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2.
Int J Biol Macromol ; 176: 26-36, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33529634

RESUMO

This study describes the development of scaffolds based on carboxyethyl chitosan (CEC) and different oxidized cashew gums (CGOx) for tissue engineering (TE) applications. After the physico-chemical characterizations of CEC and CGOx (oxidation degree of 20, 35 and 50%), these macromolecules were used for producing the CGOx-CEC hydrogels through a Schiff base reaction, in the absence of any crosslinking agent. The CGOx-CEC scaffolds obtained after a freeze-drying process were characterized for their morphology, mechanical properties, swelling ability, degradation, and porosity. Those revealed to be highly porous (25-65%), and showed a stable swelling behavior, as well as degradation properties in the absence of enzymes. The use of the cashew gum with higher degree of oxidation led to scaffolds with higher crosslinking densities and increased compressive modulus. None of the hydrogels show cytotoxicity during the 14 days of incubation. Considering all the properties mentioned, these scaffolds are excellent candidates for soft tissue regeneration, owing to the use of eco-friendly starting materials and the easy tuning of their properties.


Assuntos
Quitosana/análogos & derivados , Gomas Vegetais/química , Tecidos Suporte/química , Anacardium/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biomecânicos , Linhagem Celular , Quitosana/síntese química , Quitosana/química , Força Compressiva , Reagentes para Ligações Cruzadas , Hidrogéis , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Estrutura Molecular , Oxirredução , Gomas Vegetais/síntese química , Gomas Vegetais/toxicidade , Porosidade , Engenharia Tecidual , Tecidos Suporte/efeitos adversos
3.
Int J Mol Sci ; 22(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478069

RESUMO

It is well known that living cells interact mechanically with their microenvironment. Many basic cell functions, like migration, proliferation, gene expression, and differentiation, are influenced by external forces exerted on the cell. That is why it is extremely important to study how mechanical properties of the culture substrate influence the cellular molecular regulatory pathways. Optical microscopy is one of the most common experimental method used to visualize and study cellular processes. Confocal microscopy allows to observe changes in the 3D organization of the cytoskeleton in response to a precise mechanical stimulus applied with, for example, a bead trapped with optical tweezers. Optical tweezers-based method (OT) is a microrheological technique which employs a focused laser beam and polystyrene or latex beads to study mechanical properties of biological systems. Latex beads, functionalized with a specific protein, can interact with proteins located on the surface of the cellular membrane. Such interaction can significantly affect the cell's behavior. In this work, we demonstrate that beads alone, placed on the cell surface, significantly change the architecture of actin, microtubule, and intermediate filaments. We also show that the observed molecular response to such stimulus depends on the duration of the cell-bead interaction. Application of cytoskeletal drugs: cytochalasin D, jasplakinolide, and docetaxel, abrogates remodeling effects of the cytoskeleton. More important, when cells are plated on elastic substrates, which mimic the mechanical properties of physiological cellular environment, we observe formation of novel, "cup-like" structures formed by the microtubule cytoskeleton upon interaction with latex beads. These results provide new insights into the function of the microtubule cytoskeleton. Based on these results, we conclude that rigidity of the substrate significantly affects the cellular processes related to every component of the cytoskeleton, especially their architecture.


Assuntos
Adesão Celular/fisiologia , Citoesqueleto/metabolismo , Fibroblastos/metabolismo , Estresse Mecânico , Actinas/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/fisiologia , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Elasticidade/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fibroblastos/ultraestrutura , Dureza/fisiologia , Camundongos , Microscopia Confocal , Microesferas , Microtúbulos/metabolismo , Células Swiss 3T3 , Tecidos Suporte/efeitos adversos , Tecidos Suporte/química
4.
Int J Biol Macromol ; 166: 986-998, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152357

RESUMO

As a member of the polyhydroxyalkanoate (PHAs) family, Poly(3-hydroxybutyrate) (PHB) has attracted much attention for a variety of medical applications because of its desirable properties such as high biocompatibility, nontoxic degradation products and high mechanical strength in comparison to other polymers in different fields including tissue engineering. There are different approaches such as making PHB alloy scaffolds, using PHB as a coating for ceramic-based scaffolds and producing composite scaffolds by using a mixture of PHB with ceramic particles utilized to improve hydrophobicity, degradation rate and brittleness. In this review, different applications of PHB, its alloys and composites in tissue engineering are explained based on the common methods of fabrication such as polymeric sponge replication, electrospinning and salt leaching.


Assuntos
Hidroxibutiratos/química , Poliésteres/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Cerâmica/química , Humanos , Nanocompostos/química , Neurônios/citologia , Neurônios/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Pele/citologia , Pele/efeitos dos fármacos , Tecidos Suporte/efeitos adversos
5.
Int J Biol Macromol ; 166: 999-1008, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166555

RESUMO

INTRODUCTION: Development of a tissue-engineered construct for hepatic regeneration remains a challenging task due to the lack of an optimum environment that support the growth of hepatocytes. Hydrogel systems possess many similarities with tissues and have the potential to provide the microenvironment essential for the cells to grow, proliferate, and remain functionally active. METHODS: In this work, fibrin (FIB) incorporated injectable alginate dialdehyde (ADA) - gelatin (G) hydrogel was explored as a matrix for liver tissue engineering. ADA was prepared by periodate oxidation of sodium alginate. An injectable formulation of ADA-G-FIB hydrogel was prepared and characterized by FTIR spectroscopy, Scanning Electron Microscopy, and Micro-Computed Tomography. HepG2 cells were cultured on the hydrogel system; cellular growth and functions were analyzed using various functional markers. RESULTS: FTIR spectra of ADA-G-FIB depicted the formation of Schiff's base at 1608.53 cm-1 with a gelation time of 3 min. ADA-G-FIB depicted a 3D surface topography with a pore size in the range of 100-200 µm. The non-cytotoxic nature of the scaffold was demonstrated using L929 cells and more than 80 % cell viability was observed. Functional analysis of cultured HepG2 cells demonstrated ICG uptake, albumin synthesis, CYP-P450 expression, and ammonia clearance. CONCLUSION: ADA-G-FIB hydrogel can be used as an effective 3D scaffold system for liver tissue engineering.


Assuntos
Alginatos/química , Fibrina/análogos & derivados , Hidrogéis/síntese química , Regeneração Hepática , Engenharia Tecidual/métodos , Tecidos Suporte/química , Aldeídos/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Gelatina/química , Células Hep G2 , Humanos , Hidrogéis/efeitos adversos , Camundongos , Tecidos Suporte/efeitos adversos
6.
Int J Mol Sci ; 21(24)2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33322781

RESUMO

Amine-coated biodegradable materials based on synthetic polymers have a great potential for tissue remodeling and regeneration because of their excellent processability and bioactivity. In the present study, we have investigated the influence of various chemical compositions of amine plasma polymer (PP) coatings and the influence of the substrate morphology, represented by polystyrene culture dishes and polycaprolactone nanofibers (PCL NFs), on the behavior of vascular smooth muscle cells (VSMCs). Although all amine-PP coatings improved the initial adhesion of VSMCs, 7-day long cultivation revealed a clear preference for the coating containing about 15 at.% of nitrogen (CPA-33). The CPA-33 coating demonstrated the ideal combination of good water stability, a sufficient amine group content, and favorable surface wettability and morphology. The nanostructured morphology of amine-PP-coated PCL NFs successfully slowed the proliferation rate of VSMCs, which is essential in preventing restenosis of vascular replacements in vivo. At the same time, CPA-33-coated PCL NFs supported the continuous proliferation of VSMCs during 7-day long cultivation, with no significant increase in cytokine secretion by RAW 264.7 macrophages. The CPA-33 coating deposited on biodegradable PCL NFs therefore seems to be a promising material for manufacturing small-diameter vascular grafts, which are still lacking on the current market.


Assuntos
Aminas/química , Materiais Revestidos Biocompatíveis/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Nanofibras/química , Plasma/química , Polímeros/química , Aminas/efeitos adversos , Aminas/imunologia , Aminas/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/efeitos adversos , Materiais Revestidos Biocompatíveis/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/crescimento & desenvolvimento , Miócitos de Músculo Liso/metabolismo , Nanofibras/efeitos adversos , Espectroscopia Fotoeletrônica , Plasma/imunologia , Poliésteres/química , Polímeros/efeitos adversos , Polímeros/farmacologia , Células RAW 264.7 , Ratos , Propriedades de Superfície/efeitos dos fármacos , Tecidos Suporte/efeitos adversos , Tecidos Suporte/química
7.
Can J Surg ; 63(6): E533-E536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211643

RESUMO

SUMMARY: Biologic mesh is preferred over synthetic mesh for complex and contaminated abdominal wall repairs; however, there are very little data on the risks and complications associated with its use. We report the case of a 67-year-old man with failed synthetic mesh repair for recurrent ventral hernia, who subsequently required an abdominal wall reconstruction (AWR), including the intraperitoneal sublay of noncrosslinked biologic mesh. His postoperative course was complicated with catastrophic sepsis and sustained hemodynamic instability, responding only to mesh explantation. The biologic mesh was subsequently noted to be histologically infected with invasive Candida albicans. Although noncrosslinked biologic mesh is a valuable adjunct to AWR, it is not infection-resistant. Although it is rare, infection of any foreign tissue, including biologic mesh, can occur in the setting of complex ventral abdominal wall repairs. Clinicians should be watchful for such infections in complex repairs as they may require biologic mesh explantation for clinical recovery.


Assuntos
Parede Abdominal/cirurgia , Candida albicans/isolamento & purificação , Candidíase Invasiva/cirurgia , Remoção de Dispositivo , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Infecção da Ferida Cirúrgica/cirurgia , Tecidos Suporte/microbiologia , Idoso , Animais , Candidíase Invasiva/diagnóstico , Candidíase Invasiva/microbiologia , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Humanos , Masculino , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Recidiva , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/microbiologia , Suínos , Tecidos Suporte/efeitos adversos
8.
Acta Histochem ; 122(7): 151615, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33066837

RESUMO

Modification of Polylactic acid (PLA), a biopolymer, is a strategy still to be fully explored for the next generation of bioresorbable vascular stent (BVS) biomaterials. With this focus, inclusions upto 5% of Polycaprolactone (PCL) and Magnesium in PLA were tested in the rat subcutaneous model and their cellular and tissue interactions characterized, specifically with respect to inflammatory response, angiogenesis and capsularization. The cytokines IL6, TNF Alpha and IL-1Beta were estimated in the peri-implant tissue, all of which showed a non-significant difference between the non-implanted animals and those containing PLA by 8 weeks, speaking to the benign nature of PLA as an implant biomaterial. Both modified materials, had increased macrophage counts and cytokine levels, except IL6 at 8 weeks. Vascularization only at 8 weeks in PLA PCL containing tissue was significantly higher than pure PLA, which may be more carefully controlled along with the material hydrophobicity for possible efforts towards therapeutic angiogenesis. Capsule thickness, measured by staining with both Hematoxylin & Eosin and Masson's Trichome did not show any differences between materials, including PLA.


Assuntos
Materiais Biocompatíveis , Poliésteres/efeitos adversos , Stents , Tecidos Suporte , Animais , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/metabolismo , Anormalidades Cardiovasculares/cirurgia , Poliésteres/metabolismo , Ratos , Tecidos Suporte/efeitos adversos
9.
Int J Mol Sci ; 21(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066080

RESUMO

Poly(l-lactide-co-glycolide) (PLGA) porous scaffolds were modified with collagen type I (PLGA/coll) or hydroxyapatite (PLGA/HAp) and implanted in rabbits osteochondral defects to check their biocompatibility and bone tissue regeneration potential. The scaffolds were fabricated using solvent casting/particulate leaching method. Their total porosity was 85% and the pore size was in the range of 250-320 µm. The physico-chemical properties of the scaffolds were evaluated using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), sessile drop, and compression tests. Three types of the scaffolds (unmodified PLGA, PLGA/coll, and PLGA/HAp) were implanted into the defects created in New Zealand rabbit femoral trochlears; empty defect acted as control. Samples were extracted after 1, 4, 12, and 26 weeks from the implantation, evaluated using micro-computed tomography (µCT), and stained by Masson-Goldner and hematoxylin-eosin. The results showed that the proposed method is suitable for fabrication of highly porous PLGA scaffolds. Effective deposition of both coll and HAp was confirmed on all surfaces of the pores through the entire scaffold volume. In the in vivo model, PLGA and PLGA/HAp scaffolds enhanced tissue ingrowth as shown by histological and morphometric analyses. Bone formation was the highest for PLGA/HAp scaffolds as evidenced by µCT. Neo-tissue formation in the defect site was well correlated with degradation kinetics of the scaffold material. Interestingly, around PLGA/coll extensive inflammation and inhibited tissue healing were detected, presumably due to immunological response of the host towards collagen of bovine origin. To summarize, PLGA scaffolds modified with HAp are the most promising materials for bone tissue regeneration.


Assuntos
Osteocondrose/cirurgia , Poliglactina 910/química , Tecidos Suporte/química , Animais , Regeneração Óssea , Colágeno/química , Hidroxiapatitas/química , Porosidade , Coelhos , Tecidos Suporte/efeitos adversos
10.
Int J Mol Sci ; 21(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066403

RESUMO

The effective management of tissue integration and immunological responses to transplants decisively co-determines the success of soft and hard tissue reconstruction. The aim of this in vivo study was to evaluate the eligibility of extracorporeal shock wave therapy (ESWT) with respect to its ability to modulate angiogenesis and immune response to a collagen matrix (CM) for tissue engineering in the chorioallantoic membrane (CAM) assay, which is performed with fertilized chicken eggs. CM were placed on the CAM on embryonic development day (EDD) 7; at EDD-10, ESWT was conducted at 0.12 mJ/mm2 with 500 impulses each. One and four days later, angiogenesis represented by vascularized area, vessel density, and vessel junctions as well as HIF-1α and VEGF gene expression were evaluated. Furthermore, immune response (iNOS2, MMP-9, and MMP-13 via qPCR) was assessed and compared between ESWT- and non-ESWT-groups. At EDD-14, the vascularized area (+115% vs. +26%) and the increase in vessel junctions (+751% vs. +363%) were significantly higher in the ESWT-group. ESWT significantly increased MMP-9 gene expression at EDD-11 and significantly decreased MMP-13 gene expression at EDD-14 as compared to the controls. Using the CAM assay, an enhanced angiogenesis and neovascularization in CM after ESWT were observed. Furthermore, ESWT could reduce the inflammatory activity after a latency of four days.


Assuntos
Colágeno/imunologia , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neovascularização Fisiológica , Engenharia Tecidual/métodos , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/imunologia , Colágeno/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Tecidos Suporte/efeitos adversos , Tecidos Suporte/química , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
J Mater Sci Mater Med ; 31(8): 76, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32761269

RESUMO

Vascular grafts prepared from synthetic polymers have serious shortcomings that can be resolved by surface modification, such as by immobilizing heparin. In this study, the mechanical properties, biocompatibility, anticoagulation property, and water contact angle of two heparin-conjugated poly(ε-caprolactone) scaffolds (PCL-hexamethylendiamine-heparin, PCL-HMD-H. PCL-lysine-heparin, PCL-LYS-H) were compared to identify a preferred heparin conjugation method. An evaluation of the subcutaneous tissue biocompatibility of the scaffolds demonstrated that PCL-HMD-H had better endothelial cell proliferation than the PCL-LYS-H and was therefore a promising scaffold candidate for use in vascular tissue-engineering.


Assuntos
Heparina/química , Poliésteres/química , Tela Subcutânea/efeitos dos fármacos , Tecidos Suporte , Animais , Prótese Vascular/efeitos adversos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Heparina/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Teste de Materiais , Modelos Animais , Poliésteres/farmacologia , Polímeros/química , Polímeros/farmacologia , Implantação de Prótese/métodos , Ratos , Ratos Wistar , Engenharia Tecidual/métodos , Tecidos Suporte/efeitos adversos , Tecidos Suporte/química
12.
Int J Mol Sci ; 21(16)2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32824305

RESUMO

In order to improve the cell adhesion on poly(ε-caprolactone) (PCL) scaffolds, poly(ethylene-co-vinyl alcohol) (E-VAL) which has hydroxyl groups capable of developing hydrogen bonds with celling was blended with this polymer. To reach this goal, a series of E-VAL/PCL blends with different compositions were prepared by the solvent casting method. The miscibility of the polymer blend was proved by differential scanning calorimetry and Fourier-transform infrared spectroscopy spectrometry. Furthermore, the mechanical properties of the polymer blends were assessed in their wet state by dynamic mechanical analysis. The surfaces wettability of blends and their components were examined through static contact angle measurements. The pore interconnections in the resulted scaffolds were achieved by the incorporation of naphthalene microparticles which were used as porogen and then removed in its gas state by sublimation under reduced pressure. The presence of pores interconnected inside the polymeric materials and their surface morphologies was examined by scanning electron microscopy. The in-vitro cytotoxicity and cell adhesion on the prepared materials were examined by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.


Assuntos
Poliésteres/química , Polietilenoglicóis/química , Álcool de Polivinil/análogos & derivados , Tecidos Suporte/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Porosidade , Tecidos Suporte/efeitos adversos , Molhabilidade
13.
Mar Drugs ; 18(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796603

RESUMO

Scaffold material is essential in providing mechanical support to tissue, allowing stem cells to improve their function in the healing and repair of trauma sites and tissue regeneration. The scaffold aids cell organization in the damaged tissue. It serves and allows bio mimicking the mechanical and biological properties of the target tissue and facilitates cell proliferation and differentiation at the regeneration site. In this study, the developed and assayed bio-composite made of unique collagen fibers and alginate hydrogel supports the function of cells around the implanted material. We used an in vivo rat model to study the scaffold effects when transplanted subcutaneously and as an augment for tendon repair. Animals' well-being was measured by their weight and daily activity post scaffold transplantation during their recovery. At the end of the experiment, the bio-composite was histologically examined, and the surrounding tissues around the implant were evaluated for inflammation reaction and scarring tissue. In the histology, the formation of granulation tissue and fibroblasts that were part of the inclusion process of the implanted material were noted. At the transplanted sites, inflammatory cells, such as plasma cells, macrophages, and giant cells, were also observed as expected at this time point post transplantation. This study demonstrated not only the collagen-alginate device biocompatibility, with no cytotoxic effects on the analyzed rats, but also that the 3D structure enables cell migration and new blood vessel formation needed for tissue repair. Overall, the results of the current study proved for the first time that the implantable scaffold for long-term confirms the well-being of these rats and is correspondence to biocompatibility ISO standards and can be further developed for medical devices application.


Assuntos
Antozoários/química , Materiais Biocompatíveis , Colágenos Fibrilares/química , Implantes Experimentais , Procedimentos Ortopédicos/instrumentação , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Tecidos Suporte , Alginatos/química , Animais , Materiais Biocompatíveis/toxicidade , Modelos Animais de Doenças , Colágenos Fibrilares/isolamento & purificação , Colágenos Fibrilares/toxicidade , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Hidrogéis , Implantes Experimentais/efeitos adversos , Masculino , Procedimentos Ortopédicos/efeitos adversos , Desenho de Prótese , Ratos Wistar , Manguito Rotador/patologia , Lesões do Manguito Rotador/patologia , Fatores de Tempo , Tecidos Suporte/efeitos adversos , Cicatrização
14.
Int J Mol Sci ; 21(17)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32825046

RESUMO

The combination of induced pluripotent stem cell (iPSC) technology and 3D cell culture creates a unique possibility for the generation of organoids that mimic human organs in in vitro cultures. The use of iPS cells in organoid cultures enables the differentiation of cells into dopaminergic neurons, also found in the human midbrain. However, long-lasting organoid cultures often cause necrosis within organoids. In this work, we present carbon fibers (CFs) for medical use as a new type of scaffold for organoid culture, comparing them to a previously tested copolymer poly-(lactic-co-glycolic acid) (PLGA) scaffold. We verified the physicochemical properties of CF scaffolds compared to PLGA in improving the efficiency of iPSC differentiation within organoids. The physicochemical properties of carbon scaffolds such as porosity, microstructure, or stability in the cellular environment make them a convenient material for creating in vitro organoid models. Through screening several genes expressed during the differentiation of organoids at crucial brain stages of development, we found that there is a correlation between PITX3, one of the key regulators of terminal differentiation, and the survival of midbrain dopaminergic (mDA) neurons and tyrosine hydroxylase (TH) gene expression. This makes organoids formed on carbon scaffolds an improved model containing mDA neurons convenient for studying midbrain-associated neurodegenerative diseases such as Parkinson's disease.


Assuntos
Fibra de Carbono/química , Células-Tronco Pluripotentes Induzidas/citologia , Mesencéfalo/citologia , Organoides/citologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Resinas Acrílicas/química , Diferenciação Celular , Células Cultivadas , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tecidos Suporte/efeitos adversos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
15.
PLoS One ; 15(7): e0235673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645029

RESUMO

BACKGROUND AND OBJECTIVES: This study sought to compare clinical outcomes between bioresorbable scaffolds (BRS) and durable polymer everolimus-eluting metallic stents (DP-EES) in patients with acute myocardial infarction (AMI) undergoing successful percutaneous coronary intervention (PCI). METHODS: From March 2016 to October 2017, 952 patients with AMI without cardiogenic shock undergoing successful PCI with BRS (n = 136) or DP-EES (n = 816) were enrolled from a multicenter, observational Korea Acute Myocardial Infarction Registry. RESULTS: In the crude population, there was no significant difference in the 1-year rate of device-oriented composite endpoint (DOCE) and device thrombosis between the BRS and DP-EES groups (2.2% vs. 4.8%, hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.13-1.41, p = 0.163; 0.7% vs. 0.5%, HR 1.49, 95% CI 0.16-13.4, p = 0.719, respectively). BRS implantation was opted in younger patients (53.7 vs. 62.6 years, p < 0.001) with low-risk profiles, and intravascular image-guided PCI was more preferred in the BRS group (60.3% vs. 27.2%, p < 0.001). CONCLUSIONS: At 1-year follow-up, no differences in the rate of DOCE and device thrombosis were observed between patients with AMI treated with BRS and those treated with DP-EES. Our data suggest that imaging-guided BRS implantation in young patients with low risk profiles could be a reasonable strategy in the setting of AMI.


Assuntos
Implantes Absorvíveis/efeitos adversos , Stents Farmacológicos/efeitos adversos , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Doença Aguda/terapia , Adulto , Idoso , Fármacos Cardiovasculares/uso terapêutico , Determinação de Ponto Final , Everolimo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Modelos de Riscos Proporcionais , República da Coreia , Trombose/etiologia , Tecidos Suporte/efeitos adversos , Resultado do Tratamento
16.
Mol Biol Rep ; 47(7): 5145-5154, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32562174

RESUMO

Proper bony tissue regeneration requires mechanical stabilization, an osteogenic biological activity and appropriate scaffolds. The latter two elements can be combined in a hydrogel format for effective delivery, so it can readily adapt to the architecture of the defect. We evaluated a Good Manufacturing Practice-compliant formulation composed of bone marrow-derived mesenchymal stromal cells in combination with bone particles (Ø = 0.25 to 1 µm) and fibrin, which can be readily translated into the clinical setting for the treatment of bone defects, as an alternative to bone tissue autografts. Remarkably, cells survived with unaltered phenotype (CD73+, CD90+, CD105+, CD31-, CD45-) and retained their osteogenic capacity up to 48 h after being combined with hydrogel and bone particles, thus demonstrating the stability of their identity and potency. Moreover, in a subchronic toxicity in vivo study, no toxicity was observed upon subcutaneous administration in athymic mice and signs of osteogenesis and vascularization were detected 2 months after administration. The preclinical data gathered in the present work, in compliance with current quality and regulatory requirements, demonstrated the feasibility of formulating an osteogenic cell-based tissue engineering product with a defined profile including identity, purity and potency (in vitro and in vivo), and the stability of these attributes, which complements the preclinical package required prior to move towards its use of prior to its clinical use.


Assuntos
Hidrogéis/normas , Células-Tronco Mesenquimais/citologia , Osteogênese , Engenharia Tecidual/métodos , Tecidos Suporte/normas , Animais , Transplante Ósseo/métodos , Transplante Ósseo/normas , Células Cultivadas , Ensaios Clínicos como Assunto , Feminino , Humanos , Hidrogéis/efeitos adversos , Camundongos , Neovascularização Fisiológica , Osteoclastos/citologia , Engenharia Tecidual/normas , Tecidos Suporte/efeitos adversos
17.
Sci Rep ; 10(1): 10348, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587271

RESUMO

Foreign body reaction reflects the integration between biomaterials and host cells. At the implantation microenvironment, macrophages usually fuse into multinuclear cells, also known as foreign body giant cells, to respond to the biomaterial implants. To understand the biomaterial-induced macrophage fusion, we examined whether biomaterial alone can initiate and control the fusion rate without exogenous cytokines and chemicals. We introduced a collagen-based 3D matrix to embed Raw264.7 cell line and primary rat bone marrow-derived macrophages. We found the biomaterial-stimuli interacted regional macrophages and altered the overall fusogenic protein expressions to regulate the macrophage fusion rate. The fusion rate could be altered by modulating the cell-matrix and cell-cell adhesions. The fused macrophage morphologies, the nuclei number in the fused macrophage, and the fusion rates were matrix dependent. The phenomena were also observed in the in vivo models. These results suggest that the biomaterial-derived stimuli exert similar functions as cytokines to alter the competency of macrophage fusion as well as their drug sensitivity in the biomaterial implanted tissue environment. Furthermore, this in vitro 3D-matrix model has the potential to serve as a toolbox to predict the host tissue response on implanted biomaterials.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Adesão Celular/imunologia , Reação a Corpo Estranho/imunologia , Macrófagos/imunologia , Tecidos Suporte/efeitos adversos , Animais , Materiais Biocompatíveis/administração & dosagem , Colágeno/administração & dosagem , Colágeno/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Teste de Materiais/métodos , Camundongos , Cultura Primária de Células/métodos , Células RAW 264.7 , Ratos
18.
J Mol Neurosci ; 70(12): 1967-1976, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32436197

RESUMO

Synapses are touted as the main structural and functional components of neural cells within in the nervous system, providing tissue connectivity and integration via the formation of perineuronal nets. In the present study, we evaluated the synaptogenic activity of electrospun PLGA and PLGA-PEG nanofibers on human SH-SY5Y cells after 14 days in vitro. Electrospun PLGA and PLGA-PEG nanofibers were fabricated and physicochemical properties were examined using the HNMR technique. The cells were classified into three random groups, i.e., control (laminin-coated surface), PLGA, and PLGA-PEG. Scaffolds' features, cell morphology, attachment, and alignment were monitored by SEM imaging. We performed MTT assay to measure cell survival rate. To evaluate neurite formation and axonal outgrowth, cells were stained with an antibody against ß-tubulin III using immunofluorescence imaging. Antibodies against synapsin-1 and synaptophysin were used to explore the impact of PLGA and PLGA-PEG scaffolds on synaptogenesis and functional activity of synapses. According to SEM analysis, the PLGA-PEG scaffold had less thick nanofibers compared with the PLGA scaffold. Cell attachment, expansion, neurite outgrowth, and orientation were promoted in the PLGA-PEG group in comparison with the PLGA substrate (p < 0.05). MTT assay revealed that both scaffolds did not exert any neurotoxic effects on cell viability. Notably, PLGA-PEG surface increased cell viability compared to PLGA by time (p < 0.05). Immunofluorescence staining indicated an increased ß-tubulin III level in the PLGA-PEG group days coincided with axonal outgrowth and immature neuron marker after seven compared with the PLGA and control groups (p < 0.05). Based on our data, both synaptogenesis and functional connectivity were induced in cells plated on the PLGA-PEG surface that coincide with the increase of synapsin-1 and synaptophysin in comparsion with the PLGA and control groups (p < 0.05). Taken together, our results imply that the PLGA-PEG nanofibers could provide the desirable microenvironment to develop perineuronal net formation, contributing to efficient synaptogenesis and neuron-to-neuron crosstalk.


Assuntos
Nanofibras/química , Poliésteres/química , Polietilenoglicóis/química , Sinapses/efeitos dos fármacos , Tecidos Suporte/química , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Nanofibras/efeitos adversos , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Poliésteres/efeitos adversos , Polietilenoglicóis/efeitos adversos , Sinapses/metabolismo , Sinapsinas/metabolismo , Sinaptofisina/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte/efeitos adversos , Tubulina (Proteína)/metabolismo
19.
Coron Artery Dis ; 31(7): 578-585, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32271247

RESUMO

OBJECTIVE: To investigate the outcomes after bioresorbable scaffold (BRS) implantation in calcified coronary lesions. In calcified coronary lesions, durable metallic drug-eluting stent (DES) implantation is associated with worse clinical outcomes compared to noncalcified lesions. Although not recommended, BRSs were frequently implanted in calcified lesions in clinical practice. Their outcome is not well investigated. METHODS: Between November 2013 and January 2016, 3326 patients were enrolled in the German-Austrian ABSORB ReglstRy (GABI-R). Lesion calcification severity was classified into no (n = 1144), mild (n = 1306), and moderate-to-severe (n = 690) calcification. RESULTS: Patients with calcification were older (none: 59.1 ± 11.2 vs. mild: 61.6 ± 10.9 vs. moderate to severe: 62.4 ± 10.5 years, P < 0.001), had more diabetes (19.1 vs. 20.8 vs. 23.9%, P = 0.015), and more often had previous myocardial infarction (MI) (19.3 vs. 23.1 vs. 25.4%, P = 0.002). Despite a higher rate of postdilatations (P < 0.001), lesions with calcification had more residual stenosis (2.05 ± 9.36% vs. 3.11 ± 9.36% vs. 3.89 ± 9.39%, P < 0.001). Consequently, procedural success was achieved in 97.7 vs. 96.2 vs. 93.6% of cases in none, mild, and moderate-to-severe calcification (P < 0.001). At 24 months, cardiac death (0.3 vs. 0.7 vs. 1.6%, P = 0.009) was higher with increasing calcification. However, no significant between-group difference was observed in the incidence of target vessel MI, target vessel revascularization, or target lesion failure. The rate of probable scaffold thrombosis was significantly higher with increasing calcification. CONCLUSION: In GABI-R, ABSORB scaffolds in calcified lesions required more postdilation, led to more residual stenosis, but did not portend increased target lesion revascularization over 2 years. Nevertheless, coronary calcification severity emerged as a cardiovascular risk marker and was predictive of cardiovascular mortality. Clinicaltrial.gov NCT02066623.


Assuntos
Doença da Artéria Coronariana , Vasos Coronários , Infarto do Miocárdio , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Calcificação Vascular , Implantes Absorvíveis/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Stents Farmacológicos , Feminino , Humanos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/etiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Sistema de Registros , Índice de Gravidade de Doença , Tecidos Suporte/efeitos adversos , Calcificação Vascular/diagnóstico , Calcificação Vascular/cirurgia , Grau de Desobstrução Vascular
20.
Tissue Eng Part B Rev ; 26(5): 475-483, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32192400

RESUMO

Symptomatic stress urinary incontinence (SUI) and pelvic organ prolapse (POP) refractory to conservative management with pelvic floor muscle training or vaginal pessaries may warrant surgical intervention with different forms of biologic or synthetic material. However, in recent years, several global regulatory agencies have issued health warnings and recalled several mesh products due to an increase in complications such as mesh erosion, infection, chronic pain, and perioperative bleeding. At present, current surgical treatment strategies for SUI and POP are aimed at developing biological graft materials with similar mechanical properties to established synthetic meshes, but with improved tissue integration and minimal host response. This narrative review aims to highlight recent studies related to the development of biomimetic and biologic graft materials as alternatives to traditional synthetic materials for SUI/POP repair in female patients. We also investigate complications and technical limitations associated with synthetic mesh and biological biomaterials in conventional SUI and POP surgery. Our findings demonstrate that newly developed biologic grafts have a lower incidence of adverse events compared to synthetic biomaterials. However there remains a significant disparity between success in preclinical trials and long-term clinical translation. Further characterization on the optimal structural, integrative, and mechanical properties of biological grafts is required before they can be reliably introduced into clinical practice for SUI and POP surgery. Impact statement Our review article aims to outline the clinical history of developments and controversies associated with the use of synthetic mesh materials in the surgical treatment of stress urinary incontinence and pelvic organ prolapse, as well as highlighting recent advancements in the area of biological graft materials and their potential importance in an area that remains an enduring issue for patients and clinicians alike. This article aims to provide a concise summary of previous controversies in the field of urinary incontinence, while evaluating the future of potential biomaterials in this field.


Assuntos
Materiais Biocompatíveis/farmacologia , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/terapia , Tecidos Suporte/química , Incontinência Urinária por Estresse/complicações , Incontinência Urinária por Estresse/terapia , Animais , Materiais Biocompatíveis/efeitos adversos , Humanos , Prolapso de Órgão Pélvico/cirurgia , Tecidos Suporte/efeitos adversos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgia
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