Provided herein is technology relating to engineered tissues and particularly, but not exclusively, to methods, compositions, and systems for engineering a biosynthetic vascular network.

Systems featuring two or more encapsulation devices stacked together. The encapsulation devices house cells, such as but not limited to islet cells or stem cell derived beta cells or the like. e.g., for regulating blood glucose, or other cells or spheroids that can produce and release a therapeutic agent that is useful in the body, etc. The system may feature oxygen delivery, or in some cases no exogenous oxygen is delivered and vascularization of the device can help provide oxygen and other needed nutrient to the cells. The system of the present invention may be used in conjunction with other therapies such as an artificial pancreas. Stacking the devices with blood vessel formation around and in between them may allow for a decrease in the footprint that would be needed for implantation.

Structures and methods for tissue engineering include a multicellular body including a plurality of living cells. A plurality of multicellular bodies can be arranged in a pattern and allowed to fuse to form an engineered tissue. The arrangement can include filler bodies including a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies and that is resistant to adherence of cells to it. Three-dimensional constructs can be assembled by printing or otherwise stacking the multicellular bodies and filler bodies such that there is direct contact between adjoining multicellular bodies, suitably along a contact area that has a substantial length. The direct contact between the multicellular bodies promotes efficient and reliable fusion. The increased contact area between adjoining multicellular bodies also promotes efficient and reliable fusion. Methods of producing multicellular bodies having characteristics that facilitate assembly of the three-dimensional constructs are also provided.

The invention relates to a process for obtaining a skin substitute, comprising the following steps: a) mixing fibroblasts, endothelial cells and hydrogel of exclusively biological origin; b) incubating the mixture obtained in step a) for a sufficient time and under suitable conditions to obtain a pre-vascularized dermis; c) adding keratinocytes to the pre-vascularized dermis of step b) to obtain a skin substitute; wherein said fibroblasts, endothelial cells and keratinocytes were obtained from pluripotent stem cells.

Disclosed are methods of promoting wound healing in a patient in need thereof comprising administering to the patient a composition comprising a neonatal fibrin scaffold. Further disclosed are in vitro methods for evaluating a target composition on human wound healing comprising a neonatal porcine plasma scaffold with the target composition and evaluating scaffold properties of the plasma sample.

The composition and method of the invention relate to dental implant or orthognathic implant, graft materials and platelet-rich fibrin (PRF) applications in the field of dental and jaw health. The invention particularly relates to a therapeutic composition comprising at least one anti-sclerostin antibody and at least one anti dickkopf-1 antibody in combination for increasing osseointegration and accelerating healing in dental implantation and bone volume augmentation in filling of insufficient bone sites, and methods of local administration thereof.

Structures and methods for tissue engineering include a multicellular body including a plurality of living cells. A plurality of multicellular bodies can be arranged in a pattern and allowed to fuse to form an engineered tissue. The arrangement can include filler bodies including a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies and that is resistant to adherence of cells to it. Three-dimensional constructs can be assembled by printing or otherwise stacking the multicellular bodies and filler bodies such that there is direct contact between adjoining multicellular bodies, suitably along a contact area that has a substantial length. The direct contact between the multicellular bodies promotes efficient and reliable fusion. The increased contact area between adjoining multicellular bodies also promotes efficient and reliable fusion. Methods of producing multicellular bodies having characteristics that facilitate assembly of the three-dimensional constructs are also provided.

Described herein are compositions and methods related to derivation of human notochordal cells differentiated from induced pluripotent stem cells (iPSCs). The inventors have developed a two-step process for generating these iPSC-derived notochordal cells (iNCs), which can provide a renewable source of therapeutic material for use in degenerative disc disease (DDD). As iNCs are capable of reversing DDD and supporting regeneration of intervertebral disc (IVD) tissue based on the understanding that NC cells maintain homeostasis and repair of other IVD cell types such as nuclear pulposus (NP).

Materials and methods for preparing a hydrogel are disclosed. Specifically, two separate solutions A and B, of which the solution A comprises enzyme horseradish peroxidase and the solution B comprises hydrogen peroxide is provided. At least one of solution A or B comprises calcium ions in the form of a pharmaceutically acceptable salt, and further the solution A and/or the solution B comprises hydroxyphenyl derivative of hyaluronan of a particular formula. A hydrogel based on hydroxyphenyl derivative of hyaluronan and a method of preparing and using the same is also disclosed.

Embodiments of the invention include instruments (100, 200, 400, 1100, 1400, 2100, 2400, 3400) and methods useful in delivering graft material (1) to a surgical site. Some embodiments may particularly be directed to forming a graft (1) and accurately and effectively handling and delivering the graft (1) to a surgical site arthroscopically. Graft material (1) may include blood components such as clotted fibrin derived from a patient's or a donor's blood.