Abstract: The invention provides method of fabricating a scaffold comprising a fluidic network, including the steps of: (a) generating an initial vascular layer for enclosing the chamber and providing fluid to the cells, the initial vascular layer having a network of channels for fluid; (b) translating the initial vascular layer into a model for fluid dynamics analysis; (c) analyzing the initial vascular layer based on desired parameters selected from the group consisting of a characteristic of a specific fluid, an input pressure, an output pressure, an overall flow rate and combinations thereof to determine sheer stress and velocity within the network of channels; (d) measuring the sheer stress and the velocity and comparing the obtained values to predetermined values; (e) determining if either of the shear stress or the velocity are greater than or less than the predetermined values, and (f) optionally modifying the initial vascular layer and repeating steps (b)-(e).

Abstract: Methods and materials for making an apparatus which duplicates the functionality of a physiological system id provided.

Abstract: Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.

Abstract: Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.

Abstract: A method of determining toxicity of a test agent in a tissue including A) incubating a test agent within a three-dimensional tissue engineered structure comprising a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, and wherein the first mold or polymer scaffold has microchannels comprising vessels that bifurcate, and B) obtaining information from step A) to assess toxicity.

Abstract: Polymeric materials are used to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases.

Abstract: The present invention is related to the use of stem cells of an animal species for obtainment of biological tooth substitute, in whole or in parts, to be implanted in organism of the same animal strain, wherein said stem cells can be adult cells. The present invention still aims to develop a method of tissue engineering for culturing cells capable to form dental tissue for production of a tooth biological substitute. The said dental tissue can used for the treatment of people suffering from loss, fail or lack of these tissues, and also for cosmetic use of those tissues for a morphological modifying on a patient dentition, for example, the patient may desire to, or need to, have a bigger or smaller dentition for any aesthetic reason.

Abstract: The invention features a method for generating new tissue by obtaining a liquid hydrogel-cell composition including a hydrogel and tissue precursor cells; delivering the liquid hydrogel-cell composition into a permeable, biocompatible support structure; and allowing the liquid hydrogel-cell composition to solidify within the support structure and the tissue precursor cells to grow and generate new tissue. The invention also features a tissue forming structure including a permeable, biocompatible support structure having a predetermined shape that corresponds to the shape of desired tissue; and a hydrogel-cell composition at least partially filling the support structure, wherein the hydrogel-cell composition includes a hydrogel and tissue precursor cells. The new tissue forming structure can be used in new methods to generate various tissues (e.g., to treat defective tissue) including new bone, cartilage, and nervous tissue such as spinal cord tissue. The invention also new isolated nervous system stem cells.

Abstract: Polymeric materials are used to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases.

Abstract: The invention provides for translating two-dimensional microfabrication technology into the third dimension. Two-dimensional templates are fabricated using high-resolution molding processes. These templates are then bonded to form three-dimensional scaffold structures with closed lumens. The scaffolds can serve as the template for cell adhesion and growth by cells that are added to the scaffolds through the vessels, holes or pores. These scaffolds can be formed by layering techniques, to interconnect flat template sheets to build up a fully vascularized organ.

Abstract: The present invention relates to tissue engineered compositions and methods comprising nanotopographic surface topography (“nanotopography”) for use in modulating the organization and/or function of multiple cell types.

Abstract: Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, and anti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells.

Abstract: Tooth tissues include the pulp mesenchyme that forms the dentin and an epithelium that is responsible for enamel formation. Cells from these tissues were obtained from porcine third molars and were seeded onto a biodegradable scaffold composed of a polyglycolic acid—polylactic acid copolymer. Cell polymer constructs were then surgically implanted into the omentum of athymic nude rats so that the constructs would have a blood supply and these tissues were allowed to develop inside the rats. Infrequently, columnar epithelial cells were observed as a single layer on the outside of the dentin-like matrix similar to the actual arrangement of ameloblasts over dentin during early tooth development. Developing tooth tissues derived from such cell polymer constructs could eventually be surgically implanted into the gum of an edentulous recipient where the construct would receive a blood supply and develop to maturity, providing the recipient with a biological tooth replacement.

Abstract: Connective tissue, including neo-tendons and ligaments, has been constructed using biodegradable synthetic scaffolds seeded with tenocytes. The scaffolds are preferably formed from biodegradable fibers formed of a polymer such as polyglycolic acid-polylactic acid copolymers, and seeded with cells isolated from autologous tendon or ligament by means of enzymatic digestion or direct seeding into tissue culture dishes from explants. The cell polymer constructs are then surgically transplanted to replace missing segments of functioning tendon or ligament.

Abstract: Tooth tissues include the pulp mesenchyme that forms the dentin and an epithelium that is responsible for enamel formation. Cells from these tissues were obtained from porcine third molars and were seeded onto a biodegradable scaffold composed of a polyglycolic acid-polylactic acid copolymer. Cell polymer constructs were then surgically implanted into the omentum of athymic nude rats so that the constructs would have a blood supply and these tissues were allowed to develop inside the rats. Histological analysis of 7.5 week-old implants revealed a dentin-like collagenous matrix containing hydroxyapatite mineral surrounding a core of mesenchymal cells that appeared analogous to pulp tissue. Infrequently, columnar epithelial cells were observed as a single layer on the outside of the dentin-like matrix similar to the actual arrangement of ameloblasts over dentin during early tooth development.

Abstract: The invention features a method for generating new tissue by obtaining a liquid hydrogel-cell composition including a hydrogel and tissue precursor cells; delivering the liquid hydrogel-cell composition into a permeable, biocompatible support structure; and allowing the liquid hydrogel-cell composition to solidify within the support structure and the tissue precursor cells to grow and generate new tissue. The invention also features a tissue forming structure including a permeable, biocompatible support structure having a predetermined shape that corresponds to the shape of desired tissue; and a hydrogel-cell composition at least partially filling the support structure, wherein the hydrogel-cell composition includes a hydrogel and tissue precursor cells. The new tissue forming structure can be used in new methods to generate various tissues (e.g., to treat defective tissue) including new bone, cartilage, and nervous tissue such as spinal cord tissue. The invention also new isolated nervous system stem cells.

Abstract: Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells.

Abstract: Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells.

Abstract: Polymeric materials are used,to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases.

Abstract: The present invention relates to a method for producing a tissue-engineered organ or organ portion or specific section thereof comprising the steps of loading organoid units into a biocompatible polymer scaffold and implanting the polymer scaffold into a subject. Organs produced by this method are also encompassed by the invention. Organoid units can be derived from tissues including, but not limited to, spleen, lung, liver, kidney, pancreas, endocrine tissue, heart, esophagus, colon, stomach, gall bladder and uterus. The resulting engineered tissue can comprise spleen, lung, liver, kidney, pancreas, endocrine, cardiac muscle, esophagus, colon, stomach, gall bladder or uterus. The invention further relates to a tissue-engineered organ or organ portion or specific section thereof comprising compact tissue grown in a biocompatible polymer scaffold, wherein the tissue is derived from spleen, lung, liver, kidney, pancreas, endocrine, heart, esophagus, colon, stomach, gall bladder or uterus.