Systems, apparatus and methods for producing objects with cryogenic 3D printing with controllable micro and macrostructure with potential applications in tissue engineering, drug delivery, and the food industry. The technology can produce complex structures with controlled morphology when the printed 3D object is immersed in a liquid coolant, whose upper surface is maintained at the same level as the highest deposited layer of the object. This ensures that the computer-controlled process of freezing is controlled precisely and already printed frozen layers remain at a constant temperature. The technology controls the temperature, flow rate and volume of the printed fluid emitted by the dispenser that has X-Y positional translation and conditions at the interface between the dispenser and coolant surface. The technology can also control the temperature of the pool of liquid coolant and the vertical position of the printing surface and pool of coolant liquid.

A cell culture vessel (100) has walls and a substrate having a plurality of microcavities (120), where each microcavity of the plurality of microcavities includes a concave well and an opening to allow the microcavity to be filled with liquid. A flange (170) surrounds the substrate having an array of microcavities. A channel (175, 176) surrounds the flange, providing a moat around the microcavity substrate. The flange is angled. Methods of culturing cells in the cell culture vessel are also provided.

A cell delivery device and a method of producing a three dimensional device which is vascularized when implanted or topologically applied to human or animal body. Cell laden hydrogel (cells mixed with hydrogel) is casted or injected or 3D bioprinted in a leaf-like form, which contains removable parts (templates). After crosslinking, the templates are removed and the channel for vascularization is created. The device is ready for use in vitro or in vivo.

The systems and methods of the present disclosure can be used to generate systems and models that are physiologically relevant to the human and animal system. These physiological conditions can be designed to mimic the actual human condition for cell differentiation and proliferation. The system and methods of this present disclosure allow the formation of an appropriate biomaterial to mimic that which exists in a human or animal scaffold. Utilizing 3D printing technology, a hydrogel scaffold can be printed at various resolution very close to human physiological geometry. Additionally, the architecture can be optimized for the selected application and appropriate cells can be seeded on the scaffold prior to testing.

The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Disclosed herein is a multicellular lay-up process. The process comprises the steps of: a) forming a core material, b) forming a capsule material, c) encapsulating the core with the capsule material, d) adding the capsule to a substrate, and e) exposing the capsule to at least one bioactivating agent.

A microwell device and a method of manufacturing the same are provided. The microwell device includes a substrate and a plurality of microwells formed on the substrate. In addition, each of the microwells includes a cavity being recessed on the substrate and an opening, and the diameter of the opening is smaller than the largest inner diameter of the cavity. Furthermore, the microwells are curved.

A three-dimensional cell growth containment article is described, which includes a molded body channelized by removal of sacrificial channelizing element(s) therefrom, so that the molded body contains one or more channel(s) therein, with a matrix material in at least one of such channel(s) that is supportive of three-dimensional cell growth in the matrix material. A method for making such articles is also described, in which a molded body is formed with one or more sacrificial channelizing element(s) therein, following which the sacrificial channelizing element(s) are removed. The three-dimensional cell growth containment articles of the present disclosure may be utilized in any applications in which there exists a need to reproducibly generate three-dimensional cellular structures, e.g., islet transplantation for diabetes treatment, transplantation of hormone secreting cells, cellular scaffolds for wound healing, and generation of tissue engineering structures to regain structural usefulness for orthopedic applications.

The present disclosure relates to a method for controlling freeze-drying of a hydrogel wherein the method comprises adjusting the residual water content of the freeze-dried hydrogel, and to a freeze-dried hydrogel composition comprising nanoscale cellulose and a at least one biomolecule selected from an oligosaccharide or a disaccharide. The present disclosure further concerns the use of the freeze-dried hydrogel composition for cell culturing, a cell culturing scaffold as well as a process for manufacturing a reconstituted hydrogel.

An organ implant, such as a heart implant, including a support structure having a plurality of pores and defining passages configured for the growth of blood vessels; and stem cells from at least one soft tissue source of a patient deposited into the pores of the support structure is described. The implant is configured to repair a portion of an organ of the patient.