A biological tissue forming device that ensures a cell-cell interaction and an exchange of liquid components between cell layers of a formed biological tissues with high efficiency can be provided. A biological tissue forming device for forming a biological tissue having a plurality of cell layers formed of adherent cells has both surfaces on which culture regions of the adherent cells are disposed, and includes a culture membrane arranged between the plurality of cell layers after the adherent cells are cultured and a plurality of flow passages divided by the culture membrane. The culture membrane is formed of a readily-soluble material.

A fluidic device for culturing cells includes a microplate and plate lid. The microplate includes multiple wells and channels, the channels extending between the wells such that the channels interconnect the wells. The plate lid releasably engages the microplate to thereby enclose the wells and the channels. The wells include a culture surface such that a cell culture medium received therein is deposited over the culture surface. At least one channel that extends between adjacent ones of the wells is spaced from the culture surfaces of the adjacent wells defining a gap between the at least one channel and the culture surfaces of the adjacent wells for collection of the cell culture medium.

Hematopoietic stem cells are extremely difficult to maintain or expand in vitro. Two observations in traditional long-term bone marrow cultures strongly suggest that macrophages may be at the root of the problem: First, micromolar concentrations of hydrocortisone improve the longevity of long-term bone marrow cultures and hydrocortisone is known as a potent inhibitor of macrophage production of pro-inflammatory cytokines, chemokines, enzymes, nitrogen oxide and reactive oxygen species and redirects macrophages to the anti-inflammatory differentiation pathway; Second, the decline of hematopoiesis in long-term bone marrow cultures coincides with the development of large numbers of adherent and non-adherent macrophages including foreign body giant cells. These adherent macrophages and foreign body giant cells exhibit well-spread morphology, contain numerous lysosomes and phagolysosomes in the cytoplasm and are metabolically active. We hypothesize that hydrocortisone fails to suppress all aspects of macrophage pro-inflammatory activation/differentiation, resulting in the production of inhibitors or toxins of hematopoiesis. Macrophage adhesion in cell culture depends on serum proteins pre-adsorbed to the tissue-culture-treated polystyrene (TC-PS), which adsorbs proteins via mostly hydrophilic interactions. TC-PS is used in almost all tissue culture devices currently available. Cellular adhesion provides a strong stimulus for metabolic, mitotic and certain gene activities. Therefore, we seek to reduce macrophage adhesion and activation by culturing bone marrow cells in tissue culture devices composed of or covered with polymers with very different protein-binding characteristics than TC-PS such as polyethylene (PE) and other polyolefins, the latter bind proteins via exclusively hydrophobic interactions. As a result, polyolefins bind different proteins and in lower quantities than TC-PS. Furthermore, PE does not contain additional chemical features like the phenolic rings of polystyrene that might contribute to protein binding and macrophage adhesion/activation. Using these new culture devices, we developed a drastically different long-term bone marrow culture, the “Low Macrophage-Adhesion/Activation” (LoMAC) bone marrow culture. In LoMAC bone marrow culture, hematopoiesis continues for months to over a year and hematopoietic stem cells are amplified gradually. In stark contrast to traditional long-term bone marrow cultures, de novo erythropoiesis and megakaryocytopoiesis proceed robustly in the LoMAC bone marrow culture and B-lymphocyte and natural killer cell progenitors can be continuously derived. Thus, these new culture devices and the associated LoMAC c

The invention relates to a human in vitro model and a method of constructing the same to mimic the alveolar region of the airways to assess the respiratory toxicology and/or physiological and/or biological response of inhaled products, chemicals and particles. There is provided a three-dimensional in vitro alveolar lung model and a method of constructing the same comprising a culture well provided with a membrane configured to separate the culture well into a first compartment and a second compartment, wherein the membrane has first side configured form a wall of the first compartment and a second side configured to form a wall of the second compartment, wherein alveolar type I epithelial cells are provided in the first compartment and alveolar macrophage-like cells are provided in the second compartment.

A method of producing induced pluripotent stem cells without using a hydrogel.

The embodiments provide a bioengineered artificial functional liver which is connected to a patient suffering from acute liver failure and would functional like an ectopic liver. The device uses the cells derived from the patient's own body thereby nullifying the chances of self/non-self-recognition and related immune activation and rejection. The extracted liver cells are grown on a customized 3D matrix called as 3D cell cartridge and these cell cartridges individually function as miniature liver assemblies. Multiple such assemblies when working in parallel would rescue the condition of liver failure. A microfluidic chamber is built with the similar network as found in the liver and the chamber has flow circuits for plasma/de-cellularised blood and the flow circuits are lined by a coculture of hepatocytes, endothelial cells and fibroblasts. The array of cells in the chamber serve as a miniature liver and multiple such arrays will be stacked to achieve a significant hepatic function.

Described herein are cassettes and methods for using these cassettes for cryopreserving biomaterials (e.g., a bioengineered construct or natural tissue sample) by vitrification while reducing or preventing the loss of viability associated with conventional preservation methods.

Provided are new strategies, methods and systems, described herein as vasoactive intestinal peptide (VIP)-assisted air-liquid-interface (ALI) culture, to significantly increase the number of enteroendocrine (EEC) and enterochromaffin (EC) cells over the traditional submerged culture, while at the same time maintaining a high barrier integrity of monolayers. The new strategies, methods and systems overcome the limitations of the existing EEC enrichment methods by maintaining high cell viability and barrier integrity and without requiring complicated procedures of cocultures or genetic engineering/induction. The created EEC-enriched, contiguous monolayer platform acts as a robust analytical tool to enable functional studies of hormone secretion from EEC cells with high signal background ratio and repeatability.

Microfluidic devices with open ports and gel channels for forming perfusable hydrogel vascular networks with holes or ports for samples, and methods of making and using, are provided which integrate interstitial flows to an ex vivo vascularized tissue model. Samples of cells, spheroids, organoids, and tissues can be used for screening of agents for efficacy, toxicity and dosage. The devices create interstitial flow from the top of the gel hole, through the sample toward the vascular networks, and/or luminal flows generated by a pressure difference between two media channels across the vascular network. This system is useful for studying angiogenesis, immune cell migration and testing new immunotherapy drug candidates.

A packed-bed bioreactor system is provided, the system including a cell culture vessel having a first end, a second end, and a reservoir between the first and second ends; and a cell culture matrix disposed in the reservoir. The cell culture matrix includes a structurally defined substrate with a plurality of interwoven fibers having surfaces for adhering cells thereto. The substrate is disposed within the reservoir in a wound configuration creating a plurality of layers of substrate in the wound configuration, and none of the plurality of layers of substrate are separated by a spacer material.