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1.
ACS Appl Mater Interfaces ; 13(30): 35342-35355, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34297530

RESUMEN

Growth-factor-free bone regeneration remains a challenge in craniofacial engineering. Here, we engineered an osteogenic niche composed of a commercially modified alginate hydrogel and whitlockite microparticles (WHMPs), which impart tunable physicochemical properties that can direct osteogenesis of human gingival mesenchymal stem cells (GMSCs). Our in vitro studies demonstrate that WHMPs induce osteogenesis of GMSCs more effectively than previously demonstrated hydroxyapatite microparticles (HApMPs). Alginate-WHMP hydrogels showed higher elasticity without any adverse effects on the viability of the encapsulated GMSCs. Moreover, the alginate-WHMP hydrogels upregulate the mitogen-activated protein kinase (MAPK) pathway, which in turn orchestrates several osteogenic markers, such as RUNX2 and OCN, in the encapsulated GMSCs. Concurrent coculture studies with human osteoclasts demonstrate that GMSCs encapsulated in alginate-WHMP hydrogels downregulate osteoclastic activity, potentially due to release of Mg2+ ions from the WHMPs along with secretion of osteoprotegerin from the GMSCs. In vivo studies demonstrated that the GMSCs encapsulated in our osteogenic niche were able to promote bone repair in calvarial defects in murine models. Altogether, our results confirmed the development of a promising treatment modality for craniofacial bone regeneration based on an injectable growth-factor-free hydrogel delivery system.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Fosfatos de Calcio/uso terapéutico , Hidrogeles/uso terapéutico , Cráneo/efectos de los fármacos , Alginatos/uso terapéutico , Animales , Diferenciación Celular/efectos de los fármacos , Células Inmovilizadas , Encía/citología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos
2.
Nano Lett ; 17(10): 6235-6240, 2017 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-28819978

RESUMEN

Nanoparticles have been used for engineering composite materials to improve the intrinsic properties and/or add functionalities to pristine polymers. The majority of the studies have focused on the incorporation of spherical nanoparticles within the composite fibers. Herein, we incorporate anisotropic branched-shaped zinc oxide (ZnO) nanoparticles into fibrous scaffolds fabricated by electrospinning. The addition of the branched particles resulted in their protrusion from fibers, mimicking the architecture of a rose stem. We demonstrated that the encapsulation of different-shape particles significantly influences the physicochemical and biological activities of the resultant composite scaffolds. In particular, the branched nanoparticles induced heterogeneous crystallization of the polymeric matrix and enhance the ultimate mechanical strain and strength. Moreover, the three-dimensional (3D) nature of the branched ZnO nanoparticles enhanced adhesion properties of the composite scaffolds to the tissues. In addition, the rose stem-like constructs offered excellent antibacterial activity, while supporting the growth of eukaryote cells.


Asunto(s)
Nanofibras/química , Nanopartículas/química , Andamios del Tejido/química , Óxido de Zinc/química , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Infecciones Bacterianas/prevención & control , Línea Celular , Humanos , Ensayo de Materiales , Nanofibras/ultraestructura , Nanopartículas/ultraestructura , Nanoestructuras/química , Nanoestructuras/ultraestructura , Estrés Mecánico , Resistencia a la Tracción , Ingeniería de Tejidos , Óxido de Zinc/farmacología
3.
Adv Funct Mater ; 27(12)2017 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-30319321

RESUMEN

Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, which can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, we developed a gold nanorod (GNR) incorporated gelatin methacryloyl (GelMA)-based bioink for printing 3D functional cardiac tissue constructs. The GNR concentration was adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentration of GNR, the nanocomposite bioink had a low viscosity, similar to pristine inks, which allowed for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution was possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells showed improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridged the electrically resistant pore walls of polymers, improved the cell-to-cell coupling, and promoted synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.

4.
Biomaterials ; 103: 278-292, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27414719

RESUMEN

Due to the increased morbidity and mortality resulting from heart valve diseases, there is a growing demand for off-the-shelf implantable tissue engineered heart valves (TEHVs). Despite the significant progress in recent years in improving the design and performance of TEHV constructs, viable and functional human implantable TEHV constructs have remained elusive. The recent advances in micro and nanoscale technologies including the microfabrication, nano-microfiber based scaffolds preparation, 3D cell encapsulated hydrogels preparation, microfluidic, micro-bioreactors, nano-microscale biosensors as well as the computational methods and models for simulation of biological tissues have increased the potential for realizing viable, functional and implantable TEHV constructs. In this review, we aim to present an overview of the importance and recent advances in micro and nano-scale technologies for the development of TEHV constructs.


Asunto(s)
Órganos Bioartificiales , Válvulas Cardíacas/crecimiento & desarrollo , Dispositivos Laboratorio en un Chip , Nanopartículas/química , Técnicas de Cultivo de Órganos/instrumentación , Ingeniería de Tejidos/instrumentación , Andamios del Tejido , Diseño de Equipo , Válvulas Cardíacas/citología , Humanos , Masculino , Evaluación de la Tecnología Biomédica , Ingeniería de Tejidos/métodos
5.
Adv Drug Deliv Rev ; 105(Pt B): 255-274, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27037064

RESUMEN

Graphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two-dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering. In this review, we will highlight the recent applications of graphene-based materials in tissue engineering and regenerative medicine. In particular, we will discuss the application of graphene-based materials in cardiac, neural, bone, cartilage, skeletal muscle, and skin/adipose tissue engineering. We will also discuss the potential risk factors of graphene-based materials in tissue engineering. In conclusion, we will outline the opportunities in the usage of graphene-based materials for clinical applications.


Asunto(s)
Grafito , Ingeniería de Tejidos , Animales , Materiales Biocompatibles , Humanos , Medicina Regenerativa
6.
Small ; 12(16): 2130-45, 2016 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-27101419

RESUMEN

Tissue engineering has the potential to revolutionize the health care industry. Delivering on this promise requires the generation of efficient, controllable and predictable implants. The integration of nano- and microtechnologies into macroscale regenerative biomaterials plays an essential role in the generation of such implants, by enabling spatiotemporal control of the cellular microenvironment. Here we review the role, function and progress of a wide range of nano- and microtechnologies that are driving the advancements in the field of tissue engineering.


Asunto(s)
Materiales Biocompatibles/química , Nanotecnología/métodos , Ingeniería de Tejidos/métodos , Biotina/química , Microambiente Celular , ADN/química , Geles , Humanos , Hidrogeles/química , Cinética , Microfluídica , Microscopía Electrónica de Rastreo , Nanotecnología/tendencias , Factor de Crecimiento Derivado de Plaquetas/química , Regeneración , Electricidad Estática , Estreptavidina/química , Temperatura , Ingeniería de Tejidos/tendencias , Andamios del Tejido/química , Factor A de Crecimiento Endotelial Vascular/química , Viscosidad
7.
Chemistry ; 20(17): 4874-9, 2014 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-24700372

RESUMEN

Dimerization-macrocyclization has been a long-standing problem in the cyclization of peptides since, together with the desired cyclic product, many cyclic oligomers and linear polymers may also be formed during the reaction. Therefore, the development of a process that affords the cyclic dimer predominantly is difficult. A novel and versatile strategy for the synthesis of symmetric cyclo-tetrapeptides by palladium-promoted tandem deprotection/cyclo-dimerization from readily available Cbz-dipeptidoyl benzotriazolides is reported (Cbz=carboxybenzyl).


Asunto(s)
Compuestos Macrocíclicos/síntesis química , Péptidos Cíclicos/síntesis química , Triazoles/química , Ciclización , Dimerización , Compuestos Macrocíclicos/química , Modelos Moleculares , Paladio/química , Péptidos Cíclicos/química , Triazoles/síntesis química
8.
J Org Chem ; 78(17): 8510-23, 2013 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-23895184

RESUMEN

Open-chain N-Cbz-protected-peptidoyl benzotriazolides are converted by a novel lactamization strategy using proline as a turn introducer into both symmetrical (5a-c and 11a-c) and unsymmetrical (19a-e) bis-2,5-diketopiperazines (bis-2,5-DKPs), previously recognized as difficult targets.


Asunto(s)
Dicetopiperazinas/síntesis química , Lactamas/química , Dicetopiperazinas/química , Modelos Moleculares , Conformación Molecular , Estructura Molecular
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