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2.
Small ; : e2106357, 2022 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-35607752

RESUMEN

It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore-forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl-modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA-based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.

3.
Bioact Mater ; 15: 482-494, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35386341

RESUMEN

Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.

4.
Molecules ; 27(7)2022 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-35408547

RESUMEN

Silk fibroin, regenerated from Bombyx mori, has shown considerable promise as a printable, aqueous-based ink using a bioinspired salt-bath system in our previous work. Here, we further developed and characterized silk fibroin inks that exhibit concentration-dependent fluorescence spectra at the molecular level. These insights supported extrusion-based 3D printing using concentrated silk fibroin solutions as printing inks. 3D monolithic proteinaceous structures with high aspect ratios were successfully printed using these approaches, including cantilevers only supported at one end. This work provides further insight and broadens the utility of 3D printing with silk fibroin inks for the microfabrication of proteinaceous structures.


Asunto(s)
Bombyx , Fibroínas , Animales , Fibroínas/química , Tinta , Impresión Tridimensional , Seda/química , Agua
5.
iScience ; 25(4): 104110, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35378862

RESUMEN

The brain is arguably the most fascinating and complex organ in the human body. Recreating the brain in vitro is an ambition restricted by our limited understanding of its structure and interacting elements. One of these interacting parts, the brain microvasculature, is distinguished by a highly selective barrier known as the blood-brain barrier (BBB), limiting the transport of substances between the blood and the nervous system. Numerous in vitro models have been used to mimic the BBB and constructed by implementing a variety of microfabrication and microfluidic techniques. However, currently available models still cannot accurately imitate the in vivo characteristics of BBB. In this article, we review recent BBB models by analyzing each parameter affecting the accuracy of these models. Furthermore, we propose an investigation of the synergy between BBB models and neuronal tissue biofabrication, which results in more advanced models, including neurovascular unit microfluidic models and vascularized brain organoid-based models.

6.
Biofabrication ; 14(3)2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35344936

RESUMEN

Cancer continues to be a leading cause of mortality in modern societies; therefore, improved and more reliablein vitrocancer models are needed to expedite fundamental research and anti-cancer drug development. Here, we describe the use of a miniaturized continuous stirred tank reactor (mCSTR) to first fabricate and mature cancer spheroids (i.e. derived from MCF7 cells, DU145 cells, and a mix of MCF7 cells and fibroblasts), and then to conduct anti-cancer drug assays under continuous perfusion. This 3 ml mCSTR features an off-center agitation system that enables homogeneous chaotic laminar mixing at low speeds to support cell aggregation. We incubated cell suspensions for 3 d in ultra-low-attachment plates to allow formation of discoid cell aggregates (∼600µm in diameter). These cell aggregates were then transferred into mCSTRs and continuously fed with culture medium. We characterized the spheroid morphology and the expression of relevant tumor biomarkers at different maturation times for up to 4 weeks. The spheroids progressively increased in size during the first 5-6 d of culture to reach a steady diameter between 600 and 800µm. In proof-of-principle experiments, we demonstrated the use of this mCSTR in anti-cancer drug testing. Three drugs commonly used in breast cancer treatment (doxorubicin, docetaxel, and paclitaxel) were probed at different concentrations in MCF7-derived spheroids. In these experiments, we evaluated cell viability, glucose consumption, spheroid morphology, lactate dehydrogenase activity, and the expression of genes associated with drug resistance (ABCB1andABCC1) and anti-apoptosis (Bcl2). We envision the use of this agitated system as a tumor-on-a-chip platform to expedite efficacy and safety testing of novel anti-cancer drugs and possibly in personalized medicine applications.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular , Femenino , Humanos , Impresión Tridimensional , Esferoides Celulares
7.
Small ; : e2105255, 2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35304821

RESUMEN

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

8.
Biofabrication ; 14(2)2022 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-35226880

RESUMEN

Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two immiscible aqueous phases of gelatin methacryloyl (GelMA) and dextran, further endowed with anti-bacterial and anti-inflammatory properties. This micropore-forming GelMA-dextran (PGelDex) bioink exhibited excellent printability with vat-polymerization, extrusion, and handheld bioprinting methods. The porous structure was confirmed after bioprinting, which promoted the spreading of the encapsulated cells, exhibiting the exceptional cytocompatibility of this bioink formulation. To extend the applications of such a micropore-forming bioink, interleukin-4 (IL-4)-loaded silver-coated gold nanorods (AgGNRs) and human mesenchymal stem cells (MSCs) were simultaneously incorporated, to display synergistic anti-infection behavior and immunomodulatory function. The results revealed the anti-bacterial properties of the AgGNR-loaded PGelDex bioink for both Gram-negative and Gram-positive bacteria. The data also indicated that the presence of IL-4 and MSCs facilitated macrophage M2-phenotype differentiation, suggesting the potential anti-inflammatory feature of the bioink. Overall, this unique anti-bacterial and immunomodulatory micropore-forming bioink offers an effective strategy for the inhibition of bacterial-induced infections as well as the ability of immune-regulation, which is a promising candidate for broadened tissue bioprinting applications.


Asunto(s)
Bioimpresión , Andamios del Tejido , Antiinflamatorios , Bioimpresión/métodos , Dextranos , Gelatina/química , Gelatina/farmacología , Hidrogeles/química , Interleucina-4 , Metacrilatos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
9.
Biofabrication ; 14(2)2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-35008080

RESUMEN

Thrombosis in the circulation system can lead to major myocardial infarction and cardiovascular deaths. Understanding thrombosis formation is necessary for developing safe and effective treatments. In this work, using digital light processing (DLP)-based 3D printing, we fabricated sophisticatedin vitromodels of blood vessels with internal microchannels that can be used for thrombosis studies. In this regard, photoacoustic microscopy (PAM) offers a unique advantage for label-free visualization of the 3D-printed vessel models, with large penetration depth and functional sensitivity. We compared the imaging performances of two PAM implementations: optical-resolution PAM and acoustic-resolution PAM, and investigated 3D-printed vessel structures with different patterns of microchannels. Our results show that PAM can provide clear microchannel structures at depths up to 3.6 mm. We further quantified the blood oxygenation in the 3D-printed vascular models, showing that thrombi had lower oxygenation than the normal blood. We expect that PAM can find broad applications in 3D printing and bioprinting forin vitrostudies of various vascular and other diseases.


Asunto(s)
Técnicas Fotoacústicas , Microscopía/métodos , Técnicas Fotoacústicas/métodos , Impresión Tridimensional , Análisis Espectral
10.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-35074913

RESUMEN

The exceptional elastic resilience of some protein materials underlies essential biomechanical functions with broad interest in biomedical fields. However, molecular design of elastic resilience is restricted to amino acid sequences of a handful of naturally occurring resilient proteins such as resilin and elastin. Here, we exploit non-resilin/elastin sequences that adopt kinetically stabilized, random coil-dominated conformations to achieve near-perfect resilience comparable with that of resilin and elastin. We also show a direct correlation between resilience and Raman-characterized protein conformations. Furthermore, we demonstrate that metastable conformation of proteins enables the construction of mechanically graded protein materials that exhibit spatially controlled conformations and resilience. These results offer insights into molecular mechanisms of protein elastomers and outline a general conformation-driven strategy for developing resilient and functional protein materials.


Asunto(s)
Modelos Moleculares , Conformación Proteica , Proteínas/química , Secuencia de Aminoácidos , Fibroínas/química , Análisis Espectral , Relación Estructura-Actividad
11.
Nat Rev Nephrol ; 18(4): 241-257, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35064233

RESUMEN

The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes.


Asunto(s)
Biomimética , Enfermedades Renales , Femenino , Humanos , Riñón , Glomérulos Renales , Masculino , Microfluídica , Organoides
12.
Theranostics ; 12(2): 891-909, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34976219

RESUMEN

Osteoarthritis (OA) is a prevalent debilitating age-related joint degenerative disease. It is a leading cause of pain and functional disability in older adults. Unfortunately, there is no cure for OA once the damage is established. Therefore, it promotes an urgent need for early detection and intervention of OA. Theranostics, combining therapy and diagnosis, emerges as a promising approach for OA management. However, OA theranostics is still in its infancy. Three fundamental needs have to be firstly fulfilled: i) a reliable OA model for disease pathogenesis investigation and drug screening, ii) an effective and precise diagnostic platform, and iii) an advanced fabrication approach for drug delivery and therapy. Meanwhile, microfluidics emerges as a versatile technology to address each of the needs and eventually boost the development of OA theranostics. Therefore, this review focuses on the applications of microfluidics, from benchtop to bedside, for OA modelling and drug screening, early diagnosis, and clinical therapy. We first introduce the basic pathophysiology of OA and point out the major unfilled research gaps in current OA management including lack of disease modelling and drug screening platforms, early diagnostic modalities and disease-modifying drugs and delivery approaches. Accordingly, we then summarize the state-of-the-art microfluidics technology for OA management from in vitro modelling and diagnosis to therapy. Given the existing promising results, we further discuss the future development of microfluidic platforms towards clinical translation at the crossroad of engineering and biomedicine.


Asunto(s)
Microfluídica , Osteoartritis , Animales , Técnicas Biosensibles , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Microfluídica/tendencias , Osteoartritis/diagnóstico , Osteoartritis/tratamiento farmacológico , Osteoartritis/fisiopatología , Osteoartritis/terapia , Sistemas de Atención de Punto , Medicina de Precisión
13.
Adv Healthc Mater ; 11(7): e2100884, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34558232

RESUMEN

Multiple myeloma (MM) is a malignancy of plasma cells accounting for ≈12% of hematological malignancies. In this study, the fabrication of a high-content in vitro MM model using a coaxial extrusion bioprinting method is reported, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and the inner soft hydrogel-based core. MM cells are mono-cultured or co-cultured with HS5 stromal cells that can release interleukin-6 (IL-6), where the cells show superior behaviors and responses to bortezomib in 3D models than in the planar cultures. Tocilizumab, a recombinant humanized anti-IL-6 receptor (IL-6R), is investigated for its efficacy to enhance the chemosensitivity of bortezomib on MM cells cultured in the 3D model by inhibiting IL-6R. More excitingly, in a proof-of-concept demonstration, it is revealed that patient-derived MM cells can be maintained in 3D-bioprinted microenvironment with decent viability for up to 7 days evaluated, whereas they completely die off in planar culture as soon as 5 days. In conclusion, a 3D-bioprinted MM model is fabricated to emulate some characteristics of the human bone marrow to promote growth and proliferation of the encapsulated MM cells, providing new insights for MM modeling, drug development, and personalized therapy in the future.


Asunto(s)
Bioimpresión , Mieloma Múltiple , Bioimpresión/métodos , Bortezomib/farmacología , Bortezomib/uso terapéutico , Técnicas de Cocultivo , Humanos , Hidrogeles/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Microambiente Tumoral
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.
Biomaterials ; 280: 121302, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34894584

RESUMEN

Monotherapy with a single chemotherapeutic regimen has met with significant hurdles in terms of clinical efficacy. The complexity of cancer accentuates the need for an alternative approach with a combination of two or more therapeutic regimens to win the battle. However, it is still a challenge to develop a successful combination of drugs with high efficiency and low toxicity to control cancer growth. While gemcitabine monotherapy remains a choice of standard treatment for advanced breast cancer, the approach has not prolonged the median survival time of metastatic breast cancer patients. Here, we report a hyaluronic acid (HA)-based drug combination of gemcitabine (GEM) with imiquimod (IMQ) to stimulate immune cells for anticancer activity. Treatment of the drug combination (IMQ-HA-GEM) showed enhanced anticancer activity against 4T1 breast tumor cells in vitro. Our study with a microfluidics-based 3D, compartmentalized cancer model showed that infiltration of THP-1 monocytes occurred particularly at the site of cancer cells treated with IMQ-HA-GEM. Moreover, IMQ-HA-GEM significantly suppressed the volume of 4T1 breast tumor of mice in vivo. Flow cytometry study displayed a significantly higher activation of CD11b+ immune cells in the blood of mice treated with IMQ-HA-GEM, whereas immunohistochemistry study revealed greater prevalence of CD68+ tumor-associated macrophages in the tumor. Histological examination of isolated tumors of mice treated with IMQ-HA-GEM further confirmed the efficacy of drug combination on cancer cells. This study supports the conclusion that imiquimod potentiates the effect of gemcitabine by activating immune cells to suppress tumors in the form of combination nanoparticles.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Femenino , Humanos , Imiquimod/uso terapéutico , Ratones
16.
Adv Mater ; 34(1): e2107038, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34609032

RESUMEN

Recapitulation of complex tissues signifies a remarkable challenge and, to date, only a few approaches have emerged that can efficiently reconstruct necessary gradients in 3D constructs. This is true even though mimicry of these gradients is of great importance to establish the functionality of engineered tissues and devices. Here, a composable-gradient Digital Light Processing (DLP)-based (bio)printing system is developed, utilizing the unprecedented integration of a microfluidic mixer for the generation of either continual or discrete gradients of desired (bio)inks in real time. Notably, the precisely controlled gradients are composable on-the-fly by facilely by adjusting the (bio)ink flow ratios. In addition, this setup is designed in such a way that (bio)ink waste is minimized when exchanging the gradient (bio)inks, further enhancing this time- and (bio)ink-saving strategy. Various planar and 3D structures exhibiting continual gradients of materials, of cell densities, of growth factor concentrations, of hydrogel stiffness, and of porosities in horizontal and/or vertical direction, are exemplified. The composable fabrication of multifunctional gradients strongly supports the potential of the unique bioprinting system in numerous biomedical applications.


Asunto(s)
Bioimpresión , Hidrogeles/química , Tinta , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido
17.
Small ; 18(3): e2101699, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34817129

RESUMEN

High-performance hemostasis has become increasingly essential in treating various traumas. However, available topical hemostats still have various drawbacks and side-effects. Herein, hemostatic powders derived from the skin secretion of Andrias davidianus (SSAD) with controllable particle size are prepared using feasible frozen-ball milling following lyophilization for hemorrhage-control. Scanning electron microscopy, rheometry, and Brunauer-Emmett-Teller test are used to characterize the coagulation-promoting surface topography, rheological properties, and porous structure of the SSAD particles. The blood-coagulation assays showed that the SSAD powders can induce blood-absorption in a particle size-dependent manner. Particle sizes of the SSAD powders larger than 200 µm and smaller than 800 µm greatly affect the blood-clotting rate. Associated with the thromboelastography (TEG) and amino acid/protein composition analyses, the accessibility and diffusion of blood are mainly dependent on the wettability, adhesivity, and clotting factors of the SSAD particles. Rapid hemostasis in vivo further involves three hemorrhage models (liver, femoral artery, and tail) as well as an oral wound model, which suggest favorable hemostatic and simultaneous regenerative effects of the SSAD hemostatic powder. Considering its degradability and good biocompatibility, SSAD can be an optimal candidate for a new class of inexpensive, natural, and promising hemostatic and wound-dressing agent.


Asunto(s)
Hemostasis , Hemostáticos , Coagulación Sanguínea , Hemostáticos/farmacología , Polvos/farmacología , Cicatrización de Heridas
18.
Methods Mol Biol ; 2375: 61-75, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34591299

RESUMEN

Three-dimensional bioprinting represents promising approach for fabricating standalone and perfusable vascular conduits using biocompatible materials. Here we describe a step-by-step method by using a multichannel coaxial extrusion system (MCCES) and a blend bioink constituting gelatin methacryloyl, sodium alginate, and eight-arm poly(ethylene glycol)-acrylate with a tripentaerythritol core for the fabrication of standalone circumferentially multilayered hollow tubes. This microfluidic bioprinting method allows the fabrication of perfusable vascular conduits with a core lumen, an inner endothelial layer resembling the tunica intima, and an outer smooth muscle cell layer resembling the tunica media of the blood vessel. Biocompatible and perfusable blood vessels with a widely tunable size range in terms of luminal diameters and wall thicknesses can be successfully fabricated using the MCCES.


Asunto(s)
Bioimpresión , Gelatina , Metacrilatos , Microfluídica , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido
19.
Adv Mater ; 34(12): e2108931, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34935203

RESUMEN

Due to the poor mechanical properties of many hydrogel bioinks, conventional 3D extrusion bioprinting is usually conducted based on the X-Y plane, where the deposited layers are stacked in the Z-direction with or without the support of prior layers. Herein, a technique is reported, taking advantage of a cryoprotective bioink to enable direct extrusion bioprinting in the vertical direction in the presence of cells, using a freezing plate with precise temperature control. Of interest, vertical 3D cryo-bioprinting concurrently allows the user to create freestanding filamentous constructs containing interconnected, anisotropic microchannels featuring gradient sizes aligned in the vertical direction, also associated with enhanced mechanical performances. Skeletal myoblasts within the 3D-cryo-bioprinted hydrogel constructs show enhanced cell viability, spreading, and alignment, compared to the same cells in the standard hydrogel constructs. This method is further extended to a multimaterial format, finding potential applications in interface tissue engineering, such as creation of the muscle-tendon unit and the muscle-microvascular unit. The unique vertical 3D cryo-bioprinting technique presented here suggests improvements in robustness and versatility to engineer certain tissue types especially those anisotropic in nature, and may extend broad utilities in tissue engineering, regenerative medicine, drug discovery, and personalized therapeutics.


Asunto(s)
Bioimpresión , Andamios del Tejido , Bioimpresión/métodos , Hidrogeles , Impresión Tridimensional , Ingeniería de Tejidos/métodos
20.
Mater Today Bio ; 12: 100162, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34870141

RESUMEN

Biofabrication via light-based 3D printing offers superior resolution and ability to generate free-form architectures, compared to conventional extrusion technologies. While extensive efforts in the design of new hydrogel bioinks lead to major advances in extrusion methods, the accessibility of lithographic bioprinting is still hampered by a limited choice of cell-friendly resins. Herein, we report the development of a novel set of photoresponsive bioresins derived from ichthyic-origin gelatin, designed to print high-resolution hydrogel constructs with embedded convoluted networks of vessel-mimetic channels. Unlike mammalian gelatins, these materials display thermal stability as pre-hydrogel solutions at room temperature, ideal for bioprinting on any easily-accessible lithographic printer. Norbornene- and methacryloyl-modification of the gelatin backbone, combined with a ruthenium-based visible light photoinitiator and new coccine as a cytocompatible photoabsorber, allowed to print structures resolving single-pixel features (∼50 â€‹µm) with high shape fidelity, even when using low stiffness gels, ideal for cell encapsulation (1-2 â€‹kPa). Moreover, aqueous two-phase emulsion bioresins allowed to modulate the permeability of the printed hydrogel bulk. Bioprinted mesenchymal stromal cells displayed high functionality over a month of culture, and underwent multi-lineage differentiation while colonizing the bioresin bulk with tissue-specific neo-deposited extracellular matrix. Importantly, printed hydrogels embedding complex channels with perfusable lumen (diameter <200 â€‹µm) were obtained, replicating anatomical 3D networks with out-of-plane branches (i.e. brain vessels) that cannot otherwise be reproduced by extrusion bioprinting. This versatile bioresin platform opens new avenues for the widespread adoption of lithographic biofabrication, and for bioprinting complex channel-laden constructs with envisioned applications in regenerative medicine and hydrogel-based organ-on-a-chip devices.

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