872 results about "Osteoblast" patented technology

This invention provides novel nanofiber enhanced surface area substrates and structures comprising such substrates for use in various medical devices, as well as methods and uses for such substrates and medical devices. In one particular embodiment, methods for enhancing cellular functions on a surface of a medical device implant are disclosed which generally comprise providing a medical device implant comprising a plurality of nanofibers (e.g., nanowires) thereon and exposing the medical device implant to cells such as osteoblasts.

This invention provides novel nanofiber enhanced surface area substrates and structures comprising such substrates for use in various medical devices, as well as methods and uses for such substrates and medical devices. In one particular embodiment, methods for enhancing cellular functions on a surface of a medical device implant are disclosed which generally comprise providing a medical device implant comprising a plurality of nanofibers (e.g., nanowires) thereon and exposing the medical device implant to cells such as osteoblasts.

An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region's macrostructure and which differentiate into osteoblasts. Another embodiment is arranged for the local delivery of therapeutic agent. A preferred embodiment is a porous resorbable implant, wherein the therapy delivery may be localized in nature, rather than systemic, such that higher doses at the target site may be allowed than would be tolerable by the body systemically.

A dietary supplement for benefitting human bone health includes a calcium source, a source of vitamin D activity, and an osteoblast stimulant. A preferred calcium source is microcrystalline hydroxyapatite, which also contains protein (mostly collagen), phosphorus, fat, and other minerals. A preferred source of vitamin D activity is cholecalciferol, and a preferred osteoblast stimulant is ipriflavone. In addition to these basic ingredients, the composition can further include various other minerals known to occur in bone, vitamin C, and glucosamine sulfate, all of which exert beneficial effects on growth and maintenance of healthy bone. A method for benefitting human bone health involves administering a daily regimen of the dietary supplement.

An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region's macrostructure and which differentiate into osteoblasts. A hydrophobic barrier exists between the regions, of this embodiment. In one embodiment, the polyelectrolytic complex transforms to hydrogel, following the implant procedure.

The present invention provides methods of improving the osteogenic and / or chondrogenic activity of a bone matrix, e.g., a dermineralized bone matrix (DBM), by exposing the bone matrix to one or more treatments or conditions. In preferred embodiments the bone matrix is derived from human bone. The treatment or condition may alter the structure of the bone matrix and / or cleave one or more specific proteins. Cleavage may generate peptides or protein fragments that have osteoinductive, osteogenic, or chondrogenic activity. Preferred treatments include collagenase and various other proteases. The invention further provides improved bone and cartilage matrix compositions that have been prepared according to the inventive methods and methods of treatment using the compositions. The invention further provides methods of preparing, testing, and using the improved bone matrix compositions. Ona assay comprises exposing relatively undifferentiated mesenchymal cells to a bone matrix composition and measuring expression of a marker characteristic of osteoblast or chondrocyte lineage(s). Increased expression of the marker relative to the level of the marker in cells that have been exposed to a control matrix (e.g., an inactivated or untreated matrix) indicates that the treatment or condition increased the osteogenic and / or chondrogenic activity of the bone matrix. Suitable cells include C2C12 cells. A suitable marker is alkaline phosphatase. The inventive methods increase the osteogenic and / or chondrogenic activity of human DBM when tested using this assay system.

Compositions comprising bioactive glass compositions or extracts thereof which include ions in an appropriate concentration and ratio that they enhance osteoblast production, and methods of preparation and use thereof, are disclosed. The compositions can be included in implantable devices that are capable of inducing tissue formation in autogeneic, allogeneic and xenogeneic implants, for example as coatings and / or matrix materials. Examples of such devices include prosthetic implants, sutures, stents, screws, plates, tubes, and the like. Aqueous extracts of the bioactive glass compositions, which extracts are capable of stimulating osteoblast production, are also disclosed. The compositions can be used, for example, to induce local tissue formation from a progenitor cell in a mammal, for accelerating allograft repair in a mammal, for promoting in vivo integration of an implantable prosthetic device to enhance the bond strength between the prosthesis and the existing target tissue at the joining site, and for treating tissue degenerative conditions.

Invention embodiments described herein include methods and devices for stimulating mesenchymal stem cells in a stem cell source to differentiate into osteoblasts capable of forming bone. Devices and methods described include exposing a stem cell source, such as bone marrow aspirate, adipose tissue and / or purified allogenic stem cells, to an active agent, in a manner effective to form activated stem cells.

Three-dimensional tissue-like organization of cells by high cell-seeding-density culture termed as macromass culture is described. By macromass culture, cells can be made to organize themselves into a tissue-like form without the aid of a scaffold and three-dimensional macroscopic tissue-like constructs can be made wholly from cells. Tissue-like organization and macroscopic tissue-like constructs can be generated from fibroblastic cells of mesenchymal origin (at least), which can be either differentiated cells or multipotent adult stem cells. In this work, tissue-like organization and macroscopic tissue-like constructs have been generated from dermal fibroblasts, adipose stromal cells-derived osteogenic cells, chondrocytes, and from osteoblasts. The factor causing macroscopic tissue formation is large scale culture at high cell seeding density per unit area or three-dimensional space, that is, macromass culture done on a large scale. No scaffold or extraneous matrix is used for tissue generation, the tissues are of completely cellular origin. No other agents (except high cell-seeding-density) that aid in tissue formation such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, etc, are employed for tissue formation. These tissue-like masses have the potential for use as tissue replacements in the human body. Tissue-like organization by high cell-seeding-density macromass culture can also be generated at the microscopic level.

As a result of an effort made by us for the purpose of developing a therapeutic agent having a bone formation-stimulating effect by promoting the functions of osteoblasts, the present inventors discovered that a certain nitrogen-containing heterocyclic compound exhibits a potent bone formation-stimulating effect on the osteoblast and thus can serve as an excellent prophylactic or therapeutic agent against a metabolic bone disease, whereby establishing the present invention. Thus, the present invention provides a 3,6-disubstituted 1,2,4-triazolo[4,3-b]pyridazine compound or a pharmaceutically acceptable salt thereof as well as a pharmaceutical composition comprising such a compound and a pharmaceutically acceptable carrier, especially a bone-forming agent.

Compositions and methods for the treatment of bone diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2), acts to stimulate bone formation independently of Wnt proteins which may be inhibited and / or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

The present invention relates to placenta tissue-derived multipotent stem cells and cell therapeutic agents containing the same. More specifically, to a method for producing placenta stem cells having the following characteristics, the method comprising culturing amnion, chorion, decidua or placenta tissue in a medium containing collagenase and bFGF and collecting the cultured cells: (a) showing a positive immunological response to CD29, CD44, CD73, CD90 and CD105, and showing a negative immunological response to CD31, CD34, CD45 and HLA-DR; (b) showing a positive immunological response to Oct4 and SSEA4; (c) growing attached to plastic, showing a round-shaped or spindle-shaped morphology, and forming spheres in an SFM medium so as to be able to be maintained in an undifferentiated state for a long period of time; and (d) having the ability to differentiate into mesoderm-, endoderm- and ectoderm-derived cells. Also the present invention relates to placenta stem cells obtained using the production method. The inventive multipotent stem cells have the ability to differentiate into muscle cells, vascular endothelial cells, osteogenic cells, nerve cells, satellite cells, fat cells, cartilage-forming cells, osteogenic cells, or insuline-secreting pancreatic β-cells, and thus are effective for the treatment of muscular diseases, osteoporosis, osteoarthritis, nervous diseases, diabetes and the like, and are useful for the formation of breast tissue.

The present invention belongs to the field of biotechnology, and discloses a serum-free culture medium with specific chemical compositions for in vitro culture and amplification of bone marrow mesenchymal stem cells. By adding insulin, transferrin, ethanolamine, sodium selenite, growth factors, adherent factors, hormone, putrescine, inorganic salt, vitamin, albumin and antioxidant into a basic culture medium, the bone marrow mesenchymal stem cells can attach to the culture medium under a serum free condition, so the in vitro culture and amplification are realized, the potential of multi-directional differentiation is maintained, and the amplified cells can be induced to be osteoblast and lipocyte in vitro. The serum-free culture medium has the advantages that the clinic level cell products for human produced by the serum free culture medium can effectively avoid the potential risk of producing cell products by serum culture medium. The drawing appended is a photo of the confluence of the bone marrow mesenchymal stem cells cultured by the serum-free culture medium.

The invention relates generally to compounds which are allosteric modulators (e.g., negative and positive allosteric modulators, allosteric agonists, and ago-allosteric modulators) of the G protein coupled receptor PTHR1, also known as parathyroid hormone / parathyroid hormone related protein receptor. The PTHR1 compounds are derived from the intracellular loops and domains of the PTHR1 receptor. The invention also relates to the use of these PTHR1 receptor compounds and pharmaceutical compositions comprising the PTHR1 receptor compounds in the treatment of diseases and conditions associated with PTHR1 receptor modulation, such as osteoporosis; humoral hypercalcemia of malignancy; osteolytic and osteoblastic metastasis to bone; primary and secondary hyperparathyroidism associated increase in bone absorption; vascular calcification; psychiatric disorders and cognitive disorders associated with hyperparathyroidism; dermatological disorders; and excess hair growth.

The present invention provides a composition including an isolated or recombinant peptide component that has osteogenic cell proliferative activity. The peptide, which promotes proliferation of osteoblasts, is useful for treatment of fractures, as a filler in deficient sites of bone, for inhibition of decrease in bone substance related to osteoporosis and periodontic diseases, and for prevention of fractures associated with osteoporosis and rheumatoid arthritis. The peptide, or cells that have been genetically engineered to produce the peptide, can be combined with a bone-compatible matrix to facilitate slow release of the peptide to a treatment site and / or provide a structure for developing bone.

A transplant material which is capable of imparting desired mechanical properties, elevating bone tissue repair speed and improving biocompatibility. This transplant material comprises an artificial and biologically inactive material, which is to be implanted in vivo as a substitute for bone tissue, and at least one type of cells selected from among osteoblasts and precursory osteoblasts which are adhered to the surface of the artificial material so that the artificial material is coated with the bone matrix produced by the cells. The artificial material involves not only a biologically inactive material but also a biologically inactive material coated with a biologically active substrate. This transplant material is produced by culturing mesenchymal stem cells collected from a living body to differentiate into at least one type of cells selected from among osteoblasts and precursory osteoblasts and then culturing the cells together with the artificial material to thereby adhere the differentiated cells on the surface of the artificial material and coat the surface of the artificial material with the bone matrix produced by the differentiated cells.

Compositions and methods are provided for modulating the growth, development and repair of bone, cartilage or other connective tissue. Devices and stimulus waveforms are provided to differentially modulate the behavior of osteoblasts, chondrocytes and other connective tissue cells to promote proliferation, differentiation, matrix formation or mineralization for in vitro or in vivo applications. Continuous-mode and pulse-burst-mode stimulation of cells with charge-balanced signals may be used. Bone, cartilage and other connective tissue growth is stimulated in part by nitric oxide release through electrical stimulation and may be modulated through co-administration of NO donors and NO synthase inhibitors. Bone, cartilage and other connective tissue growth is stimulated in part by release of BMP-2 and BMP-7 in response to electrical stimulation to promote differentiation of cells. The methods and devices described are useful in promoting repair of bone fractures, cartilage and connective tissue repair as well as for engineering tissue for transplantation.

A composition for modulating bone regeneration composition comprises a matrix selected from the group consisting of glycolic acid, lactic acid, collagen, demineralized bone, or a combination thereof. A first biologically active molecule comprising a fibronectin is attached to a portion of the matrix, to facilitate osteoblast activity and for promoting an increase in bone formation. A second biologically active molecule comprising a vitronectin, selected for its ability to attract osteoclasts and produce an inhibiting effect on osteoclast activity to thereby promote a decrease in bone resorption, is also attached to a portion of the matrix.

The invention relates to bioactive surface coatings deposited on selected substrates. Surface nanostructured film coatings deposited on most metal or nonmetal substrates to provide surfaces can be engineered to promote enhanced tissue / cell adhesion. Attached cells, including osteoblasts, fibroblasts and endothelial cells, retain viability and will readily differentiate and proliferate under appropriate conditions. Fibroblasts and endothelial cells exhibit good attachment and growth on most coated substrates, except on nano surfaced structured silicone.

Compositions and methods are provided for modulating the growth, development and repair of cartilage, bone or other connective tissue. Devices and stimulus waveforms are provided to differentially modulate the behavior of chondrocytes, osteoblasts and other connective tissue cells to promote proliferation, differentiation, matrix formation or mineralization for in vitro or in vivo applications. Continuous-mode and pulse-burst-mode stimulation of cells with charge-balanced signals may be used. Cartilage, bone and other connective tissue growth is stimulated in part by nitric oxide release through electrical stimulation and may be modulated through co-administration of NO donors and NO synthase inhibitors. The methods and devices described are useful in promoting repair of bone fractures, cartilage and connective tissue repair as well as for engineering tissue for transplantation.

The invention discloses a multiplex composite engineering scaffold material capable of gradually decomposing bone tissue and a preparation method thereof. The composite scaffold material consists of calcium phosphate bone cement, biological compatible degradable synthetic high polymer and biological compatible degradable natural high polymer, has better mechanical property and gradient degradation characteristic, and can achieve the aim of regenerating and repairing bone tissue defect by implanting a bone growth factor to induce in-vivo stem cells to be differentiated into bone cells, thereby obviously improving initial strength and toughness of the scaffold material, and ensuring enough strength and toughness of the scaffold material during operating and implanting. After compounded with the high polymer material, the scaffold has excellent flexibility, so that the scaffold can be subjected to certain machining, such as cutting and the like.

The invention discloses a biomimetic artificial hip joint with an internal growth function. The joint is composed of an artificial cartilage layer, an interface bonding layer and a porous bracket, wherein the artificial cartilage layer and the porous bracket have elliptic surfaces; the surface wrapping angle of the joint is 60-120 degrees; when the wrapping angle is 80-120 degrees, 3-6 convex columnar bodies, which are uniformly distributed, are designed on the inner surface of a prosthesis along the peripheral direction; a porous coating with biological activity is prepared on the outer surface of a femoral component and materials of the coating have gradient changes from inside to outside; the porous bracket is designed into a porous structure with gradient according to a finite element optimization result, and the pore diameter is 300-800 microns; the porosity is 20%-85%. According to the biomimetic artificial hip joint disclosed by the invention, bone mass and biomechanical characteristics of thigh bones can be kept to the greatest extent; the biomimetic artificial hip joint has good mechanical properties and tribological properties; the growth of bone cells is induced or promoted so as to guarantee effective interface bonding intensity between a prosthesis implantation material and a natural bone, the stability of the planted prosthesis is improved and the service life is prolonged.

The invention provides a calcium supplementing and calcium locking health care food. The calcium supplementing and calcium locking health care food comprises calcium, colostrum basic protein, chondroitin sulfate, D-glucosamine, vitamin D, casein phosphopeptides and the like, wherein the colostrum basic protein is obtained by degreasing, separating, concentrating, removing casein, alpha-lactoalbumin, beta-lactoglobulin and substances with molecular weights of more than 30 kDa and less than 1 kDa and drying at a low temperature; the biggest difference between the calcium supplementing and calcium locking health care food prepared by the method provided by the invention and the prior art is that the capacity of the bone tissue in actively absorbing osteoblast nutrition like calcium, ossein and the like can be effectively improved and effects of activating osteoblasts and inhibiting osteoclast activity to enhance bone mineral density and length and promote the health of the bone are obtained. The calcium supplementing and calcium locking health care food provided by the invention, which is a latest generation of domestic osteoarthrosis rehabilitation product, obtains breakthrough in the calcium supplementing effect, can be also used for helping the bone to preferably absorb the calcium in the food, has no toxic and side effect after being taken for a long time.

The present invention relates to multipotent stem cells derived from the interstitial tissues of skeletal muscle. The multipotent stem cell of the present invention is capable of differentiating into skeletal muscle cells, smooth muscle cells, cardiomyocytes, blood cells, vascular endothelial cells, adipocytes, osteoblasts, nervous cells, hepatocytes and pancreatic cells, and is useful for regeneration of tissues and cells and treatment for cardiac failure, hepatic insufficiency, renal insufficiency, leukemia, nerve degeneration disease, arthritis, diabetes, arteriosclerosis, and the like.

The invention relates to a human amnion mesenchymal stem cell serum-free culture medium and a culture method thereof. The culture medium is formed by adding human serum albumin, human transferrin, human insulin and sodium selenite into a DMEM / F12 basic culture medium. The culture method for the culture medium comprises the following steps of: digesting human amnion by using trypsin, then digesting the human amnion by using collagenase IV and deoxyribonuclease I, and filtering the mixture to obtain single cell suspension; and adding the human serum albumin, the transferrin, the insulin and the sodium selenite into the DMEM / F12 basic culture medium in a ratio of VDMEM to VF12 of 1:1, and putting human amnion mesenchymal stem cells in a 37 DEG C CO2 incubator with saturated humidity and volume fraction of 5 percent under the serum-free condition, wherein culture in vitro and amplification are realized by solution change and transfer of culture, potentiality of multi-direction differentiation is maintained, and the amplified cells can be induced in vitro to form cartilage cells, osteoblasts and adipocytes. The culture medium and the culture method have the characteristics of no other animal sources, wide source and no limitation of ethics.

The invention relates to a dental implant and a preparation method of a bioactive antibacterial surface of the dental implant. The dental implant is characterized in that medical titanium or a titanium alloy is taken a substrate; a nanotube morphology is constructed on the surface of the substrate through anodic oxidation; the surface of the substrate is uniformly coated with a polydopamine bionic membrane layer formed by auto-polymerization; the dental implant with the bioactive antibacterial surface provided with in-situ grafted silver nanoparticles is obtained by means of the adsorption and reduction capabilities of a polydopamine surface for silver ions. By adopting the dental implant, a uniform discrete nanotube oxide layer is formed in situ on the surface of the titanium substrate to be taken as a storage carrier of a large quantity of antibacterial silver particles, and the bioactive antibacterial surface which grows in situ is prepared through the steps of surface dopamine auto-polymerization and in-situ soaking and reduction and the like, so that the implant surface has more durable antibacterial property, the hydrophilic performance and bioactivity of the surface are improved, the alkaline phosphatase activity of osteoblast on the implant surface is increased, the differentiation of the osteoblast is facilitated, the infection risk of the implant after the implant is implanted is lowered, and the implanting success rate is increased.

A composition and method for inducing bone growth and healing is provided. The composition is useful for promoting new bone synthesis, and to enhance the mechanical stability and longevity of orthopaedic implants. The composition includes a bone endogenous material which is used as raw material for the body's natural osteogenic mechanism to synthesize new bone. The composition has a flow phase and a congealed phase. The composition is applied, in the flow phase, within the reamed medullary canal of a long bone prior to insertion of an endoprosthesis. Following insertion of the endoprosthesis, the composition undergoes a phase change to the congealed phase, for example via cross-linking of the bone endogenous material in the composition, to provide a compliant barrier layer in the intra-medullary gap between the implanted endoprosthesis and the medullary canal wall. The resulting barrier layer has a dual mode porosity system, having a first order porosity to accommodate and promote convective diffusion of nutrient species into and through the barrier layer, and a second order porosity to accommodate osteoblastic migration therein without the need for osteoclastic resorption. Osteoblasts synthesize new bone using the barrier layer itself as raw material, essentially osteoconverting the barrier layer into synthesized new bone. In a preferred embodiment, the second order porosity is provided via a rapidly degrading polymer added to the composition, which has a half-life for degradation of 1-60 days.

The invention relates to new use of taurochenodeoxycholic acid, in particular to the new use of the taurochenodeoxycholic acid in prevention and treatment of osteoporosis. Through the study on taurochenodeoxycholic acid, the inventor found that the taurochenodeoxycholic acid can promote bone cells to secrete osteocalcin and improve lowered bone density. Thus, the taurochenodeoxycholic acid can beused in prevention or treatment of osteoporosis. After being administrated directly or being formed into various formulations, the taurochenodeoxycholic acid can be used for preventing or treating osteoporosis and other related diseases or states of osteoporosis.

A sensitive, quantitative method to assess bone forming potential of demineralized bone matrix (DBM) is provided. Cortical DBM is treated with collagenase. The treated cortical DBM is placed in a cell culture for a dwell time. After the dwell time, the cell culture is observed for osteoblastic markers. The cortical bone so treated exhibits the same bone forming potential in vivo as untreated cortical bone.