The present disclosure provides, in various aspects, a method of forming a prefabricated innervated pre-vascularized pre-laminated (PIPP) flap having a stoma or lumen. The method includes providing a cell construct including skin cells and/or mucosa cells. The method further includes forming an integrated in vivo composite at a donor site by grafting the cell construct onto a muscle. The method further includes stabilizing the composite on an obturator component. The method further includes developing a microvascular system in the composite by retaining it in vivo at the donor site for a predetermined period of time. The method further includes removing the obturator component from the stoma or lumen. In certain aspects, the present disclosure also provides a method of restoring a defect including damaged or surgically removed soft tissue using a PIPP flap. In certain aspect, the present disclosure also provides an obturator component for maintaining the stoma or lumen.

Disclosed are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture forming mature cardiomyocytes. Also disclosed is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and/or proarrhythmic screening assays of drug compounds. Also disclosed are methods for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro using such cell constructs.

The growth factor profile, connective tissue matrix constituents, and immunoprivileged status of urodele extracellular matrix (ECM) and accompanying cutaneous tissue, plus the presence of antimicrobial peptides there, render urodele-derived tissue an ideal source for biological scaffolds for xenotransplantation. In particular, a biological scaffold biomaterial can be obtained by a process that entails (A) obtaining a tissue sample from a urodele, where the tissue comprises ECM, inclusive of the basement membrane, and (B) subjecting the tissue sample to a decellularization process that maintains the structural and functional integrity of the extracellular matrix, by virtue of retaining its fibrous and on-fibrous proteins, glycoaminoglycans (GAGs) and proteoglycans, while removing sufficient cellular components of the sample to reduce or eliminate antigenicity and immunogenicity for xenograft purposes. The resultant urodele-derived biomaterial can be used to enhance restoration of skin homeostasis, to reduce the severity, durations and associated damage caused by post-surgical inflammation, and to promote progression of natural healing and regeneration processes. In addition, the biomaterial promotes the formation of remodeled tissue that is comparable in quality, function, and compliance to undamaged human tissue.

The present invention provides compositions for treating soft tissue injuries comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix. Methods of making and using compositions comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix are also provided.

An in vitro microfluidic gut-on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic culture is described, allowing for interactions between lamina propria-derived cells and gastrointestinal epithelial cells and endothelial cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal tissue, e.g., Crohn's disease, colitis and other inflammatory gastrointestinal disorders. These multicellular, layered microfluidic gut-on-chip further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal deuodejeum, small intestinal ileium, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e. healthy, pre-disease and diseased areas. Additionally, these microfluidic gut-on-chips allow identification of cells and cellular derived factors driving disease states and drug testing for reducing inflammation.

The present invention provides compositions and methods for wound healing and tissue regeneration. The compositions of the present invention comprise amniotic membrane of the placenta. In certain embodiments, the composition comprises amniotic membrane powder or solubilized amniotic membrane (SAM). In some aspects, the composition is cell-free and rich in cytokines, extracellular matrix proteins, and other components that improve tissue regeneration. In one aspect, the composition is a hydrogel scaffold that comprises amniotic membrane. The present invention reduces contraction and improves blood vessel development in regenerating tissue.

The present application provides methods and devices for the production and recovery of cell aggregates. In one embodiment, the device is a microwell device with a high density of microwells. The application also provides a device for extracting cell aggregates such as stem cells or embryoid bodies from well plates. Such cell aggregates are used for the differentiation of pluripotent stem cells such as embryonic stem cells, in the fields of developmental biology and regenerative medicine/tissue engineering.

Disclosed herein are methods of using a cell-derived extracellular matrix derived in-vitro from cells isolated from amniotic fluid (AFC-ECM) for the maturation of immature cardiomyocytes derived from human induced pluripotent stem cells (immature hiPSC-CMs) in culture forming mature cardiomyocytes. Also disclosed herein is a cell construct comprising a monolayer of these mature cardiomyocytes on an AFC-ECM useful for cardiotoxicity and/or proarrhythmic screening assays of drug compounds. Also disclosed herein are methods for determining the cardiotoxicity and/or proarrhythmic effect of a drug compound in vitro using such cell constructs.

This disclosure pertains to a non-living biological product. Particularly, exosomes derived from stem cells can help restore heart function. According to certain embodiments, a fluid-induced shear stress mechanical stimulation process of stem cells is used to augmented quantity and quality of exosomes produced from stem cells. These exosomes serve as a therapeutic agent for the regenerative repair of diseases, such as diseased heart tissues. Therefore, compositions comprising the exosomes derived from stem cells and methods of treating a degenerative disease by administering the exosomes isolated from stem cells are also provided.

This disclosure pertains to a non-living biological product. Particularly, exosomes derived from stem cells can help restore heart function. According to certain embodiments, a fluid-induced shear stress mechanical stimulation process of stem cells is used to augmented quantity and quality of exosomes produced from stem cells. These exosomes serve as a therapeutic agent for the regenerative repair of diseases, such as diseased heart tissues. Therefore, compositions comprising the exosomes derived from stem cells and methods of treating a degenerative disease by administering the exosomes isolated from stem cells are also provided.