consisting of stimuli-responsive genetically engineered silk-elastin-like protein (SELP) hydrogels and wood-derived cellulose nanofibers (CNFs), which respond to temperature and ionic strength underwater by ecofriendly methods. Programmed site-selective actuation can be predicted and folded into three-dimensional (3D) origami-like shapes. The reversible deformation performance of the SELP/CNF actuators was quantified, and complex spatial transformations of multilayer actuators were demonstrated, including a biomimetic flower design with selective petal movements. Such actuators consisting entirely of biocompatible and biodegradable materials will offer an option toward constructing stimuli-responsive systems for in vivo biomedicine soft robotics and bionic research.


Assuntos
Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Biônica/métodos , Celulose/química , Elastina/química , Elastina/genética , Hidrogéis/química , Conformação Molecular , Nanofibras/química , Engenharia de Proteínas , Robótica/métodos , Seda/química , Seda/genética
10.
Int J Nanomedicine ; 15: 3729-3740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547025

RESUMO

Background: Duraplasty is one of the most critical issues in neurosurgical procedures because the defect of dura matter will cause many complications. Electrospinning can mimic the 3D structure of the natural extracellular matrix whose structure is similar to that of dura matter. Poly(L-lactic acid) (PLLA) has been used to fabricate dura matter substitutes and showed compatibility to dural tissue. However, the mechanical properties of the PLLA substitute cannot match the mechanical properties of the human dura mater. Methods and Results: We prepared stereocomplex nanofiber membranes based on enantiomeric poly(lactic acid) and poly(D-lactic acid)-grafted tetracalcium phosphate via electrospinning. X-ray diffraction results showed the formation of stereocomplex crystallites (SC) in the composite nanofiber membranes. Scanning electron microscope observation images showed that composites nanofibers with higher SC formation can keep its original morphologies after heat treatment, suggesting the heat resistance of composite nanofiber membranes. Differential scanning calorimeter tests confirmed that the melting temperature of composite nanofiber membranes was approximately 222°C, higher than that of PLLA. Tensile testing indicated that the ultimate tensile strength and the elongation break of the stereocomplex nanofiber membranes were close to human dura matter. In vitro cytotoxicity studies proved that the stereocomplex nanofiber membranes were non-toxic. The neuron-like differentiation of marrow stem cells on the stereocomplex nanofiber membranes indicated its neuron compatibility. Conclusion: The stereocomplex nanofiber membranes have the potential to serve as a dura mater substitute.


Assuntos
Materiais Biomiméticos/química , Dura-Máter/fisiologia , Nanofibras/química , Poliésteres/química , Animais , Fosfatos de Cálcio/química , Varredura Diferencial de Calorimetria , Diferenciação Celular , Linhagem Celular , Cristalização , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Nanofibras/ultraestrutura , Neurônios/citologia , Ratos Sprague-Dawley , Estereoisomerismo , Temperatura , Difração de Raios X
11.
PLoS One ; 15(6): e0234482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520967

RESUMO

Three-dimensional polydimethylsiloxane platforms were developed to mimic the extracellular matrix with blood vessels by having scaffolds with micropatterns, porous membrane and trenches. Precisely controlled physical dimensions, layouts, and topography as well as different surface chemical treatments were applied to study their influences on nasopharyngeal carcinoma cell (10-15 µm in diameter) migration in mimicked platforms over 15-hour of time-lapse imaging. By placing the pores at different distance from the edges of the trenches, pores with different trench sidewall exposures and effective sizes were generated. Pores right next to the trench sidewalls showed the highest cell traversing probability, most likely related to the larger surface contact area with cells along the sidewalls. Straight grating oriented perpendicular to trenches below the top layer increased cell traversing probability. Pore shape as well as pore size influenced the cell traversing probability and cells could not traverse through pores that were 6 µm or less in diameter, which is much smaller than the cell size. Trench depth of 15 µm could induce more cells to traverse through the porous membrane, while shallower trenches impeded cell traversing and longer time was needed for cells to traverse because 3 and 6 µm deep trenches were much smaller than cell size which required large cell deformation. Hydrophobic surface coating on the top layer and fibronectin in pores and trenches increased the cell traversing probability and reduced the pore size that cells could traverse from 8 to 6 µm, which indicated that cells could have larger deformation with certain surface coatings.


Assuntos
Materiais Biomiméticos/química , Movimento Celular , Dimetilpolisiloxanos/química , Linhagem Celular Tumoral , Matriz Extracelular/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Porosidade , Tecidos Suporte/química
12.
Toxicol Appl Pharmacol ; 401: 115080, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497533

RESUMO

Upregulation of ABCB1/MDR1 (P-gp) and BIRC5/Survivin promotes multidrug resistance in a variety of human cancers. LCL161 is an anti-cancer DIABLO/SMAC mimetic currently being tested in patients with solid tumors, but the molecular mechanism of action of LCL161 in cancer cells is still incompletely understood. It is still unclear whether LCL161 is therapeutically applicable for patients with ABCB1-overexpressing multidrug resistant tumors. In this study, we found that the potency of LCL161 is not affected by the expression of ABCB1 in KB-TAX50, KB-VIN10, and NTU0.017 cancer cells. Besides, LCL161 is equally potent towards the parental MCF7 breast cancer cells and its BIRC5 overexpressing, hormone therapy resistance subline MCF7-TamC3 in vitro. Mechanistically, we found that LCL161 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multi-drug efflux activity at low cytotoxic concentrations (i.e. 0.5xIC50 or less). Further analysis revealed that LCL161 also decreases intracellular ATP levels in part through BIRC5 downregulation. Therapeutically, co-treatment with LCL161 at low cytotoxic concentrations restored the sensitivity to the known ABCB1 substrate, paclitaxel, in ABCB1-expressing cancer cells and increased the sensitivity to tamoxifen in MCF7-TamC3 cells. In conclusion, LCL161 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide important information to physicians for designing a more "patient-specific" LCL161 clinical trial program in the future.


Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/farmacologia , Proteínas Mitocondriais/farmacologia , Survivina/antagonistas & inibidores , Tiazóis/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/metabolismo , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Proteínas Mitocondriais/química , Estrutura Secundária de Proteína , Survivina/biossíntese , Survivina/genética , Tiazóis/química
13.
Nat Commun ; 11(1): 2105, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355158

RESUMO

3D-printing networks of droplets connected by interface bilayers are a powerful platform to build synthetic tissues in which functionality relies on precisely ordered structures. However, the structural precision and consistency in assembling these structures is currently limited, which restricts intricate designs and the complexity of functions performed by synthetic tissues. Here, we report that the equilibrium contact angle (θDIB) between a pair of droplets is a key parameter that dictates the tessellation and precise positioning of hundreds of picolitre-sized droplets within 3D-printed, multi-layer networks. When θDIB approximates the geometrically-derived critical angle (θc) of 35.3°, the resulting networks of droplets arrange in regular hexagonal close-packed (hcp) lattices with the least fraction of defects. With this improved control over droplet packing, we can 3D-print functional synthetic tissues with single-droplet-wide conductive pathways. Our new insights into 3D droplet packing permit the fabrication of complex synthetic tissues, where precisely positioned compartments perform coordinated tasks.


Assuntos
Bioengenharia/instrumentação , Bicamadas Lipídicas/química , Impressão Tridimensional , Bioengenharia/métodos , Materiais Biomiméticos/química , Cinética , Lipídeos/química , Microscopia Confocal , Temperatura , Água/química
14.
Proc Natl Acad Sci U S A ; 117(22): 11947-11953, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32424103

RESUMO

Living tissues, heterogeneous at the microscale, usually scatter light. Strong scattering is responsible for the whiteness of bones, teeth, and brain and is known to limit severely the performances of biomedical optical imaging. Transparency is also found within collagen-based extracellular tissues such as decalcified ivory, fish scales, or cornea. However, its physical origin is still poorly understood. Here, we unveil the presence of a gap of transparency in scattering fibrillar collagen matrices within a narrow range of concentration in the phase diagram. This precholesteric phase presents a three-dimensional (3D) orientational order biomimetic of that in natural tissues. By quantitatively studying the relation between the 3D fibrillar network and the optical and mechanical properties of the macroscopic matrices, we show that transparency results from structural partial order inhibiting light scattering, while preserving mechanical stability, stiffness, and nonlinearity. The striking similarities between synthetic and natural materials provide insights for better understanding the occurring transparency.


Assuntos
Materiais Biomiméticos , Colágenos Fibrilares , Animais , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Biomimética/métodos , Córnea/química , Colágenos Fibrilares/síntese química , Colágenos Fibrilares/química
15.
Proc Natl Acad Sci U S A ; 117(23): 12636-12642, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461359

RESUMO

Mammalian teeth are attached to the jawbone through an exquisitely controlled mineralization process: unmineralized collagen fibers of the periodontal ligament anchor directly into the outer layer of adjoining mineralized tissues (cementum and bone). The sharp interface between mineralized and nonmineralized collagenous tissues makes this an excellent model to study the mechanisms by which extracellular matrix macromolecules control collagen mineralization. While acidic phosphoproteins, localized in the mineralized tissues, play key roles in control of mineralization, the role of glycosaminoglycans (GAGs) is less clear. As several proteoglycans are found only in the periodontal ligament, it has been hypothesized that these inhibit mineralization of collagen in this tissue. Here we used an in vitro model based on remineralization of mouse dental tissues to determine the role of matrix GAGs in control of mineralization. GAGs were selectively removed from demineralized mouse periodontal sections via enzymatic digestion. Proteomic analysis confirmed that enzymatic GAG removal does not significantly alter protein content. Analysis of remineralized tissue sections by transmission electron microscopy (TEM) shows that GAG removal reduced the rate of remineralization in mineralized tissues compared to the untreated control, while the ligament remained unmineralized. Protein removal with trypsin also reduced the rate of mineralization, but to a lesser extent than GAG removal, despite a much larger effect on protein content. These results indicate that GAGs promote mineralization in mineralized dental tissues rather than inhibiting mineral formation in the ligament, which may have broader implications for understanding control of collagen mineralization in connective tissues.


Assuntos
Materiais Biomiméticos/metabolismo , Biomineralização , Colágeno/metabolismo , Dentina/metabolismo , Glicosaminoglicanos/metabolismo , Ligamento Periodontal/metabolismo , Animais , Apatitas/química , Materiais Biomiméticos/química , Dentina/ultraestrutura , Matriz Extracelular/metabolismo , Camundongos , Ligamento Periodontal/ultraestrutura , Proteoma
16.
Nat Methods ; 17(6): 609-613, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32424271

RESUMO

We developed entangled link-augmented stretchable tissue-hydrogel (ELAST), a technology that transforms tissues into elastic hydrogels to enhance macromolecular accessibility and mechanical stability simultaneously. ELASTicized tissues are highly stretchable and compressible, which enables reversible shape transformation and faster delivery of probes into intact tissue specimens via mechanical thinning. This universal platform may facilitate rapid and scalable molecular phenotyping of large-scale biological systems, such as human organs.


Assuntos
Hidrogéis/química , Coloração e Rotulagem/métodos , Engenharia Tecidual/métodos , Acrilamida/química , Animais , Fenômenos Biomecânicos , Materiais Biomiméticos/química , Bioimpressão , Córtex Cerebral/química , Reagentes para Ligações Cruzadas/química , Módulo de Elasticidade , Hipocampo/química , Humanos , Teste de Materiais , Camundongos , Estresse Mecânico , Resistência à Tração
17.
Nature ; 580(7802): 210-215, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269352

RESUMO

Biological materials, such as bones, teeth and mollusc shells, are well known for their excellent strength, modulus and toughness1-3. Such properties are attributed to the elaborate layered microstructure of inorganic reinforcing nanofillers, especially two-dimensional nanosheets or nanoplatelets, within a ductile organic matrix4-6. Inspired by these biological structures, several assembly strategies-including layer-by-layer4,7,8, casting9,10, vacuum filtration11-13 and use of magnetic fields14,15-have been used to develop layered nanocomposites. However, how to produce ultrastrong layered nanocomposites in a universal, viable and scalable manner remains an open issue. Here we present a strategy to produce nanocomposites with highly ordered layered structures using shear-flow-induced alignment of two-dimensional nanosheets at an immiscible hydrogel/oil interface. For example, nanocomposites based on nanosheets of graphene oxide and clay exhibit a tensile strength of up to 1,215 ± 80 megapascals and a Young's modulus of 198.8 ± 6.5 gigapascals, which are 9.0 and 2.8 times higher, respectively, than those of natural nacre (mother of pearl). When nanosheets of clay are used, the toughness of the resulting nanocomposite can reach 36.7 ± 3.0 megajoules per cubic metre, which is 20.4 times higher than that of natural nacre; meanwhile, the tensile strength is 1,195 ± 60 megapascals. Quantitative analysis indicates that the well aligned nanosheets form a critical interphase, and this results in the observed mechanical properties. We consider that our strategy, which could be readily extended to align a variety of two-dimensional nanofillers, could be applied to a wide range of structural composites and lead to the development of high-performance composites.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/síntese química , Nanocompostos/química , Resistência à Tração , Módulo de Elasticidade , Grafite/química , Hidrogéis/química , Nácar/química
18.
Nat Commun ; 11(1): 1126, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111847

RESUMO

The efficacy of nano-mediated drug delivery has been impeded by multiple biological barriers such as the mononuclear phagocyte system (MPS), as well as vascular and interstitial barriers. To overcome the abovementioned obstacles, we report a nano-pathogenoid (NPN) system that can in situ hitchhike circulating neutrophils and supplement photothermal therapy (PTT). Cloaked with bacteria-secreted outer membrane vesicles inheriting pathogen-associated molecular patterns of native bacteria, NPNs are effectively recognized and internalized by neutrophils. The neutrophils migrate towards inflamed tumors, extravasate across the blood vessels, and penetrate through the tumors. Then NPNs are rapidly released from neutrophils in response to inflammatory stimuli and subsequently taken up by tumor cells to exert anticancer effects. Strikingly, due to the excellent targeting efficacy, cisplatin-loaded NPNs combined with PTT completely eradicate tumors in all treated mice. Such a nano-platform represents an efficient and generalizable strategy towards in situ cell hitchhiking as well as enhanced tumor targeted delivery.


Assuntos
Quimiotaxia de Leucócito , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Neoplasias/terapia , Neutrófilos/fisiologia , Fototerapia , Animais , Membrana Externa Bacteriana/química , Membrana Externa Bacteriana/imunologia , Materiais Biomiméticos/administração & dosagem , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/química , Cisplatino/farmacocinética , Liberação Controlada de Fármacos , Vesículas Extracelulares/química , Vesículas Extracelulares/imunologia , Imunoterapia Adotiva , Inflamação/etiologia , Camundongos , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Ativação de Neutrófilo , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Padrões Moleculares Associados a Patógenos/imunologia , Fototerapia/efeitos adversos , Microambiente Tumoral/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Artigo em Inglês | MEDLINE | ID: mdl-32161212

RESUMO

In order to harness the functionality of metals, nature has evolved over billions of years to utilize metalloproteins as key components in numerous cellular processes. Despite this, transition metals such as ruthenium, palladium, iridium, and gold are largely absent from naturally occurring metalloproteins, likely due to their scarcity as precious metals. To mimic the evolutionary process of nature, the field of artificial metalloenzymes (ArMs) was born as a way to benefit from the unique chemoselectivity and orthogonality of transition metals in a biological setting. In its current state, numerous examples have successfully incorporated transition metals into a variety of protein scaffolds. Using these ArMs, many examples of new-to-nature reactions have been carried out, some of which have shown substantial biocompatibility. Given the rapid rate at which this field is growing, this review aims to highlight some important studies that have begun to take the next step within this field; namely the development of ArM-centered drug therapies or biotechnological tools.


Assuntos
Materiais Biomiméticos/química , Coenzimas/química , Metaloproteínas/química , Metais/química , Biocatálise , Técnicas Biossensoriais , Modelos Moleculares , Conformação Proteica , Engenharia de Proteínas , Estereoisomerismo
20.
Nat Commun ; 11(1): 1180, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132524

RESUMO

Many biological tissues offer J-shaped stress-strain responses, since their microstructures exhibit a three-dimensional (3D) network construction of curvy filamentary structures that lead to a bending-to-stretching transition of the deformation mode under an external tension. The development of artificial 3D soft materials and device systems that can reproduce the nonlinear, anisotropic mechanical properties of biological tissues remains challenging. Here we report a class of soft 3D network materials that can offer defect-insensitive, nonlinear mechanical responses closely matched with those of biological tissues. This material system exploits a lattice configuration with different 3D topologies, where 3D helical microstructures that connect the lattice nodes serve as building blocks of the network. By tailoring geometries of helical microstructures or lattice topologies, a wide range of desired anisotropic J-shaped stress-strain curves can be achieved. Demonstrative applications of the developed conducting 3D network materials with bio-mimetic mechanical properties suggest potential uses in flexible bio-integrated devices.


Assuntos
Materiais Biomiméticos/química , Biomimética/métodos , Desenho Assistido por Computador , Anisotropia , Módulo de Elasticidade , Análise de Elementos Finitos , Teste de Materiais , Software , Estresse Mecânico
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