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Lab Chip ; 19(15): 2500-2511, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31246211


Development of therapeutic approaches to treat vascular dysfunction and thrombosis at disease- and patient-specific levels is an exciting proposed direction in biomedical research. However, this cannot be achieved with animal preclinical models alone, and new in vitro techniques, like human organ-on-chips, currently lack inclusion of easily obtainable and phenotypically-similar human cell sources. Therefore, there is an unmet need to identify sources of patient primary cells and apply them in organ-on-chips to increase personalized mechanistic understanding of diseases and to assess drugs. In this study, we provide a proof-of-feasibility of utilizing blood outgrowth endothelial cells (BOECs) as a disease-specific primary cell source to analyze vascular inflammation and thrombosis in vascular organ-chips or "vessel-chips". These blood-derived BOECs express several factors that confirm their endothelial identity. The vessel-chips are cultured with BOECs from healthy or diabetic patients and form an intact 3D endothelial lumen. Inflammation of the BOEC endothelium with exogenous cytokines reveals vascular dysfunction and thrombosis in vitro similar to in vivo observations. Interestingly, our study with vessel-chips also reveals that unstimulated BOECs of type 1 diabetic pigs show phenotypic behavior of the disease - high vascular dysfunction and thrombogenicity - when compared to control BOECs or normal primary endothelial cells. These results demonstrate the potential of organ-on-chips made from autologous endothelial cells obtained from blood in modeling vascular pathologies and therapeutic outcomes at a disease and patient-specific level.

Chem Commun (Camb) ; 55(60): 8772-8775, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31172998


We introduced a new concept to the control of wetting characteristics by modulating the degree of atomic defects of two-dimensional transition metal dichalcogenide nanoassemblies of molybdenum disulfide. This work shed new light on the role of atomic vacancies on wetting characteristic that can be leveraged to develop a new class of superhydrophobic surfaces for various applications without altering their topography.

Adesão Celular , Dissulfetos/química , Células-Tronco Mesenquimais/fisiologia , Molibdênio/química , Nanoestruturas/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Molhabilidade
Adv Healthc Mater ; 8(11): e1801553, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31066517


A nanoengineered bioink loaded with therapeutic proteins is designed to direct cell function in a 3D printed construct. The bioink is developed from a hydrolytically degradable polymer and 2D synthetic nanoparticle. The synthesis of poly(ethylene glycol)-dithiothreitol (PEGDTT) via a Michael-like step growth polymerization results in acrylate terminated degradable macromer. The addition of 2D nanosilicates to PEGDTT results in formation of shear-thinning bioinks with high printability and structural fidelity. The mechanical properties, swelling kinetics, and degradation rate of 3D printed constructs can be modulated by changing the ratio of PEG:PEGDTT and nanosilicates concentration. Due to high surface area and charged characteristic of nanosilicates, protein therapeutics can be sequestered in 3D printing structure for prolong duration. Sustained release of pro-angiogenic therapeutics from 3D printed structure, promoted rapid migration of human endothelial umbilical vein cell. This approach to design biologically active inks to control and direct cell behavior can be used to engineer 3D complex tissue structure for regenerative medicine.

Adv Mater ; 31(23): e1900332, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941811


Clay nanomaterials are an emerging class of 2D biomaterials of interest due to their atomically thin layered structure, charged characteristics, and well-defined composition. Synthetic nanoclays are plate-like polyions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Due to their biocompatible characteristics, unique shape, high surface-to-volume ratio, and charge, nanoclays are investigated for various biomedical applications. Here, a critical overview of the physical, chemical, and physiological interactions of nanoclay with biological moieties, including cells, proteins, and polymers, is provided. The state-of-the-art biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery, and additive manufacturing are reviewed. In addition, recent developments that are shaping this emerging field are discussed and promising new research directions for 2D nanoclay-based biomaterials are identified.

ACS Appl Mater Interfaces ; 11(7): 6741-6750, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30676016


We present a nanoengineered system for sustained and prolonged delivery of protein therapeutics, which has the potential to impact current orthopedic regeneration strategies. Specifically, we introduce two-dimensional nanosilicates with a high surface area and charged characteristics for delivery of active proteins for more than 30 days. The nanosilicates show high binding efficacy without altering the protein conformation and bioactivity. The released proteins are able to maintain high activity as demonstrated by enhanced differentiation of human mesenchymal stem cells at 10-fold lower concentration compared to the exogenous control. Utilizing the nanosilicates as a delivery vehicle could minimize the negative side effects observed because of the use of supraphysiological dosages of protein therapeutics for orthopedic regeneration strategies.

Proteína Morfogenética Óssea 2 , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacocinética , Proteína Morfogenética Óssea 2/farmacologia , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia