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1.
Adv Healthc Mater ; : e2102697, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35362224

RESUMEN

Oxygen releasing biomaterials can facilitate the survival of living implants by creating environments with a viable oxygen level. Hydrophobic oxygen generating microparticles (HOGMPs) encapsulated calcium peroxide (CPO) have recently been used in tissue engineering to release physiologically relevant amounts of oxygen for several weeks. However, generating oxygen using CPO is mediated via the generation of toxic levels of hydrogen peroxide (H2 O2 ). The incorporation of antioxidants, such as catalases, can potentially reduce H2 O2 levels. However, the formulation in which catalases can most effectively scavenge H2 O2 within oxygen generating biomaterials has remained unexplored. In this study, three distinct catalase incorporation methods are compared based on their ability to decrease H2 O2 levels. Specifically, catalase is incorporated within HOGMPs, or absorbed onto HOGMPs, or freely laden into the hydrogel entrapping HOGMPs and compared with control without catalase. Supplementation of free catalase in an HOGMP-laden hydrogel significantly decreases H2 O2 levels reflecting a higher cellular viability and metabolic activity of all the groups. An HOGMP/catalase-laden hydrogel precursor solution containing cells is used as an oxygenating bioink allowing improved viability of printed constructs under severe hypoxic conditions. The combination of HOGMPs with a catalase-laden hydrogel has the potential to decrease peroxide toxicity of oxygen generating tissues.

2.
Adv Drug Deliv Rev ; 184: 114197, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35288219

RESUMEN

Gene therapy has emerged as a potential platform for treating several dreaded and rare diseases that would not have been possible with traditional therapies. Viral vectors have been widely explored as a key platform for gene therapy due to their ability to efficiently transport nucleic acid-based therapeutics into the cells. However, the lack of precision in their delivery has led to several off-target toxicities. As such, various strategies in the form of non-viral gene delivery vehicles have been explored and are currenlty employed in several therapies including the SARS-CoV-2 vaccine. In this review, we discuss the opportunities lipid nanoparticles (LNPs) present for efficient gene delivery. We also discuss various synthesis strategies via microfluidics for high throughput fabrication of non-viral gene delivery vehicles. We conclude with the recent applications and clinical trials of these vehicles for the delivery of different genetic materials such as CRISPR editors and RNA for different medical conditions ranging from cancer to rare diseases.


Asunto(s)
COVID-19 , Nanopartículas , Ácidos Nucleicos , Vacunas contra la COVID-19 , Humanos , Lípidos , Liposomas , Microfluídica , Enfermedades Raras , SARS-CoV-2
3.
J Biomed Mater Res A ; 110(5): 1147-1165, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35102687

RESUMEN

The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new technologies to meet clinical expectations and improve patient outcomes fusing disease modeling.


Asunto(s)
Materiales Biocompatibles , Dispositivos Laboratorio en un Chip , Humanos
4.
J Biomed Mater Res A ; 110(3): 708-724, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34558808

RESUMEN

Gelatin methacryloyl (GelMA), a photocrosslinkable gelatin-based hydrogel, has been immensely used for diverse applications in tissue engineering and drug delivery. Apart from its excellent functionality and versatile mechanical properties, it is also suitable for a wide range of fabrication methodologies to generate tissue constructs of desired shapes and sizes. Despite its exceptional characteristics, it is predominantly limited by its weak mechanical strength, as some tissue types naturally possess high mechanical stiffness. The use of high GelMA concentrations yields high mechanical strength, but not without the compromise in its porosity, degradability, and three-dimensional (3D) cell attachment. Recently, GelMA has been blended with various natural and synthetic biomaterials to reinforce its physical properties to match with the tissue to be engineered. Among these, nanomaterials have been extensively used to form a composite with GelMA, as they increase its biological and physicochemical properties without affecting the unique characteristics of GelMA and also introduce electrical and magnetic properties. This review article presents the recent advances in the formation of hybrid GelMA nanocomposites using a variety of nanomaterials (carbon, metal, polymer, and mineral-based). We give an overview of each nanomaterial's characteristics followed by a discussion of the enhancement in GelMA's physical properties after its incorporation. Finally, we also highlight the use of each GelMA nanocomposite for different applications, such as cardiac, bone, and neural regeneration.


Asunto(s)
Gelatina , Ingeniería de Tejidos , Gelatina/química , Hidrogeles/química , Metacrilatos , Nanogeles , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
5.
Acta Biomater ; 139: 141-156, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34818579

RESUMEN

Myocardial infarction (MI) represents one of the most prevalent cardiovascular diseases, with a highly relevant and impactful role in public health. Despite the therapeutic advances of the last decades, MI still begets extensive death rates around the world. The pathophysiology of the disease correlates with cardiomyocyte necrosis, caused by an imbalance in the demand of oxygen to cardiac tissues, resulting from obstruction of the coronary flow. To alleviate the severe effects of MI, the use of various biomaterials exhibit vast potential in cardiac repair and regeneration, acting as native extracellular matrices. These hydrogels have been combined with nano sized or functional materials which possess unique electrical, mechanical, and topographical properties that play important roles in regulating phenotypes and the contractile function of cardiomyocytes even in adverse microenvironments. These nano-biomaterials' differential properties have led to substantial healing on in vivo cardiac injury models by promoting fibrotic scar reduction, hemodynamic function preservation, and benign cardiac remodeling. In this review, we discuss the interplay of the unique physical properties of electrically conductive nano-biomaterials, are able to manipulate the phenotypes and the electrophysiological behavior of cardiomyocytes in vitro, and can enhance heart regeneration in vivo. Consequently, the understanding of the decisive roles of the nano-biomaterials discussed in this review could be useful for designing novel nano-biomaterials in future research for cardiac tissue engineering and regeneration. STATEMENT OF SIGNIFICANCE: This study introduced and deciphered the understanding of the role of multimodal cues in recent advances of electrically conductive nano-biomaterials on cardiac tissue engineering. Compared with other review papers, which mainly describe these studies based on various types of electrically conductive nano-biomaterials, in this review paper we mainly discussed the interplay of the unique physical properties (electrical conductivity, mechanical properties, and topography) of electrically conductive nano-biomaterials, which would allow them to manipulate phenotypes and the electrophysiological behavior of cardiomyocytes in vitro and to enhance heart regeneration in vivo. Consequently, understanding the decisive roles of the nano-biomaterials discussed in the review could help design novel nano-biomaterials in future research for cardiac tissue engineering and regeneration.


Asunto(s)
Materiales Biocompatibles , Miocitos Cardíacos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Conductividad Eléctrica , Miocitos Cardíacos/fisiología , Regeneración , Ingeniería de Tejidos/métodos
6.
Macromol Biosci ; 22(2): e2100340, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34957668

RESUMEN

Bioadhesives have been widely used in healthcare and biomedical applications due to their ease-of-operation for wound closure and repair compared to conventional suturing and stapling. However, several challenges remain for developing ideal bioadhesives, such as unsatisfied mechanical properties, non-tunable biodegradability, and limited biological functions. Considering these concerns, naturally derived biopolymers have been considered good candidates for making bioadhesives owing to their ready availability, facile modification, tunable mechanical properties, and desired biocompatibility and biodegradability. Over the past several years, remarkable progress has been made on biopolymer-based adhesives, covering topics from novel materials designs and advanced processing to clinical translation. The developed bioadhesives have been applied for diverse applications, including tissue adhesion, hemostasis, antimicrobial, wound repair/tissue regeneration, and skin-interfaced bioelectronics. Here in this comprehensive review, recent progress on biopolymer-based bioadhesives is summarized with focuses on clinical translations and multifunctional bioadhesives. Furthermore, challenges and opportunities such as weak adhesion strength at the hydrated state, mechanical mismatch with tissues, and unfavorable immune responses are discussed with an aim to facilitate the future development of high-performance biopolymer-based bioadhesives.


Asunto(s)
Adhesivos Tisulares , Adhesivos , Materiales Biocompatibles/uso terapéutico , Biopolímeros/uso terapéutico , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/uso terapéutico , Cicatrización de Heridas
7.
Adv Healthc Mater ; 11(6): e2101678, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34971210

RESUMEN

In vitro cardiomyocyte (CM) maturation is an imperative step to replicate native heart tissue-like structures as cardiac tissue grafts or as drug screening platforms. CMs are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behavior, organization, and maturation. In this regard, a silk-based cardiac tissue (CT) coupled with a dynamic perfusion-based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro is tried to be delivered. Silk fibroin (SF) is used to fabricate lamellar scaffolds to provide native tissue-like anisotropic architecture and is found to be nonimmunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds display excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when places in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, are applied to the cardiomyocyte culture seeded on lamellar silk scaffolds in the DMM. A strain-dependent difference in cardiomyocyte maturation, gene expression, sarcomere elongation, and extracellular matrix formation is observed. These silk-based CTs matured in the DMM can open up several avenues toward the development of host-specific grafts and in vitro models for drug screening.


Asunto(s)
Fibroínas , Materiales Biocompatibles , Fibroínas/química , Mecanotransducción Celular , Perfusión , Seda , Ingeniería de Tejidos , Andamios del Tejido/química
8.
ACS Omega ; 6(49): 33511-33522, 2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34926900

RESUMEN

Biodegradable cellular and acellular scaffolds have great potential to regenerate damaged tissues or organs by creating a proper extracellular matrix (ECM) capable of recruiting endogenous cells to support cellular ingrowth. However, since hydrogel-based scaffolds normally degrade through surface erosion, cell migration and ingrowth into scaffolds might be inhibited early in the implantation. This could result in insufficient de novo tissue formation in the injured area. To address these challenges, continuous and microsized strand-like networks could be incorporated into scaffolds to guide and recruit endogenous cells in rapid manner. Fabrication of such microarchitectures in scaffolds is often a laborious and time-consuming process and could compromise the structural integrity of the scaffold or impact cell viability. Here, we have developed a fast single-step approach to fabricate colloidal hydrogels, which are made up of randomly packed human serum albumin-based photo-cross-linkable microparticles with continuous internal networks of microscale voids. The human serum albumin conjugated with methacrylic groups were assembled to microsized aggregates for achieving unique porous structures inside the colloidal gels. The albumin hydrogels showed tunable mechanical properties such as elastic modulus, porosity, and biodegradability, providing a suitable ECM for various cells such as cardiomyoblasts and endothelial cells. In addition, the encapsulated cells within the hydrogel showed improved cell retention and increased survivability in vitro. Microporous structures of the colloidal gels can serve as a guide for the infiltration of host cells upon implantation, achieving rapid recruitment of hematopoietic cells and, ultimately, enhancing the tissue regeneration capacity of implanted scaffolds.

9.
Adv Funct Mater ; 31(42)2021 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-34924912

RESUMEN

Bioengineering of tissues and organs has the potential to generate functional replacement organs. However, achieving the full-thickness vascularization that is required for long-term survival of living implants has remained a grand challenge, especially for clinically sized implants. During the pre-vascular phase, implanted engineered tissues are forced to metabolically rely on the diffusion of nutrients from adjacent host-tissue, which for larger living implants results in anoxia, cell death, and ultimately implant failure. Here it is reported that this challenge can be addressed by engineering self-oxygenating tissues, which is achieved via the incorporation of hydrophobic oxygen-generating micromaterials into engineered tissues. Self-oxygenation of tissues transforms anoxic stresses into hypoxic stimulation in a homogenous and tissue size-independent manner. The in situ elevation of oxygen tension enables the sustained production of high quantities of angiogenic factors by implanted cells, which are offered a metabolically protected pro-angiogenic microenvironment. Numerical simulations predict that self-oxygenation of living tissues will effectively orchestrate rapid full-thickness vascularization of implanted tissues, which is empirically confirmed via in vivo experimentation. Self-oxygenation of tissues thus represents a novel, effective, and widely applicable strategy to enable the vascularization living implants, which is expected to advance organ transplantation and regenerative medicine applications.

10.
Cells ; 10(12)2021 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-34943930

RESUMEN

Experimental models of the central nervous system (CNS) are imperative for developmental and pathophysiological studies of neurological diseases. Among these models, three-dimensional (3D) induced pluripotent stem cell (iPSC)-derived brain organoid models have been successful in mitigating some of the drawbacks of 2D models; however, they are plagued by high organoid-to-organoid variability, making it difficult to compare specific gene regulatory pathways across 3D organoids with those of the native brain. Single-cell RNA sequencing (scRNA-seq) transcriptome datasets have recently emerged as powerful tools to perform integrative analyses and compare variability across organoids. However, transcriptome studies focusing on late-stage neural functionality development have been underexplored. Here, we combine and analyze 8 brain organoid transcriptome databases to study the correlation between differentiation protocols and their resulting cellular functionality across various 3D organoid and exogenous brain models. We utilize dimensionality reduction methods including principal component analysis (PCA) and uniform manifold approximation projection (UMAP) to identify and visualize cellular diversity among 3D models and subsequently use gene set enrichment analysis (GSEA) and developmental trajectory inference to quantify neuronal behaviors such as axon guidance, synapse transmission and action potential. We showed high similarity in cellular composition, cellular differentiation pathways and expression of functional genes in human brain organoids during induction and differentiation phases, i.e., up to 3 months in culture. However, during the maturation phase, i.e., 6-month timepoint, we observed significant developmental deficits and depletion of neuronal and astrocytes functional genes as indicated by our GSEA results. Our results caution against use of organoids to model pathophysiology and drug response at this advanced time point and provide insights to tune in vitro iPSC differentiation protocols to achieve desired neuronal functionality and improve current protocols.


Asunto(s)
Encéfalo/metabolismo , Diferenciación Celular/genética , Células Madre Pluripotentes Inducidas/metabolismo , Modelos Biológicos , Organoides/metabolismo , Transcriptoma/genética , Encéfalo/embriología , Bases de Datos Genéticas , Regulación del Desarrollo de la Expresión Génica , Humanos , Neuronas/citología , Neuronas/metabolismo , Reproducción , Análisis de Secuencia de ARN , Transducción de Señal/genética , Análisis de la Célula Individual
11.
Nanomicro Lett ; 13(1): 212, 2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34664123

RESUMEN

More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

12.
Adv Mater ; 33(42): e2102660, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34476848

RESUMEN

Cell-matrix interactions govern cell behavior and tissue function by facilitating transduction of biomechanical cues. Engineered tissues often incorporate these interactions by employing cell-adhesive materials. However, using constitutively active cell-adhesive materials impedes control over cell fate and elicits inflammatory responses upon implantation. Here, an alternative cell-material interaction strategy that provides mechanotransducive properties via discrete inducible on-cell crosslinking (DOCKING) of materials, including those that are inherently non-cell-adhesive, is introduced. Specifically, tyramine-functionalized materials are tethered to tyrosines that are naturally present in extracellular protein domains via enzyme-mediated oxidative crosslinking. Temporal control over the stiffness of on-cell tethered 3D microniches reveals that DOCKING uniquely enables lineage programming of stem cells by targeting adhesome-related mechanotransduction pathways acting independently of cell volume changes and spreading. In short, DOCKING represents a bioinspired and cytocompatible cell-tethering strategy that offers new routes to study and engineer cell-material interactions, thereby advancing applications ranging from drug delivery, to cell-based therapy, and cultured meat.


Asunto(s)
Materiales Biocompatibles/química , Mecanotransducción Celular , Animales , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Linaje de la Célula , Dextranos/química , Peroxidasa de Rábano Silvestre/metabolismo , Humanos , Hidrogeles/química , Integrinas/metabolismo , Mecanotransducción Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Oligopéptidos/química , Oxidación-Reducción , Tiramina/química
13.
Biofabrication ; 13(3)2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33962404

RESUMEN

Engineering three-dimensional (3D) sensible tissue constructs, along with the complex microarchitecture wiring of the sensory nervous system, has been an ongoing challenge in the tissue engineering field. By combining 3D bioprinting and human pluripotent stem cell (hPSC) technologies, sensible tissue constructs could be engineered in a rapid, precise, and controllable manner to replicate 3D microarchitectures and mechanosensory functionalities of the native sensory tissue (e.g. response to external stimuli). Here, we introduce a biofabrication approach to create complex 3D microarchitecture wirings. We develop an hPSC-sensory neuron (SN) laden bioink using highly purified and functional SN populations to 3D bioprint microarchitecture wirings that demonstrate responsiveness to warm/cold sense-inducing chemicals and mechanical stress. Specifically, we tailor a conventional differentiation strategy to our purification method by utilizing p75 cell surface marker and DAPT treatment along with neuronal growth factors in order to selectively differentiate neural crest cells into SNs. To create spatial resolution in 3D architectures and grow SNs in custom patterns and directions, an induced pluripotent stem cell (iPSC)-SN-laden gelatin bioink was printed on laminin-coated substrates using extrusion-based bioprinting technique. Then the printed constructs were covered with a collagen matrix that guided SNs growing in the printed micropattern. Using a sacrificial bioprinting technique, the iPSC-SNs were seeded into the hollow microchannels created by sacrificial gelatin ink printed in the gelatin methacryloyl supporting bath, thereby demonstrating controllability over axon guidance in curved lines up to several tens of centimeters in length on 2D substrates and in straight microchannels in 3D matrices. Therefore, this biofabrication approach could be amenable to incorporate sensible SN networks into the engineered skin equivalents, regenerative skin implants, and augmented somatosensory neuro-prosthetics that have the potential to regenerate sensible functions by connecting host neuron systems in injured areas.


Asunto(s)
Bioimpresión , Células Madre Pluripotentes Inducidas , Impresión Tridimensional , Separación Celular , Humanos , Red Nerviosa , Células Receptoras Sensoriales , Ingeniería de Tejidos , Andamios del Tejido
14.
Int J Biol Macromol ; 183: 918-926, 2021 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-33971227

RESUMEN

Gelatin methacryloyl (GelMA) is widely used for tissue engineering applications as an extracellular matrix (ECM) mimicking scaffold due to its cost-effectiveness, ease of synthesis, and high biocompatibility. GelMA is widely synthesized from porcine skin gelatin, which labors under clinical, religious, and economical restrictions. In order to overcome these limitations, GelMA can be produced from fish skin gelatin, which is eco-friendly as well. Here, we present a comparative study of the physicochemical (structural, thermal, water uptake, swelling, rheological, and mechanical) and biological (cell viability, proliferation, and spreading) properties of porcine and fish skin GelMA with low and high methacrylation degrees, before and after crosslinking, to check whether fish skin can replace porcine skin as the source of GelMA. Porcine and fish skin GelMA presented similar structural, thermal, and water uptake properties prior to crosslinking. However, subsequent to crosslinking, fish skin GelMA hydrogels exhibited a higher mass swelling ratio and a lower elastic and compressive Young's moduli than porcine skin GelMA hydrogels of similar methacrylation level. Both types of GelMA hydrogels showed great biocompatibility toward encapsulated mouse myoblast cells (C2C12), however, improved cell spreading was observed in fish skin GelMA hydrogels, and cell proliferation was only induced in low methacrylated GelMA. These results suggest that fish skin GelMA is a promising substitute for porcine skin GelMA for biomedical applications and that low methacrylated fish skin GelMA can be used as a potential scaffold for skeletal muscle tissue engineering.


Asunto(s)
Materiales Biocompatibles/química , Gelatina/química , Ingeniería de Tejidos/métodos , Animales , Peces , Hidrogeles/química , Ratones , Piel/química , Porcinos , Andamios del Tejido/química
15.
Nat Protoc ; 16(5): 2564-2593, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33911259

RESUMEN

Organs-on-chips have emerged as viable platforms for drug screening and personalized medicine. While a wide variety of human organ-on-a-chip models have been developed, rarely have there been reports on the inclusion of sensors, which are critical in continually measuring the microenvironmental parameters and the dynamic responses of the microtissues to pharmaceutical compounds over extended periods of time. In addition, automation capacity is strongly desired for chronological monitoring. To overcome this major hurdle, in this protocol we detail the fabrication of electrochemical affinity-based biosensors and their integration with microfluidic chips to achieve in-line microelectrode functionalization, biomarker detection and sensor regeneration, allowing continual, in situ and noninvasive quantification of soluble biomarkers on organ-on-a-chip platforms. This platform is almost universal and can be applied to in-line detection of a majority of biomarkers, can be connected with existing organ-on-a-chip devices and can be multiplexed for simultaneous measurement of multiple biomarkers. Specifically, this protocol begins with fabrication of the electrochemically competent microelectrodes and the associated microfluidic devices (~3 d). The integration of electrochemical biosensors with the chips and their further combination with the rest of the platform takes ~3 h. The functionalization and regeneration of the microelectrodes are subsequently described, which require ~7 h in total. One cycle of sampling and detection of up to three biomarkers accounts for ~1 h.


Asunto(s)
Técnicas Biosensibles/instrumentación , Equipo Reutilizado , Dispositivos Laboratorio en un Chip , Biomarcadores/metabolismo , Electroquímica , Microelectrodos , Factores de Tiempo
16.
Trends Biotechnol ; 39(11): 1144-1159, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33602609

RESUMEN

Oxygen is essential for the survival, function, and fate of mammalian cells. Oxygen tension controls cellular behaviour via metabolic programming, which in turn controls tissue regeneration, stem cell differentiation, drug metabolism, and numerous pathologies. Thus, oxygen-releasing biomaterials represent a novel and unique strategy to gain control over a variety of in vivo processes. Consequently, numerous oxygen-generating or carrying materials have been developed in recent years, which offer innovative solutions in the field of drug efficiency, regenerative medicine, and engineered living systems. In this review, we discuss the latest trends, highlight current challenges and solutions, and provide a future perspective on the field of oxygen-releasing materials.


Asunto(s)
Oxígeno , Ingeniería de Tejidos , Animales , Materiales Biocompatibles , Diferenciación Celular , Mamíferos , Oxígeno/metabolismo , Medicina Regenerativa
17.
Nano Today ; 362021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33425002

RESUMEN

Sutures, staples, clips and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology - uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide toward innovation of tissue bioadhesive materials and their associated biomedical applications.

18.
Biofabrication ; 13(3)2021 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-33482658

RESUMEN

Vascularization is considered to be one of the key challenges in engineering functional 3D tissues. Engineering suturable vascular grafts containing pores with diameter of several tens of microns in tissue engineered constructs may provide an instantaneous blood perfusion through the grafts improving cell infiltration and thus, allowing rapid vascularization and vascular branching. The aim of this work was to develop suturable tubular scaffolds to be integrated in biofabricated constructs, enabling the direct connection of the biofabricated construct with the host blood stream, providing an immediate blood flow inside the construct. Here, tubular grafts with customizable shapes (tubes, Y-shape capillaries) and controlled diameter ranging from several hundreds of microns to few mm are fabricated based on poly(glycerol sebacate) (PGS)/poly(vinyl alcohol) (PVA) electrospun scaffolds. Furthermore, a network of pore channels of diameter in the order of 100µm was machined by laser femtosecond ablation in the tube wall. Both non-machined and laser machined tubular scaffolds elongated more than 100% of their original size have shown suture retention, being 5.85 and 3.96 N mm-2respectively. To demonstrate the potential of application, the laser machined porous grafts were embedded in gelatin methacryloyl (GelMA) hydrogels, resulting in elastomeric porous tubular graft/GelMA 3D constructs. These constructs were then co-seeded with osteoblast-like cells (MG-63) at the external side of the graft and human umbilical vein endothelial cells inside, forming a bone osteon model. The laser machined pore network allowed an immediate endothelial cell flow towards the osteoblasts enabling the osteoblasts and endothelial cells to interact and form 3D structures. This rapid vascularization approach could be applied, not only for bone tissue regeneration, but also for a variety of tissues and organs.


Asunto(s)
Ingeniería de Tejidos , Andamios del Tejido , Gelatina , Células Endoteliales de la Vena Umbilical Humana , Humanos , Metacrilatos , Porosidad
19.
Macromol Biosci ; 21(1): e2000317, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33043610

RESUMEN

Bioinks play a key role in determining the capability of the biofabricatoin processes and the resolution of the printed constructs. Excellent biocompatibility, tunable physical properties, and ease of chemical or biological modifications of gelatin methacryloyl (GelMA) have made it an attractive choice as bioinks for biomanufacturing of various tissues or organs. However, the current preparation methods for GelMA-based bioinks lack the ability to tailor their physical properties for desired bioprinting methods. Inherently, GelMA prepolymer solution exhibits a fast sol-gel transition at room temperature, which is a hurdle for its use in stereolithography (SLA) bioprinting. Here, synthesis parameters are optimized such as solvents, pH, and reaction time to develop GelMA bioinks which have a slow sol-gel transition at room temperature and visible light crosslinkable functions. A total of eight GelMA combinations are identified as suitable for digital light processing (DLP)-based SLA (DLP-SLA) bioprinting through systematic characterizations of their physical and rheological properties. Out of various types of GelMA, those synthesized in reverse osmosis (RO) purified water (referred to as RO-GelMA) are regarded as most suitable to achieve high DLP-SLA printing resolution. RO-GelMA-based bioinks are also found to be biocompatible showing high survival rates of encapsulated cells in the photocrosslinked gels. Additionally, the astrocytes and fibroblasts are observed to grow and integrate well within the bioprinted constructs. The bioink's superior physical and photocrosslinking properties offer pathways of tuning the scaffold microenvironment and highlight the applicability of developed GelMA bioinks in various tissue engineering and regenerative medicine applications.


Asunto(s)
Bioimpresión , Gelatina/farmacología , Metacrilatos/farmacología , Estereolitografía , Ingeniería de Tejidos , Supervivencia Celular/efectos de los fármacos , Gelatina/síntesis química , Gelatina/efectos de la radiación , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Tinta , Luz , Metacrilatos/síntesis química , Metacrilatos/efectos de la radiación , Impresión Tridimensional , Andamios del Tejido/química
20.
Small ; 17(15): e2004258, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33094918

RESUMEN

Cardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy-induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with preexisting cardiac dysfunctions may lead to different incident levels of CIC. Here, a model is presented for investigating CIC where not only induced pluripotent stem cell (iPSC)-derived cardiac tissues are interacted with BC tissues on a dual-organ platform, but electrochemical immuno-aptasensors can also monitor cell-secreted multiple biomarkers. Fibrotic stages of iPSC-derived cardiac tissues are promoted with a supplement of transforming growth factor-ß 1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno-aptasensors well-matches the outcomes from conventional enzyme-linked immunosorbent assay, demonstrating the accuracy of the authors' sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle-based DOX-delivery system. The proposed platform would potentially help allow early detection and prediction of CIC in individual patients in the future.


Asunto(s)
Neoplasias de la Mama , Cardiotoxicidad , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/etiología , Doxorrubicina/efectos adversos , Femenino , Corazón , Humanos , Dispositivos Laboratorio en un Chip , Miocitos Cardíacos
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