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1.
Carbohydr Polym ; 250: 116800, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049807

RESUMO

Chitosan, as a biodegradable and biocompatible polymer, is characterized by anti-microbial and anti-cancer properties. It lately has received a widespread interest for use as the pulmonary particulate backbone materials of drug carrier for the treatment of infectious disease and cancer. The success of chitosan as pulmonary particulate drug carrier is a critical interplay of their mucoadhesive, permeation enhancement and site/cell-specific attributes. In the case of nanocarriers, various microencapsulation and micro-nano blending systems have been devised to equip them with an appropriate aerodynamic character to enable efficient pulmonary aerosolization and inhalation. The late COVID-19 infection is met with acute respiratory distress syndrome and cancer. Chitosan and its derivatives are found useful in combating HCoV and cancer as a function of their molecular weight, substituent type and its degree of substitution. The interest in chitosan is expected to rise in the next decade from the perspectives of drug delivery in combination with its therapeutic performance.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Quitosana/análogos & derivados , Portadores de Fármacos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Betacoronavirus/isolamento & purificação , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Neoplasias Pulmonares/patologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Pneumonia Viral/virologia
2.
PLoS One ; 15(9): e0237463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970688

RESUMO

Titanium is essentially absent from biological systems yet reliably integrates into bone. To achieve osseointegration, titanium must activate biological processes without entering cells, defining it as a bio-activating material. Nanostructuring bulk titanium reduces grain size, increases strength, and improves other quantifiable physical properties, including cytocompatibility. The biological processes activated by increasing grain boundary availability were detected with total RNA-sequencing in mouse pre-osteoblasts grown for 72 hours on nanometrically smooth substrates of either coarse grain or nanostructured ultrafine grain titanium. The average grain boundary length under cells on the conventional coarse grain substrates is 273.0 µm, compared to 70,881.5 µm for cells adhered to the nanostructured ultrafine grain substrates; a 260-fold difference. Cells on both substrates exhibit similar expression profiles for genes whose products are critical for mechanosensation and transduction of cues that trigger osteoconduction. Biological process Gene Ontology term enrichment analysis of differentially expressed genes reveals that cell cycle, chromatin modification, telomere maintenance, and RNA metabolism processes are upregulated on ultrafine grain titanium. Processes related to immune response, including apoptosis, are downregulated. Tumor-suppressor genes are upregulated while tumor-promoting genes are downregulated. Upregulation of genes involved in chromatin remodeling and downregulation of genes under the control of the peripheral circadian clock implicate both processes in the transduction of mechanosensory information. Non-coding RNAs may also play a role in the response. Merging transcriptomics with well-established mechanobiology principles generates a unified model to explain the bio-activating properties of titanium. The modulation of processes is accomplished through chromatin remodeling in which the nucleus responds like a rheostat to grain boundary concentration. This convergence of biological and materials science reveals a pathway toward understanding the biotic-abiotic interface and will inform the development of effective bio-activating and bio-inactivating materials.


Assuntos
Materiais Biocompatíveis/química , Regeneração Óssea , Nanoestruturas/química , Osteoblastos/citologia , Titânio/química , Animais , Linhagem Celular , Teste de Materiais , Mecanotransdução Celular , Camundongos , Osseointegração , Osteoblastos/metabolismo , Análise de Sequência de RNA , Propriedades de Superfície , Transcriptoma
3.
Nat Commun ; 11(1): 4465, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901012

RESUMO

Titanium implants have been widely used in bone tissue engineering for decades. However, orthopedic implant-associated infections increase the risk of implant failure and even lead to amputation in severe cases. Although TiO2 has photocatalytic activity to produce reactive oxygen species (ROS), the recombination of generated electrons and holes limits its antibacterial ability. Here, we describe a graphdiyne (GDY) composite TiO2 nanofiber that combats implant infections through enhanced photocatalysis and prolonged antibacterial ability. In addition, GDY-modified TiO2 nanofibers exert superior biocompatibility and osteoinductive abilities for cell adhesion and differentiation, thus contributing to the bone tissue regeneration process in drug-resistant bacteria-induced implant infection.


Assuntos
Antibacterianos/química , Grafite , Nanofibras/química , Próteses e Implantes , Infecções Relacionadas à Prótese/prevenção & controle , Titânio , Células 3T3 , Animais , Materiais Biocompatíveis/química , Regeneração Óssea , Sobrevivência Celular , Modelos Animais de Doenças , Feminino , Teste de Materiais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Nanocompostos/química , Osteogênese , Processos Fotoquímicos , Infecções Estafilocócicas/prevenção & controle
4.
Nature ; 584(7822): 535-546, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32848221

RESUMO

Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials-they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell-matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.


Assuntos
Elasticidade , Matriz Extracelular/metabolismo , Substâncias Viscoelásticas , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Técnicas de Cultura de Células , Forma Celular , Matriz Extracelular/química , Humanos , Mecanotransdução Celular , Células-Tronco Mesenquimais/citologia , Modelos Biológicos , Medicina Regenerativa
5.
PLoS One ; 15(8): e0237231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853250

RESUMO

In this study, we examined the effect of differing gap lengths on regeneration of transected recurrent laryngeal nerves using silicon tubes containing type I collagen gel and the ability of this regeneration to result in restoration of vocal fold movements in rats. We simulated nerve gaps in Sprague-Dawley rats by transecting the left recurrent laryngeal nerves and bridged the nerve stumps using silicon tubes containing type 1 collagen gel. Three experimental groups, in which the gap lengths between the stumps were 1, 3, or 5 mm, were compared with a control group in which the nerve was transected but was not bridged. After surgery, we observed vocal fold movements over time with a laryngoscope. At week 15, we assessed the extent of nerve regeneration in the tube, histologically and electrophysiologically. We also assessed the degree of atrophy of the thyroarytenoid muscle (T/U ratio). Restoration of vocal fold movements was observed in 9 rats in the 1-mm group, in 6 rats in the 3-mm group, and in 3 rats in the 5-mm group. However, in most rats, restoration was temporary, with only one rat demonstrating continued vocal fold movements at week 15. In electromyograph, evoked potentials were observed in rats in the 1-mm and 3-mm groups. Regenerated tissue in the tube was thickest in the 1-mm group, followed by the 3-mm and 5-mm groups. The regenerated tissue showed the presence of myelinated and unmyelinated nerve fibers. In assessment of thyroarytenoid muscle atrophy, the T/U ratio was highest in the 1-mm group, followed by the 3-mm and 5-mm groups. We successfully regenerated the nerves and produced a rat model of recurrent laryngeal nerve regeneration that demonstrated temporary recovery of vocal fold movements. This rat model could be useful for assessing novel treatments developing in the future.


Assuntos
Colágeno/uso terapêutico , Regeneração Nervosa , Traumatismos do Nervo Laríngeo Recorrente/terapia , Nervo Laríngeo Recorrente/fisiopatologia , Animais , Materiais Biocompatíveis/química , Colágeno/administração & dosagem , Modelos Animais de Doenças , Géis/administração & dosagem , Géis/uso terapêutico , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Laríngeo Recorrente/fisiologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Silício/química
6.
Int J Nanomedicine ; 15: 4311-4324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606679

RESUMO

Purpose: By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy. Materials and Methods: In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-DFDFG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model. Results: The self-assembling peptide was constrained into a classical ß-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the ß-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function. Conclusion: This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling ß-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Hidrogéis/química , Fator de Crescimento Insulin-Like I/química , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Peptídeos/química , Lesão Renal Aguda/fisiopatologia , Animais , Materiais Biocompatíveis/química , Sobrevivência Celular , Feminino , Fibrose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hidrogéis/síntese química , Rim/patologia , Rim/fisiopatologia , Camundongos Transgênicos , Neovascularização Fisiológica , Placenta/citologia , Gravidez , Conformação Proteica em Folha beta , Domínios Proteicos
7.
Adv Exp Med Biol ; 1250: 97-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601940

RESUMO

The clinical need for effective bone regeneration remains in huge demands. Although autologous and allogeneic bone grafts are generally considered "gold standard" treatments for bone defects, these approaches may result in various complications. Furthermore, safety considerations of gene- and cell-based therapies require further clarification and approval from regulatory authorities. Therefore, developing new therapeutic biomaterials that can empower endogenous regenerative properties to accelerate bone repair and regeneration is of great significance. Extracellular vesicles (EVs) comprise a heterogeneous population of naturally derived nanoparticles that play a critical role in mediating cell-cell communication. The vast amount of biological processes that EVs are involved in, such as immune modulation, senescence, and angiogenesis, and the versatility of manner in which they can influence the behavior of recipient cells make EVs an interesting source for both diagnostic and therapeutic applications. Advancement of knowledge in the fields of immunology and cell biology has sparked the exploration of the potential of EVs in the field of regenerative medicine. EVs travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating the recruitment, proliferation, and differentiation of recipient cells. Numerous studies have demonstrated the pivotal role of EVs in tissue regeneration both in vitro and in vivo. In this chapter, we will outline current knowledge surrounding EVs, summarize their functional roles in bone regenerative medicine, and elaborate on potential application and challenges of EV-integrated biomaterials in bone tissue engineering.


Assuntos
Materiais Biocompatíveis , Regeneração Óssea , Vesículas Extracelulares , Medicina Regenerativa , Engenharia Tecidual , Materiais Biocompatíveis/química , Materiais Biocompatíveis/normas , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos
8.
Adv Exp Med Biol ; 1250: 189-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601946

RESUMO

Bulk blending is considered as one of the most effective and straightforward ways to improve the hemo-compatibility of blood-contacting polymeric biomaterials among many surface modification methods. Zwitterionic structure-, glycocalyx-like structure-, and heparin-like structure-based oligomers have been synthesized as additives and blended with base polymers to improve the blood compatibility of base polymers. Fluorinated end- and side-functionalized oligomers could promote the migration of functionalized groups to the surface of biomedical polymers without changing their bulk properties, and it highly depends on the number and concentration of functional groups. Moreover, oligomers having both zwitterion and fluorine are receiving considerable attention due to their desirable phase separation, which can avoid undesired protein adsorption and platelet adhesion. The surface analysis of the surface-modified materials is usually investigated by analytical tools such as contact angle measurement, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Blood compatibility is mainly evaluated via platelet adhesion and protein adsorption test, and the result showed a significant decrease in the amount of undesirable adsorption. These analyses indicated that surface modification using bulk blending technique effectively improves blood compatibility of polymeric biomaterials.


Assuntos
Materiais Biocompatíveis , Polímeros , Adsorção , Materiais Biocompatíveis/química , Humanos , Adesividade Plaquetária , Polímeros/química , Propriedades de Superfície
9.
PLoS One ; 15(7): e0235842, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32639989

RESUMO

Biodegradable stents are promising treatments for many diseases, e.g., coronary artery disease, urethral diseases, tracheal diseases, and esophageal strictures. The mechanical properties of biodegradable stent materials play a key role in the safety and efficacy of treatment. In particular, insufficient creep resistance of the stent material could result in premature stent collapse or narrowing. Commercially available biodegradable self-expandable SX-ELLA stents made of polydioxanone monofilament were tested. A new, simple, and affordable method to measure the shear modulus of tiny viscoelastic wires is presented. The important mechanical parameters of the polydioxanone filament were obtained: the median Young's modulus was [Formula: see text] = 958 (922, 974) MPa and the shear modulus was [Formula: see text] = 357 (185, 387) MPa, resulting in a Poisson's ratio of ν = 0.34. The SX-ELLA stents exhibited significant force relaxation due to the stress relaxation of the polydioxanone monofilament, approximately 19% and 36% 10 min and 48 h after stent application, respectively. However, these results were expected, and the manufacturer and implanting clinician should be aware of the known behavior of these biodegradable materials. If possible, a biodegradable stent should be designed considering therapeutic force rather than initial force. Additionally, new and more advanced biodegradable shape-memory polymers should be considered for future study and use.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis/química , Polidioxanona/química , Stents , Módulo de Elasticidade , Humanos , Teste de Materiais , Fenômenos Mecânicos , Desenho de Prótese
10.
Int J Nanomedicine ; 15: 4205-4224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606673

RESUMO

Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.


Assuntos
Materiais Biocompatíveis/química , Coração/fisiologia , Nanocompostos/química , Nanomedicina , Polímeros/química , Engenharia Tecidual/métodos , Animais , Humanos , Nanocompostos/ultraestrutura
11.
Proc Natl Acad Sci U S A ; 117(27): 15482-15489, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571918

RESUMO

Bioelectronic scaffolds that support devices while promoting tissue integration could enable tissue hybrids with augmented electronic capabilities. Here, we demonstrate a photo-cross-linkable silk fibroin (PSF) derivative and investigate its structural, electrical, and chemical properties. Lithographically defined PSF films offered tunable thickness and <1-µm spatial resolution and could be released from a relief layer yielding freestanding scaffolds with centimeter-scale uniformity. These constructs were electrically insulating; multielectrode arrays with PSF-passivated interconnects provided stable electrophysiological readouts from HL-1 cardiac model cells, brain slices, and hearts. Compared to SU8, a ubiquitous biomaterial, PSF exhibited superior affinity toward neurons which we attribute to its favorable surface charge and enhanced attachment of poly-d-lysine adhesion factors. This finding is of significant importance in bioelectronics, where tight junctions between devices and cell membranes are necessary for electronic communication. Collectively, our findings are generalizable to a variety of geometries, devices, and tissues, establishing PSF as a promising bioelectronic platform.


Assuntos
Materiais Biocompatíveis/efeitos da radiação , Fontes de Energia Bioelétrica , Fibroínas/efeitos da radiação , Engenharia Tecidual , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Encéfalo , Adesão Celular , Linhagem Celular , Feminino , Fibroínas/química , Coração , Teste de Materiais , Camundongos , Células-Tronco Neurais , Raios Ultravioleta
12.
Proc Natl Acad Sci U S A ; 117(27): 15497-15503, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32576692

RESUMO

Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display several limitations including slow adhesion formation, weak bonding, low biocompatibility, poor mechanical match with tissues, and/or lack of triggerable benign detachment. Here, we report a bioadhesive that can form instant tough adhesion on various wet dynamic tissues and can be benignly detached from the adhered tissues on demand with a biocompatible triggering solution. The adhesion of the bioadhesive relies on the removal of interfacial water from the tissue surface, followed by physical and covalent cross-linking with the tissue surface. The triggerable detachment of the bioadhesive results from the cleavage of bioadhesive's cross-links with the tissue surface by the triggering solution. After it is adhered to wet tissues, the bioadhesive becomes a tough hydrogel with mechanical compliance and stretchability comparable with those of soft tissues. We validate in vivo biocompatibility of the bioadhesive and the triggering solution in a rat model and demonstrate potential applications of the bioadhesive with triggerable benign detachment in ex vivo porcine models.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Ferida Cirúrgica/terapia , Adesivos Teciduais/química , Adesividade , Animais , Reagentes para Ligações Cruzadas/química , Modelos Animais de Doenças , Feminino , Teste de Materiais , Ratos , Bicarbonato de Sódio/química , Soluções , Succinimidas/química , Suínos , Técnicas de Fechamento de Ferimentos/instrumentação
13.
PLoS One ; 15(6): e0235168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579611

RESUMO

OBJECTIVE: There is an increasing need for small diameter vascular grafts with superior host hemo- and cytocompatibilities, such as low activation of platelets and leukocytes. Therefore, we aimed to investigate whether the preparation of bacterial nanocellulose grafts with different inner surfaces has an impact on in vitro host cytocompatibility. METHODS: We have synthesized five different grafts in a bioreactor, namely open interface surface (OIS), inverted (INV), partially air dried (PAD), surface formed in air contact (SAC) and standard (STD) that were characterized by a different surface roughness. The grafts (length 55 mm, inner diameter 5 mm) were attached to heparinized polyvinyl chloride tubes, loaded with human blood and rotated at 37°C for 4 hours. Then, blood was analyzed for frequencies of cellular fractions, oxidative products, soluble complement and thrombin factors. The results were compared to clinically approved grafts made of polyethylene terephthalate and expanded polytetrafluoroethylene. Additionally, blood platelets were labelled with 111Indium-oxine to visualize the distribution of adherent platelets in the loop by scintigraphy. RESULTS: SAC nanocellulose grafts with the lowest surface roughness exhibited superior performance with <10% leukocyte and <50% thrombocyte loss in contrast to other grafts that exhibited >65% leukocyte and >90% thrombocyte loss. Of note, SAC nanocellulose grafts showed lowest radioactivity with scintigraphy analyses, indicating reduced platelet adhesion. Although the levels of reactive oxygen species and cell free DNA did not differ significantly, the levels of thrombin-antithrombin complexes were lowest in SAC grafts. However, all nanocellulose grafts exhibited enhanced complement activation. CONCLUSION: The systematic variation of the inner surfaces of BNC vascular grafts significantly improves biocompatibility. Especially, SAC grafts exhibited the lowest loss of platelets as well as leukocytes and additionally significantly diminished activation of the coagulation system. Further animal studies are needed to study in vivo biocompatibilities.


Assuntos
Materiais Biocompatíveis/química , Prótese Vascular , Celulose/química , Polissacarídeos Bacterianos/química , Grau de Desobstrução Vascular/fisiologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Implante de Prótese Vascular/métodos , Celulose/ultraestrutura , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/prevenção & controle , Heparina/farmacologia , Humanos , Teste de Materiais/métodos , Microscopia Eletrônica de Varredura , Adesividade Plaquetária/fisiologia , Polietilenotereftalatos/química , Politetrafluoretileno/química , Propriedades de Superfície , Grau de Desobstrução Vascular/efeitos dos fármacos
14.
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
15.
AAPS PharmSciTech ; 21(5): 173, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32548717

RESUMO

Innovative strategies for periodontal regeneration have been the focus of research clusters across the globe for decades. In order to overcome the drawbacks of currently available options, investigators have suggested a novel concept of functionally graded membrane (FGM) templates with different structural and morphological gradients. Chitosan (CH) has been used in the past for similar purpose. However, the composite formulation of composite and tetracycline when cross-linked with glutaraldehyde have received little attention. Therefore, the purpose of the study was to investigate the drug loading and release characteristics of novel freeze gelated chitosan templates at different percentages of glutaraldehyde. These were cross-linked with 0.1 and 1% glutaraldehyde and loaded with doxycycline hyclate. The electron micrographs depicted porous morphology of neat templates. After cross-linking, these templates showed compressed ultrastructures. Computerized tomography analysis showed that the templates had 88 to 92% porosity with average pore diameter decreased from 78 to 44.9 µm with increasing concentration. Fourier transform infrared spectroscopy showed alterations in the glycosidic segment of chitosan fingerprint region which after drug loading showed a dominant doxycycline spectral composite profile. Interestingly, swelling profile was not affected by cross-linking either at 0.1 and 1% glutaraldehyde and template showed a swelling ratio of 80%, which gained equilibrium after 15 min. The drug release pattern also showed a 40 µg/mL of release after 24 h. These doxycycline-loaded templates show their tendency to be used in a functionally graded membrane facing the defect site.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Reagentes para Ligações Cruzadas/química , Congelamento , Regeneração Tecidual Guiada Periodontal/métodos , Materiais Biocompatíveis/farmacocinética , Quitosana/farmacocinética , Reagentes para Ligações Cruzadas/farmacocinética , Liberação Controlada de Fármacos , Géis , Glutaral/química , Glutaral/farmacocinética , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
16.
Nat Commun ; 11(1): 2424, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415122

RESUMO

Lipid-like nanoparticles (LNPs) have potential as non-viral delivery systems for mRNA therapies. However, repeated administrations of LNPs may lead to accumulation of delivery materials and associated toxicity. To address this challenge, we have developed biodegradable lipids which improve LNPs clearance and reduce toxicity. We modify the backbone structure of Dlin-MC3-DMA by introducing alkyne and ester groups into the lipid tails. We evaluate the performance of these lipids when co-formulated with other amine containing lipid-like materials. We demonstrate that these formulations synergistically facilitate robust mRNA delivery with improved tolerability after single and repeated administrations. We further identify albumin-associated macropinocytosis and endocytosis as an ApoE-independent LNP cellular uptake pathway in the liver. Separately, the inclusion of alkyne lipids significantly increases membrane fusion to enhance mRNA release, leading to synergistic improvement of mRNA delivery. We believe that the rational design of LNPs with multiple amine-lipids increases the material space for mRNA delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Lipídeos/química , Fígado/metabolismo , Nanopartículas/química , RNA Mensageiro/metabolismo , Receptores de Albumina/metabolismo , Alquinos/química , Aminas/química , Animais , Apolipoproteínas E/metabolismo , Materiais Biocompatíveis/química , Endossomos/metabolismo , Eritrócitos/metabolismo , Eritropoetina/química , Ésteres/química , Hepatócitos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Dinâmica Molecular , RNA Interferente Pequeno/metabolismo
17.
Food Chem ; 326: 126969, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32438229

RESUMO

Biocompatible magnetic molecularly imprinted polymers (BMMIPs) were prepared with Zein for the first time, and were used to enrich tetracycline compounds selectively. Innovative combination of BMMIPs and electrochemistry to obtain lower detection line to satisfy industrial detection demands. Using Zein as the crosslinking agent, the polymers were synthesized on the surface of Fe3O4 particles. The scanning electron microscope, transmission electron microscope and X-ray diffraction technologies were used to characterize BMMIPs. Through optimization, BMMIPs attained large adsorption capacity (236.40 mg/g) with fast kinetics (40 min) and followed the Langmuir isotherm and pseudo-second-order kinetic models. BMMIPs had good recognition ability, the selective factors of oxytetracycline, chlortetracycline, doxycycline were 4.78, 4.23, and 3.39, respectively. Excellent linearity was attained in the range of 0.025-500 µg/mL, with low detection limits and low quantitation limits of 0.025 and 0.083 µg/mL. According to our exploring, BMMIPs was ideal materials for enrichment of tetracycline in complex biological samples.


Assuntos
Materiais Biocompatíveis/química , Contaminação de Alimentos/análise , Leite/química , Impressão Molecular/métodos , Tetraciclinas/análise , Adsorção , Animais , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/isolamento & purificação , Técnicas Eletroquímicas , Análise de Alimentos/métodos , Limite de Detecção , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Polímeros/química , Tetraciclina/análise , Tetraciclina/química , Tetraciclina/isolamento & purificação , Tetraciclinas/química , Tetraciclinas/isolamento & purificação , Difração de Raios X , Zeína/química
18.
J Vis Exp ; (159)2020 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-32421007

RESUMO

During the extrusion-based three-dimensional bioprinting process, liquid-like bioinks with low viscosity can protect cells from membrane damage induced by shear stress and improve the survival of the encapsulated cells. However, rapid gravity-driven cell sedimentation in the reservoir could lead to an inhomogeneous cell distribution in bioprinted structures and therefore hinder the application of liquid-like bioinks. Here, we developed a novel multilayered modified strategy for liquid-like bioinks (e.g., gelatin methacryloyl with low viscosity) to prevent the sedimentation of encapsulated cells. Multiple liquid interfaces were manipulated in the multilayered bioink to provide interfacial retention. Consequently, the cell sedimentation action going across adjacent layers in the multilayered system was retarded in the bioink reservoir. It was found that the interfacial retention was much higher than the sedimental pull of cells, demonstrating a critical role of the interfacial retention in preventing cell sedimentation and promoting a more homogeneous dispersion of cells in the multilayered bioink.


Assuntos
Materiais Biocompatíveis/química , Bioimpressão , Células/metabolismo , Hidrogéis/química , Tinta , Impressão Tridimensional , Animais , Sobrevivência Celular , Fibroínas/química , Gelatina/química , Metacrilatos/química , Camundongos , Células NIH 3T3 , Viscosidade
19.
Pharm Res ; 37(6): 97, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409985

RESUMO

PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. METHODS: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (µCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. RESULTS: Our findings demonstrate that synchrotron µCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. CONCLUSIONS: The method outlined in this study provides a proof of concept feasibility for µCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design. Graphical abstract.


Assuntos
Materiais Biocompatíveis/química , Meios de Contraste/química , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Suspensões/química , Tomografia Computadorizada por Raios X/métodos , Animais , Composição de Medicamentos , Imageamento Tridimensional , Injeções Subcutâneas , Intensificação de Imagem Radiográfica , Suínos , Síncrotrons , Tecidos Suporte/química
20.
PLoS One ; 15(5): e0226791, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374764

RESUMO

Over the past two decades, measurements of carbon nanotube toxicity and biodistribution have yielded a wide range of results. Properties such as nanotube type (single-walled vs. multi-walled), purity, length, aggregation state, and functionalization, as well as route of administration, greatly affect both the biocompatibility and biodistribution of carbon nanotubes. These differences suggest that generalizable conclusions may be elusive and that studies must be material- and application-specific. Here, we assess the short- and long-term biodistribution and biocompatibility of a single-chirality DNA-encapsulated single-walled carbon nanotube complex upon intravenous administration that was previously shown to function as an in-vivo reporter of endolysosomal lipid accumulation. Regarding biodistribution and fate, we found bulk specificity to the liver and >90% signal attenuation by 14 days in mice. Using near-infrared hyperspectral microscopy to measure single nanotubes, we found low-level, long-term persistence in organs such as the heart, liver, lung, kidney, and spleen. Measurements of histology, animal weight, complete blood count; biomarkers of organ function all suggest short- and long-term biocompatibility. This work suggests that carbon nanotubes can be used as preclinical research tools in-vivo without affecting acute or long-term health.


Assuntos
Materiais Biocompatíveis/farmacologia , Biomarcadores/sangue , Nanotecnologia , Nanotubos de Carbono/efeitos adversos , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/química , DNA de Cadeia Simples/química , DNA de Cadeia Simples/farmacologia , Endossomos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Camundongos , Nanotubos de Carbono/química , Imagem Óptica , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição Tecidual/efeitos dos fármacos
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