Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D‐print thick, vascularized, and ...perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels. The ability to print functional vascularized patches according to the patient's anatomy is demonstrated. Blood vessel architecture is further improved by mathematical modeling of oxygen transfer. The structure and function of the patches are studied in vitro, and cardiac cell morphology is assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. Finally, as a proof of concept, cellularized human hearts with a natural architecture are printed. These results demonstrate the potential of the approach for engineering personalized tissues and organs, or for drug screening in an appropriate anatomical structure and patient‐specific biochemical microenvironment.
A small biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to induce pluripotent stem cells and differentiate to cardiac and endothelial cells, the extra‐cellular matrix is processed into a thermoresponsive, hydrogel‐based bioink. These components are used to 3D‐print functional vascularized cardiac patches and even small scale, whole cellularized human hearts.
Despite incremental improvements in the field of tissue engineering, no technology is currently available for producing completely autologous implants where both the cells and the scaffolding ...material are generated from the patient, and thus do not provoke an immune response that may lead to implant rejection. Here, a new approach is introduced to efficiently engineer any tissue type, which its differentiation cues are known, from one small tissue biopsy. Pieces of omental tissues are extracted from patients and, while the cells are reprogrammed to become induced pluripotent stem cells, the extracellular matrix is processed into an immunologically matching, thermoresponsive hydrogel. Efficient cell differentiation within a large 3D hydrogel is reported, and, as a proof of concept, the generation of functional cardiac, cortical, spinal cord, and adipogenic tissue implants is demonstrated. This versatile bioengineering approach may assist to regenerate any tissue and organ with a minimal risk for immune rejection.
Fatty tissues are extracted from patients and the cellular and a‐cellular materials are separated. While the cells are reprogrammed to induced pluripotent stem cells (iPSCs), the extracellular matrix is processed to a personalized, nonimmunogenic hydrogel. The iPSCs are encapsulated within the hydrogel and differentiated to engineer autologous cardiac, cortical, dopaminergic, spinal cord, and adipogenic implants.
Two dehydrogenases, cellobiose dehydrogenase from Corynascus thermophilus and pyranose dehydrogenase from Agaricus meleagris, were displayed for the first time on the surface of Saccharomyces ...cerevisiae using the yeast surface display system. Surface displayed dehydrogenases were used in a microbial fuel cell and generated high power outputs. Surface displayed cellobiose dehydrogenase has demonstrated a midpoint potential of −28mV (vs. Ag/AgCl) at pH=6.5 and was used in a mediator-less anode compartment of a microbial fuel cell producing a power output of 3.3μWcm−2 using lactose as fuel. Surface-displayed pyranose dehydrogenase was used in a microbial fuel cell and generated high power outputs using different substrates, the highest power output that was achieved was 3.9μWcm−2 using d-xylose. These results demonstrate that surface displayed cellobiose dehydrogenase and pyranose dehydrogenase may successfully be used in microbial bioelectrochemical systems.
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•Yeast surface displayed CDH communicates with the anode through DET.•Yeast surface displayed CDH possesses a middle point potential of −28mV vs. Ag/AgCl.•Yeast surface displayed CDH yielded 3.3μWcm−2 in a mediator-less MFC.•Yeast surface displayed PDH yielded 3.9μWcm−2 in an air-cathode MFC.
In a myocardial infarction, blood supply to the left ventricle is abrogated due to blockage of one of the coronary arteries, leading to ischemia, which further triggers the generation of reactive ...oxygen species (ROS). These sequential processes eventually lead to the death of contractile cells and affect the integrity of blood vessels, resulting in the formation of scar tissue. A new heart therapy comprised of cardiac implants encapsulated within an injectable extracellular matrix‐gold nanoparticle composite hydrogel is reported. The particles on the collagenous fibers within the hydrogel promote fast transfer of electrical signal between cardiac cells, leading to the functional assembly of the cardiac implants. The composite hydrogel is shown to absorb reactive oxygen species in vitro and in vivo in mice ischemia reperfusion model. The reduction in ROS levels preserve cardiac tissue morphology and blood vessel integrity, reduce the scar size and the inflammatory response, and significantly prevent the deterioration of heart function.
This study presents a new heart therapy comprised of cardiac implants encapsulated within an injectable extracellular matrix‐gold nanoparticle composite hydrogel in mice ischemia‐reperfusion model. The particles promote the fast transfer of electrical signal between cardiac cells, whereas the composite hydrogel can absorb reactive oxygen species. The reduction in reactive oxygen species levels can preserve cardiac tissue morphology and functionality.
In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current ...cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.
One of the strategies for heart regeneration includes cell delivery to the defected heart. However, most of the injected cells do not form quick cell–cell or cell–matrix interactions, therefore, ...their ability to engraft at the desired site and improve heart function is poor. Here, the use of a microfluidic system is reported for generating personalized hydrogel‐based cellular microdroplets for cardiac cell delivery. To evaluate the system's limitations, a mathematical model of oxygen diffusion and consumption within the droplet is developed. Following, the microfluidic system's parameters are optimized and cardiac cells from neonatal rats or induced pluripotent stem cells are encapsulated. The morphology and cardiac specific markers are assessed and cell function within the droplets is analyzed. Finally, the cellular droplets are injected to mouse gastrocnemius muscle to validate cell retention, survival, and maturation within the host tissue. These results demonstrate the potential of this approach to generate personalized cellular microtissues, which can be injected to distinct regions in the body for treating damaged tissues.
An omentum specimen is extracted from the patient and while the extracellular matrix is processed into a personalized hydrogel, the cells are reprogrammed to become induced pluripotent stem cells and differentiate to cardiac cells. These are used in a microfluidics system to generate personalized hydrogel‐based cellular microdroplets for cardiac cell delivery.
Cardiac tissue engineering aims to create cardiac tissue constructs that recapitulate the structure and function of the native heart. This approach has been widely used for creating myocardial ...implants for regenerative medicine, and more recently, for developing in vitro cardiotoxicity screening assays. However, once the engineered myocardial tissues are implanted or subjected to pharmacological stimuli, their performance should be monitored. Currently, there is no biomaterial that promotes functional tissues assembly while providing real‐time information about their function, in situ. In this study, the piezoelectric phenomenon is sought to be exploited, to measure the contractions generated by engineered cardiac tissues. A poly‐(vinylidene fluoride) (PVDF)‐based electrospun fiber scaffold is developed, and it is hypothesized that the contractions of cardiomyocytes in the scaffold will induce mechanical deformations, which will result in measurable electric voltage. The PVDF scaffolds are characterized and optimized for supporting formation of aligned, functional, cardiac tissues. The scaffolds' function is then validated as sensors for tissue contraction and it is demonstrated that they can sense contractions of tissues constructed from as few as 5 × 105 cardiomyocytes. Furthermore, it is demonstrated that human induced pluripotent stem cells can be directly seeded and differentiated to cardiomyocytes, and then mature over the course of 40 days on the PVDF fiber scaffolds.
Poly(vinylidene fluoride) scaffolds are electrospun to obtain highly aligned fibers with enriched β phase, contributing to prominent piezoelectricity. These fabricated fibers demonstrate dual function, serving as bioscaffolds that promote cell assembly into functional cardiac tissues, and as biosensors for monitoring contractile activity of the cardiac tissue. These scaffolds support differentiation and long‐term maturation of induced pluripotent stem cell‐derived cardiac tissues.
Personalized hydrogels for engineering patient‐specific tissues are reported by Tal Dvir and co‐workers in article number 1803895. A small fatty tissue biopsy is taken from the patient by a minimally ...invasive procedure and the cellular and the a‐cellular materials then separated. While the cells are reprogrammed to become induced pluripotent stem cells (iPSCs), the a‐cellular material is processed into a personalized hydrogel. After re‐integration, it is possible to engineer any tissue type, including spinal cord implants.
In article number 1900344, Tal Dvir and co‐workers take a biopsy of an omental tissue from patients. While the cells are reprogrammed to induced pluripotent stem cells and differentiate into ...cardiomyocytes and endothelial cells, the remaining extracellular matrix is processed into a thermoresponsive hydrogel. These personalized materials and cells are used as bioinks to print functional vascularized cardiac patches and small‐scale human hearts.
Electroelasticity of copolymer networks Friedberg, Idan Z.; deBotton, Gal
Journal of the mechanics and physics of solids,
June 2023, 2023-06-00, Letnik:
175
Journal Article
Recenzirano
We introduce a novel statistical mechanics-based analysis of electroactive copolymer networks. This enables to express the coupled response of a multi-species polymer network in terms of a Gibbs-like ...energy-density function. Following the common affine deformation assumption we derive the expressions for the network response in terms of the species’ properties and molar fraction. Next, we specialize the results to the class of monomers with spontaneous electric dipoles and determine the monomers’ orientational distribution in terms of a generalized Langevin function. We reveal that the coupled response of the copolymer depends on the contrast between the intensities of the dipolar moments of the species and their fraction of the chain end-to-end length. In the long chains limit we obtain closed-form expressions for the electrical and mechanical fields. Next, we consider two-species copolymers and find that the long chains approximation is valid for actuation stretch ratios up to 40% of the locking stretch. We also demonstrate that the maximal susceptibility is attained when the contour lengths of the two species are equal. Moreover, the overall electroelastic response is enhanced if the monomers with the weaker dipole are longer than those with the stronger one. Finally, we show that an appropriate choice of actual monomers may lead to copolymers with relative dielectric constants of more than 30.
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