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1.
Electrophoresis ; 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35452525

RESUMEN

Accurate manipulation of fluids in microfluidic devices is an important factor affecting their functions. Since the emergence of microfluidic technology to transport fluids in microchannels, the electric field has been utilized as an effective dynamic pumping mechanism. This review attempts to provide a fundamental insight of the various electric-driven flows in microchannels and their working mechanisms as micropumps for microfluidic devices. Different electrokinetic mechanisms implemented in electrohydrodynamic-, electroosmosis-, electrothermal, and dielectrophoresis-based micropumps are discussed. A detailed description of different mechanisms is presented to provide a comprehensive overview on the key parameters used in electric micropumps. Furthermore, electrode configurations and their shapes in different micropumps are explored and categorized to provide conclusive information for the selection of efficient, simple, and affordable strategies to transport fluids in microfluidic devices. In this paper, recent theoretical, numerical and experimental investigations are covered to provide a better insight both on the operational mechanisms and strategies for lab-on-chip applications.

2.
Trends Biotechnol ; 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35483990

RESUMEN

Bioprinting has emerged as a strong tool for devising regenerative therapies to address unmet medical needs. However, the translation of conventional in vitro bioprinting approaches is partially hindered due to challenges associated with the fabrication and implantation of irregularly shaped scaffolds and their limited accessibility for immediate treatment by healthcare providers. An alternative strategy that has recently drawn significant attention is to directly print the bioink into the patient's body, so-called 'in situ bioprinting'. The bioprinting strategy and the associated bioink need to be specifically designed for in situ bioprinting to meet the particular requirements of direct deposition in vivo. In this review, we discuss the developed in situ bioprinting strategies, their advantages, challenges, and possible future improvements.

3.
Adv Mater ; 34(12): e2105883, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34773667

RESUMEN

Skeletal muscles play important roles in critical body functions and their injury or disease can lead to limitation of mobility and loss of independence. Current treatments result in variable functional recovery, while reconstructive surgery, as the gold-standard approach, is limited due to donor shortage, donor-site morbidity, and limited functional recovery. Skeletal muscle tissue engineering (SMTE) has generated enthusiasm as an alternative solution for treatment of injured tissue and serves as a functional disease model. Recently, bioprinting has emerged as a promising tool for recapitulating the complex and highly organized architecture of skeletal muscles at clinically relevant sizes. Here, skeletal muscle physiology, muscle regeneration following injury, and current treatments following muscle loss are discussed, and then bioprinting strategies implemented for SMTE are critically reviewed. Subsequently, recent advancements that have led to improvement of bioprinting strategies to construct large muscle structures, boost myogenesis in vitro and in vivo, and enhance tissue integration are discussed. Bioinks for muscle bioprinting, as an essential part of any bioprinting strategy, are discussed, and their benefits, limitations, and areas to be improved are highlighted. Finally, the directions the field should expand to make bioprinting strategies more translational and overcome the clinical unmet needs are discussed.


Asunto(s)
Bioimpresión , Músculo Esquelético , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido/química
4.
Bioact Mater ; 8: 296-308, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34541402

RESUMEN

Acute and chronic wounds affect millions of people around the world, imposing a growing financial burden on patients and hospitals. Despite the application of current wound management strategies, the physiological healing process is disrupted in many cases, resulting in impaired wound healing. Therefore, more efficient and easy-to-use treatment modalities are needed. In this study, we demonstrate the benefit of in vivo printed, growth factor-eluting adhesive scaffolds for the treatment of full-thickness wounds in a porcine model. A custom-made handheld printer is implemented to finely print gelatin-methacryloyl (GelMA) hydrogel containing vascular endothelial growth factor (VEGF) into the wounds. In vitro and in vivo results show that the in situ GelMA crosslinking induces a strong scaffold adhesion and enables printing on curved surfaces of wet tissues, without the need for any sutures. The scaffold is further shown to offer a sustained release of VEGF, enhancing the migration of endothelial cells in vitro. Histological analyses demonstrate that the administration of the VEGF-eluting GelMA scaffolds that remain adherent to the wound bed significantly improves the quality of healing in porcine wounds. The introduced in vivo printing strategy for wound healing applications is translational and convenient to use in any place, such as an operating room, and does not require expensive bioprinters or imaging modalities.

5.
Nanoscale ; 14(3): 797-814, 2022 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-34951427

RESUMEN

Extreme loss of skeletal muscle overwhelms the natural regenerative capability of the body, results in permanent disability and substantial economic burden. Current surgical techniques result in poor healing, secondary injury to the autograft donor site, and incomplete recuperation of muscle function. Most current tissue engineering and regenerative strategies fail to create an adequate mechanical and biological environment that enables cell infiltration, proliferation, and myogenic differentiation. In this study, we present a nanoengineered skeletal muscle scaffold based on functionalized gelatin methacrylate (GelMA) hydrogel, optimized for muscle progenitors' proliferation and differentiation. The scaffold was capable of controlling the release of insulin-like growth factor 1 (IGF-1), an important myogenic growth factor, by utilizing the electrostatic interactions with LAPONITE® nanoclays (NCs). Physiologically relevant levels of IGF-1 were maintained during a controlled release over two weeks. The NC was able to retain 50% of the released IGF-1 within the hydrogel niche, significantly improving cellular proliferation and differentiation compared to control hydrogels. IGF-1 supplemented medium controls required 44% more IGF-1 than the comparable NC hydrogel composites. The nanofunctionalized scaffold is a viable option for the treatment of extreme muscle injuries and offers scalable benefits for translational interventions and the growing field of clean meat production.


Asunto(s)
Desarrollo de Músculos , Ingeniería de Tejidos , Gelatina , Hidrogeles , Músculo Esquelético
6.
Appl Phys Rev ; 8(4): 041415, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34970378

RESUMEN

Poor cellular spreading, proliferation, and infiltration, due to the dense biomaterial networks, have limited the success of most thick hydrogel-based scaffolds for tissue regeneration. Here, inspired by whipped cream production widely used in pastries, hydrogel-based foam bioinks are developed for bioprinting of scaffolds. Upon cross-linking, a multiscale and interconnected porous structure, with pores ranging from few to several hundreds of micrometers, is formed within the printed constructs. The effect of the process parameters on the pore size distribution and mechanical and rheological properties of the bioinks is determined. The developed foam bioinks can be easily printed using both conventional and custom-built handheld bioprinters. In addition, the foam inks are adhesive upon in situ cross-linking and are biocompatible. The subcutaneous implantation of scaffolds formed from the engineered foam bioinks showed their rapid integration and vascularization in comparison with their non-porous hydrogel counterparts. In addition, in vivo application of the foam bioink into the non-healing muscle defect of a murine model of volumetric muscle loss resulted in a significant functional recovery and higher muscle forces at 8 weeks post injury compared with non-treated controls.

7.
Nanomaterials (Basel) ; 11(9)2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34578572

RESUMEN

Polymeric hydrogels are currently at the center of research due to their particular characteristics. They have tunable physical, chemical, and biological properties making them a material of choice for a large range of applications. Polymer-composite and nanocomposite hydrogels were developed to enhance the native hydrogel's properties and to include numerous functionalities. In this work, alginate/gelatin-methacryloyl-based interpenetrating polymer network hydrogels were prepared with different alginate concentrations and investigated before and after the functionalization with nanoliposomes. The multiscale analysis was obtained through Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. The results show interactions between two polymers as well as between the nanoliposomes and biopolymer.

8.
ACS Biomater Sci Eng ; 7(10): 4694-4717, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34498461

RESUMEN

Biological additive manufacturing (Bio-AM) has emerged as a promising approach for the fabrication of biological scaffolds with nano- to microscale resolutions and biomimetic architectures beneficial to tissue engineering applications. However, Bio-AM processes tend to introduce flaws in the construct during fabrication. These flaws can be traced to material nonhomogeneity, suboptimal processing parameters, changes in the (bio)printing environment (such as nozzle clogs), and poor construct design, all with significant contributions to the alteration of a scaffold's mechanical properties. In addition, the biological response of endogenous and exogenous cells interacting with the defective scaffolds could become unpredictable. In this review, we first described extrusion-based Bio-AM. We highlighted the salient architectural and mechanotransduction parameters affecting the response of cells interfaced with the scaffolds. The process phenomena leading to defect formation and some of the tools for defect detection are reviewed. The limitations of the existing developments and the directions that the field should grow in order to overcome said limitations are discussed.


Asunto(s)
Mecanotransducción Celular , Ingeniería de Tejidos , Andamios del Tejido
10.
ACS Biomater Sci Eng ; 7(8): 3964-3979, 2021 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-34197076

RESUMEN

The use of three-dimensional (3D) printing for biomedical applications has expanded exponentially in recent years. However, the current portfolio of 3D printable inks is still limited. For instance, only few protein matrices have been explored as printing/bioprinting materials. Here, we introduce the use of zein, the primary constitutive protein in maize seeds, as a 3D printable material. Zein-based inks were prepared by dissolving commercial zein powder in ethanol with or without polyethylene glycol (PEG400) as a plasticizer. The rheological characteristics of our materials, studied during 21 days of aging/maturation, showed an increase in the apparent viscosity as a function of time in all formulations. The addition of PEG400 decreased the apparent viscosity. Inks with and without PEG400 and at different maturation times were tested for printability in a BioX bioprinter. We optimized the 3D printing parameters for each ink formulation in terms of extrusion pressure and linear printing velocity. Higher fidelity structures were obtained with inks that had maturation times of 10 to 14 days. We present different proof-of-concept experiments to demonstrate the versatility of the engineered zein inks for diverse biomedical applications. These include printing of complex and/or free-standing 3D structures, tablets for controlled drug release, and scaffolds for cell culture.


Asunto(s)
Bioimpresión , Zeína , Tinta , Impresión Tridimensional , Zea mays
12.
Appl Phys Rev ; 8(2): 021404, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34084254

RESUMEN

Controlling cellular organization is crucial in the biofabrication of tissue-engineered scaffolds, as it affects cell behavior as well as the functionality of mature tissue. Thus far, incorporation of physiochemical cues with cell-size resolution in three-dimensional (3D) scaffolds has proven to be a challenging strategy to direct the desired cellular organization. In this work, a rapid, simple, and cost-effective approach is developed for continuous printing of multicompartmental hydrogel fibers with intrinsic 3D microfilaments to control cellular orientation. A static mixer integrated into a coaxial microfluidic device is utilized to print alginate/gelatin-methacryloyl (GelMA) hydrogel fibers with patterned internal microtopographies. In the engineered microstructure, GelMA compartments provide a cell-favorable environment, while alginate compartments offer morphological and mechanical cues that direct the cellular orientation. It is demonstrated that the organization of the microtopographies, and consequently the cellular alignment, can be tailored by controlling flow parameters in the printing process. Despite the large diameter of the fibers, the precisely tuned internal microtopographies induce excellent cell spreading and alignment, which facilitate rapid cell proliferation and differentiation toward mature biofabricated constructs. This strategy can advance the engineering of functional tissues.

13.
Adv Healthc Mater ; 10(13): e2001922, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34050600

RESUMEN

Microneedle arrays (MNAs) have been used for decades to deliver drugs transdermally and avoid the obstacles of other delivery routes. Hydrogels are another popular method for delivering therapeutics because they provide tunable, controlled release of their encapsulated payload. However, hydrogels are not strong or stiff, and cannot be formed into constructs that penetrate the skin. Accordingly, it has so far been impossible to combine the transdermal delivery route provided by MNAs with the therapeutic encapsulation potential of hydrogels. To address this challenge, a low cost and simple, but robust, strategy employing MNAs is developed. These MNAs are formed from a rigid outer layer, 3D printed onto a conformal backing, and filled with drug-eluting hydrogels. Microneedles of different lengths are fabricated on a single patch, facilitating the delivery of various agents to different tissue depths. In addition to spatial distribution, temporal release kinetics can be controlled by changing the hydrogel composition or the needles' geometry. As a proof-of-concept, MNAs are used for the delivery of vascular endothelial growth factor (VEGF). Application of the rigid, resin-based outer layer allows the use of hydrogels regardless of their mechanical properties and makes these multicomponent MNAs suitable for a range of drug delivery applications.


Asunto(s)
Hidrogeles , Factor A de Crecimiento Endotelial Vascular , Administración Cutánea , Sistemas de Liberación de Medicamentos , Microinyecciones , Agujas , Impresión Tridimensional , Piel
14.
Bioact Mater ; 6(11): 3904-3923, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33997485

RESUMEN

Natural hydrogels are one of the most promising biomaterials for tissue engineering applications, due to their biocompatibility, biodegradability, and extracellular matrix mimicking ability. To surpass the limitations of conventional fabrication techniques and to recapitulate the complex architecture of native tissue structure, natural hydrogels are being constructed using novel biofabrication strategies, such as textile techniques and three-dimensional bioprinting. These innovative techniques play an enormous role in the development of advanced scaffolds for various tissue engineering applications. The progress, advantages, and shortcomings of the emerging biofabrication techniques are highlighted in this review. Additionally, the novel applications of biofabricated natural hydrogels in cardiac, neural, and bone tissue engineering are discussed as well.

15.
Acta Biomater ; 127: 313-326, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33705990

RESUMEN

Bone defects are commonly caused by traumatic injuries and tumor removal and critically sized defects overwhelm the regenerative capacity of the native tissue. Reparative strategies such as auto, xeno, and allografts have proven to be insufficient to reconstruct and regenerate these defects. For the first time, we introduce the use of handheld melt spun three dimensional printers that can deposit materials directly within the defect site to properly fill the cavity and form free-standing scaffolds. Engineered composite filaments were generated from poly(caprolactone) (PCL) doped with zinc oxide nanoparticles and hydroxyapatite microparticles. The use of PCL-based materials allowed low-temperature printing to avoid overheating of the surrounding tissues. The in situ printed scaffolds showed moderate adhesion to wet bone tissue, which can prevent scaffold dislocation. The printed scaffolds showed to be osteoconductive and supported the osteodifferentiation of mesenchymal stem cells. Biocompatibility of the scaffolds upon in vivo printing subcutaneously in mice showed promising results. STATEMENT OF SIGNIFICANCE.


Asunto(s)
Impresión Tridimensional , Andamios del Tejido , Animales , Regeneración Ósea , Huesos , Durapatita , Ratones , Osteogénesis , Poliésteres , Ingeniería de Tejidos
16.
Adv Healthc Mater ; 10(10): e2002152, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33644996

RESUMEN

Extremity skeletal muscle injuries result in substantial disability. Current treatments fail to recoup muscle function, but properly designed and implemented tissue engineering and regenerative medicine techniques can overcome this challenge. In this study, a nanoengineered, growth factor-eluting bioink that utilizes Laponite nanoclay for the controlled release of vascular endothelial growth factor (VEGF) and a GelMA hydrogel for a supportive and adhesive scaffold that can be crosslinked in vivo is presented. The bioink is delivered with a partially automated handheld printer for the in vivo formation of an adhesive and 3D scaffold. The effect of the controlled delivery of VEGF alone or paired with adhesive, supportive, and fibrilar architecture has not been studied in volumetric muscle loss (VML) injuries. Upon direct in vivo printing, the constructs are adherent to skeletal muscle and sustained release of VEGF. The in vivo printing of muscle ink in a murine model of VML injury promotes functional muscle recovery, reduced fibrosis, and increased anabolic response compared to untreated mice. The in vivo construction of a therapeutic-eluting 3D scaffold paves the way for the immediate treatment of a variety of soft tissue traumas.


Asunto(s)
Músculo Esquelético/lesiones , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Heridas y Lesiones/terapia , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular
17.
Adv Healthc Mater ; 10(8): e2001800, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33586339

RESUMEN

A major impediment preventing normal wound healing is insufficient vascularization, which causes hypoxia, poor metabolic support, and dysregulated physiological responses to injury. To combat this, the delivery of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to provide modest improvement in wound healing. Here, the importance of specialty delivery systems is explored in controlling wound bed drug distribution and consequently improving healing rate and quality. Two intradermal drug delivery systems, miniaturized needle arrays (MNAs) and liquid jet injectors (LJIs), are evaluated to compare effective VEGF delivery into the wound bed. The administered drug's penetration depth and distribution in tissue are significantly different between the two technologies. These systems' capability for efficient drug delivery is first confirmed in vitro and then assessed in vivo. While topical administration of VEGF shows limited effectiveness, intradermal delivery of VEGF in a diabetic murine model accelerates wound healing. To evaluate the translational feasibility of the strategy, the benefits of VEGF delivery using MNAs are assessed in a porcine model. The results demonstrate enhanced angiogenesis, reduced wound contraction, and increased regeneration. These findings show the importance of both therapeutics and delivery strategy in wound healing.


Asunto(s)
Preparaciones Farmacéuticas , Factor A de Crecimiento Endotelial Vascular , Inductores de la Angiogénesis , Animales , Ratones , Neovascularización Fisiológica , Porcinos , Factores de Crecimiento Endotelial Vascular , Cicatrización de Heridas
18.
Adv Healthc Mater ; 10(7): e2001305, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33576158

RESUMEN

Tendon and ligament injuries caused by trauma and degenerative diseases are frequent and affect diverse groups of the population. Such injuries reduce musculoskeletal performance, limit joint mobility, and lower people's comfort. Currently, various treatment strategies and surgical procedures are used to heal, repair, and restore the native tissue function. However, these strategies are inadequate and, in some cases, fail to re-establish the lost functionality. Tissue engineering and regenerative medicine approaches aim to overcome these disadvantages by stimulating the regeneration and formation of neotissues. Design and fabrication of artificial scaffolds with tailored mechanical properties are crucial for restoring the mechanical function of tendons. In this review, the tendon and ligament structure, their physiology, and performance are presented. On the other hand, the requirements are focused for the development of an effective reconstruction device. The most common fiber-based scaffolding systems are also described for tendon and ligament tissue regeneration like strand fibers, woven, knitted, braided, and braid-twisted fibrous structures, as well as electrospun and wet-spun constructs, discussing critically the advantages and limitations of their utilization. Finally, the potential of multilayered systems as the most effective candidates for tendon and ligaments tissue engineering is pointed out.


Asunto(s)
Tendones , Andamios del Tejido , Humanos , Ligamentos , Medicina Regenerativa , Ingeniería de Tejidos
19.
Appl Biochem Biotechnol ; 193(5): 1558-1573, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33484448

RESUMEN

Biological hydrogen (H2) is a promising candidate for production of renewable hydrogen. Using entrapped cells rather than conventional suspended cell cultures for the production of H2 offers several advantages, such as improved production yields related to higher cell density, and enhanced resistance to substrate and end-product inhibition. In this study, H2 production by a novel isolate of Clostridium intestinale (strain URNW) was evaluated using cells entrapped within 2% calcium-alginate beads under strictly anaerobic conditions. Both immobilized cells and suspended cultures were studied in sequential batch-mode anaerobic fermentation over 192 h. The production of H2 in the headspace was examined for four different initial cellobiose concentrations (5, 10, 20, and 40 mM). Although a lag period for initiation of the fermentation process was observed for bacteria entrapped within hydrogel beads, the immobilized cells achieved both higher volumetric production rates (mmol H2/(L culture h)) and molar yields (mol H2/mol glucose equivalent) of H2 compared with suspended cultures. In the current study, the maximum cellobiose consumption rate of 0.40 mM/h, corresponding to 133.3 mg/(L h), was achieved after 72 h of fermentation by immobilized cells, generating a high hydrogen yield of 3.57 mol H2/mol cellobiose, whereas suspended cultures only yielded 1.77 mol H2/mol cellobiose. The results suggest that cells remain viable within the hydrogels and proliferated with a slow rate over the course of fermentation. The stable productivity of immobilized cells over 8 days with four changes of medium depicted that the immobilized cells of the isolated strain can successfully yield higher hydrogen and lower soluble metabolites than suspended cells suggesting a feasible process for future applications for bioH2 production.


Asunto(s)
Clostridium/metabolismo , Hidrógeno/química , Alginatos/metabolismo , Celobiosa/metabolismo , Fermentación/fisiología , Hidrogeles/química
20.
Sci Rep ; 10(1): 20428, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33235239

RESUMEN

Non-healing wounds have placed an enormous stress on both patients and healthcare systems worldwide. Severe complications induced by these wounds can lead to limb amputation or even death and urgently require more effective treatments. Electrospun scaffolds have great potential for improving wound healing treatments by providing controlled drug delivery. Previously, we developed fibrous scaffolds from complex carbohydrate polymers [i.e. chitin-lignin (CL) gels]. However, their application was limited by solubility and undesirable burst drug release. Here, a coaxial electrospinning is applied to encapsulate the CL gels with polycaprolactone (PCL). Presence of a PCL shell layer thus provides longer shelf-life for the CL gels in a wet environment and sustainable drug release. Antibiotics loaded into core-shell fibrous platform effectively inhibit both gram-positive and -negative bacteria without inducting observable cytotoxicity. Therefore, PCL coated CL fibrous gel platforms appear to be good candidates for controlled drug release based wound dressing applications.


Asunto(s)
Antibacterianos/farmacología , Quitina/química , Lignina/química , Poliésteres/química , Animales , Antibacterianos/química , Vendajes , Cápsulas , Preparaciones de Acción Retardada , Estabilidad de Medicamentos , Geles/síntesis química , Geles/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/crecimiento & desarrollo , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Células 3T3 NIH , Cicatrización de Heridas/efectos de los fármacos
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