The present invention relates to a method for producing hair microfollicles comprising the steps of: a) providing de novo papillae, b) providing other cell populations selected from the group of fibroblasts, keratinocytes and melanocytes, and co-culturing the de novo papillae with at least one other cell population in non-adherent culture vessels. The present invention relates also to methods of producing de novo papillae usable in said method for producing hair microfollicles.

The present invention provides: a method for producing mixed cells comprising cardiomyocytes, endothelial cells and mural cells from induced pluripotent stem cells, the method comprising (a) a step of producing cardiomyocytes from induced pluripotent stem cells and (b) a step of culturing the cardiomyocytes in the presence of VEGF; and a therapeutic agent for heart diseases, comprising the mixed cells produced by the method.

An implantable medical device and methods for making and using the same are provided. In various embodiments, the device comprises a central hub structure in communication with at least one housing or pod capable of containing cells and therapeutic materials. Also provided are membrane structures and methods of forming the same, the membranes comprising a gradient of varying porosity for use with devices of the present disclosure, as well as other uses.

A scaffold-free microtissue is disclosed that includes one or more gold nanostructures linked to a functional moiety, wherein the functional moiety is one or more vasculogenic peptides, one or more anti-inflammatory peptides, one or more antiapoptotic peptides, one or more antinecrotic peptides, one or more antioxidant peptides, one or more oligonucleotides, one or more lipid particles, one or more phospholipid particles, one or more liposomes, one or more nanoliposomes, one or more microRNAs, or one or more siRNAs. The scaffold-free microtissue further includes a plurality of cardiac myocytes or cardiac myoblasts, which are conjugated to the one or more gold nanostructures, wherein the plurality of cardiac myocytes or cardiac myoblasts are arranged in a cluster. The scaffold-free microtissue further includes a plurality of fibroblasts, wherein the fibroblasts are arranged in at least one layer of fibroblasts that substantially surrounds the cluster of gold-nanostructure-conjugated cardiac myocytes or gold-nanostructure-conjugated cardiac myoblasts.

The present invention generally relates to a therapeutic hydrogel device. More particularly, the present invention describes various embodiments of a hydrogel macrodevice, such as a planar hybrid hydrogel macrodevice that can achieve spatially controlled distribution of microtissues and support establishment of intra-device vasculature for enhanced cell survival, and individually encapsulated microtissues, and methods of use.

The present invention provides customized hybrid bone-implant grafts and a method of manufacture thereof.

The present invention provides tissue equivalent scaffold structures and methods of production thereof. Such methods include providing a casting chamber comprising an elongate mould portion, axially disposing a lumen template within the elongate mould portion, and at least partly filling the casting chamber with a gel casting material comprising a matrix of fibrils or fibres and an interstitial fluid phase, such that a portion of the lumen template extends above the casting material. The fluid phase of the gel is allow to flow axially out of the elongate mould portion, in a restricted manner, thereby resulting in axial densification of the gel casting material to form a tissue equivalent tubular scaffold. Tissue equivalent scaffold structures according to the present invention are able to support cell populations both within the walls and on the surface of the construct. They have enhanced mechanical strength due to increased collagen density, and are customisable in terms of luminal diameter and wall thickness. They may find application in tubular tissue engineering.

The present invention provides a method of constituting a tissue construct in vitro using a tissue without depending on scaffold materials.

A method of integrating a biological tissue with a vascular system in vitro, comprising coculturing a biological tissue with vascular cells and mesenchymal cells. A biological tissue which has been integrated with a vascular system by the above-described method. A method of preparing a tissue or an organ, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of regeneration or function recovery of a tissue or an organ, comprising transplanting the biological tissue described above into a human or a non-human animal and differentiating the biological tissue into a tissue or an organ in which vascular networks have been constructed. A method of preparing a non-human chimeric animal, comprising transplanting the biological tissue described above into a non-human animal and differentiating the biological tissue into a tissue or organ in which vascular networks have been constructed. A method of evaluating a drug, comprising using at least one member selected from the group consisting of the biological tissue described above, the tissue or organ prepared by the method described above, and the non-human chimeric animal prepared by the method described above. A composition for regenerative medicine, comprising a biological tissue which has been integrated with a vascular system by the method described above.

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.

Engineered human tissue seed constructs are provided that are suitable for implantation in subjects. Methods of making and using the engineered tissue seed constructs are provided.