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1.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360734

RESUMO

Biomimetic design provides novel opportunities for enhancing and functionalizing biomaterials. Here we created a zirconia surface with cactus-inspired meso-scale spikes and bone-inspired nano-scale trabecular architecture and examined its biological activity in bone generation and integration. Crisscrossing laser etching successfully engraved 60 µm wide, cactus-inspired spikes on yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) with 200-300 nm trabecular bone-inspired interwoven structures on the entire surface. The height of the spikes was varied from 20 to 80 µm for optimization. Average roughness (Sa) increased from 0.10 µm (polished smooth surface) to 18.14 µm (80 µm-high spikes), while the surface area increased by up to 4.43 times. The measured dimensions of the spikes almost perfectly correlated with their estimated dimensions (R2 = 0.998). The dimensional error of forming the architecture was 1% as a coefficient of variation. Bone marrow-derived osteoblasts were cultured on a polished surface and on meso- and nano-scale hybrid textured surfaces with different spike heights. The osteoblastic differentiation was significantly promoted on the hybrid-textured surfaces compared with the polished surface, and among them the hybrid-textured surface with 40 µm-high spikes showed unparalleled performance. In vivo bone-implant integration also peaked when the hybrid-textured surface had 40 µm-high spikes. The relationships between the spike height and measures of osteoblast differentiation and the strength of bone and implant integration were non-linear. The controllable creation of meso- and nano-scale hybrid biomimetic surfaces established in this study may provide a novel technological platform and design strategy for future development of biomaterial surfaces to improve bone integration and regeneration.


Assuntos
Materiais Biomiméticos , Diferenciação Celular/efeitos dos fármacos , Nanoestruturas/química , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Zircônio , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Cactaceae , Masculino , Nanoestruturas/ultraestrutura , Osteoblastos/citologia , Ratos , Ratos Sprague-Dawley , Zircônio/química , Zircônio/farmacologia
2.
J Chem Phys ; 155(5): 054902, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364346

RESUMO

Long chain molecules can be entropically compacted in a crowded medium. We study the compaction transition of a heterogeneous polymer with ring topology by crowding effects in a free or confined space. For this, we use molecular dynamics simulations in which the effects of crowders are taken into account through effective interactions between chain segments. Our parameter choices are inspired by the Escherichia coli chromosome. The polymer consists of small and big monomers; the big monomers dispersed along the backbone are to mimic the binding of RNA polymerases. Our results show that the compaction transition is a two-step process: initial compaction induced by the association (clustering) of big monomers followed by a gradual overall compaction. They also indicate that cylindrical confinement makes the initial transition more effective; for representative parameter choices, the initial compaction accounts for about 60% reduction in the chain size. Our simulation results support the view that crowding promotes clustering of active transcription units into transcription factories.


Assuntos
Transição de Fase , Polímeros/química , Materiais Biomiméticos/química , Cromossomos Bacterianos/química , Entropia , Escherichia coli/química , Simulação de Dinâmica Molecular , Pressão Osmótica
3.
Commun Biol ; 4(1): 960, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381153

RESUMO

Protein-based targeting reagents, such as antibodies and non-antibody scaffold proteins, are rapidly inactivated in the upper gastrointestinal (GI) tract. Hydrochloric acid in gastric juice denatures proteins and activates pepsin, concentrations of which reach 1 mg/mL in the mammalian stomach. Two stable scaffold proteins (nanobody and nanofitin), previously developed to be protease-resistant, were completely digested in less than 10 min at 100-fold lower concentration of pepsin than found in the stomach. Here we present gastrobodies, a protein scaffold derived from Kunitz soybean trypsin inhibitor (SBTI). SBTI is highly resistant to the challenges of the upper GI tract, including digestive proteases, pH 2 and bile acids. Computational prediction of SBTI's evolvability identified two nearby loops for randomization, to create a potential recognition surface which was experimentally validated by alanine scanning. We established display of SBTI on full-length pIII of M13 phage. Phage selection of gastrobody libraries against the glucosyltransferase domain of Clostridium difficile toxin B (GTD) identified hits with nanomolar affinity and enzyme inhibitory activity. Anti-GTD binders retained high stability to acid, digestive proteases and heat. Gastrobodies show resilience to exceptionally harsh conditions, which should provide a foundation for targeting and modulating function within the GI tract.


Assuntos
Anticorpos/farmacologia , Materiais Biomiméticos/química , Clostridioides difficile/fisiologia , Ácido Clorídrico/farmacologia , Pepsina A/farmacologia , Inibidor da Tripsina de Soja de Kunitz/química , Animais , Anticorpos/química , Materiais Biomiméticos/farmacologia , Galinhas , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Inibidor da Tripsina de Soja de Kunitz/farmacologia
4.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443477

RESUMO

Here, the hierarchical assembly of a collagen mimetic peptide (CMP) displaying four bipyridine moieties is described. The CMP was capable of forming triple helices followed by self-assembly into disks and domes. Treatment of these disks and domes with metal ions such as Fe(II), Cu(II), Zn(II), Co(II), and Ru(III) triggered the formation of microcages, and micron-sized cup-like structures. Mechanistic studies suggest that the formation of the microcages proceeds from the disks and domes in a metal-dependent fashion. Fluorescently-labeled dextrans were encapsulated within the cages and displayed a time-dependent release using thermal conditions.


Assuntos
Materiais Biomiméticos/química , Colágeno/química , Metais/química , Peptídeos/química , Dextranos/química , Íons/química , Ligantes , Estrutura Molecular
5.
ACS Appl Mater Interfaces ; 13(33): 39135-39141, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34374274

RESUMO

Many physiochemical properties of the extracellular matrix (ECM) of muscle tissues, such as nanometer scale dimension, nanotopography, negative charge, and elasticity, must be carefully reproduced to fabricate scaffold materials mimicking muscle tissues. Hence, we developed a muscle tissue ECM-mimicking scaffold using Mo6S3I6 inorganic molecular wires (IMWs). Composed of bio-essential elements and having a nanofibrous structure with a diameter of ∼1 nm and a negative surface charge with high stability, Mo6S3I6 IMWs are ideal for mimicking natural ECM molecules. Once Mo6S3I6 IMWs were patterned on a polydimethylsiloxane surface with an elasticity of 1877.1 ± 22.2 kPa, that is, comparable to that of muscle tissues, the proliferation and α-tubulin expression of myoblasts enhanced significantly. Additionally, the repetitive one-dimensional patterns of Mo6S3I6 IMWs induced the alignment and stretching of myoblasts with enhanced α-tubulin expression and differentiation into myocytes. This study demonstrates that Mo6S3I6 IMWs are promising for mimicking the ECM of muscle tissues.


Assuntos
Materiais Biomiméticos/química , Dimetilpolisiloxanos/química , Matriz Extracelular/metabolismo , Nanofios/química , Tecidos Suporte/química , Materiais Biomiméticos/metabolismo , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Iodo/química , Molibdênio/química , Músculos/citologia , Mioblastos/citologia , Mioblastos/metabolismo , Enxofre/química , Propriedades de Superfície , Engenharia Tecidual , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
6.
ACS Appl Mater Interfaces ; 13(33): 39142-39156, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433244

RESUMO

The reconstruction of the intra/interfibrillar mineralized collagen microstructure is extremely important in biomaterial science and regeneration medicine. However, certain problems, such as low efficiency and long period of mineralization, are apparent, and the mechanism of interfibrillar mineralization is often neglected in the present literature. Thus, we propose a novel model of biomimetic collagen mineralization that uses molecules with the dual function of cross-linking collagen and regulating collagen mineralization to construct the intrafibrillar and interfibrillar collagen mineralization of the structure of mineralized collagen hard tissues. In the present study completed in vitro, N-2-(3,4-dihydroxyphenyl) acrylamide (DAA) is used to bind and cross-link collagen molecules and further stabilize the self-assembled collagen fibers. The DAA-collagen complex provides more affinity with calcium and phosphate ions, which can reduce the calcium phosphate/collagen interfacial energy to promote hydroxyapatite (HA) nucleation and accelerate the rate of collagen fiber mineralization. Besides inducing intrafibrillar mineralization, the DAA-collagen complex mineralization template can realize interfibrillar mineralization with the c-axis of the HA crystal on the surface of collagen fibers and between fibers that are parallel to the long axis of collagen fibers. The DAA-collagen complex, as a new type of mineralization template, may provide a new collagen mineralization strategy to produce a mineralized scaffold material for tissue engineering or develop bone-like materials.


Assuntos
Acrilamida/química , Materiais Biomiméticos/química , Colágeno/química , Dopamina/química , Osso e Ossos , Cálcio/química , Cálcio/metabolismo , Fosfatos de Cálcio/química , Reagentes para Ligações Cruzadas/química , Cristalização , Durapatita/química , Durapatita/metabolismo , Matriz Extracelular/metabolismo , Humanos , Simulação de Dinâmica Molecular , Polimerização , Medicina Regenerativa , Propriedades de Superfície , Engenharia Tecidual
7.
Chem Commun (Camb) ; 57(64): 7914-7917, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34279527

RESUMO

A phosphopeptide-modified nanochannel was prepared based on a conical polymeric nanopore. It shows a reversible Ca2+-induced inactivation effect toward the ion flow and molecular transport, resulting from Ca2+ binding-caused surface charge neutralization and hydrophilicity reduction, and Ca2+ removal by the competitive binding.


Assuntos
Materiais Biomiméticos/farmacologia , Canais de Cálcio/metabolismo , Fosfopeptídeos/farmacologia , Materiais Biomiméticos/química , Estrutura Molecular , Fosfopeptídeos/química
8.
Nat Commun ; 12(1): 4224, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244502

RESUMO

Nucleic acid-based constitutional dynamic networks (CDNs) have recently emerged as versatile tools to control a variety of catalytic processes. A key challenge in the application of these systems is achieving intercommunication between different CDNs to mimic the complex interlinked networks found in cellular biology. In particular, the possibility to interface photochemical 'energy-harvesting' processes with dark-operating 'metabolic' processes, in a similar way to plants, represents an up to now unexplored yet enticing research direction. The present study introduces two CDNs that allow the intercommunication of photocatalytic and dark-operating catalytic functions mediated by environmental components that facilitate the dynamic coupling of the networks. The dynamic feedback-driven intercommunication of the networks is accomplished via information transfer between the two CDNs effected by hairpin fuel strands in the environment of the system, leading to the coupling of the photochemical and dark-operating modules.


Assuntos
Materiais Biomiméticos/química , DNA Catalítico/química , Técnicas Genéticas , Processos Fotoquímicos , DNA Catalítico/genética , Luz , Conformação de Ácido Nucleico
9.
Inorg Chem ; 60(15): 11206-11213, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34289695

RESUMO

The catalytic cycle of a peroxidase-mimicking heme-DNAzyme involves an iron(IV)oxo porphyrin π-cation radical intermediate known as compound I formed through heterolytic O-O bond cleavage of an Fe3+-bound hydroperoxo ligand (Fe-OOH) in compound 0, like that of a heme enzyme such as horseradish peroxidase (HRP). Peroxidase assaying of complexes composed of chemically modified hemes possessing various electron densities of the heme iron atom (ρFe) and parallel-stranded tetrameric G-quadruplex DNAs of oligonucleotides d(TTAGGG), d(TTAGGGT), and d(TTAGGGA) was performed to elucidate the effects of the heme electronic structure and local heme environment on the catalytic activity of the heme-DNAzyme. The study revealed that the DNAzyme activity is enhanced through an increase in the ρFe and general base catalysis of the adenine base adjacent to the heme, which are reminiscent of the "push" and "pull" mechanisms in the catalytic cycle of HRP, respectively, and that the activity of the heme-DNAzyme can be independently controlled through the heme electronic structure and local heme environment. These findings allow a deeper understanding of the structure-function relationship of the peroxidase-mimicking heme-DNAzyme.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , DNA Catalítico/química , DNA Catalítico/metabolismo , Heme/química , Heme/metabolismo , Peroxidase/metabolismo , Biocatálise , Elétrons
10.
Phys Chem Chem Phys ; 23(30): 16157-16164, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34297025

RESUMO

Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 ß-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching. The two nanoperforated PLA layers are separated by an electroactive layer, which is successfully electropolymerized by introducing a conducting sacrificial substrate under the first PLA nanosheet. Finally, the nanomaterial is consolidated by immobilizing the VDAC36 protein, active as an ion channel, into the nanoperforations of the upper layer. The integration of the protein causes a significant reduction of the material resistance, which decreases from 21.9 to 3.9 kΩ cm2. Electrochemical impedance spectroscopy studies using inorganic ions and molecular metabolites (i.e.l-lysine and ATP) not only reveal that the hybrid films behave as electrochemical supercapacitors but also indicate the most appropriate conditions to obtain selective responses against molecular ions as a function of their charge. The combination of polymers and proteins is promising for the development of new devices for engineering, biotechnological and biomedical applications.


Assuntos
Materiais Biomiméticos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Nanoestruturas/química , Poliésteres/química , Polímeros/química , Poliestirenos/química , Álcool de Polivinil/química , Canais de Ânion Dependentes de Voltagem/química , Trifosfato de Adenosina/química , Espectroscopia Dielétrica , Condutividade Elétrica , Canais Iônicos/química , Transporte de Íons , Íons/isolamento & purificação , Lisina/química , Relação Estrutura-Atividade , Propriedades de Superfície
11.
Inorg Chem ; 60(16): 12392-12404, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34319113

RESUMO

A water-soluble strapped iron(III)tetraarylporphyrin (FeIIIPor-1) bearing two propylpyridinium groups at the side chains and a carboxylic acid group at the overhanging position of the strap was synthesized to mimic the function of myoglobin with the distal polar functionality in aqueous solution. FeIIIPor-1 forms a stable 1:1 inclusion complex with a per-O-methylated ß-cyclodextrin dimer having a pyridine linker (Py3OCD), providing a hydrophobic environment and a proximal fifth ligand to stabilize the O2-complex. The ferrous complex (FeIIPorCD-1) binds both O2 and CO in aqueous solution. The O2 and CO binding affinities (P1/2O2 and P1/2CO) and half-life time (t1/2) of the O2 complex of FeIIPorCD-1 are 6.3 and 0.021 Torr, and 7 h, respectively, at pH 7 and 25 °C. The control compound without the strap structure (FeIIPorCD-2) has similar oxygen binding characteristics (P1/2O2 = 8.0 Torr), but much higher CO binding affinity (P1/2CO = 3.8 × 10-4 Torr), and longer t1/2 (30 h). The O2 and CO kinetics indicate that the strapped structure in FeIIPorCD-1 inhibits the entrance of these gaseous ligands into the iron(II) center, as evidenced by lower konO2 and konCO values. Interestingly, the CO complex of FeIIPorCD-1 is significantly destabilized (relatively larger koffCO), while the koffO2 value is much smaller than that of FeIIPorCD-2, resulting in significantly increased O2/CO selectivity (reduced M value, where M = P1/2O2/P1/2CO = 320) in FeIIPorCD-1 compared to FeIIPorCD-2 (M = 21000).


Assuntos
Materiais Biomiméticos/química , Monóxido de Carbono/química , Ciclodextrinas/química , Mioglobina/química , Oxigênio/química , Porfirinas/química , Água/química , Concentração de Íons de Hidrogênio , Soluções , Temperatura
12.
Int J Biol Macromol ; 185: 604-619, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34216662

RESUMO

Hepatic cancer is one of the most widespread maladies worldwide that requires urgent therapies and thus reliable means for testing anti-cancer drugs. The switch from two-dimensional (2D) to three-dimensional (3D) cell cultures produced an improvement in the in vitro outcomes for testing anti-cancer drugs. We aimed to develop a novel hyaluronic acid (HA)-based 3D cell model of human hepatocellular carcinoma (HepG2 cells) for drug testing and to assess comparatively in 3D vs. 2D, the cytotoxicity and the apoptotic response to the anti-tumor agent, cisplatin. The 3D model was developed by seeding HepG2 cells in a HA/poly(methylvinylether-alt-maleic acid) (HA3P50)-based scaffold. Compared to 2D, the cells grown in the HA3P50 scaffold proliferate into larger-cellular aggregates that exhibit liver-like functions by controlling the release of hepatocyte-specific biomarkers (albumin, urea, bile acids, transaminases) and the synthesis of cytochrome-P450 (CYP)7A1 enzyme. Also, growing the cells in the scaffold sensitize the hepatocytes to the anti-tumor effect of cisplatin, by a mechanism involving the activation of ERK/p38α-MAPK and dysregulation of NF-kB/STAT3/Bcl-2 pathways. In conclusion, the newly developed HA-based 3D model is suitable for chemotherapeutic drug testing on hepatocellular carcinoma. Moreover, the system can be adapted and employed as experimental platform functioning as a proper tissue/tumor surrogate.


Assuntos
Materiais Biomiméticos/química , Carcinoma Hepatocelular/metabolismo , Cisplatino/farmacologia , Ácido Hialurônico/química , Neoplasias Hepáticas/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol 7-alfa-Hidroxilase/metabolismo , Cisplatino/química , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Tecidos Suporte
13.
ACS Appl Mater Interfaces ; 13(27): 31331-31336, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34227383

RESUMO

The distinct physical and chemical properties of nanoparticles (NPs) offer great opportunities to develop new strategies for diagnostic and therapeutic purposes. Whereas NPs often serve as inert nanocarriers, their inherent "biological" activities have recently been extensively unveiled and explored. These protein-mimicking NPs (dubbed protmins) have been reported to modulate a cellular homeostasis without displaying a general toxicity, which may act as potential nanomedicines to provide a monotherapy or combination therapy in a disease treatment. In the meanwhile, the unexpected behaviors of protmins in complex biological systems also raise new concerns on the biosafety issue. Herein, we summarize several categories of the protmin-based regulation of cellular homeostasis and discuss their broad effects on cell functions and behaviors.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Homeostase , Nanopartículas/química , Proteínas/metabolismo , Animais , Humanos
14.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198794

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, causing approximately 17.9 million deaths annually, an estimated 31% of all deaths, according to the WHO. CVDs are essentially rooted in atherosclerosis and are clinically classified into coronary heart disease, stroke and peripheral vascular disorders. Current clinical interventions include early diagnosis, the insertion of stents, and long-term preventive therapy. However, clinical diagnostic and therapeutic tools are subject to a number of limitations including, but not limited to, potential toxicity induced by contrast agents and unexpected bleeding caused by anti-platelet drugs. Nanomedicine has achieved great advancements in biomedical area. Among them, cell membrane coated nanoparticles, denoted as CMCNPs, have acquired enormous expectations due to their biomimetic properties. Such membrane coating technology not only helps avoid immune clearance, but also endows nanoparticles with diverse cellular and functional mimicry. In this review, we will describe the superiorities of CMCNPs in treating cardiovascular diseases and their potentials in optimizing current clinical managements.


Assuntos
Materiais Biomiméticos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Membrana Celular/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas
15.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198955

RESUMO

Hyaluronic acid (HA) is one of the most used biopolymers in the development of drug delivery systems, due to its biocompatibility, biodegradability, non-immunogenicity and intrinsic-targeting properties. HA specifically binds to CD44; this property combined to the EPR effect could provide an option for reinforced active tumor targeting by nanocarriers, improving drug uptake by the cancer cells via the HA-CD44 receptor-mediated endocytosis pathway. Moreover, HA can be easily chemically modified to tailor its physico-chemical properties in view of specific applications. The derivatization with cholesterol confers to HA an amphiphilic character, and then the ability of anchoring to niosomes. HA-Chol was then used to coat Span® or Tween® niosomes providing them with an intrinsic targeting shell. The nanocarrier physico-chemical properties were analyzed in terms of hydrodynamic diameter, ζ-potential, and bilayer structural features to evaluate the difference between naked and HA-coated niosomes. Niosomes stability was evaluated over time and in bovine serum. Moreover, interaction properties of HA-coated nanovesicles with model membranes, namely liposomes, were studied, to obtain insights on their interaction behavior with biological membranes in future experiments. The obtained coated systems showed good chemical physical features and represent a good opportunity to carry out active targeting strategies.


Assuntos
Materiais Biomiméticos/química , Colesterol/química , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/farmacologia , Animais , Bovinos , Membrana Celular , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Lipossomos , Nanoestruturas , Tamanho da Partícula , Soro/química
16.
Chem Commun (Camb) ; 57(62): 7669-7672, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34254065

RESUMO

A novel nanozyme comprised of graphene encapsuled Ru nanocrystals (Ru@G) with effective and stable peroxidase-like activity prepared using a chemical vapor deposition (CVD) method was used for the detection of glutathione at near-physiological pH.


Assuntos
Materiais Biomiméticos/química , Glutationa/análise , Grafite/química , Nanopartículas Metálicas/química , Peroxidase/metabolismo , Rutênio/química , Concentração de Íons de Hidrogênio
17.
Chem Commun (Camb) ; 57(54): 6644-6647, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34126626

RESUMO

The first diiron(iii,iv)-µ2-oxo tetracarbene complex is isolated and characterized by SC-XRD, UV/Vis, EPR, Evans' NMR and elemental analysis. CV indicates the presence of a transient high-valent diiron(iv)-µ2-oxo species. Its formation and decay is investigated via UV/Vis kinetics and NMR.


Assuntos
Materiais Biomiméticos/química , Complexos de Coordenação/química , Enzimas/metabolismo , Ferro/química , Metano/análogos & derivados , Cinética , Metano/química , Modelos Moleculares , Conformação Molecular
18.
Nat Commun ; 12(1): 3961, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172721

RESUMO

Current materials used in biomedical devices do not match tissue's mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.


Assuntos
Materiais Biomiméticos/administração & dosagem , Elastômeros/administração & dosagem , Procedimentos Cirúrgicos Reconstrutivos/métodos , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Proliferação de Células/efeitos dos fármacos , Elastômeros/química , Elastômeros/farmacologia , Géis , Injeções , Camundongos , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacologia , Ratos , Fatores de Tempo
19.
Int J Biol Macromol ; 183: 2131-2141, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34111481

RESUMO

Enamel regeneration currently -is limited by our inability to duplicate artificially its complicated and well-aligned hydroxyapatite structure. The initial formation of enamel occurs in enamel organs where the ameloblasts secret enamel extracellular matrix formed a unique gel-like microenvironment. The enamel extracellular matrix is mainly composed by amelogenin and non-amelogenin. In this study, an innovative strategy was proposed to regenerate enamel-like tissue by constructing a microenvironment using biomimetic enamel matrix proteins (biomimetic EMPs) composed of modified leucine-rich amelogenin peptide (mLRAP) and non-amelogenin analog (NAA). Impressively, the regenerated enamel in this biomimetic EMPs on etched enamel surface produced prismatic structures, and showed similar mechanical properties to natural enamel. The results of X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that regenerated crystal was hydroxyapatite. Molecular dynamics simulation analysis showed the binding energy between mLRAP and NAA were electrostatic forces and Van der Walls. These results introduced a promising strategy to induce crystal growth of enamel-like hydroxyapatite for biomimetic reproduction of materials with complicated hierarchical microstructures.


Assuntos
Amelogênese , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Proteínas do Esmalte Dentário/metabolismo , Esmalte Dentário/metabolismo , Células-Tronco Mesenquimais/metabolismo , Regeneração , Engenharia Tecidual , Proliferação de Células , Células Cultivadas , Cristalização , Esmalte Dentário/química , Esmalte Dentário/ultraestrutura , Proteínas do Esmalte Dentário/química , Proteínas do Esmalte Dentário/ultraestrutura , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação Proteica , Relação Estrutura-Atividade
20.
ACS Appl Mater Interfaces ; 13(27): 32084-32093, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34189902

RESUMO

Transparent e-skin that can fully mimic human skin with J-shaped mechanical-behavior and tactile sensing attributes have not yet been reported. In this work, the skin-like hydrogel composite with J-shaped mechanical behavior and highly transparent, tactile, soft but strong, flexible, and stretchable attributes is developed as structural strain sensing element for e-skin. Piezo-resistive polyacrylamide (PAAm) hydrogel is used as supporting matrix to endow high transparency, softness, flexibility, stretch-ability and strain sensing capability desired for e-skin. Ultrahigh molecular weight polyethylene (UHMWPE) fiber with a wavy configuration is designed as reinforcement filler to provide the tunable strain-limiting effect. As a result, the as-prepared UHMWPE fiber/PAAm composite e-skin presents unique "J-shape" stress-strain behavior akin to human skin. And the PAAm composite can switch from supersoft to highly stiff in the designed strain range up to 100% with a prominent tensile strength of 48.3 MPa, which enables it to have the high stretch-ability and excellent load-bearing ability, simultaneously. Moreover, finite element model is developed to clarify the stress distribution and damage evolution for the UHMWPE fiber/PAAm composite during the tensile process. The PAAm composite exhibits not only an excellent strain sensing performance with a long-term reliability up to 5000 loading-unloading cycles but also an extraordinary softness and mechanical strength with a low initial modulus of 6.7 kPa, which is matchable with soft human epidermis. Finally, the e-skin is used for demonstrations in monitoring various human activities and protecting structural integrity in designed strain ranges. The strategy for reinforcing piezo-resistive hydrogel with wavy-shaped UHMWPE fibers proposed here is promising for the development of transparent, flexible, soft but strong e-skin with a tunable strain-limiting effect akin to human skin.


Assuntos
Resinas Acrílicas/química , Materiais Biomiméticos/química , Hidrogéis/química , Pele , Humanos , Resistência à Tração
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