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1.
Designing biomimetic scaffolds with in vivo–like microenvironments using biomaterials is an essential component of successful tissue engineering approaches. The intestinal smooth muscle layers exhibit a complex tubular structure consisting of two concentric muscle layers in which the inner circular layer is orthogonally oriented to the outer longitudinal layer. Here, a 3D bi‐layered tubular scaffold is presented based on flexible, mechanically robust, and well aligned silk protein microfibers to mimic the native human intestinal smooth muscle structure. The scaffolds are seeded with primary human intestinal smooth muscle cells to replicate intestinal muscle tissues in vitro. Characterization of the tissue constructs reveals good biocompatibility and support for cell alignment and elongation in the different scaffold layers to enhance cell differentiation and functions. Furthermore, the engineered smooth muscle constructs support oriented neurite outgrowth, a requisite step to achieve functional innervation. These results suggest these microfiber scaffolds as functional templates for in vitro regeneration of human intestinal smooth muscle systems. The scaffolding provides a crucial step toward engineering functional human intestinal tissue in vitro, as well as engineering other types of smooth muscles in terms of their similar phenotypes. Such utility may lead to a better understanding of smooth muscle associated diseases and treatments.  相似文献   

2.
Survival of tissue engineered constructs after implantation depends on proper vascularization. The differentiation of endothelial cells into mature microvasculature requires dynamic interactions between cells, scaffold, and growth factors, which are difficult to recapitulate in artificial systems. Previously, photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels displaying collagen mimetic peptides (CMPs), dubbed PEGDA‐CMP, that can be further conjugated with bioactive molecules via CMP‐CMP triple helix hybridization were reported. Here, it is shown that a bifunctional peptide featuring pro‐angiogenic domain mimicking vascular endothelial growth factor (VEGF) and a collagen mimetic domain that can fold into a triple helix conformation can hybridize with CMP side chains of the PEGDA‐CMP hydrogel, which results in presentation of insoluble VEGF‐like signals to endothelial cells. Presentation of VEGF‐like signals on the surface of micropatterned scaffolds in this way transforms cells from a quiescent state to elongated and aligned phenotype suggesting that this system could be used to engineer organized microvasculature. It is also shown that the pro‐angiogenic peptide, when applied topically in combination with modified dextran/PEGDA hydrogels, can enhance neovascularization of burn wounds in mice demonstrating the potential clinical use of CMP‐mediated matrix‐bound bioactive molecules for dermal injuries.  相似文献   

3.
Rapid formation of a confluent endothelial monolayer is the key to the success of small‐diameter vascular grafts, which is significantly important for treating dangerous and even sometimes deadly vascular disorders. However, the difficulty to homogenously locate endothelial cells onto the lumen of small‐diameter tubular scaffolds makes 3D endothelialization greatly challenging. Here, novel shape‐morphing scaffolds enabling programmed deformation from planar shapes to small‐diameter tubular shapes are designed and developed by combining biocompatible shape memory polymer and electrospun nanofibrous membrane. Endothelial cells can be conveniently seeded and attached on the 2D surface of the scaffolds and subsequently self‐rolled into 3D organization at physiological temperature. Endothelial cell responses and functions are varied on the shape‐morphing scaffolds with different nanofibrous electrospun membranes as the inner layer, arisen from the inducement of scaffolds with different morphological, physical, and biochemical characteristics. Owing to excellent properties of the nanofibrous membrane fabricated by the coelectrospinning of poly‐ε‐caprolactone (PCL) and gelatin methacrylate (GelMA), the shape‐morphing scaffolds with a nanofibrous PCL/GelMA inner layer support desirable homogeneous endothelial cell attachment as well as the rapid formation of biomimetic cell–scaffold interaction and cell–cell interaction under the 3D cell culture condition, therefore offering a visible approach for facile 3D endothelialization.  相似文献   

4.
Porous grafts facilitate constructive remodeling of blood vessels. Incorporating multiple biomimetic cues to porous grafts can promote vascular regeneration. However, the fabrication of such medical devices remains challenging. Here, beta-sheet rich silk nanofibers (BSN) are added to poly(vinyl alcohol) (PVA) solution and aggregated under a cylindric electric field to form circumferentially and axially oriented tubular structures, to simulate the endothelial and media layers of blood vessels. PVA in the aligned tubes is then crystallized through repeat freezing–thawing process to offer mechanical performances. Through tuning the ratio of BSN and PVA, the composite tubes with dual anisotropic microstructures exhibit better mechanical properties than pure PVA vascular grafts. Significantly improved cell adhesion, spreading, proliferation, and alignment are achieved. Both endothelial and smooth muscle cells show improved biological activity on the grafts due to the regulatory roles of the aligned structures. In vivo studies reveal the formation of endothelial layers within four weeks of implantation, ensuring long-term patency. The endothelial and smooth muscle double layers are regenerated after eight months postimplantation, forming hierarchical microstructures and compositions similar to native vessels. The porous composite grafts with multiple aligned structures guide vascular remodeling to regenerate blood vessels, demonstrating potential for clinical translation.  相似文献   

5.
3D ordered structures beyond microscale with targeted modification are catching increasing attention due to its application as tissue scaffolds. Especially scaffolds with necessary growth factors at designated locations are meaningful for induced cell differentiation and tissue formation. However, few fabrication methods can address the challenge of introducing bioactive species to the interior targeted places during the preparation process. Herein, for the first time macroscopic supramolecular assembly is applied to obtain such 3D ordered structures and established a proof‐of‐concept idea of complex scaffold with targeted modification. Taking strip‐like polydimethylsilicon building block as a model system, microscaled multilayered structures have been fabricated with parallel aligned building blocks in each layer. The morphology can be adjusted in a flexible way by tuning the number of layer, the space between two adjacent building blocks, and the position and orientation of each PDMS. The as‐prepared 3D structures are demonstrated biocompatible and potential as scaffolds for 3D cell culture. Moreover, bioactive species can be in situ incorporated into designated locations within the 3D structure precisely. In this way, a novel strategy is provided to address the current challenges in fabricating complex 3D tissue scaffolds with localized protein for future induced cell differentiation.  相似文献   

6.
Long‐term survival and success of artificial tissue constructs depend greatly on vascularization. Endothelial‐cell (EC) differentiation and vasculature formation are dependent on spatiotemporal cues in the extracellular matrix that dynamically interact with cells; a process that is difficult to reproduce in artificial systems. Here, a novel bifunctional peptide is presented that mimics matrix‐bound vascular endothelial growth factor (VEGF) which can be used to encode spatially controlled angiogenic signals in collagen scaffolds. The peptide is comprised of a collagen mimetic domain that was previously reported to bind to type I collagen by a unique hybridization mechanism, and a VEGF‐mimetic domain with pro‐angiogenic activity. Circular dichroism and collagen‐binding studies confirm the triple‐helical structure and the collagen binding affinity of the collagen‐mimetic domain, and EC‐culture studies demonstrate the peptide's ability to induce endothelial cell morphogenesis and network formation as a matrix‐bound factor in 2D and 3D collagen scaffolds. Spatial modification of collagen substrates is also shown with this peptide, which allows localized EC activation and network formation. These results demonstrate that the peptide can be used to present spatially directed angiogenic cues in collagen scaffolds, which may be useful for engineering organized microvasculature.  相似文献   

7.
Novel carbon films with different graphene layer orientations are investigated as electrode materials for Li‐ion batteries. It is demonstrated that engineering the crystallographic orientation with graphene layers oriented perpendicular to the surface substantially alters stress evolution during Li insertion. With this crystallographic orientation the intercalating/de‐intercalating Li‐ions also have direct access to the graphene interlayer spaces, resulting in higher capacity at faster electrochemical cycling, compared to carbon films with graphene layers parallel to the film surface. Electrodes with perpendicular alignment are prepared by supramolecular synthesis using either spin coating or bar coating of chromonic liquid crystal precursors into precursor organic films followed by in situ carbonization. These materials are compared with in situ stress measurements during lithiation/delithiation cycles, and the bar‐coated films exhibit a highly anisotropic stress which is consistent with long‐range alignment of the graphene layers. In contrast, the in‐plane stresses in the spin‐coated films are isotropic, which is consistent with the presence of randomly oriented domains (still with graphene layers oriented perpendicular to the surface). Overall, the use of thin film graphitic materials with controlled crystallographic orientations provides a valuable platform for investigating the impact of graphene structure on the properties of Li‐ion battery electrode materials.  相似文献   

8.
Three–dimensional, microperiodic scaffolds of regenerated silk fibroin have been fabricated for tissue engineering by direct ink writing. The ink, which consisted of silk fibroin solution from the Bombyx mori silkworm, was deposited in a layer‐by‐layer fashion through a fine nozzle to produce a 3D array of silk fibers of diameter 5 µm. The extruded fibers crystallized when deposited into a methanol‐rich reservoir, retaining a pore structure necessary for media transport. The rheological properties of the silk fibroin solutions were investigated and the crystallized silk fibers were characterized for structure and mechanical properties by infrared spectroscopy and nanoindentation, respectively. The scaffolds supported human bone marrow‐derived mesenchymal stem cell (hMSC) adhesion, and growth. Cells cultured under chondrogenic conditions on these scaffolds supported enhanced chondrogenic differentiation based on increased glucosaminoglycan production compared to standard pellet culture. Our results suggest that 3D silk fibroin scaffolds may find potential application as tissue engineering constructs due to the precise control of their scaffold architecture and their biocompatibility.  相似文献   

9.
The proximity effect is used to engineer interface effects such as magnetoelectric coupling, exchange bias, and emergent interfacial magnetism. However, the presence of a magnetic “dead layer” adversely affects the functionality of a heterostructure. Here, it is shown that by utilizing (111) polar planes, the magnetization of a manganite ultrathin layer can be maintained throughout its thickness. Combining structural characterization, magnetometry measurements, and magnetization depth profiling with polarized neutron reflectometry, it is found that the magnetic dead layer is absent in the (111)‐oriented manganite layers, however, it occurs in the films with other orientations. Quantitative analysis of local structural and elemental spatial evolutions using scanning transmission electron microscopy and electron energy loss spectroscopy reveals that atomically sharp interfaces with minimal chemical intermixing in the (111)‐oriented superlattices. The polar discontinuity across the (111) interfaces inducing charge redistribution within the SrTiO3 layers is suggested, which promotes ferromagnetism throughout the (111)‐oriented ultrathin manganite layers. The approach of eliminating problematic magnetic dead layers by changing the crystallographic orientation suggests a conceptually useful recipe to engineer the intriguing physical properties of oxide interfaces, especially in low dimensionality.  相似文献   

10.
Helical fibers are versatile building blocks used by Nature to improve mechanical performance and to tune local behavior of load‐bearing materials. Helicoidal biocomposites are arranged in multiple layers with different fiber orientations. Such heterogeneity, not matched in synthetic materials, provides biological structures with superior properties. This is the case of the multilayer tube‐like structure of the wood cell wall, where each ply features a compliant matrix reinforced by stiff helicoidal microfibrils. Here, 3D polyjet printing and computer simulations are combined to investigate wood‐inspired helix‐reinforced cylinders. Composites with a main layer containing helicoidal fibers, bordered by inner and outer plies having thinner fibrils are considered. It is shown how the mechanical functionalities of the synthetic structures can be programmed by varying fibers/fibrils orientation and matrix compliance. It is demonstrated that failure resistance can be enhanced by enclosing the main helicoidal layer with a minimum amount of thin fibrils oriented perpendicular to the applied load, as observed in wood. Finite element simulations are used to highlight the critical role of the matrix in load‐transfer mechanisms among stiff elements. These structures have the potential to be assembled into larger systems, leading to graded composites with region‐specific properties optimized for multiple functionalities.  相似文献   

11.
This work innovatively develops a dual solution‐shearing method utilizing the semiconductor concentration region close to the solubility limit, which successfully generates large‐area and high‐performance semiconductor monolayer crystals on the millimeter scale. The monolayer crystals with poly(methyl methacrylate) encapsulation show the highest mobility of 10.4 cm2 V?1 s?1 among the mobility values in the reported solution‐processed semiconductor monolayers. With similar mobility to multilayer crystals, light is shed on the charge accumulation mechanism in organic field‐effect transistors (OFETs), where the first layer on interface bears the most carrier transport task, and the other above layers work as carrier suppliers and encapsulations to the first layer. The monolayer crystals show a very low dependency on channel directions with a small anisotropic ratio of 1.3. The positive mobility–temperature correlation reveals a thermally activated carrier transport mode in the monolayer crystals, which is different from the band‐like transport mode in multilayer crystals. Furthermore, because of the direct exposure of highly conductive channels, the monolayer crystal based OFETs can sense ammonia concentrations as low as 10 ppb. The decent sensitivity indicates the monolayer crystals are potential candidates for sensor applications.  相似文献   

12.
Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.  相似文献   

13.
Spectroscopic evidence of directed excitonic energy transfer (ET) is presented through size‐gradient CdSe/ZnS nanocrystal quantum dot (NQD) layers into an underlying Si substrate. NQD monolayers are chemically grafted on hydrogen‐terminated Si surfaces via a self‐assembled monolayer of amine modified carboxy‐alkyl chains. Subsequent NQD monolayers are linked with short alkyldiamines. The linking approach enables accurate positioning and enhanced passivation of the layers. Two different sizes of NQDs (energy donors emitting at 545 nm, and energy acceptors emitting at 585 nm) are used in comparing different monolayer and bilayer samples grafted on SiO2 and oxide‐free Si surfaces via time‐resolved photoluminescence measurements. The overall efficiency of ET from the top‐layer donor NQDs into Si is estimated to approach ≈90% through a combination of different energy relaxation pathways. These include sequential ET through the intermediate acceptor layer realized mainly via the non‐radiative mechanism and direct ET into the Si substrate realized by means of the radiative coupling. The experimental observations are quantitatively rationalized by the theoretical modeling without introducing any extraneous energy scavenging processes. This indicates that the linker‐assisted fabrication enables the construction of defect‐free, bandgap‐gradient multilayer NQD/Si hybrid structures suitable for thin‐film photovoltaic applications.  相似文献   

14.
Bioinspired scaffolds with two distinct regions resembling stratified anatomical architecture provide potential strategies for osteochondral defect repair and are studied in preclinical animals. However, delamination of the two layers often causes tissue disjunction between the regenerated cartilage and subchondral bone, leading to few commercially available clinical applications. This study develops an integrated poly(ε-caprolactone) (PCL)-based scaffold for repairing osteochondral defects. An extracellular matrix (ECM)-incorporated 3D printing composite scaffold (ECM/PCL) coated with ECM hydrogel (E-co-E/PCL) is fabricated as the upper layer, and magnesium oxide nanoparticles coated with polydopamine (MgO@PDA)-incorporated composite scaffold (MD/PCL) is fabricated using 3D printing as the bottom layer. The physicochemical and mechanical properties of the bilayer scaffold meet the requirements in designing and fabricating the osteochondral scaffold, especially a strong interface possessed between the two layers. By in vitro study, the integrated scaffold stimulates proliferation, chondrogenic differentiation, and osteogenic differentiation of human bone mesenchymal stem cells. Moreover, the integrated bilayer scaffold exhibits well repair ability to facilitate simultaneous regeneration of cartilage and subchondral bone after implanting into the osteochondral defect in rats. In addition, cartilage “tidemarks” completely regenerated after 12 weeks of implantation of the bilayer scaffold, which indicates no tissue disjunctions formed between the regenerated cartilage and subchondral bone.  相似文献   

15.
In the field of regenerative medicine there is a need for scaffolds that support large, critically‐sized tissue formation. Major limitations in reaching this goal are the delivery of oxygen and nutrients throughout the bulk of the engineered tissue as well as host tissue integration and vascularization upon implantation. To address these limitations, the development of a porous scaffold platform made from biodegradable silk protein that contains an array of vascular‐like structures that extend through the bulk of the scaffold was previously reported. Here, the hollow channels play a pivotal role in enhancing cell infiltration, delivering oxygen and nutrients to the scaffold bulk, and promoting in vivo host tissue integration and vascularization. The unique features of this protein biomaterial system, including the vascular structures and tunable material properties, render this scaffold a robust and versatile tool for implementation in a variety of tissue engineering, regenerative medicine, and disease modeling applications.  相似文献   

16.
There is critical clinical demand for tissue‐engineered (TE), 3D constructs for tissue repair and organ replacements. Current efforts toward this goal are prone to necrosis at the core of larger constructs because of limited oxygen and nutrient diffusion. Therefore, critically sized 3D TE constructs demand an immediate vascular system for sustained tissue function upon implantation. To address this challenge the goal of this project was to develop a strategy to incorporate microchannels into a porous silk TE scaffold that could be fabricated reproducibly using microfabrication and soft lithography. Silk is a suitable biopolymer material for this application because it is mechanically robust, biocompatible, slowly degrades in vivo, and has been used in a variety of TE constructs. Here, the fabrication of a silk‐based TE scaffold that contains an embedded network of porous microchannels is reported. Enclosed porous microchannels support endothelial lumen formation, a critical step toward development of the vascular niche, while the porous scaffold surrounding the microchannels supports tissue formation, demonstrated using human mesenchymal stem cells. This approach for fabricating vascularized TE constructs is advantageous compared to previous systems, which lack porosity and biodegradability or degrade too rapidly to sustain tissue structure and function. The broader impact of this research will enable the systemic study and development of complex, critically‐sized engineered tissues, from regenerative medicine to in vitro tissue models of disease states.  相似文献   

17.
Fully simulating the components and microstructures of soft tissue is a challenge for its functional regeneration. A new aligned hydrogel microfiber scaffold for spinal cord regeneration is constructed with photocrosslinked gelatin methacryloyl (GelMA) and electrospinning technology. The directional porous hydrogel fibrous scaffold consistent with nerve axons is vital to guide cell migration and axon extension. The GelMA hydrogel electrospun fibers soak up water more than six times their weight, with a lower Young's modulus, providing a favorable survival and metabolic environment for neuronal cells. GelMA fibers further demonstrate higher antinestin, anti‐Tuj‐1, antisynaptophysin, and anti‐CD31 gene expression in neural stem cells, neuronal cells, synapses, and vascular endothelial cells, respectively. In contrast, anti‐GFAP and anti‐CS56 labeled astrocytes and glial scars of GelMA fibers are shown to be present in a lesser extent compared with gelatin fibers. The soft bionic scaffold constructed with electrospun GelMA hydrogel fibers not only facilitates the migration of neural stem cells and induces their differentiation into neuronal cells, but also inhibits the glial scar formation and promotes angiogenesis. Moreover, the scaffold with a high degree of elasticity can resist deformation without the protection of a bony spinal canal. The bioinspired aligned hydrogel microfiber proves to be efficient and versatile in triggering functional regeneration of the spinal cord.  相似文献   

18.
Novel biological vascular conduits, such as decellularized tissue engineered vascular grafts (TEVGs) are hindered by high thrombogenicity. To mimic the antithrombogenic surface of native vessels with a continuous glycosaminoglycan layer that is present on endothelial cells (ECs), a hyaluronic acid (HA) modified surface is established, to effectively shield blood platelets from collagen‐triggered activation. Using the amine groups present on 4 mm diameter decellularized TEVGs, a continuous HA hydrogel coating is built via a bifunctional thiol‐reactive cross‐linker, thereby avoiding nonspecific collagen matrix cross‐linking. The HA hydrogel layer recreates a luminal wall, “hiding” exposed collagen from the bloodstream. In vitro blood tests show that adhered platelets, fibrinogen absorption, and fibrin formation on HA‐coated decellularized TEVGs are significantly lower than on uncoated decellularized TEVGs. The HA surface also inhibits macrophage adhesion in vitro. HA‐coated decellularized syngeneic rat aortae (≈1.5 mm diameter), and TEVGs in rat and canine models, respectively, are protected from aggressive thrombus formation, and preserve normal blood flow. Re‐endothelialization is also observed. HA‐coated TEVGs may be an off‐the‐shelf small‐diameter vascular graft with dual benefits: antithrombogenic protection and promotion of endothelium.  相似文献   

19.
Polymer scaffolds intended to provide a substrate for cell attachment and proliferation benefit if the geometric architecture, mechanical properties, and surface chemistry are controllable within the range applicable for the target tissue. Such scaffolds may be made bioinductive through the inclusion of surface proteins and release of growth factors. Furthermore, the polymer support may be formed of biodegradable polymers for use as tissue‐engineering scaffolds. In this study, a new scaffold‐fabrication technique based on the direct writing of polymer colloidal‐gel‐based inks is described. The colloidal approach allows for the modular design of inks where the structure and composition of the colloidal particles, surface adsorbed molecules, and dissolved species may be easily controlled. Polyacrylate latex particles are formulated into colloidal gels by using a thermoreversible gel‐forming poly(ethylene oxide)–poly(propylene oxide) block‐copolymer adsorbed layer. The resulting colloidal gels are laced with the model protein bovine serum albumin (BSA) either dissolved in the solvent phase of the ink or dispersed in chitosan nanoparticles as a second colloid. Ink development and rheological characterization are presented along with demonstration of assembly of mesoporous scaffolds. After assembly and drying of the scaffold structure, the drug‐release kinetics are measured upon re‐exposure to an aqueous environment. Protein activity appears to be unaffected by the processing route of these scaffolds. Finally, the assembly of heterogeneous scaffolds is demonstrated to illustrate the possibilities for staged or heterogeneous drug release. This approach to scaffold fabrication offers a new route for scaffold assembly from water‐insoluble polymers while allowing the inclusion of sensitive biomolecules without risk of denaturation.  相似文献   

20.
In this article, a study of a flower like nanostructured CdS buffer layer for improving the performance of a submicron‐thick (CIGS) solar cell (SC) is presented. Both its synthesis and properties are discussed in detail. The surface reflectance of the device is dramatically decreased. SCs with flower like nanostructured CdS buffer layers enhance short‐circuit current density, fill factor, and open‐circuit voltage. These enhancements contribute to an increase in power conversion efficiency of about 55% on average compared to SCs that don't have a flower like nanostructured CdS buffer layer, despite them both having the same CIGS light absorbing layer.  相似文献   

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