The invention provides a decellularized tissue hydrogel cross-linked with a polyphenol, and a method of preparing a cross-linked decellularized tissue hydrogel, the method comprising the steps of: a) providing at least one decellularized tissue hydrogel; and b) cross-linking the at least one decellularized tissue hydrogel with a polyphenol.

The disclosure provides a method of using blood or fractions thereof, e.g., serum, obtained from a mammal subjected to liver surgery, for example, obtained following a partial hepatectomy, to increase the engraftment, proliferation and/or functionality of cells on a biocompatible scaffold.

The present disclosure provides engineered tissue constructs having a population of cells. such as hepatocytes and stromal cells. and methods of implanting the same (e.g., for treating a disease or disorder, such as acute liver failure, a urea cycle disorder, or hyperbilirubinemia (e.g., in a subject having Crigler-Najjar syndrome) in a human subject in need thereof).

The disclosure provides a method of using blood or fractions thereof, e.g., serum, obtained from a mammal subjected to liver surgery, for example, obtained following a partial hepatectomy, to increase the engraftment, proliferation and/or functionality of cells on a biocompatible scaffold.

A method of repairing diseased or dysfunctional pancreas or liver is provided. The method involves preparation of a suspension of stem cells and/or progenitor cells such as biliary tree stem cells, hepatic stem cells, pancreatic stem cells or their descendants, committed progenitor cells, from healthy tissue of the patient or of the biliary tree of a non-autologous donor and engrafting the cells into the wall of bile ducts near to the organ to be treated. The graft consists of stem cells or progenitors that are admixed with biomaterials and, optionally, with cytokines and/or native epithelial-mesenchymal cells appropriate for the maturational lineage stage of the cells to be engrafted. The cells are specifically introduced to the hepato-pancreatic common duct of the subject for treatment of pancreatic conditions or to the bile duct wall near to the liver for treatment of liver conditions and allowed to migrate to the pancreas or to the liver and expand and then rebuild part or the entirety of the diseased or dysfunctional organ.

The present invention provides engineered tissue scaffolds, engineered tissues, and methods of using them. The scaffolds and tissues are derived from natural tissues and are created using non-thermal irreversible electroporation (IRE). Use of IRE allows for ablation of cells of the tissue to be treated, but allows vascular and neural structures to remain essentially unharmed. Use of IRE thus permits preparation of thick tissue scaffolds and tissues due to the presence of vasculature within the scaffolds. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

The present invention provides a means for reconstituting tissues and organs having mature functions.

A method of preparing a tissue or an organ, comprising coculturing an organ cell with a vascular endothelial cell and a mesenchymal cell, generating an organ bud, transplanting the organ bud into a non-human animal, and then isolating from the non-human animal the transplanted organ bud-derived tissue or organ.

This invention relates to methods for decellularising human liver tissue to produce human hepatic extracellular matrix (ECM) scaffolds, for example for use in therapy or disease modelling. The methods involve mechanically damaging cells in the tissue, for example by freeze thaw, and then subjecting the liver tissue to multiple cycles of osmotic stress, detergent treatment and protease and/or DNAase treatment to produce a decellularised human ECM scaffold.

The present invention provides engineered tissue scaffolds, engineered tissues, and methods of using them. The scaffolds and tissues are derived from natural tissues and are created using non-thermal irreversible electroporation (IRE). Use of IRE allows for ablation of cells of the tissue to be treated, but allows vascular and neural structures to remain essentially unharmed. Use of IRE thus permits preparation of thick tissue scaffolds and tissues due to the presence of vasculature within the scaffolds. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

The present invention finds out find out the requirements necessary for preparing a cell condensate in vitro from a large number of cells (several ten thousand to several million cells) and provides a method of forming a cell condensate for self-organization which is capable of realizing complex higher structures (such as liver and kidney) and interactions with other organs.

A method of preparing a cell condensate in vitro, comprising culturing a mixture of cells and/or tissues of a desired type in a total cell count of 400,000 or more and 100,000 to 400,000 mesenchymal cells to form a cell condensate of 1 mm or more in size. A cell condensate prepared by the above-described method. A method of preparing a three-dimensional tissue structure, comprising allowing self-organization of a cell condensate prepared by the above-described method to form a three-dimensional tissue structure that has been provided with higher structures. A gel-like support wherein the side on which culture is to be performed has a U- or V-shaped cross-section.