Abstract: A method of detecting prostate tumorigenesis in a subject, the method including the steps of (a) obtaining a sample from the prostate of the human subject, (b) detecting quantitatively or semi-quantitatively in the sample a level of expression for PKC-? and (c) comparing the expression level in (b) to a level of expression in a normal control, wherein overexpression of PKC-?, with respect to the control, indicates the presence of prostate cancer in the subject. The present invention is based upon the discovery that PKC-? levels are elevated during prostate tumorigenesis. Furthermore, the proliferation rate of the tumor correlates with the level of PKC-?. The invention also provides methods of treating prostate cancer by administering to the subject a compound that inhibits the expression of PKC-?. The compound can be a small interfering RNA (siRNA) molecule.

Abstract: The present invention provides a simple method for controlled differentiation of adipose-derived precursor cells. A method is provided for preparing a differentiated cell. The method comprises A) obtaining a mixture by mixing a) an adipose-derived precursor cell and b) a differentiated cell corresponding to a desired site; and B) culturing the mixture under sufficient conditions which allow the adipose-derived precursor cell to differentiate. The present invention also provides a composition for cell implantation comprising a) an adipose-derived precursor cell and b) a differentiated cell corresponding to a desired site.

Abstract: A bone graft composition includes a biologically-resorbable cement and a plurality of processed bone particles, where each of the bone particles have a shape configured to interconnect with adjacent bone particles. A method for treating a bone defect using the bone graft compositions includes providing the bone graft composition and administering an effective amount of the bone graft composition to a site of a bone defect in a subject. Kits including a biologically-resorbable cement powder and a plurality of processed bone particles are also provided.

Abstract: Disclosed are advantageous methods for patterning and/or mineralizing biomaterial surfaces. The techniques described are particularly useful for generating three-dimensional or contoured bioimplant materials with patterned surfaces or patterned, mineralized surfaces. Also provided are various methods of using the mineralized and/or patterned biomaterials in tissue engineering, such as bone tissue engineering, providing more control over ongoing biological processes, such as mineralization, growth factor release, cellular attachment and tissue growth.

Abstract: A remodelable encasement structure comprising a pouch formed from at least one sheet of bioremodelable material, the pouch having an internal region configured to receive a device therein, the bioremodelable material comprising an extracellular matrix (ECM) composition that includes an ECM scaffold component derived from a mammalian source and at least a bioactive component selected from the group consisting of a statin and a chitin derivative.

Abstract: Composites and methods of producing a moldable bone substitute are described. A scaffold for bone growth comprises nanocrystalline hydroxyapatite (HA), a bioresorbable plasticizer, and a biodegradable polymer. Plasticizers of the invention include oleic acid, tocopherol, eugenol, 1,2,3-triacetoxypropane, monoolein, and octyl-beta-D-glucopyranoside. Polymers of the invention include poly(caprolactone), poly(D,L-Lactic acid), and poly(glycolide-co lactide). Methods of regulating porosity, hardening speed, and shapeability are also described. Composites and methods are described using nanocrystalline HA produced with and without amino acids. The scaffold for bone growth described herein displays increased strength and shapeability.

Abstract: Methods, apparatus, and systems for improving the performance of articulating prostheses. Some embodiments may comprise a first component comprising a first articulating surface and a second component comprising a second articulating surface configured for articulating with the first articulating surface. One or both of the first and second components may comprise a silicon nitride ceramic material. One or both of the first and second articulating surfaces may comprise a coating that is configured to accomplish at least one of increasing the hardness of the first articulating interface surface, reducing the coefficient of friction between the first and second articulating surfaces, decreasing the effects of wearing between the first and second articulating surfaces, and decreasing the intensity of audible noises produced by the endoprosthesis resulting from articulation between the first and second articulating surfaces during use.

Abstract: Disclosed herein are substrates for cell delivery to target tissues requiring treatment for various diseases that induce cell death, damage or loss of function. The substrates are configured to provide seeded cells, including stem cells, with a structural support that allows interconnection with and transmission of biological signals between the cells and the target tissue.

Abstract: Biocompatible, biodegradable copolymer-xerogel nanocomposites contain a biodegradable, biocompatible copolymer, silica nanoparticles and one or more therapeutic agents, that are useful for wound dressings, medical devices and drug delivery applications.

Abstract: The present invention relates to a material for induction of hard tissue regeneration, comprising platelet-rich plasma and gelatin ?-TCP sponge, which promotes angiogenesis, osteogenesis, chondrogenesis and the like.

Abstract: A method for manufacturing a stationary state of polymer crystallinity of an active substance charged polylactide matrix for a stent, comprising the steps of: preparing the active substance charged polylactide matrix containing (a) a polylactide in amorphous or semicrystalline modification or with amorphous domains, and (b) at least one active substance on a surface or in a cavity of the stent communicating with the surface; and heating of the active substance charged polylactide matrix to a temperature ranging from TG-20° C. to TS-10° C., where TG represents a glass transition temperature and TS a melting temperature of the crystallites of the polylactide.

Abstract: This invention provides porated cartilage products, methods of producing porated cartilage products, and methods of treating subjects by administering cartilage products. Optionally, the cartilage products are sized, porated, and digested to provide a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

Abstract: Tissue repair compositions, particularly bone repair compositions, containing demineralized bone fragments and homogenized connective tissues, and methods for making the same. The compositions can be used in the form of an injectable gel, an injectable paste, a paste, a putty, or a rehydratable freeze-dried form.

Abstract: A polymeric composition capable of releasing nitric oxide and modulating biological responses comprises a biocompatible polymer and S-nitrosated thiol bonded to the biocompatible polymer. The polymeric composition can have a thiol conversion of at least 40%. The polymeric composition can also have a nitric oxide recovery of at least 40% when under thermal decomposition conditions.

Abstract: A method and device for local delivery of water-soluble or water-insoluble therapeutic agents to the surface of a normal or diseased body lumen is disclosed. An expandable structure of a medical disposable device, such as a balloon of a balloon catheter, is coated with an amphiphilic polymer coating comprising a therapeutic agent and an amphiphilic polymer or co-polymer. The medical disposable device is inserted into a body lumen, and expanded to contact the amphiphilic polymer coating against the body lumen. The total solubility of the polymer or co-polymer in vivo prevents any embolic hazard associated with the amphiphilic polymer coating.

Abstract: The present invention relates to a plurality of dosage forms comprising a first dosage form and second dosage form each comprising a therapeutic agent, such as an opioid; wherein the dosage strength of the second dosage form is greater than that of the first dosage form; and wherein the steady state Cave and the steady state AUC of the first and second dosage forms are dose proportional and the single dose Cmax of the second dosage form is less than the minimum level for dose proportionality with respect to the first dosage form. The present invention also relates to methods of administering such dosage forms to a patient, as well as to kits comprising such dosage forms and instructions for administration of the dosage forms to a patient. The inventors believe that the dosage forms and methods of the present invention will lead to improved safety and patient acceptance.

Abstract: The present invention relates to a method for preparing a porous scaffold for tissue engineering. It is another object of the present invention to provide a porous scaffold obtainable by the method as above described, and its use for tissue engineering, cell culture and cell delivery. The method of the invention comprise the steps consisting of a) preparing an alkaline aqueous solution comprising an amount of at least one polysaccharide and one cross-linking agent b) freezing the aqueous solution of step a) c) sublimating the frozen solution of step b). characterized in that step b) is performed before the cross-linking of the polysaccharide occurs in the solution of step a).

Abstract: Compositions, implantation devices and methods for stimulating an immune response to infection are discussed. In some examples, the compositions, implantation devices or methods of regulating the amplification of an adaptive immune response to infection involves use of one or more particles locally at a surgical or implant site to control bacterial infections without detrimental systemic side-effects. In some examples, the particles can be coated or layered onto the surface of an implantable device or material. In other examples, the particles can be injected into the site of implantation.

Abstract: A medicament carrier composition includes a medicament and a polymer component including a polyvinylpyrrolidone having a weight average molecular weight of at least 700,000 g/mol. The medicament carrier composition has a viscosity of from 500 to 5,000 cps at 250 C, is substantially free of cellulose, and includes an auxiliary polymer. The medicament carrier composition is used to form a film that is also substantially free of cellulose. The film has a consistent thickness and size, and an increased flexibility and increased moisture resistance due to the polyvinylpyrrolidone. The medicament carrier composition is also used in a method of forming the film. The method includes the steps of providing the medicament and the polymer component. The method also includes the step of combining the polymer component and the medicament to form the medicament carrier composition. The method further includes the step of drying the medicament carrier composition to form the film.

Abstract: A biodegradable drug delivery compositions comprising a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as a pharmaceutically active principle is disclosed.

Abstract: The invention provides a biodegradable drug-eluting particle useful for the delivery of diagnostic or therapeutic agents. In certain embodiments, the drug-eluting particle of the invention comprises a biodegradable porous silicon body, a reservoir formed within the porous silicon body having at least one opening to an exterior of the body, wherein the reservoir contains a therapeutic or diagnostic agent, and an agent-permeable seal disposed over the at least one opening. The invention further provides a method for treating a patient to obtain a desired local or systemic physiological or pharmacological effect comprising administering a sustained release drug delivery particle of the invention. The invention also provides methods of fabricating a drug-eluting particle for releasing therapeutic agents.

Abstract: A method and composition for hyperthermally treating tumor cells in a patient under conditions that affect tumor stem cells and tumor cells.

Abstract: Described herein are apparatus, compositions, systems and methods for occluding vascular structures and vascular malformations with radiopaque hydrogel filaments. The filaments can contain no support members and can be CT and MR compatible. Methods of forming such filaments are also disclosed.

Abstract: Devices and methods for transplanting cells in a host body are described. The cell comprises a porous scaffold that allows ingrowth of vascular and connective tissues, a plug or plug system configured for placement within the porous scaffold, and a seal configured to enclose a proximal opening in the porous scaffold. The device may further comprise a cell delivery device for delivering cells into the porous scaffold. The method of cell transplantation comprises a two step process. The device is incubated in the host body to form a vascularized collagen matrix around a plug positioned within the porous scaffold. The plug is then retracted from the porous scaffold, and cells are delivered into the vascularized space created within the porous scaffold.

Abstract: A light activated collagen-flavin composite layer incorporating riboflavin is applied as treatment for infected lesions. These composites have also been found to be strong tissue adheives that are effective in closing and sealing wounds, fixation of grafts/ implants and anastomoses. Advantages include speed of closure, reduced infection due to the elimination of foreign matter, evidence of accelerated wound healing and the ease of use in complex surgery, especially when watertight seals, limited access or small repair size are important factors. The riboflavin in the collagen layer is exposed to light (e.g., light having a wavelength between 360-375 nm or 440-480 nm), decomposing the riboflavin to form reactive oxygen species (ROS). Strong crosslinks between the collagen composite and tissue results. In addition, similar exposures eradicate pathogens in the wound.

Abstract: The present invention relates to a biocompatible ceramic material comprising Baghdadite (Ca3ZrSi2O9), and a method for its preparation. Preferably the Baghdadite is synthetically prepared. The present invention also relates to an implantable medical device comprising biocompatible Baghdadite, and a method for its production. The present invention further relates to a method for improving the long term stability of an implantable medical device and an implantable drug delivery device comprising Baghdadite. Further, the present invention relates to the use of comprising biocompatible Baghdadite in the regeneration or resurfacing of tissue.

Abstract: Tissue repair compositions, particularly bone repair compositions, containing (a) bone fragments and (b) homogenized connective tissue, and methods for making the same are provided. Some of the inventive tissue repair compositions contain a radioprotectant. The compositions can be used in the form of an injectable gel, an injectable paste, a paste, a putty, or a rehydratable freeze-dried form. Kits for using such tissue repair compositions are also provided.

Abstract: Bone cages are disclosed including devices for biocompatible implantation. The structures of bone are useful for providing living cells and tissues as well as biologically active molecules to subjects.

Abstract: The present invention relates to a functionalized semi-permeable membrane composed of a porous biocompatible support pretreated so as to increase the surface energy thereof and characterized in that it includes at least two layers, each having a hydrophilic polymer and at least one biological active molecule, and to the use thereof in particular for producing a bioartificial organ.

Abstract: In alternative embodiments, the invention provides articles of manufacture comprising biocompatible nanostructures comprising PolyEther EtherKetone (PEEK) surface-modified (surface-nanopatterned) to exhibit nanostructured surfaces that promote osseointegration and bone-bonding for, e.g., joint (e.g., knee, hip and shoulder) replacements, bone or tooth reconstruction and/or implants, including their use in making and using artificial tissues and organs, and related, diagnostic, screening, research and development and therapeutic uses, e.g., as primary or ancillary drug delivery devices. In alternative embodiments, the invention provides biocompatible nanostructures that promote osseointegration and bone-bonding for enhanced cell and bone growth and e.g., for in vitro and in vivo testing, restorative and reconstruction procedures, implants and therapeutics.

Abstract: Implantable devices formed of or coated with a material that includes a polymer having a non-fouling acrylate or methacrylate polymer are provided. The implantable device can be used for treating or preventing a disorder such as atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, patent foramen ovale, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, or combinations thereof.

Abstract: Catechol-bearing polycarbonates (catechol polymers) were prepared comprising i) a catechol repeat unit comprising a side chain catechol group, ii) a cationic repeat unit comprising a side chain cationic group selected from the group consisting of quaternary amine groups, quaternary phosphine groups, and combinations thereof, and iii) a PEG repeat unit comprising a side chain poly(ethylene oxide) group having a degree of polymerization of about 5 to about 30. The catechol polymers form antimicrobial and antifouling films on a variety of substrate surfaces, in particular silicone rubber.

Abstract: Implantable medical device eluting drug locally and in a prolonged fashion are provided.

Abstract: The present invention is directed to a novel poly(diol citrates)-based bioceramic composite materials created using completely biodegradable and a bioceramic material polymers that may be used in implantable devices. More specifically, the specification describes methods and compositions for making and using bioceramic composites comprised of citric acid copolymers and a bioceramic material.

Abstract: There is described inter alia a medical device having a surface which comprises a coating layer, said coating layer being a biocompatible composition comprising an entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation, which entity is covalently attached to said surface through a link comprising a 1,2,3-triazole.

Abstract: A covering for delivering a substance or material to a surgical site is provided. The covering, with substance provided therein, may be referred to as a delivery system. Generally, the covering may be formed of polymers for providing extended shelf life and/or increased moisture and radiation resistance, and may include a single or multi-compartment structure capable of at least partially retaining a substance provided therein until the covering is placed at a surgical site. Upon placement, the covering may facilitate transfer of the substance or surrounding materials. For example, the substance may be released (actively or passively) to the surgical site. The covering may participate in, control, or otherwise adjust the release of the substance. In various embodiments, the covering may be formed of a biocompatible material and is suitable for a variety of procedure specific uses.

Abstract: An osmotic delivery system flow modulator includes an outer shell constructed and arranged for positioning in an opening, an inner core inserted in the outer shell, and a fluid channel having a spiral shape defined between the outer shell and the inner core. The fluid channel is adapted for delivery of an active agent formulation from the reservoir of the osmotic delivery system.

Abstract: This invention relates to stable non-aqueous single phase viscous vehicles and to formulations utilizing such vehicles. The formulations comprise at least one beneficial agent uniformly suspended in the vehicle. The formulation is capable of being stored at temperatures ranging from cold to body temperature for long periods of time. The formulations are capable of being uniformly delivered from drug delivery systems at an exit shear rate of between about 1 to 1×10?7 reciprocal second.

Abstract: The invention relates to a method for producing an unshrunken tissue equivalent. Said method is comprising in that: a mixture is produced that contains at least one element of an extracellular matrix; at least one pluridimensional medium is soaked with said mixture; from the components of the mixture, a lattice comprising at least one element of an extracellular matrix is produced, at least at the medium; at least part of the components of said mixture is attached to the structure of the medium; the shrinking of at least the lattice is prevented and at least said lattice is tensioned on said medium; fibroblasts are integrated into the lattice and at least one cell culture of said fibroblasts is carried out, at least in the lattice. The invention also relates to a method for producing a skin equivalent that comprises at least one dermal equivalent formed by an unshrunken tissue equivalent and at least one epidermal equivalent.

Abstract: Provided are systems for controlled release of proteins from decomposable thin films constructed by layer-by-layer deposition. Such films generally comprise alternating layers of polymers and proteins, and may further comprise additional layers of polyions. In some embodiments, decomposable thin films and methods of using such films allow proteins to be released over an extended period of time and/or retention of as much as 100% of function of released protein.

Abstract: Medical devices having a catalyst capable of catalyzing the generation of nitric oxide in vivo and methods of treating a vascular condition using the devices are provided.

Abstract: A composition comprising a structural component comprising linear acrylic homopolymers or linear acrylic copolymers and a biobeneficial component comprising copolymers having an acrylate moiety and a biobeneficial moiety is disclosed. A medical article comprising the composition in the coating thereof and a method of fabricating the medical article are also disclosed.

Abstract: A method of treating or preventing infection at a surgical site comprising a bony defect and an implanted metal device is disclosed. Biodegradable microspheres are placed at the site and are capable of near-linear controlled release of an antibiotic agent for a predetermined period of time. The microspheres are configured to be large enough to avoid being phagocytosed and removed from the body, and small enough in diameter to not physically inhibit bone growth at said bony defect site. The microspheres are formed of polylactic-co-glycolic acid (PLGA), with or without polyethylene glycol (PEG), and sufficient antibiotic agent to produce bactericidal levels in body tissues. The microspheres exhibit near-linear delivery of the antibiotic agent for at least 4 weeks at levels exceeding the minimum inhibitory concentration (MIC) for organisms commonly found to be the cause of infections, and facilitate bone ingrowth or regrowth at the site.

Abstract: The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

Abstract: Methods of making a biologically active three-dimensional scaffold capable of supporting growth and differentiation of a cell are described. Biologically active three-dimensional scaffold made by the methods of the invention and an engineered tissue made from the scaffolds are described. Fibers of desired porosity can be obtained from non-structural ECM by lyophilization and/or electrospinning which can be useful for numerous tissue engineering applications requiring complex scaffolds, such as wound healing, artificial skin (burns), soft tissue replacement/repair and spinal cord injury.

Abstract: A lubricious antiseptic coating material containing various solvents to achieve mutual miscibility and provide a generally homogenous product. A coating material is provided having an antipathogenic agent and a solvent for dissolving the same. The coating further includes a lubricious agent and a solvent for dissolving the same. Thus, the coating material contains antiseptic and lubricious properties suitable for application to a desired surface to kill or inhibit the growth of pathogens known to cause catheter related bloodstream infections.

Abstract: Methods for inhibiting a biomaterial-associated thrombotic event comprise reducing the number of platelets that bind to the biomaterial, or inhibiting platelet activation, by attaching CD47 or the Ig domain thereof to the surface of the biomaterial. Methods of the present invention inhibit thrombi formation on or near a biomaterial that is on the surface of an implant, medical device, tube, or therapeutic delivery vehicle. Also provided are kits for practicing these methods and the modified biomaterials.

Abstract: Biomaterials that support cell attachment and growth are provided. In one aspect, biomaterials are provided comprising a first polymer matrix comprising reactive amino moieties and a second polymer matrix that interpenetrates with the first polymer matrix, where the second polymer matrix comprises a poly(alkylene oxide) comprising two or more alkylene oxide oligomers joined by gamma-thioether carbonyl linkages. In another aspect, biomaterials are provided comprising at least one biopolymer comprising amino groups, thiol groups, and bifunctional modifiers connecting at least some of the amino groups to at least some of the thiol groups; and at least one poly(alkylene oxide) cross-linked to at least two thiol groups of the biopolymer. The biomaterials may further comprise a pharmacologically active agent or cells. Methods of administering such biomaterials to a patient in need thereof are also provided.

Abstract: The present invention provides compositions for extended release of an active ingredient, comprising a lipid-saturated matrix formed from a biodegradable polymer. The present invention also provides methods of producing the matrix compositions and methods for using the matrix compositions to provide controlled release of an active ingredient in the body of a subject in need thereof.

Abstract: A particle includes a ferromagnetic material, a radiopaque material, and/or an MRI-visible material.