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1.
ACS Appl Mater Interfaces ; 13(27): 31371-31378, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34196172

RESUMO

Owing to their remarkable infiltrative traits, glioblastomas develop unclear tumor margins toward the brain, hampering the complete resection. Since the remaining invasive cells tend to have resistance to therapeutics and cause recurrence around the surgical voids, this has been a major challenge for glioblastoma treatment. Thus, we design a cancer cell-sticky hydrogel (CSH) that interacts with the glioblastoma cells to impede their invasive motility by modifying the cell membrane with active thiol-enriched interfaces. Highly reactive thiols at the cell surface can make the infiltrated cancer cells adhere to the hydrogel, resulting in increased cell adhesion and decreased motility. Cotreatment with the CSH and chemical inhibitors of the major proinvasive molecules, focal adhesion kinase and hyaluronic acid synthase, maximized the invasion-inhibitory effect. In addition, a significant decrease in tumor mass was achieved via CSH implantation in mouse models. Overall, our results highlight the use of the CSH to inhibit the aggressive invasion as a novel therapeutic strategy against glioblastoma.


Assuntos
Neoplasias Encefálicas/patologia , Membrana Celular/efeitos dos fármacos , Glioblastoma/patologia , Hidrogéis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Desenho de Fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Hidrogéis/química , Invasividade Neoplásica , Compostos de Sulfidrila/química
2.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201385

RESUMO

Hydrogels are known as water-swollen networks formed from naturally derived or synthetic polymers. They have a high potential for medical applications and play a crucial role in tissue repair and remodeling. MSC-derived exosomes are considered to be new entities for cell-free treatment in different human diseases. Recent progress in cell-free bone tissue engineering via combining exosomes obtained from human mesenchymal stem cells (MSCs) with hydrogel scaffolds has resulted in improvement of the methodologies in bone tissue engineering. Our research has been actively focused on application of biotechnological methods for improving osteogenesis and bone healing. The following text presents a concise review of the methodologies of fabrication and preparation of hydrogels that includes the exosome loading properties of hydrogels for bone regenerative applications.


Assuntos
Diferenciação Celular , Exossomos/química , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Osteogênese , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Humanos
3.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201667

RESUMO

Human plasma-derived bilayered skin substitutes were successfully used by our group to produce human-based in vitro skin models for toxicity, cosmetic, and pharmaceutical testing. However, mechanical weakness, which causes the plasma-derived fibrin matrices to contract significantly, led us to attempt to improve their stability. In this work, we studied whether an increase in fibrin concentration from 1.2 to 2.4 mg/mL (which is the useful fibrinogen concentration range that can be obtained from plasma) improves the matrix and, hence, the performance of the in vitro skin cultures. The results show that this increase in fibrin concentration indeed affected the mechanical properties by doubling the elastic moduli and the maximum load. A structural analysis indicated a decreased porosity for the 2.4 mg/mL hydrogels, which can help explain this mechanical behavior. The contraction was clearly reduced for the 2.4 mg/mL matrices, which also allowed for the growth and proliferation of primary fibroblasts and keratinocytes, although at a somewhat reduced rate compared to the 1.2 mg/mL gels. Finally, both concentrations of fibrin gave rise to organotypic skin cultures with a fully differentiated epidermis, although their lifespans were longer (25-35%) in cultures with more concentrated matrices, which improves their usefulness. These systems will allow the generation of much better in vitro skin models for the testing of drugs, cosmetics and chemicals, or even to "personalized" skin for the diagnosis or determination of the most effective treatment possible.


Assuntos
Diferenciação Celular , Derme/citologia , Epiderme/fisiologia , Fibrina/metabolismo , Hidrogéis/metabolismo , Queratinócitos/citologia , Tecidos Suporte/química , Proliferação de Células , Células Cultivadas , Derme/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Hidrogéis/química , Queratinócitos/metabolismo , Pele/citologia , Pele/metabolismo , Engenharia Tecidual
4.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201769

RESUMO

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.


Assuntos
Materiais Biocompatíveis/química , Gelatina/química , Ácido Hialurônico/química , Hidrogéis/química , Metacrilatos/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Humanos , Polímeros/química
5.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202115

RESUMO

The literature indicates the existence of a relationship between rhamnolipids and bacterial biofilm, as well as the ability of selected bacteria to produce rhamnolipids and alginate. However, the influence of biosurfactant molecules on the mechanical properties of biofilms are still not fully understood. The aim of this research is to determine the effect of rhamnolipids concentration, CaCl2 concentration, and ionic cross-linking time on the mechanical properties of alginate hydrogels using a Box-Behnken design. The mechanical properties of cross-linked alginate hydrogels were characterized using a universal testing machine. It was assumed that the addition of rhamnolipids mainly affects the compression load, and the value of this parameter is lower for hydrogels produced with biosurfactant concentration below CMC than for hydrogels obtained in pure water. In contrast, the addition of rhamnolipids in an amount exceeding CMC causes an increase in compression load. In bacterial biofilms, the presence of rhamnolipid molecules does not exceed the CMC value, which may confirm the influence of this biosurfactant on the formation of the biofilm structure. Moreover, rhamnolipids interact with the hydrophobic part of the alginate copolymer chains, and then the hydrophilic groups of adsorbed biosurfactant molecules create additional calcium ion trapping sites.


Assuntos
Alginatos/química , Bactérias/crescimento & desenvolvimento , Biofilmes/crescimento & desenvolvimento , Glicolipídeos/química , Hidrogéis/química , Líquidos Iônicos/química , Algoritmos , Modelos Teóricos
6.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199374

RESUMO

BACKGROUND: Skinboosters represent the latest category of hyaluronan (HA) hydrogels released for aesthetic purposes. Different from originally developed gels, they are intended for more superficial injections, claiming a skin rejuvenation effect through hydration and possibly prompting biochemical effects in place of the conventional volumetric action. Here, three commercial skinboosters were characterized to unravel the scientific basis for such indication and to compare their performances. METHODS: Gels were evaluated for water-soluble/insoluble-HA composition, rheology, hydration, cohesivity, stability and effect, in vitro, on human dermal fibroblasts towards the production of extracellular matrix components. RESULTS: Marked differences in the insoluble-hydrogel amount and in the hydrodynamic parameters for water-soluble-HA chains were evidenced among the gels. Hydration, rigidity and cohesivity also varied over a wide range. Sensitivity to hyaluronidases and Reactive Oxygen Species was demonstrated allowing a stability ranking. Slight differences were found in gels' ability to prompt elastin expression and in ColIV/ColI ratio. CONCLUSIONS: A wide panel of biophysical and biochemical parameters for skinboosters was provided, supporting clinicians in the conscious tuning of their use. Data revealed great variability in gels' behavior notwithstanding the same clinical indication and unexpected similarities to the volumetric formulations. Data may be useful to improve customization of gel design toward specific uses.


Assuntos
Ácido Hialurônico/química , Hialuronoglucosaminidase/genética , Hidrogéis/química , Pele/efeitos dos fármacos , Elastina/química , Fibroblastos/efeitos dos fármacos , Humanos , Hialuronoglucosaminidase/química , Injeções , Espécies Reativas de Oxigênio/química , Rejuvenescimento/fisiologia , Reologia , Pele/crescimento & desenvolvimento , Pele/patologia , Envelhecimento da Pele/genética , Viscosidade
7.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202196

RESUMO

Three-dimensional (3D) printing is regarded as a critical technology in material engineering for biomedical applications. From a previous report, silk fibroin (SF) has been used as a biomaterial for tissue engineering due to its biocompatibility, biodegradability, non-toxicity and robust mechanical properties which provide a potential as material for 3D-printing. In this study, SF-based hydrogels with different formulations and SF concentrations (1-3%wt) were prepared by natural gelation (SF/self-gelled), sodium tetradecyl sulfate-induced (SF/STS) and dimyristoyl glycerophosphorylglycerol-induced (SF/DMPG). From the results, 2%wt SF-based (2SF) hydrogels showed suitable properties for extrusion, such as storage modulus, shear-thinning behavior and degree of structure recovery. The 4-layer box structure of all 2SF-based hydrogel formulations could be printed without structural collapse. In addition, the mechanical stability of printed structures after three-step post-treatment was investigated. The printed structure of 2SF/STS and 2SF/DMPG hydrogels exhibited high stability with high degree of structure recovery as 70.4% and 53.7%, respectively, compared to 2SF/self-gelled construct as 38.9%. The 2SF/STS and 2SF/DMPG hydrogels showed a great potential to use as material for 3D-printing due to its rheological properties, printability and structure stability.


Assuntos
Fibroínas/química , Hidrogéis/química , Impressão Tridimensional , Engenharia Tecidual , Tecidos Suporte/química
8.
Int J Nanomedicine ; 16: 4373-4390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234432

RESUMO

Current treatments for Alzheimer's disease (AD) attenuate the progression of symptoms and aim to improve the patient's quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood-brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Portadores de Fármacos/química , Hidrogéis/química , Lipídeos/química , Nanoestruturas/química , Nariz , Doença de Alzheimer/tratamento farmacológico , Animais , Emulsões , Humanos
9.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207389

RESUMO

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model.


Assuntos
Regeneração Tecidual Guiada/métodos , Ácido Hialurônico/química , Hidrogéis/química , Laminina/química , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/cirurgia , Animais , Células Cultivadas , Feminino , Ratos , Ratos Endogâmicos Lew
10.
Int J Nanomedicine ; 16: 4239-4250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194227

RESUMO

Purpose: Pore-forming toxins (PFTs) perform important functions during bacterial infections. Among various virulence-targeting therapies, nanosponges (NSs) have excellent neutralization effects on multiple PFTs. To enhance treatment efficacy, NSs tend to be incorporated into other biomaterials, such as hydrogels. Methods: In the present work, red blood cell (RBC) vesicles were harvested to wrap polymer nanoparticles, leading to the formation of NSs, and the optimal Pluronic F127 hydrogel concentration was determined for gelation. Then, a novel detoxification system was constructed by incorporating NSs into an optimized Pluronic F127 hydrogel (NS-pGel). Next, the system was characterized by rheological and sustained release behavior as well as micromorphology. Then, the in vitro neutralization effect of NS-pGel on various PFTs was examined by a hemolysis protocol. Finally, therapeutic and prophylactic detoxification efficiency was evaluated in a mouse subcutaneous infection model in vivo. Results: A thermosensitive, injectable detoxification system was successfully constructed by loading NSs into a 30% Pluronic F127 hydrogel. Characterization results demonstrated that the NS-pGel hybrid system sustained an ideal fluidity and viscosity at lower temperatures but exhibited a quick sol-gel transition capacity near body temperature. In addition, this hybrid system had a sustained release behavior accompanied by good biocompatibility and biodegradability. Finally, the NS-pGel system showed neutralization effects similar to those of NSs both in vitro and in vivo, indicating a good preservation of NS functionality. Conclusion: In conclusion, we constructed a novel temperature-sensitive detoxification system with good biocompatibility and biodegradability, which may be applied to the clinical treatment of PFT-induced local lesions and infections.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/química , Hidrogéis/administração & dosagem , Hidrogéis/química , Poloxâmero/química , Animais , Proteínas de Bactérias , Materiais Biocompatíveis , Eritrócitos/química , Proteínas Hemolisinas , Hemólise/efeitos dos fármacos , Masculino , Teste de Materiais , Camundongos Endogâmicos ICR , Nanopartículas/química , Testes de Neutralização , Reologia , Staphylococcus aureus/patogenicidade , Temperatura , Vibrio vulnificus/patogenicidade , Viscosidade
11.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208633

RESUMO

The clinical application of human platelet lysate (HPL) holds promise for tissue regeneration, and the development of an efficient vehicle for its delivery is desired. Chitosan-based hydrogels are potential candidates, but they often exhibit weak mechanical properties. In this study, a chitosan/gelatin (CS-GE) hydrogel crosslinked by glyoxal was fabricated for sustained release of HPL. The influence of HPL on Hs68 fibroblast and human umbilical vein endothelial cell (HUVEC) culture was evaluated, and we found that supplementing 5% HPL in the medium could significantly improve cell proliferation relative to supplementing 10% fetal bovine serum (FBS). Moreover, HPL accelerated the in vitro wound closure of Hs68 cells and facilitated the tube formation of HUVECs. Subsequently, we fabricated CS-GE hydrogels crosslinked with different concentrations of glyoxal, and the release pattern of FITC-dextrans (4, 40 and 500 kDa) from the hydrogels was assessed. After an ideal glyoxal concentration was determined, we further characterized the crosslinked CS-GE hydrogels encapsulated with different amounts of HPL. The HPL-incorporated hydrogel was shown to significantly promote the proliferation of Hs68 cells and the migration of HUVECs. Moreover, the release pattern of transforming growth factor-ß1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB) from hydrogel was examined in vitro, demonstrating a sustained release profile of the growth factors. Finally, the chick chorioallantoic membrane assay revealed that HPL encapsulation in the hydrogel significantly stimulated angiogenesis in ovo. These results demonstrate the great potential of the crosslinked CS-GE hydrogel to serve as an effective delivery system for HPL to promote tissue regeneration.


Assuntos
Produtos Biológicos/farmacologia , Plaquetas/metabolismo , Quitosana , Gelatina , Glioxal , Hidrogéis , Regeneração/efeitos dos fármacos , Proliferação de Células , Quitosana/química , Dextranos/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Gelatina/química , Glioxal/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Neovascularização Fisiológica , Porosidade , Cicatrização/efeitos dos fármacos
12.
Int J Nanomedicine ; 16: 4251-4276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211271

RESUMO

Aim: Retinyl palmitate (RP), the most stable vitamin A derivative, is used to treat photoaging and other skin disorders. The need to minimize the adverse effects of topical drug administration has led to an enhanced interest in loading RP on ethosomes for topical drug delivery. The aim of the current study was to prepare and compare the performance of RP decorated ethosomal hydrogel with tretinoin cream in the treatment of acne vulgaris as an approach to improve drug efficacy and decrease its side effects. Methods: RP-loaded ethosomes were prepared using the injection sonication technique. A Box-Behnken design using Design Expert® software was used for the optimization of formulation variables. Particle size, zeta potential (ZP), entrapment efficiency percent (EE%), % drug release, and permeation over 24 h of different formulations were determined. The optimal formulation was incorporated into a hydrogel. Finally, the efficacy and tolerability of the optimized RP ethosomal hydrogel were clinically evaluated for acne treatment using a split-face comparative clinical study. Results: The optimized ethosomal RP showed particle size of 195.8±5.45 nm, ZP of -62.1±2.85 mV, EE% of 92.63±4.33%, drug release % of 96.63±6.81%, and drug permeation % of 85.98 ±4.79%. Both the optimized RP ethosomal hydrogel and tretinoin effectively reduced all types of acne lesions (inflammatory, non-inflammatory, and total lesions). However, RP resulted in significantly lower non-inflammatory and total acne lesion count than the marketed tretinoin formulation. Besides, RP-loaded ethosomes showed significantly improved tolerability compared to marketed tretinoin with no or minimal skin irritation symptoms. Conclusion: RP ethosomal hydrogel is considerably effective in controlling acne vulgaris with excellent skin tolerability. Therefore, it represents an interesting alternative to conventional marketed tretinoin formulation for topical acne treatment.


Assuntos
Acne Vulgar/tratamento farmacológico , Diterpenos/administração & dosagem , Hidrogéis/química , Hidrogéis/farmacologia , Ésteres de Retinil/administração & dosagem , Administração Cutânea , Adulto , Animais , Diterpenos/efeitos adversos , Diterpenos/química , Diterpenos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/efeitos adversos , Masculino , Tamanho da Partícula , Estudos Prospectivos , Ratos Wistar , Ésteres de Retinil/efeitos adversos , Ésteres de Retinil/química , Ésteres de Retinil/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele , Tretinoína/administração & dosagem , Tretinoína/farmacologia
13.
Nat Commun ; 12(1): 4419, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285208

RESUMO

Electroadhesion, i.e., adhesion induced by an electric field, occurs between non-sticky cationic and anionic hydrogels. Here, we demonstrate electroadhesion between cationic gels and animal (bovine) tissues. When gel and tissue are placed under an electric field (DC, 10 V) for 20 s, the pair strongly adhere, and the adhesion persists indefinitely thereafter. Applying the DC field with reversed polarity eliminates the adhesion. Electroadhesion works with the aorta, cornea, lung, and cartilage. We demonstrate the use of electroadhesion to seal cuts or tears in tissues or model anionic gels. Electroadhered gel-patches provide a robust seal over openings in bovine aorta, and a gel sleeve is able to rejoin pieces of a severed gel tube. These studies raise the possibility of using electroadhesion in surgery while obviating the need for sutures. Advantages include the ability to achieve adhesion on-command, and moreover the ability to reverse this adhesion in case of error.


Assuntos
Hidrogéis/administração & dosagem , Procedimentos Cirúrgicos sem Sutura/métodos , Ferimentos e Lesões/cirurgia , Testes de Impedância Acústica , Adesividade , Animais , Aorta/cirurgia , Bovinos , Estudos de Viabilidade , Humanos , Hidrogéis/química , Teste de Materiais , Resistência ao Cisalhamento
14.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071329

RESUMO

Avascular transplantation of frozen-thawed testicular tissue fragments represents a potential future technique for fertility restoration in boys with cancer. A significant loss of spermatogonia was observed in xeno-transplants of human tissue most likely due to the hypoxic period before revascularization. To reduce the effect of hypoxia-reoxygenation injuries, several options have already been explored, like encapsulation in alginate hydrogel and supplementation with nanoparticles delivering a necrosis inhibitor (NECINH) or VEGF. While these approaches improved short-term (5 days) vascular surfaces in grafts, neovessels were not maintained up to 21 days; i.e., the time needed for achieving vessel stabilization. To better support tissue grafts, nanoparticles loaded with VEGF, PDGF and NECINH were developed. Testicular tissue fragments from 4-5-week-old mice were encapsulated in calcium-alginate hydrogels, either non-supplemented (control) or supplemented with drug-loaded nanoparticles (VEGF-nanoparticles; VEGF-nanoparticles + PDGF-nanoparticles; NECINH-nanoparticles; VEGF-nanoparticles + NECINH-nanoparticles; and VEGF-nanoparticles + PDGF-nanoparticles + NECINH-nanoparticles) before auto-transplantation. Grafts were recovered after 5 or 21 days for analyses of tissue integrity (hematoxylin-eosin staining), spermatogonial survival (immuno-histo-chemistry for promyelocytic leukemia zinc finger) and vascularization (immuno-histo-chemistry for α-smooth muscle actin and CD-31). Our results showed that a combination of VEGF and PDGF nanoparticles increased vascular maturity and induced a faster maturation of vascular structures in grafts.


Assuntos
Hidrogéis/química , Nanopartículas/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Testículo/transplante , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Alginatos/química , Animais , Liberação Controlada de Fármacos , Preservação da Fertilidade/métodos , Humanos , Masculino , Camundongos Endogâmicos , Nanopartículas/química , Fator de Crescimento Derivado de Plaquetas/química , Fator de Crescimento Derivado de Plaquetas/farmacocinética , Espermatogônias/efeitos dos fármacos , Testículo/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/farmacocinética
15.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072090

RESUMO

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.


Assuntos
Alginatos/química , Betametasona/administração & dosagem , Portadores de Fármacos , Hidrogéis/química , Metacrilatos/química , Polímeros/química , Tecidos Suporte/química , Animais , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Condrócitos , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Hidrogéis/síntese química , Cinética , Camundongos , Estrutura Molecular , Análise Espectral
16.
ACS Appl Mater Interfaces ; 13(23): 26735-26747, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34081856

RESUMO

Microfluidic gradient generators have been used to study cellular migration, growth, and drug response in numerous biological systems. One type of device combines a hydrogel and polydimethylsiloxane (PDMS) to generate "flow-free" gradients; however, their requirements for either negative flow or external clamps to maintain fluid-tight seals between the two layers have restricted their utility among broader applications. In this work, a two-layer, flow-free microfluidic gradient generator was developed using thiol-ene chemistry. Both rigid thiol-acrylate microfluidic resin (TAMR) and diffusive thiol-acrylate hydrogel (H) layers were synthesized from commercially available monomers at room temperature and pressure using a base-catalyzed Michael addition. The device consisted of three parallel microfluidic channels negatively imprinted in TAMR layered on top of the thiol-acrylate hydrogel to facilitate orthogonal diffusion of chemicals to the direction of flow. Upon contact, these two layers formed fluid-tight channels without any external pressure due to a strong adhesive interaction between the two layers. The diffusion of molecules through the TAMR/H system was confirmed both experimentally (using fluorescent microscopy) and computationally (using COMSOL). The performance of the TAMR/H system was compared to a conventional PDMS/agarose device with a similar geometry by studying the chemorepulsive response of a motile strain of GFP-expressing Escherichia coli. Population-based analysis confirmed a similar migratory response of both wild-type and mutant E. coli in both of the microfluidic devices. This confirmed that the TAMR/H hybrid system is a viable alternative to traditional PDMS-based microfluidic gradient generators and can be used for several different applications.


Assuntos
Acrilatos/química , Quimiotaxia , Escherichia coli/fisiologia , Hidrogéis/química , Microfluídica/instrumentação , Cimentos de Resina/química , Compostos de Sulfidrila/química , Adesivos , Microfluídica/métodos
17.
ACS Appl Mater Interfaces ; 13(23): 27645-27655, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34081862

RESUMO

A combined approach to signal enhancement in fluorescence affinity biosensors and assays is reported. It is based on the compaction of specifically captured target molecules at the sensor surface followed by optical probing with a tightly confined surface plasmon (SP) field. This concept is utilized by using a thermoresponsive hydrogel (HG) binding matrix that is prepared from a terpolymer derived from poly(N-isopropylacrylamide) (pNIPAAm) and attached to a metallic sensor surface. Epi-illumination fluorescence and SP-enhanced total internal reflection fluorescence readouts of affinity binding events are performed to spatially interrogate the fluorescent signal in the direction parallel and perpendicular to the sensor surface. The pNIPAAm-based HG binding matrix is arranged in arrays of sensing spots and employed for the specific detection of human IgG antibodies against the Epstein-Barr virus (EBV). The detection is performed in diluted human plasma or with isolated human IgG by using a set of peptide ligands mapping the epitope of the EBV nuclear antigen. Alkyne-terminated peptides were covalently coupled to the pNIPAAm-based HG carrying azide moieties. Importantly, using such low-molecular-weight ligands allowed preserving the thermoresponsive properties of the pNIPAAm-based architecture, which was not possible for amine coupling of regular antibodies that have a higher molecular weight.


Assuntos
Resinas Acrílicas/química , Técnicas Biossensoriais/métodos , Infecções por Vírus Epstein-Barr/diagnóstico , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Hidrogéis/química , Imunoglobulina G/análise , Fragmentos de Peptídeos/metabolismo , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Fluorescência , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hidrogéis/metabolismo , Imunoglobulina G/imunologia , Fragmentos de Peptídeos/imunologia , Polímeros/química
18.
ACS Appl Mater Interfaces ; 13(23): 26673-26681, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34085806

RESUMO

Fast sampling followed by sequence-independent sensing and length-dependent detection of short double-stranded DNA fragments, the size of those found in blood and other bodily fluids, is achieved using engineered molecular sensors, dubbed hydrogel-filled nanopores (HFNs). Fragments as short as 100 base pairs were blindly sampled and concentrated at the tip of an HFN before reversing the applied potential to detect and distinguish individual molecules based on fragment length as they translocate out of the nanopore. A remarkable 16-fold increase in the signal-to-noise ratio was observed in the eject configuration compared to the load configuration, enabling the resolution of fragments with a size difference of 50 nucleotides in length. This fast and versatile technology offers great tunability for both sampling and detection. While increasing sampling time leads to an increase in the local DNA concentration at the tip prior to detection, a linear correlation between the peak current and DNA fragment size enables good resolution of fragments up to 250 bp long.


Assuntos
Ácidos Nucleicos Livres/análise , DNA/análise , Hidrogéis/química , Nanoporos , Nanotecnologia/métodos , Imagem Individual de Molécula/métodos , Ácidos Nucleicos Livres/química , DNA/química
19.
ACS Appl Mater Interfaces ; 13(23): 26770-26781, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34096258

RESUMO

Diabetic foot ulcers (DFUs) are hard-healing chronic wounds and susceptible to bacterial infection. Conventional hydrogel dressings easily lose water at high temperature or freeze at low temperature, making them unsuitable for long-term use or in extreme environments. Herein, a temperature-tolerant (-20 to 60 °C) antibacterial hydrogel dressing is fabricated by the assembly of polyacrylamide, gelatin, and ε-polylysine. Owing to the water/glycerin (Gly) binary solvent system, the resultant hydrogel (G-PAGL) displayed good heat resistance and antifreezing properties. Within the wide temperature range (-20 to 60 °C), all the desirable features of the hydrogel, including superstretchability (>1400%), enduring water retention, adhesiveness, and persistent antibacterial property, are quite stable. Remarkably, the hydrogel wound dressing displayed lasting and broad antibacterial activity against Gram-positive and Gram-negative bacteria. Satisfactorily, the double-network (DN) G-PAGL hydrogel dressing could effectively promote the healing of DFUs by accelerating collagen deposition, promoting angiogenesis, and inhibiting bacterial breed. As far as we know, this is the first time that the extensive temperature-tolerant DN hydrogel with antibacterial ability is developed to use as DFU wound dressing. The G-PAGL hydrogel provides more choices for DFU wound dressings that could be used in extreme environments.


Assuntos
Antibacterianos/administração & dosagem , Diabetes Mellitus Experimental/complicações , Pé Diabético/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hidrogéis/administração & dosagem , Cicatrização/efeitos dos fármacos , Adesivos , Animais , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Bandagens , Pé Diabético/etiologia , Pé Diabético/patologia , Hidrogéis/química , Ratos , Temperatura
20.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064401

RESUMO

Hydrogel adhesives are attractive for applications in intelligent soft materials and tissue engineering, but conventional hydrogels usually have poor adhesion. In this study, we designed a strategy to synthesize a novel adhesive with a thin hydrogel adhesive layer integrated on a tough substrate hydrogel. The adhesive layer with positive charges of ammonium groups on the polymer backbones strongly bonds to a wide range of nonporous materials' surfaces. The substrate layer with a dual hydrogen bond system consists of (i) weak hydrogen bonds between N,N-dimethyl acrylamide (DMAA) and acrylic acid (AAc) units and (ii) strong multiple hydrogen bonds between 2-ureido-4[1H]-pyrimidinone (UPy) units. The dual hydrogen-bond network endowed the hydrogel adhesives with unique mechanical properties, e.g., toughness, highly stretchability, and insensitivity to notches. The hydrogel adhesion to four types of materials like glass, 316L stainless steel, aluminum, Al2O3 ceramic, and two biological tissues including pig skin and pig kidney was investigated. The hydrogel bonds strongly to dry solid surfaces and wet tissue, which is promising for biomedical applications.


Assuntos
Hidrogéis/química , Acrilamidas/química , Acrilatos/química , Adesividade , Animais , Ligação de Hidrogênio , Suínos
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