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1.
Acta Cir Bras ; 36(3): e360303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33825787

RESUMO

PURPOSE: This study aimed to elaborate a hydrogel constituted by carboxymethyl chitosan (CMC), hyaluronic acid (HA) and silver (Ag) and to evaluate its healing effect on partial-thickness burn wounds experimentally induced in rats. METHODS: CMC was obtained by chitosan reacting with monochloroacetic acid. The carboxymethylation was confirmed by Fourier-transform infrared spectroscopy and hydrogen nuclear magnetic resonance (NMR). Scanning electron microscopy was used to determine the morphologicalcharacteristics of chitosan and CMC. After the experimental burn wound induction, the animals (n = 126) were treated with different CMC formulations, had their occlusive dressings changed daily and were followed through 7, 14 and 30 days. Morphometric, macroscopic and microscopic aspects and collagen quantification were evaluated. RESULTS: Significative wound contraction, granulation tissue formation, inflammatory infiltration and collagen fibers deposit throughout different phases of the healing process were observed in the CMC hydrogels treated groups. CONCLUSIONS: The results showed that, in the initial phase of the healing process, the most adequate product was the CMC/HA/Ag association, while in the other phases the CMC/HA association was the best one to promote the healing of burn wounds.


Assuntos
Queimaduras , Quitosana , Animais , Queimaduras/tratamento farmacológico , Colágeno , Hidrogéis , Ratos , Cicatrização
2.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809175

RESUMO

A flexible and bioactive scaffold for adipose tissue engineering was fabricated and evaluated by dual nozzle three-dimensional printing. A highly elastic poly (L-lactide-co-ε-caprolactone) (PLCL) copolymer, which acted as the main scaffolding, and human adipose tissue derived decellularized extracellular matrix (dECM) hydrogels were used as the printing inks to form the scaffolds. To prepare the three-dimensional (3D) scaffolds, the PLCL co-polymer was printed with a hot melting extruder system while retaining its physical character, similar to adipose tissue, which is beneficial for regeneration. Moreover, to promote adipogenic differentiation and angiogenesis, adipose tissue-derived dECM was used. To optimize the printability of the hydrogel inks, a mixture of collagen type I and dECM hydrogels was used. Furthermore, we examined the adipose tissue formation and angiogenesis of the PLCL/dECM complex scaffold. From in vivo experiments, it was observed that the matured adipose-like tissue structures were abundant, and the number of matured capillaries was remarkably higher in the hydrogel-PLCL group than in the PLCL-only group. Moreover, a higher expression of M2 macrophages, which are known to be involved in the remodeling and regeneration of tissues, was detected in the hydrogel-PLCL group by immunofluorescence analysis. Based on these results, we suggest that our PLCL/dECM fabricated by a dual 3D printing system will be useful for the treatment of large volume fat tissue regeneration.


Assuntos
Tecido Adiposo/crescimento & desenvolvimento , Hidrogéis/síntese química , Regeneração/genética , Engenharia Tecidual , Tecido Adiposo/química , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Elasticidade/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Polímeros/síntese química , Polímeros/farmacologia , Impressão Tridimensional , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos
3.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803546

RESUMO

Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell-cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.


Assuntos
Alginatos/química , Hidrogéis/química , Tecidos Suporte/química , Animais , Callithrix , Cápsulas , Sobrevivência Celular , Criopreservação , Derme/citologia , Humanos , Células-Tronco Mesenquimais/citologia , Tamanho da Partícula , Análise Espectral Raman , Fatores de Tempo , Água/química
4.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803717

RESUMO

New fluconazole-loaded, 6-Anhydro-α-l-Galacto-ß-d-Galactan hydrogels incorporated with nanohydroxyapatite were prepared and their physicochemical features (XRD, X-ray Diffraction; SEM-EDS, Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy; ATR-FTIR, Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy), fluconazole release profiles and enzymatic degradation were determined. Antifungal activity of pure fluconazole was tested using Candida species (C. albicans, C. tropicalis, C. glabarata), Cryptococcus species (C. neoformans, C. gatti) and Rhodotorula species (R. mucilaginosa, R. rubra) reference strains and clinical isolates. Standard microdilution method was applied, and fluconazole concentrations of 2-250 µg/mL were tested. Moreover, biofilm production ability of tested isolates was tested on the polystyrene surface at 28 and 37 ± 0.5 °C and measured after crystal violet staining. Strains with the highest biofilm production ability were chosen for further analysis. Confocal microscopy photographs were taken after live/dead staining of fungal suspensions incubated with tested hydrogels (with and without fluconazole). Performed analyses confirmed that polymeric hydrogels are excellent drug carriers and, when fluconazole-loaded, they may be applied as the prevention of chronic wounds fungal infection.


Assuntos
Antifúngicos/farmacologia , Durapatita/química , Fluconazol/farmacologia , Galactanos/química , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Doença Crônica , Fungos/efeitos dos fármacos , Hidrogéis/química , Cinética , Testes de Sensibilidade Microbiana , Muramidase/metabolismo , Nanopartículas/ultraestrutura , Plâncton/efeitos dos fármacos , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo , Difração de Raios X
5.
Bioresour Technol ; 331: 125046, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33827016

RESUMO

A FeCl3-activated seaweed carbon/MCM-41/alginate hydrogel composite (ECAC/MCM-41/ ALG) cross-linked with calcium chloride (2% CaCl2) was synthesized for the biosorption of bisphenol A (BPA) plasticizer and basic blue (BB) dye. Biosorption uptakes of BPA and BB were performed in a batch mode with varying solution pH from 3 to 11, initial sorbate concentration from 25 to 300 mg/L, reaction time from 0 to 10 h, and biosorption temperature from 30 to 50 °C. The maximum BPA and BB uptake mechanisms were fast, which occurred within contact times of 1 and 2 h with monolayer coverage capacities of 222.32 and 190.11 mg/g at 50 °C, respectively. Cyclic biosorption/desorption behavior was evaluated via an ethanol elution to evaluate the feasibility of the ECAC/MCM-41/ALG for long-term application. Results revealed the biosorption renewability for five cycles up to 80% of the newly synthesized hydrogel composite for the purification of industrial wastewater laden with emerging contaminants.


Assuntos
Alga Marinha , Poluentes Químicos da Água , Adsorção , Alginatos , Compostos Benzidrílicos , Hidrogéis , Concentração de Íons de Hidrogênio , Cinética , Fenóis , Plastificantes , Dióxido de Silício , Termodinâmica
6.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802425

RESUMO

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, ß-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,ß-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Nanoestruturas/química , Peptídeos/química , Peptidomiméticos/química , Aminoácidos/química , Animais , Humanos , Estrutura Secundária de Proteína
7.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802469

RESUMO

In this study, nanocomposite hydrogels composed of sodium carboxymethylated starch (CMS)-containing CuO nanoparticles (CMS@CuO) were synthesized and used as experimental wound healing materials. The hydrogels were fabricated by a solution-casting technique using citric acid as a crosslinking agent. They were characterized by Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA) to evaluate their physicochemical properties. In addition, swelling, antibacterial activities, antioxidant activities, cytotoxicity, and in vivo wound healing were investigated to evaluate the wound healing potential of the CMS@CuO nanocomposite hydrogels. Growth inhibition of the Gram-positive and Gram-negative pathogens, antioxidant activity, and swelling were observed in the CMS@CuO nanocomposite hydrogels containing 2 wt.% and 4 wt.% CuO nanoparticles. The hydrogel containing 2 wt.% CuO nanoparticles displayed low toxicity to human fibroblasts and exhibited good biocompatibility. Wounds created in rats and treated with the CMS@2%CuO nanocomposite hydrogel healed within 13 days, whereas wounds were still present when treated for the same time-period with CMS only. The impact of antibacterial and antioxidant activities on accelerating wound healing could be ascribed to the antibacterial and antioxidant activities of the nanocomposite hydrogel. Incorporation of CuO nanoparticles in the hydrogel improved its antibacterial properties, antioxidant activity, and degree of swelling. The present nanocomposite hydrogel has the potential to be used clinically as a novel wound healing material.


Assuntos
Antibacterianos/química , Antioxidantes/química , Cobre/química , Hidrogéis/química , Nanopartículas/química , Amido/análogos & derivados , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Células Cultivadas , Quitosana/química , Fibroblastos/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Nanocompostos/química , Ratos , Ratos Wistar , Amido/química , Difração de Raios X
8.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803967

RESUMO

The life expectancy of patients with high-grade glioma (HGG) has not improved in decades. One of the crucial tools to enable future improvement is advanced models that faithfully recapitulate the tumour microenvironment; they can be used for high-throughput screening that in future may enable accurate personalised drug screens. Currently, advanced models are crucial for identifying and understanding potential new targets, assessing new chemotherapeutic compounds or other treatment modalities. Recently, various methodologies have come into use that have allowed the validation of complex models-namely, spheroids, tumouroids, hydrogel-embedded cultures (matrix-supported) and advanced bioengineered cultures assembled with bioprinting and microfluidics. This review is designed to present the state of advanced models of HGG, whilst focusing as much as is possible on the paediatric form of the disease. The reality remains, however, that paediatric HGG (pHGG) models are years behind those of adult HGG. Our goal is to bring this to light in the hope that pGBM models can be improved upon.


Assuntos
Antineoplásicos/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Glioblastoma/tratamento farmacológico , Esferoides Celulares/efeitos dos fármacos , Adulto , Antineoplásicos/química , Bioimpressão/métodos , Criança , Glioblastoma/patologia , Humanos , Hidrogéis/química , Hidrogéis/uso terapêutico , Microfluídica/métodos , Microambiente Tumoral/efeitos dos fármacos
9.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803999

RESUMO

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 µL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.


Assuntos
Ácido Hialurônico/farmacologia , Degeneração do Disco Intervertebral/terapia , Disco Intervertebral/transplante , Queratina-19/genética , Transplante de Células-Tronco Mesenquimais , Animais , Batroxobina/farmacologia , Bovinos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Hidrogéis/química , Hidrogéis/farmacologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Células-Tronco Mesenquimais/citologia , Núcleo Pulposo/crescimento & desenvolvimento , Núcleo Pulposo/transplante , Técnicas de Cultura de Órgãos , Plasma Rico em Plaquetas/química
10.
Int J Mol Sci ; 22(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668410

RESUMO

Supramolecular hydrogels formed by self-assembly of low-molecular-weight amphiphiles (hydrogelators) have attracted significant attention, as smart and soft materials. However, most of the observed stimuli-responsive behaviour of these supramolecular hydrogels are limited to gel-sol transitions. In this study, we present bola-amphiphilic glycosylated lipopeptide-type supramolecular hydrogelators that exhibit reversible thermochromism along with a gel-sol transition. The bola-amphiphiles have mono-, di-, tri- or tetra-phenylalanine (F) as a short peptide moiety. We investigate and discuss the effects of the number of F residues on the gelation ability and the morphology of the self-assembled nanostructures.


Assuntos
Hidrogéis , Lipopeptídeos , Cor , Hidrogéis/síntese química , Hidrogéis/química , Lipopeptídeos/síntese química , Lipopeptídeos/química , Transição de Fase
11.
Nat Commun ; 12(1): 1670, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723267

RESUMO

Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-ß (TGFß) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFß signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFß can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-ß inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.


Assuntos
Cicatriz/terapia , Hidrogéis/farmacologia , Iminas/química , Iminas/efeitos da radiação , Cicatrização/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Cicatriz/patologia , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Feminino , Fibroblastos , Masculino , Camundongos , Coelhos , Transdução de Sinais , Pele/patologia , Sus scrofa , Fator de Crescimento Transformador beta/efeitos dos fármacos
12.
Cell Prolif ; 54(4): e13016, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33660290

RESUMO

OBJECTIVES: Mouse incisor mesenchymal stem cells (MSCs) have self-renewal ability and osteo/odontogenic differentiation potential. However, the mechanism controlling the continuous self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs remains unclear. Special AT-rich sequence-binding protein 2 (SATB2) positively regulates craniofacial patterning, bone development and regeneration, whereas SATB2 deletion or mutation leads to craniomaxillofacial dysplasia and delayed tooth and root development, similar to bone morphogenetic protein (BMP) loss-of-function phenotypes. However, the detailed mechanism underlying the SATB2 role in odontogenic MSCs is poorly understood. The aim of this study was to investigate whether SATB2 can regulate self-renewal and osteo/odontogenic differentiation of odontogenic MSCs. MATERIALS AND METHODS: Satb2 expression was detected in the rapidly renewing mouse incisor mesenchyme by immunofluorescence staining, quantitative RT-PCR and Western blot analysis. Ad-Satb2 and Ad-siSatb2 were constructed to evaluate the effect of Satb2 on odontogenic MSCs self-renewal and osteo/odontogenic differentiation properties and the potential role of Satb2 with the osteogenic factor bone morphogenetic protein 9 (Bmp9) in vitro and in vivo. RESULTS: Satb2 was found to be expressed in mesenchymal cells and pre-odontoblasts/odontoblasts. We further discovered that Satb2 effectively enhances mouse incisor MSCs self-renewal. Satb2 acted synergistically with the potent osteogenic factor Bmp9 in inducing osteo/odontogenic differentiation of mouse incisor MSCs in vitro and in vivo. CONCLUSIONS: Satb2 promotes self-renewal and osteo/odontogenic differentiation of mouse incisor MSCs. Thus, Satb2 can cooperate with Bmp9 as a new efficacious bio-factor for osteogenic regeneration and tooth engineering.


Assuntos
Diferenciação Celular , Fator 2 de Diferenciação de Crescimento/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Odontoblastos/citologia , Fatores de Transcrição/metabolismo , Adenoviridae/genética , Animais , Regeneração Óssea , Adesão Celular , Linhagem Celular , Proliferação de Células , Autorrenovação Celular , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Fator 2 de Diferenciação de Crescimento/genética , Hidrogéis/química , Incisivo/citologia , Proteínas de Ligação à Região de Interação com a Matriz/antagonistas & inibidores , Proteínas de Ligação à Região de Interação com a Matriz/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Odontoblastos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Tecidos Suporte/química , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética
13.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670029

RESUMO

Hair follicle morphogenesis is heavily dependent on reciprocal, sequential, and epithelial-mesenchymal interaction (EMI) between epidermal stem cells and the specialized cells of the underlying mesenchyme, which aggregate to form the dermal condensate (DC) and will later become the dermal papilla (DP). Similar models were developed with a co-culture of keratinocytes and DP cells. Previous studies have demonstrated that co-culture with keratinocytes maintains the in vivo characteristics of the DP. However, it is often challenging to develop three-dimensional (3D) DP and keratinocyte co-culture models for long term in vitro studies, due to the poor intercellular adherence between keratinocytes. Keratinocytes exhibit exfoliative behavior, and the integrity of the DP and keratinocyte co-cultured spheroids cannot be maintained over prolonged culture. Short durations of culture are unable to sufficiently allow the differentiation and re-programming of the keratinocytes into hair follicular fate by the DP. In this study, we explored a microgel array approach fabricated with two different hydrogel systems. Using poly (ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA), we compare their effects on maintaining the integrity of the cultures and their expression of important genes responsible for hair follicle morphogenesis, namely Wnt10A, Wnt10B, and Shh, over prolonged duration. We discovered that low attachment surfaces such as PEGDA result in the exfoliation of keratinocytes and were not suitable for long-term culture. GelMA, on the hand, was able to sustain the integrity of co-cultures and showed higher expression of the morphogens overtime.


Assuntos
Derme/citologia , Queratinócitos/citologia , Microgéis/química , Polietilenoglicóis/farmacologia , Adesão Celular/efeitos dos fármacos , Agregação Celular/efeitos dos fármacos , Linhagem Celular , Técnicas de Cocultura , Proteínas de Fluorescência Verde/metabolismo , /efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Proteínas Luminescentes/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Proteínas Wnt/metabolismo
14.
Nat Commun ; 12(1): 1412, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658506

RESUMO

Cardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural "mold" for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/administração & dosagem , Infarto do Miocárdio/terapia , Animais , Procedimentos Cirúrgicos Cardíacos , Diferenciação Celular/fisiologia , Exossomos/metabolismo , Matriz Extracelular/química , Hidrogéis/química , Células-Tronco Pluripotentes Induzidas/transplante , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Camundongos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Pericárdio , Ratos , Suínos
15.
Int J Nanomedicine ; 16: 1617-1630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688182

RESUMO

Introduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil. Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the "solvent-switch" method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN®60 and SPAN®60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays. Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20-40 min) and the drug release (16-28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20-40%) after 72 h. Empty HGs and NGs show a high cell viability (>95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49-57%) and 72 h (7-25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug. Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Nanogéis/química , Peptídeos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Endocitose/efeitos dos fármacos , Humanos
16.
Carbohydr Polym ; 259: 117696, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33673985

RESUMO

Doxorubicin (DOX), an anthracycline drug, is widely used for the treatment of several cancers like osteosarcoma, cervical carcinoma, breast cancer, etc. DOX lacks target specificity; thereby it also affects normal cells thus resulting in several side-effects. A drug delivery system (DDS) can be used to deliver the drug in a controlled and sustained manner at a targeted site within the body. Various DDS like nanoemulsions, polymeric nanoparticles, and liposomes are used for loading DOX. Alginate, a polysaccharide is widely used for fabricating DDS due to its biodegradable and bio-compatible properties. Alginates, in combination with other biomaterials, have been extensively used as a novel drug delivery carrier for DOX. Alginate provides a platform for drug delivery in different forms like hydrogels, nanogels, nanoparticles, microparticles, graphene oxide systems, magnetic systems, etc. Herein, we briefly describe alginate in combination with other materials as a nanocarrier for targeted delivery of DOX for anti-cancer treatment.


Assuntos
Alginatos/química , Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Hidrogéis/química , Nanogéis/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia
17.
Carbohydr Polym ; 259: 117707, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33673987

RESUMO

Chitin hydrogels have multiple advantages of nontoxicity, biocompatibility, biodegradability, and three-dimensional hydrophilic polymer network structure similar to the macromolecular biological tissue. However, the mechanical strength of chitin hydrogels is relatively weak. Construction of chitin hydrogels with high mechanical strength and good biocompatibility is essential for the successful applications in biomedical field. Herein, we developed double crosslinked chitin hydrogels by dissolving chitin in KOH/urea aqueous solution with freezing-thawing process, then using KH560 as cross-linking agent and coagulating in ethanol solution at low temperature. The obtained chitin/ KH560 (CK) hydrogels displayed good transparency and toughness with compressed nanofibrous network and porous structure woven with chitin nanofibers. Moreover, the optimal CK hydrogels exhibited excellent mechanical properties (σb = 1.92 ± 0.21 Mpa; εb = 71 ± 5 %), high swelling ratio, excellent blood compatibility, biocompatibility and biodegradability, which fulfill the requirements of biomedical materials and showing potential applications in biomedicine.


Assuntos
Materiais Biocompatíveis/química , Quitina/química , Reagentes para Ligações Cruzadas/química , Hidrogéis/química , Animais , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Força Compressiva , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Camundongos , Nanofibras/química , Porosidade , Coelhos
18.
Carbohydr Polym ; 259: 117716, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33673992

RESUMO

We report on a procedure for the preparation, printing and curing of antibacterial poly(N-isopropylacrylamide) nanocellulose-reinforced hydrogels. These composites present a highly anisotropic microstructure which allows to control and modulate the resulting mechanical properties. The incorporation of such nanoparticles enables us to modify both the strength and the humidity-dependent swelling direction of printed parts, offering a fourth-dimensional property to the resulting composite. Antibacterial properties of the hydrogels were obtained by incorporating the functionalized peptide ε-polylysine, modified with the addition of a methacrylate group to ensure UV-immobilization. We highlight the relevance of well-adapted viscoelastic properties of our material for 3D printing by direct ink writing of self-supporting complex structures reaching inclination angles of 45°. The addition of cellulose nanoparticles, the overall ink composition and the printing parameters strongly determine the resulting degree of orientation. The achieved control over the anisotropic swelling properties paves the way to complex three-dimensional structures with programmable actuation.


Assuntos
Antibacterianos/química , Celulose/química , Hidrogéis/química , Nanopartículas/química , Resinas Acrílicas/química , Antibacterianos/farmacologia , Força Compressiva , Escherichia coli/efeitos dos fármacos , Hidrogéis/farmacologia , Tinta , Impressão Tridimensional , Reologia , Staphylococcus/efeitos dos fármacos
19.
Carbohydr Polym ; 259: 117735, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33673996

RESUMO

This review examines investigations into the functionalization of polysaccharides by substituents containing multiple (CC) bonds and thiol (SH) groups that are prone to (co)polymerization in the presence of thermal, redox and photoinitiators or Michael addition reactions. A comparative analysis of the approaches to grafting the mentioned substituents onto the polysaccharide macromolecules was conducted. The use of the modified polysaccharides for the design of the 3D structures, including for the development of the pore bearing matrixes of cells or scaffolds utilized in regenerative medicine was examined. These modified polymers were also examined toward the design of excipient matrixes in pharmacological compositions, including with controllable release of active pharmaceuticals, as wel as of antibacterial and antifungal agents and others. In addition, a few examples of the use of modified derivatives in other areas are given.


Assuntos
Polissacarídeos/química , Compostos de Sulfidrila/química , Engenharia Tecidual , Materiais Biocompatíveis/química , Hidrogéis/química , Medicina Regenerativa
20.
Carbohydr Polym ; 259: 117737, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33673998

RESUMO

Tough hydrogels with shape memory property are highly desirable for actuators and smart engineering materials. Herein, super-tough polyacrylamide/iota-carrageenan double-network hydrogels were synthesized via a one-pot radical polymerization and strengthened by incorporating bacterial cellulose microclusters, through the intermolecular hydrogen bonds and topological interlock between microclusters and polymer network. Such hydrogels were able to withstand over 200 kPa of tensile stress, or be stretched over 27 times of initial length, and reached a high toughness of ∼2000 kJ/m3. By tension-drying and post-annealing treatments on the strongest hydrogel, dry strands were fabricated to withstand over 100 MPa of tensile stress. Moreover, these strands presented water-stimulated shape memory by a recovery ratio of 84.3 % in 4 min. Based on these characteristics, this super-tough hydrogel may serve as smart textile or actuator for a variety of applications.


Assuntos
Celulose/química , Hidrogéis/química , Resinas Acrílicas/química , Carragenina/química , Porosidade , Resistência à Tração
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