The present invention relates to a three-dimensional multiphasic synthetic tissue scaffold comprising first, second and third compartments, wherein: each said compartment comprises distinct microstructural, and/or chemical, and/or mechanical properties, and is connected with at least one other compartment of the scaffold via a continuous interface; the tissue scaffold is porous; and the external morphology of the tissue scaffold mimics that of a mammalian joint or a component thereof. The invention further relates to a method for producing the three dimensional multiphasic synthetic tissue scaffold using a polymeric material, the method comprising using a three-dimensional (3D) bioprinter to print the tissue scaffold by continuously deposit the polymeric material onto a platform until the tissue scaffold is produced in its entirety.

The present invention relates to preparation of bioink composed of cellulose nanofibril hydrogel with native or synthetic Calcium containing particles. The concentration of the calcium containing particles can be between 1% and 40% w/v. Such bioink can be 3D Bioprinted with or without human or animal cells. Coaxial needle can be used where cellulose nanofibril hydrogel filled with Calcium particles can be used as shell and another hydrogel based bioink mixed with cells can be used as core or opposite. Such 3D Bioprinted constructs exhibit high porosity due to shear thinning properties of cellulose nanofibrils which provides excellent printing fidelity. They also have excellent mechanical properties and are easily handled as large constructs for patient-specific bone cavities which need to be repaired. The porosity promotes vascularization which is crucial for oxygen and nutrient supply. The porosity also makes it possible for further recruitment of cells which accelerate bone healing process. Calcium containing particles can be isolated from autologous bone, allogenic bone or xenogeneic bone but can be also isolated from minerals or be prepared by synthesis. Preferable Calcium containing particles consist of β-tricalcium phosphate which is resorbable or natural bone powder, preferably of human or porcine origin. The particles described in the present invention have particle size smaller than 400 microns, or more preferably smaller than 200 microns, to make it possible to handle in printing nozzle without clogging and to obtain a good resolution. Cellulose nanofibrils can be produced by bacteria orbe isolated from plants. They can be neutral, charged or oxidized to be biodegradable. The bioink can be additionally supplemented by other biopolymers which provide crosslinking. Such biopolymers can be alginates, chitosans, modified hyaluronic acid or modified collagen derived biopolymers.

Described herein are methods and apparatus for constructing tissue replacements, such as bone replacements that may be used to repair damaged or missing segments of bone, such as may occur in wound repair or as a repair of a congenital anomaly. These methods involve a three-dimensional (3D) cell growth medium made from a yield stress material that allows cells and structures to be easily deposited and positioned.

A bioprinter comprises one or more dispensing units. Each dispensing unit may include (i) a syringe including a hollow body and a plunger dimensioned to translate in the body wherein the body has an exit orifice; (ii) an actuator in contact with a proximal end of the plunger; (iii) a controller for moving the actuator; and (iv) a nozzle having a wall defining a fluid path extending from an inlet of the nozzle to an outlet of the nozzle. The inlet of the nozzle is in fluid communication with the exit orifice of the syringe body. The nozzle includes a fluid passageway in fluid communication with a source of fluid and the fluid path. The bioprinter can be used in a method of preparing microtissue comprising dispensing a bioink from one or more dispensing units of the bioprinter on a plate. The microtissue may comprise cartilage cells or tumor cells or liver cells.

An orthopedic device for implanting between adjacent vertebrae comprising: an arcuate balloon and a hardenable material within said balloon. In some embodiments, the balloon has a footprint that substantially corresponds to a perimeter of a vertebral endplate. An inflatable device is inserted through a cannula into an intervertebral space and oriented so that, upon expansion, a natural angle between vertebrae will be at least partially restored. At least one component selected from the group consisting of a load-bearing component and an osteobiologic component is directed into the inflatable device through a fluid communication means.

A composition including, (a) a mineral particle, (b) endothelial cells and mesenchymal cells, and (3) hyaluronic acid, is provided. Moreover, a kit which includes: a syringe, a mineral particle covered with endothelial cells and mesenchymal cells organized in 2 or more cell layers attached to the mineral particle, and hyaluronic acid, is also provided. Last, a method for filling a gap in a bone of a subject in need thereof, including contacting the gap with a composition of: (a) a mineral particle, (b) endothelial cells and mesenchymal cells, and (3) hyaluronic acid is provided.

A method of modulating transdifferentiation of chondrocytes to osteoblast includes administering to the chondrocytes an agent that modulates GP130 receptor signaling and expression of at least one of Sox2, Oct4, or Nanog of the chondrocytes.

A bioprinter comprises one or more dispensing units. Each dispensing unit may include (i) a syringe including a hollow body and a plunger dimensioned to translate in the body wherein the body has an exit orifice; (ii) an actuator in contact with a proximal end of the plunger; (iii) a controller for moving the actuator; and (iv) a nozzle having a wall defining a fluid path extending from an inlet of the nozzle to an outlet of the nozzle. The inlet of the nozzle is in fluid communication with the exit orifice of the syringe body. The nozzle includes a fluid passageway in fluid communication with a source of fluid and the fluid path. The bioprinter can be used in a method of preparing microtissue comprising dispensing a bioink from one or more dispensing units of the bioprinter on a plate. The microtissue may comprise cartilage cells or tumor cells or liver cells.

The current invention relates to a composition for parenteral administration comprising a canine plasma and hyaluronic acid or a salt or ester thereof, wherein said plasma comprises lipids and/or phospholipids. The inventions also relates to a kit comprising one or more aliquots of a composition, said composition comprising a canine plasma comprising lipids and/or phospholipids and hyaluronic acid or a derivative thereof and optionally one or more pharmaceutical active ingredients, wherein said kit further comprises one or more aliquots of a calcium source, preferably a calcium chloride solution. The invention also pertains to the composition and kit of current invention for use in the treatment of musculoskeletal diseases.

An object of the present invention is to provide a bone regenerative agent showing a high bone regeneration effect. According to the present invention, a bone regenerative agent containing gelatin-containing granules and stem cells is provided. Gelatin preferably has repetitions of a sequence represented by Gly-X-Y, which is characteristic of collagen. Here, a plurality of Gly-X-Y's may be the same as or different from each other, and in the formula, X and Y each independently represent any of amino acid. A molecular weight of the gelatin is preferably 2 KDa or more and 100 KDa or less.