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1.
Adv Mater ; : e2313776, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639337

RESUMEN

Advancing biofabrication toward manufacturing living constructs with well-defined architectures and increasingly biologically relevant cell densities is highly desired to mimic the biofunctionality of native human tissues. The formulation of tissue-like, cell-dense inks for biofabrication remains, however, challenging at various levels of the bioprinting process. Promising advances have been made toward this goal, achieving relatively high cell densities that surpass those found in conventional platforms, pushing the current boundaries closer to achieving tissue-like cell densities. On this focus, herein the overarching challenges in the bioprocessing of cell-rich living inks into clinically grade engineered tissues are discussed, as well as the most recent advances in cell-rich living ink formulations and their processing technologies are highlighted. Additionally, an overview of the foreseen developments in the field is provided and critically discussed.

2.
ACS Appl Mater Interfaces ; 16(15): 18386-18399, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38591243

RESUMEN

Cryogels exhibit unique shape memory with full recovery and structural stability features after multiple injections. These constructs also possess enhanced cell permeability and nutrient diffusion when compared to typical bulk hydrogels. Volumetric processing of cryogels functionalized with nanosized units has potential to widen their biomedical applications, however this has remained challenging and relatively underexplored. In this study, we report a novel methodology that combines suspension 3D printing with directional freezing for the fabrication of nanocomposite cryogels with configurable anisotropy. When compared to conventional bulk or freeze-dried hydrogels, nanocomposite cryogel formulations exhibit excellent shape recovery (>95%) and higher pore connectivity. Suspension printing, assisted with a prechilled metal grid, was optimized to induce anisotropy. The addition of calcium- and phosphate-doped mesoporous silica nanoparticles into the cryogel matrix enhanced bioactivity toward orthopedic applications without hindering the printing process. Notably, the nanocomposite 3D printed cryogels exhibit injectable shape memory while also featuring a lamellar topography. The fabrication of these constructs was highly reproducible and exhibited potential for a cell-delivery injectable cryogel with no cytotoxicity to human-derived adipose stem cells. Hence, in this work, it was possible to combine a gravity defying 3D printed methodology with injectable and controlled anisotropic macroporous structures containing bioactive nanoparticles. This methodology ameliorates highly tunable injectable 3D printed anisotropic nanocomposite cryogels with a user-programmable degree of structural complexity.


Asunto(s)
Criogeles , Impresión Tridimensional , Humanos , Criogeles/química , Anisotropía , Adipocitos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
3.
Methods Mol Biol ; 2764: 279-288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38393601

RESUMEN

Embedded extrusion 3D bioprinting is a rapidly emerging additive manufacturing methodology that provides a precise spatial deposition of synthetic or natural-origin low-viscosity bioinks during the extrusion printing process. Such a strategy has to date unlocked the freeform extrusion biofabrication of complex micro-to-macro-scale living architectures for numerous applications, including tissue engineering and in vitro disease modeling. In this chapter, we describe a suspension bioprinting methodology leveraging a continuous viscoelastic biopolymer supporting bath functionalized with divalent calcium cations to enable a rapid processing of user-defined bioinks toward architecturally complex 3D in vitro tumor models. This highly simple and cost-effective viscoelastic supporting bath enables a full freeform biofabrication of cell-laden 3D tumor-mimetic architectures that exhibit structural stability in culture post-printing. The cytocompatibility of the supporting bath, its ease of removal from biofabricated living constructs, and its adaptability for processing different ECM-mimetic bioinks open avenues for multi-scale fabrication of numerous types of physiomimetic 3D tumor models for preclinical screening of candidate therapeutics.


Asunto(s)
Bioimpresión , Neoplasias , Humanos , Bioimpresión/métodos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Biomimética , Neoplasias/terapia , Andamios del Tejido/química , Hidrogeles/química
4.
Nanoscale Horiz ; 9(3): 334-364, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38204336

RESUMEN

Hyperthermic nanomedicines are particularly relevant for tackling human cancer, providing a valuable alternative to conventional therapeutics. The early-stage preclinical performance evaluation of such anti-cancer treatments is conventionally performed in flat 2D cell cultures that do not mimic the volumetric heat transfer occurring in human tumors. Recently, improvements in bioengineered 3D in vitro models have unlocked the opportunity to recapitulate major tumor microenvironment hallmarks and generate highly informative readouts that can contribute to accelerating the discovery and validation of efficient hyperthermic treatments. Leveraging on this, herein we aim to showcase the potential of engineered physiomimetic 3D tumor models for evaluating the preclinical efficacy of hyperthermic nanomedicines, featuring the main advantages and design considerations under diverse testing scenarios. The most recent applications of 3D tumor models for screening photo- and/or magnetic nanomedicines will be discussed, either as standalone systems or in combinatorial approaches with other anti-cancer therapeutics. We envision that breakthroughs toward developing multi-functional 3D platforms for hyperthermia onset and follow-up will contribute to a more expedited discovery of top-performing hyperthermic therapies in a preclinical setting before their in vivo screening.


Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Nanomedicina , Neoplasias/tratamiento farmacológico , Técnicas de Cultivo de Célula , Modelos Biológicos , Microambiente Tumoral
5.
Biomolecules ; 13(10)2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37892208

RESUMEN

The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5'UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.


Asunto(s)
Andrógenos , Neoplasias de la Próstata , Masculino , Humanos , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Metilación de ADN , Línea Celular Tumoral , Regiones Promotoras Genéticas , Neoplasias de la Próstata/metabolismo , Epigénesis Genética/genética , Regulación Neoplásica de la Expresión Génica
6.
Adv Sci (Weinh) ; 10(34): e2304040, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37823678

RESUMEN

Breakthroughs in precision cell surface engineering tools are supporting the rapid development of programmable living assemblies with valuable features for tackling complex biological problems. Herein, the authors overview the most recent technological advances in chemically- and biologically-driven toolboxes for engineering mammalian cell surfaces and triggering their assembly into living architectures. A particular focus is given to surface engineering technologies for enabling biomimetic cell-cell social interactions and multicellular cell-sorting events. Further advancements in cell surface modification technologies may expand the currently available bioengineering toolset and unlock a new generation of personalized cell therapeutics with clinically relevant biofunctionalities. The combination of state-of-the-art cell surface modifications with advanced biofabrication technologies is envisioned to contribute toward generating living materials with increasing tissue/organ-mimetic bioactivities and therapeutic potential.


Asunto(s)
Ingeniería Biomédica , Ingeniería de Tejidos , Animales , Ingeniería Celular , Bioingeniería , Biomimética , Mamíferos
7.
Vet Sci ; 10(6)2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37368765

RESUMEN

Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory context. Both female dogs and female rats have contributed to the advancement of scientific knowledge in this field, and, in a "One Health" approach, they have allowed broad understanding of specific biopathological pathways, influence of environmental factors and screening/discovery of candidate therapies. This review aims to clearly showcase the similarities and differences among woman, female dog and female rat concerning to anatomical, physiological and histological features of the mammary gland and breast/mammary cancer epidemiology, in order to better portray breast tumorigenesis, and to ensure appropriate conclusions and extrapolation of results among species. We also discuss the major aspects that stand out in these species. The mammary glands of female dogs and women share structural similarities, especially with respect to the lactiferous ducts and lymphatic drainage. In contrast, female rats have only one lactiferous duct per nipple. A comprehensive comparison between humans and dogs is given a special focus, as these species share several aspects in terms of breast/mammary cancer epidemiology, such as age of onset, hormonal etiology, risk factors, and the clinical course of the disease. Holistically, it is clear that each species has advantages and limitations that researchers must consider during the development of experimental designs and data analysis.

8.
Molecules ; 28(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37110775

RESUMEN

Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean label and vegan source of ingredients for the replacement of food additives and protein from animal sources. To achieve this, structure/function relationships were performed by isolating polysaccharides with distinct structural features from BSY, either by using alkaline extraction (mild treatment) or subcritical water extraction (SWE) using microwave technology (hard treatment), and assessment of their emulsifying properties. Alkaline extractions solubilized mostly highly branched mannoproteins (N-linked type; 75%) and glycogen (25%), while SWE solubilized mannoproteins with short mannan chains (O-linked type; 55%) and (1→4)- and (ß1→3)-linked glucans, 33 and 12%, respectively. Extracts with high protein content yielded the most stable emulsions obtained by hand shaking, while the extracts composed of short chain mannans and ß-glucans yielded the best emulsions by using ultraturrax stirring. ß-Glucans and O-linked mannoproteins were found to contribute to emulsion stability by preventing Ostwald ripening. When applied in mayonnaise model emulsions, BSY extracts presented higher stability and yet similar texture properties as the reference emulsifiers. When used in a mayonnaise formulation, the BSY extracts were also able to replace egg yolk and modified starch (E1422) at 1/3 of their concentration. This shows that BSY alkali soluble mannoproteins and subcritical water extracted ß-glucans can be used as replacers of animal protein and additives in sauces.


Asunto(s)
Saccharomyces cerevisiae , beta-Glucanos , Animales , Humanos , Saccharomyces cerevisiae/metabolismo , Emulsiones/metabolismo , Veganos , Polisacáridos/química , Mananos/metabolismo , Agua/análisis , Pared Celular/química , beta-Glucanos/metabolismo , Extractos Vegetales/análisis
9.
Foods ; 12(5)2023 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-36900495

RESUMEN

This study tested hyperbaric storage (25-150 MPa, for 30 days) at room-temperature (HS/RT, 18-23 °C) in order to control the development of Byssochlamys nivea ascospores in apple juice. In order to mimic commercially pasteurized juice contaminated with ascospores, thermal pasteurization (70 and 80 °C for 30 s) and nonthermal high pressure pasteurization (600 MPa for 3 min at 17 °C, HPP) took place, and the juice was afterwards placed under HS/RT conditions. Control samples were also placed in atmospheric pressure (AP) conditions at RT and were refrigerated (4 °C). The results showed that HS/RT, in samples without a pasteurization step and those pasteurized at 70 °C/30 s, was able to inhibit ascospore development, contrarily to samples at AP/RT and refrigeration. HS/RT for samples pasteurized at 80 °C/30 s evidenced ascospore inactivation, especially at 150 MPa, wherein an overall reduction of at least 4.73 log units of ascospores was observed to below detection limits (1.00 Log CFU/mL); meanwhile, for HPP samples, especially at 75 and 150 MPa, an overall reduction of 3 log units (to below quantification limits, 2.00 Log CFU/mL) was observed. Phase-contrast microscopy revealed that the ascospores do not complete the germination process under HS/RT, hence avoiding hyphae formation, which is important for food safety since mycotoxin development occurs only after hyphae formation. These findings suggest that HS/RT is a safe food preservation methodology, as it prevents ascospore development and inactivates them following commercial-like thermal or nonthermal HPP pasteurization, preventing mycotoxin production and enhancing ascospore inactivation.

10.
Biomaterials ; 287: 121653, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35803021

RESUMEN

Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovative therapeutics. Diverse bioengineering approaches exploiting patient-derived organoids, cancer-on-a-chip platforms, and 3D bioprinted living constructs have been rapidly emerging in an endeavor to seamlessly recapitulate major tumor-stroma biodynamic interactions in a preclinical setting. Gathering on this, herein we showcase and discuss the most recent advances in bio-assembling pancreatic tumor-stroma models that mimic key disease hallmarks and its desmoplastic biosignature. A reverse engineering perspective of pancreatic tumor-stroma key elementary units is also provided and complemented by a detailed description of biodesign guidelines that are to be considered for improving 3D models physiomimetic features. This overview provides valuable examples and starting guidelines for researchers envisioning to engineer and characterize stroma-rich biomimetic tumor models. All in all, leveraging advanced bioengineering tools for capturing stromal heterogeneity and dynamics, opens new avenues toward generating more predictive and patient-personalized organotypic 3D in vitro platforms for screening transformative therapeutics targeting the tumor-stroma interplay.

11.
Adv Healthc Mater ; 11(13): e2102574, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35426253

RESUMEN

Bioengineering close-to-native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modeling toolboxes. Herein, pancreatic cancer living units-so termed cancer-on-a-bead models-are generated. Such user-programmable in vitro platforms exhibit biomimetic multicompartmentalization and tunable integration of cancer associated stromal elements. These stratified units can be rapidly assembled in-air, exhibit reproducible morphological features, tunable size, and recapitulate spatially resolved tumor-stroma extracellular matrix (ECM) niches. Compartmentalization of pancreatic cancer and stromal cells in well-defined ECM microenvironments stimulates the secretion of key biomolecular effectors including transforming growth factor ß and Interleukin 1-ß, closely emulating the signatures of human pancreatic tumors. Cancer-on-a-bead models also display increased drug resistance to chemotherapeutics when compared to their reductionistic counterparts, reinforcing the importance to differentially model ECM components inclusion and their spatial stratification as observed in vivo. Beyond providing a universal technology that enables spatial modularity in tumor-stroma elements bioengineering, a scalable, in-air fabrication of ECM-tunable 3D platforms that can be leveraged for recapitulating differential matrix composition occurring in other human neoplasias is provided here.


Asunto(s)
Neoplasias Pancreáticas , Microambiente Tumoral , Bioingeniería , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas
12.
Biomed Pharmacother ; 150: 113031, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35483199

RESUMEN

Castration-resistant prostate cancer (CRPC) is an incurable form of prostate cancer (PCa), with DNMT1 and G9a being reported as overexpressed, rendering them highly attractive targets for precision medicine. CM-272 is a dual inhibitor of both methyltransferases' activity. Herein, we assessed the response of different PCa cell lines to CM-272, in both 2D and 3D models, and explored the molecular mechanisms underlying CM-272 inhibitory effects. CRPC tissues displayed significantly higher DNMT1, G9a and H3K9me2 expression than localized PCa. In vitro, CM-272 caused a significant decrease in PCa cell viability and proliferation alongside with increased apoptotic levels. We disclose that, under the evaluated dose, CM-272 led to G9a activity inhibition, while not significantly affecting DNMT1 activity. Upon G9a knockdown, DU145 and PC3 showed decreased cell viability. Remarkably, DU145 cells treated with CM-272 or with G9a knockdown displayed no differences in viability, suggesting a SET-dependent mechanism. Contrarily, PC3 cell viability impact was higher in G9a knockdown, compared with CM-272 treatment, suggesting an additional G9a function. Moreover, DU145 cells overexpressing catalytically functional G9a disclosed higher resistance to CM-272 treatment, reinforcing that the drug mechanism of action is dependent on G9a catalytic function. Importantly, we successfully assembled spheroids from several prostate cell lines. Our results showed that CM-272 retained its anti-tumoral effects in 3D PCa models, leading to a clear reduction in cancer cell survival. We concluded that inhibition of G9a methyltransferase activity by CM-272 has anti-tumor effect in PCa cells, holding therapeutic potential against CRPC.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Células PC-3 , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología
13.
Nanomedicine ; 42: 102548, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35301158

RESUMEN

This study reports the formulation and delivery of hyaluronic acid-Zein (HA-Zein) nanogels loaded with Shikonin (SK) to selectively attenuate macrophage inflammasome. The self-assembled nanogels, produced by nanoprecipitation, exhibited high encapsulation efficiency, and were selectively internalized by human THP-1-derived macrophages without eliciting cytotoxic responses. Cell treatment with HA-Zein-SK nanogels before stimulation with LPS and Nigericin significantly suppressed caspase-1 activation and IL-1ß production, indicating inflammasome inhibition. Importantly, HA-Zein-SK nanogels bioinstructed inflammasome activated macrophages towards an anti-inflammatory CD163highHLA-DRlow phenotype and led to a marked reduction in the release of pro-inflammatory mediators (TNF-α, IL-6 and IP-10). Extracellular metabolic profiling additionally revealed SK-mediated downregulation of cellular glycolytic activity, which was corroborated by a significant decrease of glycolytic genes transcription. All in all, our findings demonstrate the potential of bioactive SK-containing, self-assembled nanogels to modulate exacerbated responses in innate immune cells and, prospectively, in human tissues where NRLP3 inflammasome is abnormally activated upon injury or disease.


Asunto(s)
Inflamasomas , Zeína , Inflamasomas/metabolismo , Interleucina-1beta/genética , Macrófagos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Nanogeles , Naftoquinonas
14.
Trends Biotechnol ; 40(4): 432-447, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34556340

RESUMEN

Combinatorial conjugation of organ-on-a-chip platforms with additive manufacturing technologies is rapidly emerging as a disruptive approach for upgrading cancer-on-a-chip systems towards anatomic-sized dynamic in vitro models. This valuable technological synergy has potential for giving rise to truly physiomimetic 3D models that better emulate tumor microenvironment elements, bioarchitecture, and response to multidimensional flow dynamics. Herein, we showcase the most recent advances in bioengineering 3D-bioprinted cancer-on-a-chip platforms and provide a comprehensive discussion on design guidelines and possibilities for high-throughput analysis. Such hybrid platforms represent a new generation of highly sophisticated 3D tumor models with improved biomimicry and predictability of therapeutics performance.


Asunto(s)
Bioimpresión , Neoplasias , Bioimpresión/métodos , Humanos , Dispositivos Laboratorio en un Chip , Neoplasias/patología , Neoplasias/terapia , Impresión Tridimensional , Microambiente Tumoral
15.
Carbohydr Polym ; 277: 118826, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34893243

RESUMEN

Recent advances on brewer's yeast cell wall polysaccharides have unraveled exquisite structural features and diverse composition with (ß1→3), (ß1→6), (α1→4), (ß1→4)-mix-linked glucans that are recognized to interact with different cell receptors and trigger specific biological responses. Herein, a comprehensive showcase of structure-biofunctional relationships between yeast polysaccharides and their biological targets is highlighted, with a focus on polysaccharide features that govern the biomedical activity. The insolubility of ß-glucans is a crucial factor for binding and activation of Dectin-1 receptor, operating as adjuvants of immune responses. Contrarily, soluble low molecular weight ß-glucans have a strong inhibition of reactive oxygen species production, acting as antagonists of Dectin-1 mediated signaling. Soluble glucan-protein moieties can also act as antitumoral agents. The balance between mannoproteins-TLR2 and ß-glucans-Dectin-1 receptors-activation is crucial for osteogenesis. Biomedical applications value can also be obtained from yeast microcapsules as oral delivery systems, where highly branched (ß1→6)-glucans lead to higher receptor affinity.


Asunto(s)
Sistemas de Liberación de Medicamentos , Polisacáridos/química , Saccharomyces cerevisiae/química , Administración Oral , Animales , Pared Celular/química , Humanos , Polisacáridos/administración & dosificación
16.
Small Methods ; 5(5): e2001207, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34928079

RESUMEN

Cancer-associated pancreatic stellate cells installed in periacinar/periductal regions are master players in generating the characteristic biophysical shield found in pancreatic ductal adenocarcinoma (PDAC). Recreating this unique PDAC stromal architecture and its desmoplastic microenvironment in vitro is key to discover innovative treatments. However, this still remains highly challenging to realize. Herein, organotypic 3D microtumors that recapitulate PDAC-stroma spatial bioarchitecture, as well as its biomolecular, metabolic, and desmoplastic signatures, are bioengineered. Such newly engineered platforms, termed stratified microenvironment spheroid models - STAMS - mimic the spatial stratification of cancer-stromal cells, exhibit a reproducible morphology and sub-millimeter size. In culture, 3D STAMS secrete the key molecular biomarkers found in human pancreatic cancer, namely TGF-ß, FGF-2, IL-1ß, and MMP-9, among others. This is accompanied by an extensive desmoplastic reaction where collagen and glycosaminoglycans (GAGs) de novo deposition is observed. These stratified models also recapitulate the resistance to various chemotherapeutics when compared to standard cancer-stroma random 3D models. Therapeutics resistance is further evidenced upon STAMS inclusion in a tumor extracellular matrix (ECM)-mimetic hydrogel matrix, reinforcing the importance of mimicking PDAC-stroma bioarchitectural features in vitro. The 3D STAMS technology represents a next generation of biomimetic testing platforms with improved potential for advancing high-throughput screening and preclinical validation of innovative pancreatic cancer therapies.


Asunto(s)
Modelos Biológicos , Esferoides Celulares/metabolismo , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/patología , Técnicas de Cultivo Tridimensional de Células , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Colágeno/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Transición Epitelial-Mesenquimal/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Hidrogeles/química , Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias Pancreáticas/patología , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos , Microambiente Tumoral
17.
EBioMedicine ; 74: 103717, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34839265

RESUMEN

Engineered living materials represent a new generation of human-made biotherapeutics that are highly attractive for a myriad of medical applications. In essence, such cell-rich platforms provide encodable bioactivities with extended lifetimes and environmental multi-adaptability currently unattainable in conventional biomaterial platforms. Emerging cell bioengineering tools are herein discussed from the perspective of materializing living cells as cooperative building blocks that drive the assembly of multiscale living materials. Owing to their living character, pristine cellular units can also be imparted with additional therapeutically-relevant biofunctionalities. On this focus, the most recent advances on the engineering of mammalian living materials and their biomedical applications are herein outlined, alongside with a critical perspective on major roadblocks hindering their realistic clinical translation. All in all, transposing the concept of leveraging living materials as autologous tissue-building entities and/or self-regulated biotherapeutics opens new realms for improving precision and personalized medicine strategies in the foreseeable future.


Asunto(s)
Ingeniería Celular/métodos , Animales , Terapia Biológica , Humanos , Mamíferos , Medicina Regenerativa
18.
ACS Appl Mater Interfaces ; 13(30): 35469-35483, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34284573

RESUMEN

Osteoporosis therapies leveraging bisphosphonates and mineral components (e.g., magnesium, calcium, and strontium) have been raising attention because of their potential for managing this ever-growing disease. The administration of multicomponent therapeutics (combined therapy) in elderly patients is complex and suffers from low patient adherence. Herein, we report an all-in-one combination of four antiosteoporotic components into a new family of coordination complexes: [M2(H4alen)4(H2O)2]·1.5H2O [where M2+ = Mg2+ (1), (Mg0.535Ca0.465)2+ (2) and (Mg0.505Ca0.450Sr0.045)2+ (3)]. These solid-state complexes were prepared, for the first time, through microwave-assisted synthesis. It is demonstrated that the compounds are capable of releasing their antiosteoporotic components, both in conditions that mimic the path along the gastrointestinal tract and in long periods under physiological conditions (pH ∼7.4). More importantly, when administered in low concentrations, the compounds did not elicit a cytotoxic effect toward liver, kidney, and osteoblast-like cell lines. Besides, it is important to highlight the unique coordination complex with four bone therapeutic components, [(Mg0.505Ca0.450Sr0.045)2(H4alen)4(H2O)2]·1.5H2O (3), which significantly promoted osteoblast metabolic activity up to ca. 1.4-fold versus the control group. These findings bring this type of compounds one-step closer to be considered as an all-in-one and more effective treatment for managing chronic bone diseases, prompting further research on their therapeutic properties.


Asunto(s)
Alendronato/análogos & derivados , Alendronato/farmacología , Conservadores de la Densidad Ósea/farmacología , Complejos de Coordinación/farmacología , Conservadores de la Densidad Ósea/síntesis química , Complejos de Coordinación/síntesis química , Liberación de Fármacos , Quimioterapia , Células Hep G2 , Humanos , Magnesio/química , Osteoblastos/efectos de los fármacos , Osteoporosis/tratamiento farmacológico
19.
Biomaterials ; 275: 120983, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34186236

RESUMEN

Decellularized extracellular matrix (dECM) is emerging as a valuable tool for generating 3D in vitro tumor models that better recapitulate tumor-stroma interactions. However, the development of dECM-3D heterotypic microtumors exhibiting a controlled morphology is yet to be materialized. Precisely controlling microtumors morphologic features is key to avoid an inaccurate evaluation of therapeutics performance during preclinical screening. To address this, herein we employed ultra-low adhesion surfaces for bioengineering organotypic 3D metastatic breast cancer-fibroblast models enriched with dECM microfibrillar fragments, as a bottom-up strategy to include major matrix components and their associated biomolecular cues during the early stages of 3D microtissue spheroids assembly, simulating pre-existing ECM presence in the in vivo setting. This biomimetic approach enabled the self-assembly of dECM-3D tumor-stroma spheroids with tunable size and reproducible morphology. Along time, dECM enriched and stroma-rich microtumors exhibited necrotic core formation, secretion of key biomarkers and higher cancer-cell specific resistance to different chemotherapeutics in comparison to standard spheroids. Exometabolomics profiling of dECM-Spheroid in vitro models further identified important breast cancer metabolic features including glucose/pyruvate consumption and lactate excretion, which suggest an intense glycolytic activity, recapitulating major hallmarks of the native microenvironment. Such organotypic dECM-enriched microtumors overcome the morphologic variability generally associated with cell-laden dECM models, while providing a scalable testing platform that can be foreseeable leveraged for high-throughput screening of candidate therapeutics.


Asunto(s)
Neoplasias de la Mama , Ensayos Analíticos de Alto Rendimiento , Neoplasias de la Mama/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Matriz Extracelular , Femenino , Fibroblastos , Humanos , Esferoides Celulares , Microambiente Tumoral
20.
Biofabrication ; 13(3)2021 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-34075894

RESUMEN

The design of dynamically crosslinked hydrogel bioinks for three-dimensional (3D) bioprinting is emerging as a valuable strategy to advance the fabrication of mechanically tuneable cell-laden constructs for 3Din vitrodisease modelling and tissue engineering applications. Herein, a dynamic bioink comprising boronic acid-functionalised laminarin and alginate is explored for bioprinting 3D constructs under physiologically relevant conditions. The formulated bioink takes advantage of a double crosslinked network that combines covalent but reversible boronate ester bonds and ionic gelation via divalent cations. Moreover, it exhibits suitable rheological properties and improved mechanical features owing to its modular crosslinking chemistry, yielding stable constructs with user-programmable architecture. We explored such dynamic bioink as a supporting matrix for different cell classes, namely osteoblast precursors, fibroblasts and breast cancer cells. The resulting cell-laden bioprinted hydrogels display a homogeneous cell distribution post-printing and exceptional cell viability (>90%) that can be maintained for prolonged time periods in culture (14 days) for all cell lines. This simple and chemically versatile approach is envisaged to accelerate the development of multifunctional bioinks and contribute towards the fabrication of biomimetic 3D scaffolds with applicability in a wide range of predictive or exploratory biomedical platforms.


Asunto(s)
Bioimpresión , Ingeniería de Tejidos , Andamios del Tejido , Alginatos , Boro , Glucanos , Hidrogeles , Impresión Tridimensional
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