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1.
Nano Lett ; 24(19): 5690-5698, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700237

RESUMO

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.


Assuntos
Hidrogéis , Hidrogéis/química , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Feminino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Imunoterapia , Gelatina/química , Metacrilatos/química , Metacrilatos/farmacologia , Neoplasias da Mama/imunologia
2.
BMC Oral Health ; 24(1): 557, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735940

RESUMO

BACKGROUND: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. METHODS: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO2 and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. RESULTS: SiO2 and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO2-TRIS excelled in stiffness, BisGMA-SiO2-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO2-TRIS offered a balanced combination of mechanical properties. CONCLUSION: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO2-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.


Assuntos
Materiais Biocompatíveis , Resinas Compostas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Dióxido de Silício , Resinas Compostas/química , Dióxido de Silício/química , Materiais Biocompatíveis/química , Materiais Dentários/química , Metacrilatos/química , Poliuretanos/química , Ácidos Polimetacrílicos/química , Polietilenoglicóis/química , Resinas Acrílicas/química
3.
J Biomed Mater Res B Appl Biomater ; 112(5): e35412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701383

RESUMO

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.


Assuntos
Polpa Dentária , Gelatina , Hidrogéis , Endodontia Regenerativa , Alicerces Teciduais , Hidrogéis/química , Humanos , Alicerces Teciduais/química , Gelatina/química , Polpa Dentária/citologia , Metacrilatos/química , Engenharia Tecidual , Regeneração , Materiais Biocompatíveis/química , Animais
4.
Biomacromolecules ; 25(5): 2863-2874, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38564884

RESUMO

With the rapid increase of the number of patients with gastrointestinal diseases in modern society, the need for the development of physiologically relevant in vitro intestinal models is key to improve the understanding of intestinal dysfunctions. This involves the development of a scaffold material exhibiting physiological stiffness and anatomical mimicry of the intestinal architecture. The current work focuses on evaluating the scaffold micromorphology of gelatin-methacryloyl-aminoethyl-methacrylate-based nonporous and porous intestinal 3D, intestine-like constructs, fabricated via digital light processing, on the cellular response. To this end, Caco-2 intestinal cells were utilized in combination with the constructs. Both porous and nonporous constructs promoted cell growth and differentiation toward enterocyte-like cells (VIL1, ALPI, SI, and OCLD expression showed via qPCR, ZO-1 via immunostaining). The porous constructs outperformed the nonporous ones regarding cell seeding efficiency and growth rate, confirmed by MTS assay, live/dead staining, and TEER measurements, due to the presence of surface roughness.


Assuntos
Hidrogéis , Alicerces Teciduais , Humanos , Porosidade , Hidrogéis/química , Células CACO-2 , Alicerces Teciduais/química , Proliferação de Células , Gelatina/química , Intestinos/citologia , Metacrilatos/química , Engenharia Tecidual/métodos , Diferenciação Celular
5.
ACS Biomater Sci Eng ; 10(5): 3306-3315, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38634810

RESUMO

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.


Assuntos
Técnicas de Cocultura , Fator 2 de Crescimento de Fibroblastos , Gelatina , Células Endoteliais da Veia Umbilical Humana , Hidrogéis , Metacrilatos , Engenharia Tecidual , Fator A de Crescimento do Endotélio Vascular , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Gelatina/química , Gelatina/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Engenharia Tecidual/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Tecido Adiposo/citologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
6.
ACS Biomater Sci Eng ; 10(5): 3017-3028, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38655791

RESUMO

Macroporous cryogels are attractive scaffolds for biomedical applications, such as biomolecular immobilization, diagnostic sensing, and tissue engineering. In this study, thiol-reactive redox-responsive cryogels with a porous structure are prepared using photopolymerization of a pyridyl disulfide poly(ethylene glycol) methacrylate (PDS-PEG-MA) monomer. Reactive cryogels are produced using PDS-PEG-MA and hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) monomers, along with a PEG-based cross-linker and photoinitiator. Functionalization of cryogels using a fluorescent dye via the disulfide-thiol exchange reactions is demonstrated, followed by release under reducing conditions. For ligand-mediated protein immobilization, first, thiol-containing biotin or mannose is conjugated onto the cryogels. Subsequently, fluorescent dye-labeled proteins streptavidin and concanavalin A (ConA) are immobilized via ligand-mediated conjugation. Furthermore, we demonstrate that the mannose-decorated cryogel could capture ConA selectively from a mixture of lectins. The efficiency of protein immobilization could be easily tuned by changing the ratio of the thiol-sensitive moiety in the scaffold. Finally, an integrin-binding cell adhesive peptide is attached to cryogels to achieve successful attachment, and the on-demand detachment of integrin-receptor-rich fibroblast cells is demonstrated. Redox-responsive cryogels can serve as potential scaffolds for a variety of biomedical applications because of their facile synthesis and modification.


Assuntos
Criogéis , Oxirredução , Polietilenoglicóis , Criogéis/química , Polietilenoglicóis/química , Animais , Concanavalina A/química , Concanavalina A/metabolismo , Metacrilatos/química , Camundongos , Manose/química , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Compostos de Sulfidrila/química , Estreptavidina/química , Estreptavidina/metabolismo , Proteínas/química , Proteínas/metabolismo , Biotina/química , Biotina/metabolismo , Biotina/análogos & derivados , Porosidade
7.
ACS Biomater Sci Eng ; 10(5): 3108-3119, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38659287

RESUMO

Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes. Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.


Assuntos
Antifúngicos , Agulhas , Tinha dos Pés , Tinha dos Pés/tratamento farmacológico , Animais , Concentração de Íons de Hidrogênio , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/administração & dosagem , Metaloproteinases da Matriz/metabolismo , Humanos , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Cobaias , Gelatina/química , Metacrilatos/química
8.
Colloids Surf B Biointerfaces ; 238: 113886, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608461

RESUMO

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.


Assuntos
Coloides , Sistemas de Liberação de Medicamentos , Fosforilcolina , Coloides/química , Animais , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Nanopartículas/química , Poliésteres/química , Camundongos , Polímeros/química , Polímeros/farmacologia , Distribuição Tecidual , Pulmão/metabolismo , Ácidos Polimetacrílicos/química , Ativação do Complemento/efeitos dos fármacos , Metacrilatos/química , Humanos
9.
J Colloid Interface Sci ; 667: 54-63, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38615623

RESUMO

Type 1 diabetes mellitus (T1DM) is a chronic disease affecting millions worldwide. Insulin therapy is currently the golden standard for treating T1DM; however, it does not restore the normal glycaemic balance entirely, which increases the risk of secondary complications. Beta-cell therapy may be a possible way of curing T1DM and has already shown promising results in the clinic. However, low retention rates, poor cell survival, and limited therapeutic potential are ongoing challenges, thus increasing the need for better cell encapsulation devices. This study aimed to develop a mechanically reinforced vascular endothelial growth factor (VEGF)-delivering encapsulation device suitable for beta cell encapsulation and transplantation. Poly(l-lactide-co-ε-caprolactone) (PLCL)/gelatin methacryloyl (GelMA)/alginate coaxial nanofibres were produced using electrospinning and embedded in an alginate hydrogel. The encapsulation device was physically and biologically characterised and was found to be suitable for INS-1E beta cell encapsulation, vascularization, and transplantation in terms of its biocompatibility, porosity, swelling ratio and mechanical properties. Lastly, VEGF was incorporated into the hydrogel and the release kinetics and functional studies revealed a sustained release of bioactive VEGF for at least 14 days, making the modified alginate system a promising candidate for improving the beta cell survival after transplantation.


Assuntos
Alginatos , Gelatina , Hidrogéis , Células Secretoras de Insulina , Fator A de Crescimento do Endotélio Vascular , Hidrogéis/química , Alginatos/química , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Gelatina/química , Animais , Poliésteres/química , Ratos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Diabetes Mellitus Tipo 1/terapia , Metacrilatos/química , Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Indutores da Angiogênese/administração & dosagem , Propriedades de Superfície
10.
Biosensors (Basel) ; 14(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38667160

RESUMO

Galactose monitoring in individuals allows the prevention of harsh health conditions related to hereditary metabolic diseases like galactosemia. Current methods of galactose detection need development to obtain cheaper, more reliable, and more specific sensors. Enzyme-containing amperometric sensors based on galactose oxidase activity are a promising approach, which can be enhanced by means of their inclusion in a redox polymer coating. This strategy simultaneously allows the immobilization of the biocatalyst to the electroactive surface and hosts the electron shuttling units. An additional deposition of capping polymers prevents external interferences like ascorbic or uric acid as well as biofouling when measuring in physiological fuels. This work studies the protection effect of poly(2-methacryloyloxyethyl phosphorylcholine-co-glycidyl methacrylate (MPC) and polyvinylimidazole-polysulfostyrene (P(VI-SS)) when incorporated in the biosensor design for the detection of galactose in human plasma.


Assuntos
Técnicas Biossensoriais , Galactose , Polímeros , Humanos , Polímeros/química , Galactose Oxidase , Metacrilatos/química
11.
Biomater Sci ; 12(10): 2717-2729, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38619816

RESUMO

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.


Assuntos
Materiais Revestidos Biocompatíveis , Hidrogéis , Fosforilcolina , Propriedades de Superfície , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Teste de Materiais , Poli-Hidroxietil Metacrilato/química , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Metacrilatos/química , Polímeros/química , Polímeros/farmacologia , Próteses Valvulares Cardíacas , Valvas Cardíacas/efeitos dos fármacos , Humanos , Camundongos , Interações Hidrofóbicas e Hidrofílicas
12.
ACS Sens ; 9(4): 1735-1742, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38572917

RESUMO

Carbon dioxide (CO2) gas sensing and monitoring have gained prominence for applications such as smart food packaging, environmental monitoring of greenhouse gases, and medical diagnostic tests. Although CO2 sensors based on metal oxide semiconductors are readily available, they often suffer from limitations such as high operating temperatures (>250 °C), limited response at elevated humidity levels (>60% RH), bulkiness, and limited selectivity. In this study, we designed a chemiresistive sensor for CO2 detection to overcome these problems. The sensing material of this sensor consists of a CO2 switchable polymer based on N-3-(dimethylamino)propyl methacrylamide (DMAPMAm) and methoxyethyl methacrylate (MEMA) [P(D-co-M)], and diethylamine. The designed sensor has a detection range for CO2 between 103 and 106 ppm even at high humidity levels (>80% RH), and it is capable of differentiating ammonia at low concentrations (0.1-5 ppm) from CO2. The addition of diethylamine improved sensor performance such as selectivity, response/recovery time, and long-term stability. These data demonstrate the potential of using this sensor for the detection of food spoilage.


Assuntos
Dióxido de Carbono , Dióxido de Carbono/análise , Umidade , Acrilamidas/química , Polímeros/química , Metacrilatos/química , Gases/análise
13.
Biomed Mater ; 19(3)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38626774

RESUMO

Bioinks play a crucial role in tissue engineering, influencing mechanical and chemical properties of the printed scaffold as well as the behavior of encapsulated cells. Recently, there has been a shift from animal origin materials to their synthetic alternatives. In this context, we present here bioinks based on fully synthetic and biodegradable poly(α,L-amino acids) (PolyAA) as an alternative to animal-based gelatin methacrylate (Gel-Ma) bioinks. Additionally, we first reported the possibility of the visible light photoinitiated incorporation of the bifunctional cell adhesive RGD peptide into the PolyAA hydrogel matrix. The obtained hydrogels are shown to be cytocompatible, and their mechanical properties closely resemble those of gelatin methacrylate-based scaffolds. Moreover, combining the unique properties of PolyAA-based bioinks, the photocrosslinking strategy, and the use of droplet-based printing allows the printing of constructs with high shape fidelity and structural integrity from low-viscosity bioinks without using any sacrificial components. Overall, presented PolyAA-based materials are a promising and versatile toolbox that extends the range of bioinks for droplet bioprinting.


Assuntos
Aminoácidos , Materiais Biocompatíveis , Gelatina , Hidrogéis , Luz , Engenharia Tecidual , Alicerces Teciduais , Hidrogéis/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Gelatina/química , Aminoácidos/química , Materiais Biocompatíveis/química , Animais , Bioimpressão/métodos , Oligopeptídeos/química , Tinta , Metacrilatos/química , Humanos , Impressão Tridimensional , Teste de Materiais , Camundongos , Viscosidade
14.
J Biomed Mater Res B Appl Biomater ; 112(5): e35408, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38676958

RESUMO

Gelatin methacrylate (GelMA) hydrogels are expected to be ideal skin tissue engineering dressings for a wide range of clinical treatments. Herein, we report the preparation of GelMA or antifreeze GelMA hydrogel sheets with different GelMA concentrations, crosslinking times, and cryoprotectant (CPA) concentrations. The crystallization properties of GelMA or antifreeze GelMA hydrogel sheets were studied by cryomicroscopy and differential scanning calorimetry (DSC). It was found that the growth of ice crystals was slower when GelMA hydrogel concentration was more than 7%. The 10% DMSO-7% GelMA hydrogel sheets crosslinked for 60 min showed no ice crystal formation and growth during cooling and warming. The DSC results showed that the vitrification temperature of the 10% DMSO-7% GelMA hydrogel sheet was -111°C. Furthermore, slow freezing and rapid freezing of fibroblast-laden GelMA or antifreeze GelMA hydrogel sheets, and tissue-engineered skin constructs were studied. The results showed no significant difference in cell survival between slow (88.8% ± 1.51) and rapid (89.2% ± 3.00) freezing of fibroblast-loaded 10% DMSO-7% GelMA hydrogel sheets, and significantly higher than that of 7% GelMA hydrogel sheets (33.4% ± 5.46). The cell viability was higher in tissue-engineered skin constructs after slow freezing (86.34% ± 1.45) than rapid freezing (72.74% ± 1.34). We believe that the combination of antifreeze hydrogels and tissue engineering will facilitate the cryopreservation of tissue engineering constructs.


Assuntos
Criopreservação , Fibroblastos , Gelatina , Hidrogéis , Engenharia Tecidual , Hidrogéis/química , Hidrogéis/farmacologia , Gelatina/química , Animais , Fibroblastos/citologia , Fibroblastos/metabolismo , Cristalização , Crioprotetores/farmacologia , Crioprotetores/química , Metacrilatos/química , Pele/metabolismo , Camundongos , Proteínas Anticongelantes/química , Proteínas Anticongelantes/farmacologia , Humanos , Sobrevivência Celular/efeitos dos fármacos
15.
Artigo em Chinês | MEDLINE | ID: mdl-38664026

RESUMO

Objective: To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice. Methods: This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3rd and 4th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification (n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results: The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group (P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550±23, 235±9, and 856±35, respectively, which were significantly higher than 188±14, 97±6, and 370±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively, P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups (P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group (P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group (P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions: hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.


Assuntos
Vesículas Extracelulares , Hidrogéis , Células-Tronco Mesenquimais , Cicatrização , Animais , Humanos , Camundongos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Vesículas Extracelulares/química , Gelatina/química , Células Endoteliais da Veia Umbilical Humana , Hidrogéis/química , Queratinócitos/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Metacrilatos/química , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Cordão Umbilical/citologia , Cicatrização/efeitos dos fármacos
16.
ACS Nano ; 18(18): 11688-11702, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38665009

RESUMO

Designing an efficient nanocarrier to target multiple types of cancer remains a major challenge in the development of cancer nanomedicines. The majority of systemically administered nanoparticles (NPs) are rapidly cleared by the liver, resulting in poor tumor-targeting efficiency and severe side effects. Here, we present a delicately tailored design and synthesis of fluorescent bottle-brush polymers and screen nine derived NPs, each varying in size and surface coatings, for tumor imaging and targeted delivery. Our optimized polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains shows reduced macrophage uptake, prolonged blood-circulation time (up to 27 h), and exceptionally high accumulation in the tumor compared to the liver, elucidating an immune-evasion-induced tumor-targeting mechanism. High tumor accumulation significantly improved the antitumor efficacy. The outstanding tumor-targeting ability has been further validated across five distinct tumor models, including orthotopic glioblastoma and pancreatic cancer, which demonstrate the universality of our polymeric nanocarrier for tumor-targeting delivery.


Assuntos
Polímeros , Animais , Humanos , Camundongos , Polímeros/química , Nanopartículas/química , Nanomedicina Teranóstica , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Metacrilatos/química , Polietilenoglicóis/química
17.
Biomater Adv ; 160: 213850, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626580

RESUMO

Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2-2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5-83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting.


Assuntos
Matriz Extracelular , Hidrogéis , Metacrilatos , Polimerização , Animais , Metacrilatos/química , Suínos , Hidrogéis/química , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Fígado , Humanos , Impressão Tridimensional , Processos Fotoquímicos , Bioimpressão/métodos , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Reagentes de Ligações Cruzadas/química , Compostos de Epóxi/química
18.
Int J Biol Macromol ; 266(Pt 2): 131357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580010

RESUMO

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.


Assuntos
Regeneração Óssea , Fibroínas , Hidrogéis , Inflamação , Células-Tronco Mesenquimais , Nanocompostos , Osteogênese , Polifenóis , Espécies Reativas de Oxigênio , Taninos , Regeneração Óssea/efeitos dos fármacos , Animais , Fibroínas/química , Fibroínas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Camundongos , Inflamação/tratamento farmacológico , Nanocompostos/química , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células RAW 264.7 , Osteogênese/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124326, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38669978

RESUMO

Based on the fact that not all chemical substances possess good Raman signals, this article focuses on the Raman silent region signals of pesticides with cyano group. Under the optimized conditions of methanol-water (1:1, v/v) as the solvent, irradiation at 302 nm light source for 20 min, and the use of 0.5 mol/L KI as the aggregating agent, Surface-enhanced Raman spectroscopy (SERS) method for azoxystrobin detection was developed by the Raman silent region signal of 2230 cm-1, and verified by detecting the spiked grapes with different concentrations of azoxystrobin. Other four pesticides with cyano group also could be identified at the peak of 2180 cm-1, 2205 cm-1, 2125 cm-1, and 2130 cm-1 for acetamiprid, phoxim, thiacloprid and cymoxanil, respectively. When azoxystrobin or acetamiprid was mixed respectively with chlorpyrifos without cyano group, their SERS signals in the Raman silent region of chlorpyrifos were not interfered, while mixed with cymoxanil in different ratios (1:4, 1:1 and 4:1), respectively, each two pesticides with cyano group could be distinguished by the changes in the Raman silent region. In further, four pesticides with or without cyano group were mixed together in 1:1:1:1 (acetamiprid, cymoxanil, azoxystrobin chlorpyrifos), and each pesticide still could be identified even at 0.5 mg/L. The results showed that the SERS method combined with UV irradiation may provide a new way to monitor the pesticides with C≡N performance in the Raman silent region without interference from the food matrix.


Assuntos
Praguicidas , Análise Espectral Raman , Estrobilurinas , Análise Espectral Raman/métodos , Praguicidas/análise , Estrobilurinas/análise , Pirimidinas/análise , Pirimidinas/química , Vitis/química , Metacrilatos/química , Metacrilatos/análise , Neonicotinoides/análise
20.
Biomacromolecules ; 25(5): 2728-2739, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38563621

RESUMO

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.


Assuntos
Lentes de Contato , Metacrilatos , Compostos de Organossilício , Polietilenoglicóis , Polietilenoglicóis/química , Metacrilatos/química , Animais , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Camundongos , Materiais Biocompatíveis/química , Humanos , Miopia/tratamento farmacológico
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