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Large bone defects caused by congenital deformities and acquired accidents are increasing day by day. A large number of patients mainly rely on artificial bone for repair. However, artificial bone cannot fully imitate the structure and composition of human bone, resulting in a large gap with autologous bone function. Therefore, this article proposes a continuous preparation method for inorganic/organic biphasic composite gradient biomimetic bulk bone scaffolds. First, a controllable gradient hybrid forming platform for inorganic/organic dual-phase biomaterials was constructed, and the feeding control strategy was studied to achieve precise control of the feeding of sodium alginate/gelatin composite organic materials and hydroxyapatite inorganic materials. The speed is, respectively, sent from the corresponding feeding nozzle to the mixing chamber to realize the uniform mixing of the biphasic material and the extrusion of the composite material, and the inorganic/organic biphasic composite gradient biomimetic bone scaffold with gradual structure and composition is prepared. Second, to prove the superiority of the preparation method, the physicochemical and biological properties of the prepared scaffolds were evaluated. The test results showed that the morphological characteristics of the biphasic composite gradient bone scaffold showed good microscopic porosity and the structure and composition showed gradients. The mechanical properties are close to that of human bone tissue and in vitro cell experiments show that the scaffold has good biocompatibility and bioactivity. In conclusion, this article provides a new type of bone scaffold preparation technology and equipment for the field of tissue engineering, which has research value and application prospects.
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The use of endovascular stent-graft has become an important option in the treatment of aortic pathologies. However, the currently used endograft membranes have limited ability to prevent bacterial colonization. This makes them unsuitable for the treatment of mycotic aneurysms, as the infection is prone to progress after endograft implantation. Moreover, even in non-mycotic aortic pathologies, endograft infections can occur in the short or long term, especially for patients with diabetes mellitus or in immune insufficiency conditions. So, this study aimed to develop a kind of Ag-NPs-loaded endograft membrane by coaxial electrospinning technique, and a series of physical and chemical properties and biological properties of the Ag-NPs-loaded membrane were characterized. Animal experiments conducted in pigs confirmed that the Ag-NPs-loaded membrane was basically non-toxic, exhibited good biocompatibility, and effectively prevented bacterial growth in a mycotic aortic aneurysm model. In conclusion, the Ag-NPs-loaded membrane exhibited good biocompatibility, good anti-infection function and slow-release of Ag-NPs for long-term bacteriostasis. Thus, the Ag-NPs-loaded membrane might hold potential for preventing infection progression and treating mycotic aortic aneurysms in an endovascular way.
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Skin injuries and defects, as a common clinical issue, still cannot be perfectly repaired at present, particularly large-scale and infected skin defects. Therefore, in this work, a drug-loaded bilayer skin scaffold was developed for repairing full-thickness skin defects. Briefly, amoxicillin (AMX) was loaded on polycaprolactone (PCL) nanofiber via electrospinning to form the antibacterial nanofiber membrane (PCL-AMX) as the outer layer of scaffold to mimic epidermis. To maintain wound wettability and promote wound healing, external human epidermal growth factor (rhEGF) was loaded in sodium alginate-gelatin to form the hydrogel structure (SG-rhEGF) via 3D printing as inner layer of scaffold to mimic dermis. AMX and rhEGF were successfully loaded into the scaffold. The scaffold exhibited excellent physicochemical properties, with elongation at break and tensile modulus were 102.09 ± 6.74% and 206.83 ± 32.10 kPa, respectively; the outer layer was hydrophobic (WCA was 112.09 ± 4.67°), while the inner layer was hydrophilic (WCA was 48.87 ± 5.52°). Meanwhile, the scaffold showed excellent drug release and antibacterial characteristics. In vitro and in vivo studies indicated that the fabricated scaffold could enhance cell adhesion and proliferation, and promote skin wound healing, with favorable biocompatibility and great potential for skin regeneration and clinical application.
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Alginatos , Antibacterianos , Gelatina , Hidrogeles , Nanofibras , Poliésteres , Impresión Tridimensional , Piel , Andamios del Tejido , Cicatrización de Heridas , Gelatina/química , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Antibacterianos/farmacología , Antibacterianos/química , Poliésteres/química , Alginatos/química , Alginatos/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Andamios del Tejido/química , Piel/efectos de los fármacos , Animales , Amoxicilina/farmacología , Amoxicilina/química , Humanos , Liberación de FármacosRESUMEN
Tailored intestinal fistula stents with a hollow bent pipe structure prepared by using a three-axis bio-printing platform are often unsuitable due to low printing efficiency and quality caused by the unavoidable need for a supporting structure. Herein, a 5 + 1-axis 3D printing platform was built and developed for producing support-free intestinal fistula stents. A 3D model of the target stent shape and dimensions was treated by a dynamic slicing algorithm, which was then used to prepare a motion control code. Our printing method showed improved printing efficiency, superior stent surface properties and structure and ideal elasticity and mechanical strength to meet the mechanical requirements of the human body. Static simulations showed the importance of axial printing techniques, whereas the stent itself was shown to have excellent biocompatibility with wettability and cell proliferation tests. We present a customizable, efficient, and high-quality method with the potential for preparing bespoke stents for treating intestinal fistulas.
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In the past few decades, although tissue engineering has made significant progress and achieved many accomplishments, there are still some key problems that remain unsolved. One of the urgent research challenges in this field is how to prepare large-scale tissue engineering scaffolds with spatially complex structures. In this work, a sacrificial template process using sucrose as the sacrificial material and a gelatin/microbial transglutaminase mixed solution as the bio-scaffold material is proposed to fabricate a bio-scaffold with multi-level branching and spatially complex vascular network channels that mimic the structure and function of the human vascular network. To validate the feasibility of the fabrication process and the rationality of the process parameters, the morphological characteristics, connectivity of vascular network channels, shaping accuracy, and mechanical properties of the bio-scaffold were tested and analyzed. The results showed that the bio-scaffold fabricated using this process had a complete morphology and excellent connectivity. The diameter of the sucrose sacrificial template showed a linear relationship with the feeding speed, and the average diameter error rate between the sucrose sacrificial template and the vascular network channels inside the bio-scaffold was less than 8%. The mechanical properties of the bio-scaffold met the requirements for large-scale tissue defect repair. To evaluate the effect of the bio-scaffold on cell activity, human umbilical vein endothelial cells (HUVECs) were seeded into the vascular network channels of the bio-scaffold, and their attachment, growth, and proliferation on the surface of the vascular network channels were observed. To further assess the biocompatibility of the bio-scaffold, the bio-scaffold was implanted subcutaneously in the dorsal tissue of rats, and the tissue regeneration status was compared and analyzed through immunohistochemical analysis. The results showed that the vascular network channels within the bio-scaffold allowed uniform cell attachment, growth, with fewer dead cells and high cell viability. Moreover, clear cell attachment and growth were observed within the vascular network channels of the bio-scaffold after implantation in rats. These results indicate that the fabricated bio-scaffold meets the basic performance requirements for the repair and regeneration of large-scale tissue defects, providing a new approach for oxygen and nutrient transport in large-scale tissues and opening up new avenues for clinical applications.
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Gelatina , Oxígeno , Humanos , Animales , Ratas , Supervivencia Celular , Células Endoteliales de la Vena Umbilical Humana , SacarosaRESUMEN
The coaxial electrospinning process has been widely used in the biomedical field, and its process parameters affect product quality seriously. In this paper, the influence of key process parameters of coaxial electrostatic spinning (solution concentration, electrospinning voltage, acceptance distance and liquid supply velocity) on the preparation of a membrane with Chitosan, Polyethylene oxide and nano-silver as the core layer and Polycaprolactone as the shell layer was studied. The optimal combination of key process parameters was obtained by using an orthogonal test, scanning electron microscope, transmission electron microscope and macro-characterization diagram. The results showed that the coaxial electrospun membrane had good mechanical properties (tensile strength is about 2.945 Mpa), hydrophilicity (the water contact angle is about 72.28°) and non-cytotoxicity, which was conducive to cell adhesion and proliferation. The coaxial electrospun membrane with nano-silver has an obvious inhibitory effect on Escherichia coli and Staphylococcus aureus. In summary, the coaxial electrospun membrane that we produced is expected to be used in clinical medicine, such as vascular stent membranes and bionic blood vessels.
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Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs.
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Three-dimensional microextrusion bioprinting has attracted great interest for fabrication of hierarchically structured, functional tissue substitutes with spatially defined cell distribution. Despite considerable progress, several significant limitations remain such as a lack of suitable bioinks which combine favorable cell response with high shape fidelity. Therefore, in this work a novel bioink of alginate-methylcellulose (AlgMC) blend functionalized with egg white (EW) was developed with the aim of solving this limitation. In this regard, a stepwise strategy was proposed to improve and examine the cell response in low-viscosity alginate inks (3%, w/v) with different EW concentrations, and in high-viscosity inks after gradual methylcellulose addition for enhancing printability. The rheological properties and printability of these cell-responsive bioinks were characterized to obtain an optimized formulation eliciting balanced physicochemical and biological properties for fabrication of volumetric scaffolds. The bioprinted AlgMC + EW constructs exhibited excellent shape fidelity while encapsulated human mesenchymal stem cells showed high post-printing viability as well as adhesion and spreading within the matrix. In a proof-of-concept experiment, the impact of these EW-mediated effects on osteogenesis of bioprinted primary human pre-osteoblasts (hOB) was evaluated. Results confirmed a high viability of hOB (93.7 ± 0.15%) post-fabrication in an EW-supported AlgMC bioink allowing cell adhesion, proliferation and migration. EW even promoted the expression of osteogenic genes, coding for bone sialoprotein (integrin binding sialoprotein/bone sialoprotein precursor (IBSP)) and osteocalcin (BGLAP) on mRNA level. To demonstrate the suitability of the novel ink for future fabrication of multi-zonal bone substitutes, AlgMC + EW was successfully co-printed together with a pasty calcium phosphate bone cement biomaterial ink to achieve a partly mineralized 3D volumetric environment with good cell viability and spreading. Along with the EW-mediated positive effects within bioprinted AlgMC-based scaffolds, this highlighted the promising potential of this novel ink for biofabrication of bone tissue substitutes in clinically relevant dimensions.
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Bioimpresión , Sustitutos de Huesos , Humanos , Andamios del Tejido/química , Metilcelulosa/química , Bioimpresión/métodos , Alginatos/química , Clara de Huevo , Sialoproteína de Unión a Integrina , Huesos , Tinta , Impresión Tridimensional , Ingeniería de Tejidos/métodosRESUMEN
Abdominal wall defects are a frequently occurring condition in surgical practice. The most important are material structure and biocompatibility. In this study, polylactic acid (PLA) mesh composited with a 3D printing of acellular dermal matrix (ADM) material is used to repair abdominal wall defects. The results show that the adhesion score of ADM/PLA composite scaffolds is smaller than PLA meshes. Immunohistochemical assessment reveals that the ADM/PLA composite scaffold can effectively reduce the inflammatory response at the contact surface between the meshes and the abdominal organs. And the ADM/PLA composite scaffold can effectively reduce the expression levels of the inflammation-related factors IL-6 and IL-10. In addition, the ADM/PLA composite scaffold repair is rich in the expression levels of tissue regeneration-related factors vascular endothelial growth factor and transforming growth factor ß. Thus, ADM/PLA composite scaffolds can effectively reduce surrounding inflammation to effectively promote the repair of abdominal wall defects.
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Pared Abdominal , Dermis Acelular , Ratas , Animales , Pared Abdominal/cirugía , Factor A de Crecimiento Endotelial Vascular , Poliésteres , Impresión Tridimensional , Andamios del Tejido/químicaRESUMEN
Biocompatible hydrogels have been considered one of the most well-known and promising in various materials used in the fabrication of tissue-engineering scaffolds. Although considerable progress has been made in recent decades, many limitations remain, such as poor mechanical and degradation properties of biomaterials. In addition, vascularization of tissue-engineering scaffold is an enduring challenge, which limited the fabrication and application of scaffold with clinically relevant dimension. To cover these challenges, in this work, a novel nanocomposite interpenetrating polymer networks (IPN) hydrogel scaffold consists of methacrylated gelatin (GelMA), poly(vinyl alcohol) (PVA), and copper oxide nanoparticles (CuONPs) is fabricated by extrusion-based 3D printing. A series of physiochemical and biological characterizations of the nanocomposite GelMA/PVA scaffolds are performed. Results showed that the mechanical and degradation properties of the nanocomposite GelMA/PVA scaffolds are obviously improved compared to GelMA scaffolds with single network. In vitro cell experiments and chick embryo angiogenesis (CEA) assay confirmed good cytocompatibility of the fabricated scaffold and its potential to promote cell migration and angiogenesis. In conclusion, altogether the results demonstrated that GelMA/PVA IPN scaffolds modified with CuONPs have great potential for fabrication of volumetric scaffolds and promote angiogenesis during tissue growth and repair.
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Gelatina , Nanopartículas , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Embrión de Pollo , Cobre/farmacología , Gelatina/química , Gelatina/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Metacrilatos/química , Nanopartículas/uso terapéutico , Óxidos , Polímeros , Alcohol Polivinílico/farmacología , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Hernia repair mesh is associated with a number of complications, including adhesions and limited mobility, due to insufficient mechanical strength and nonresorbability. Among them, visceral adhesions are one of the most serious complications of patch repair. In this study, a degradable patch with an antiadhesive layer is prepared for hernia repair by 3D printing and electrospinning techniques using polycaprolactone, polyvinyl alcohol, and soybean peptide (SP). The study into the physicochemical properties of the patch is found that it has adequate mechanical strength requirements (16 N cm-1 ) and large elongation at break, which are superior than commercial polypropylene patches. In vivo and in vitro experiments show that human umbilical vein endothelial cells proliferated well on composite patches, and showed excellent biocompatibility with the host and little adhesion through a rat abdominal wall defect model. In conclusion, the results of this study show that composite patch can effectively reduce the occurrence of adhesions, while the addition of SP in the patch further enhances its biocompatibility. It is believed that a regenerative biological patch with great potential in hernia repair provides a new strategy for the development of new biomimetic biodegradable patches.
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Herniorrafia , Mallas Quirúrgicas , Animales , Células Endoteliales , Herniorrafia/métodos , Polipropilenos/química , Ratas , Adherencias TisularesRESUMEN
The most widely used 3D process, fused deposition modeling (FDM), has insufficient interlayer adhesion due to its layer-by-layer forming method. A support material is also essential for the hollow parts and cantilevers. Moreover, the polymer materials used have limited mechanical properties. These issues have restricted the application of FDM in high-performance fields. Continuous fiber-reinforced thermoplastic composites (CFRTPCs) have high mechanical properties and have recently become the focus of research in the field of 3D printing. This paper, using pipe parts as an example, proposes a hybrid of pure polymer (pure PLA used) and CFRTPC (flax fiber pre-impregnated filament) material to develop a printing method based on the outstanding mechanical properties of CFRTPC material. After studying the printing path planning algorithm, the CFRTPC filament is laid along the axial and radial directions on the surface of the polymer base to improve the printed parts' properties. The method feasibility and algorithm accuracy are verified through the development of five-axis printing equipment with a double nozzle. Through the printed sample's tensile, compression and bending tests, the results show that the tensile, compressive and bending properties of PLA pipe can be significantly enhanced by laying CFRTPC filament along the axial and radial directions of the pipe. To summarize, the introduction of CFRTPCs greatly improved the mechanical properties of the printed parts, and the implementation of our method provides an effective way to solve the defects of the FDM process.
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In recent years, 3D bioprinting has attracted broad research interest in biomedical engineering and clinical applications. However, there are two issues need to be solved urgently at present, the development of ink is the first pressing thing for 3D printing tissue engineering scaffold, other thing is the promotion of angiogenesis in the scaffold. Therefore, a gelatin/sodium alginate-based hydrogel with protein-rich is developed here, which is prepared by gelatin, sodium alginate, and soy protein/soy peptide powder. The prepared inks exhibit excellent shear-thinning behavior, which contribute to extrusion-based printing; also shown good crosslinking ability by calcium chloride. The macroporous composite scaffolds are printed by 3D printing using the developed ink and the physicochemical properties of the scaffolds are evaluated. Moreover, the cytocompatibility of printed scaffold is characterized by using human umbilical vein epidermal cells, results show that the scaffolds with soy protein and soy peptide powder can promote cell attach, spread, migration, and proliferation. The further research of chicken embryo allantoic membrane assay and animal experiment are carried, and results present that the scaffold can promote the growth of neo-vessels in the scaffold, which means the developed ink with soy protein and soy peptide powder has great potential for angiogenesis.
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Bioimpresión , Gelatina , Alginatos/química , Alginatos/farmacología , Animales , Bioimpresión/métodos , Embrión de Pollo , Gelatina/química , Gelatina/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Péptidos/farmacología , Polvos , Impresión Tridimensional , Proteínas de Soja/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
R-loops play versatile roles in many physiological and pathological processes, and are of great interest to scientists in multiple fields. However, controversy about their genomic localization and incomplete understanding of their regulatory network raise great challenges for R-loop research. Here, we present R-loopBase (https://rloopbase.nju.edu.cn) to tackle these pressing issues by systematic integration of genomics and literature data. First, based on 107 high-quality genome-wide R-loop mapping datasets generated by 11 different technologies, we present a reference set of human R-loop zones for high-confidence R-loop localization, and spot conservative genomic features associated with R-loop formation. Second, through literature mining and multi-omics analyses, we curate the most comprehensive list of R-loop regulatory proteins and their targeted R-loops in multiple species to date. These efforts help reveal a global regulatory network of R-loop dynamics and its potential links to the development of cancers and neurological diseases. Finally, we integrate billions of functional genomic annotations, and develop interactive interfaces to search, visualize, download and analyze R-loops and R-loop regulators in a well-annotated genomic context. R-loopBase allows all users, including those with little bioinformatics background to utilize these data for their own research. We anticipate R-loopBase will become a one-stop resource for the R-loop community.
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ADN/genética , Genoma , Neoplasias/genética , Enfermedades del Sistema Nervioso/genética , Estructuras R-Loop , ARN/genética , Programas Informáticos , Línea Celular Tumoral , Mapeo Cromosómico , Biología Computacional/métodos , ADN/química , ADN/metabolismo , Bases de Datos de Ácidos Nucleicos , Conjuntos de Datos como Asunto , Redes Reguladoras de Genes , Inestabilidad Genómica , Células HEK293 , Humanos , Internet , Anotación de Secuencia Molecular , Neoplasias/metabolismo , Neoplasias/patología , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/patología , Mapeo de Interacción de Proteínas/métodos , ARN/química , ARN/metabolismo , Transcripción GenéticaRESUMEN
Three dimensional printable formulation of self-standing and vascular-supportive structures using multi-materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self-standing and vascular-supportive structures using an in-house formulated multi-material combination of albumen/alginate/gelatin-based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed before the printing process. The suitability of the hydrogel in 3D printing of various customizable and self-standing structures, including a human ear model, was examined by extrusion-based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self-standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion-based 3D printing technique for manufacturing complex shapes and structures using multi-materials with high fidelity, which have great potential in organ engineering.
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Endotelio Vascular , Hidrogeles/química , Neovascularización Fisiológica , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Animales , Vasos Sanguíneos/citología , Vasos Sanguíneos/efectos de los fármacos , Células Cultivadas , Oído/irrigación sanguínea , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/fisiología , Andamios del Tejido/químicaRESUMEN
The meshes for hernia repair result in many problems that are related to complications including chronic pain and limited movement due to inadequate mechanical strength, non-absorbability, or low elasticity. In this study, degradable polylactic acid (PLA), synthetic thermoplastic polyurethane (TPU), and acellular dermal matrix (ADM) powders are combined to prepare a novel PLA/TPU/ADM mesh with three different topological structures (square, circular, and diamond) by 3D printing. The physicochemical properties and structural characteristics of mesh are studied, the results show that the diamond structure mesh with the pore size of 3 mm has sufficient elasticity and tensile strength, which provides the efficient mechanical strength required for hernia repair (16 N cm-1 ) and the value more than polypropylene(PP) mesh. Besides, in vitro and in vivo experiments demonstrate human umbilical vein endothelial cells could successfully proliferate on the PLA/TPU/ADM mesh whose biocompatibility with the host is shown using a rat model of abdominal wall defect. In conclusion, the results of this study demonstrate that the PLA/TPU/ADM mesh may be considered a good choice for hernia repair as its potential to overcome the elastic and strength challenges associated with a highly flexible abdominal wall, as well as its good biocompatibility.
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Dermis Acelular , Materiales Biocompatibles/farmacología , Hernia Abdominal/cirugía , Herniorrafia/métodos , Poliésteres/farmacología , Poliuretanos/farmacología , Mallas Quirúrgicas , Pared Abdominal/cirugía , Animales , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Elasticidad , Herniorrafia/instrumentación , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Masculino , Poliésteres/química , Poliuretanos/química , Impresión Tridimensional , Ratas , Ratas Sprague-Dawley , Resistencia a la TracciónRESUMEN
Cardiovascular disorders (CVDs) are the leading cause of global death, widely occurs due to irreparable loss of the functional cardiomyocytes. Stem cell-based therapeutic approaches, particularly the use of Mesenchymal Stem Cells (MSCs) is an emerging strategy to regenerate myocardium and thereby improving the cardiac function after myocardial infarction (MI). Most of the current approaches often employ the use of various biological and chemical factors as cues to trigger and modulate the differentiation of MSCs into the cardiac lineage. However, the recent advanced methods of using specific epigenetic modifiers and exosomes to manipulate the epigenome and molecular pathways of MSCs to modify the cardiac gene expression yield better profiled cardiomyocyte like cells in vitro. Hitherto, the role of cardiac specific inducers triggering cardiac differentiation at the cellular and molecular level is not well understood. Therefore, the current review highlights the impact and recent trends in employing biological and chemical inducers on cardiac differentiation of MSCs. Thereby, deciphering the interactions between the cellular microenvironment and the cardiac inducers will help us to understand cardiomyogenesis of MSCs. Additionally, the review also provides an insight on skeptical roles of the cell free biological factors and extracellular scaffold assisted mode for manipulation of native and transplanted stem cells towards translational cardiac research.
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Diferenciación Celular , Células Madre Mesenquimatosas , Infarto del Miocardio , Miocitos Cardíacos , Diferenciación Celular/genética , Humanos , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/genética , Infarto del Miocardio/terapia , Miocitos Cardíacos/citologíaRESUMEN
One of the biggest hindrances in tissue engineering in recent decades has been the complexity of the prevascularized channels of the engineered scaffold, which was still lower than that of human tissues. Another relative difficulty was the lack of precision molding capability, which restricted the clinical applications of the huge engineered scaffold. In this study, a promising approach was proposed to prepare hydrogel scaffold with prevascularized channels by liquid bath printing, in which chitosan/ß-sodium glycerophosphate served as the ink hydrogel, and gelation/nanoscale bacterial cellulose acted as the supporting hydrogel. Here, the ink hydrogel was printed by a versatile nozzle and embedded in the supporting hydrogel. The ink hydrogel transformed into liquid effluent at low temperature after the cross-linking of gelatin by microbial transglutaminase (mTG). No residual template was seen on the channel surface after template removal. This preparation had a high degree of freedom in the geometry of the channel, which was demonstrated by making various prevascularized channels including circular, branched, and tree-shaped networks. The molding accuracy of the channel was assessed by studying the roundness of the cross section of the molded hollow channel, and the effect of the mechanical properties by adding bacterial cellulose to the supporting hydrogel was analyzed. Human umbilical vein endothelial cells were injected into the aforementioned channels which formed a confluent and homogeneous distribution on the surface of the channels. Altogether, these results showed that this approach can construct hydrogel scaffolds with complex and accurate molding prevascularized channels, and hs great potential to resolve the urgent vascularization issue of bulk tissue-engineering scaffold.
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Gelatina , Andamios del Tejido , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hidrogeles , Impresión Tridimensional , Regeneración , Ingeniería de Tejidos/métodosRESUMEN
Compared with native blood vessels and existing vascular grafts, design and manufacture of vascular grafts with a three-dimensional topological structure is a key to induce cells and tissue growth, which remains an essential issue in both tissue engineering and regenerative medicine. This study sought to develop a novel triple-layer vascular graft (TLVG) with oriented microgrooves to investigate the mechanical property and endothelialization. The TLVGs were composed of electrospun Poly-ε-caprolactone (PCL)/thermoplastic polyurethane (TPU) as the inner layer, albumen/sodium alginate (SA) hydrogel as the middle layer, and electrospun PCL/TPU as the outer layer. In detail, a cylindrical sacrificial template was designed and printed using polyvinyl alcohol (PVA), served as the electrospinning receiving platform to form the oriented microgrooves in the inner layer of TLVGs. The highly elastic albumen/SA hydrogel and PCL/TPU nanofibers were able to simulate the elastin in blood vessels. In addition, the introduction of the albumen/SA hydrogel layer not only solves the leakage problem of a porous vascular graft but also improves the wettability of the scaffolds. The physicochemical properties and biological characteristics of TLVGs were evaluated by tensile testing, Surface wettability test, Fourier transform-infrared spectroscopy (FTIR) measurement, Live-Dead cell staining assay, and CCK-8 assay. Especially, the oriented microgrooves on the inner surface of the TLVGs can promote human umbilical vein endothelial cells (HUVECs) directed growth and migration in favor of endothelialization. All results showed that the fabricated TLVGs with excellent physicochemical properties and biocompatibility has great potential in clinic application.