Abstract: Disclosed herein is a modified tissue graft (120, 200, 300, 500, 630) with improved properties for tissue integration and regeneration. The tissue graft (120, 200, 300, 500, 630) has biological properties that are enhanced by removing lipids (615) and other contaminants (e.g., blood components, micro-organisms) using enzymes, enzyme aggregates, or immobilized enzymes. This application describes the process (10) for removing bio-contaminants while maintaining optimal biological properties.

Abstract: A patient-specific tissue graft and a method of forming the graft is disclosed. A 3D image of a patient's targeted implant site and surrounding anatomy is obtained to note the boundary of the implant site. A 3D model of the graft is formed by utilizing the boundary of the implant site, a surface curvature, extrapolated from the patient's target implant site surrounding anatomy, and a depth, defined by a plane parallel to a plane normal to a point of curvature at the surface. Donor tissue is chosen that has a location with a close approximation to the 3D model of the graft. The donor tissue is visualized to determine a cutting path to shape or modify the architecture of the tissue. A cutting path is determined with imaging technology and computational methods. The graft is cut out of the donor tissue utilizing a fluid cutting process.

Abstract: Among the various aspects of the present disclosure is the provision of compositions and methods of making genetically modified cells comprising a synthetic circuit that is responsive to a circadian input to the cell and methods of use thereof. This disclosure uses a cells circadian rythym to provide gene-based delivery of biologic drugs at prescribed times, phases and frequencies. Once reprogrammed, the cells can be reimplanted in the body for this purpose.

Abstract: Among the various aspects of the present disclosure is the provision of compositions and methods of making genetically modified cells comprising a synthetic circuit that is responsive to a mechanical input to the cell and methods of use thereof. This disclosure uses mechanotransduction to provide gene-based delivery of biologic drugs at prescribed times, phases and frequencies. Once reprogrammed, the cells can be reimplanted in the body for this purpose.

Abstract: A flexible osteochondral tissue graft or graft containing cartilage and underlying bone is provided with slits formed by water cutting. Various slit designs, or grooves enhance the flexibility of the graft and create a controlled open-pore structure to enhance cell infiltration and/or tissue integration.

Abstract: Among the various aspects of the present disclosure is the provision of compositions and methods for stem cell chondrogenesis. An aspect of the present disclosure provides for a method of differentiating pluripotent stem cells (e.g., induced pluripotent stem cells (iPSCs), human induced pluripotent stem cells (hiPSCs)) into chondrocyte-like cells (e.g., cartilage).

Abstract: Among the various aspects of the present disclosure relates to methods and compositions useful in convert inflammatory dietary fatty acids (omega 6) to anti-inflammatory fatty acids (omega 3). Specifically, the present disclosure provides methods and compositions for increasing n-3 desaturase expression or activity in a subject. The disclosure provides various compositions for providing increased n-3 desaturase expression or activity including a variety of viral vector and engineered microorganisms The disclosure provides, in part, methods for reducing local and/or systemic inflammation, improving wound healing, preventing premature cellular enescence, treating or preventing a disease, disorder, or condition related to inflammation or obesity and treating or preventing arthritis.

Abstract: Disclosed herein are compositions and methods for cell therapy comprising an engineered cell. The present invention is directed to a composition for treating a subject having or suspected of having a disease, the composition comprising a modified cell comprising a modified endogenous gene, wherein an endogenous gene or fragment thereof is replaced with a transgene using a CRISPR/Cas9 system to generate the modified endogenous gene, the modified cell having an altered response to a cell signal or stimulus.

Abstract: A product for implantation within a soft tissue site of the human or animal body comprises a matrix of pulverized or morselized substantially non-mineralized native soft tissue (NSTM) of the human or animal body, provided in a therapeutic amount to induce growth of native tissue or organs and healing at the tissue site. The NSTM is composed of at least one soft tissue selected from the group consisting of cartilage, meniscus, intervertebral disc, ligament, tendon, muscle, fascia, periosteum, pericardium, perichondrium, skin, nerve, blood vessels, and heart valves or from organs such as bladder, lung, kidney, liver, pancreas, thyroid, or thymus. Preferably, the NSTM is composed of a soft tissue of the same type of tissue native to the repair site.

Abstract: A live tissue storage solution is formed of an aqueous culture medium including additives, inorganic salts and nutrients. The additives preferably include amino acids including but not limited to L-Arg, L-Cys, Gly, L-His, L-Ile, L-Lys, L-Leu, L-Met, L-Phe, L-Ser, L-Try, L-Try, and L-Val. The inorganic salts preferably include calcium chloride, sodium chloride, magnesium sulphate, sodium bicarbonate, sodium phosphate. The nutrients preferably include glucose, choline, folic acid, nicinamide, riboflavin, which are known to maintain cell culture. Examples include Dulbecco's Modified Eagle Medium DMEM or Minimal Essential Medium MEM with or without serum. The culture medium contains additives to reduce, inhibit, or mitigate lipid oxidation, lipotoxicy, lipid-induced responses, and lipid inflammation.

Abstract: A live tissue storage solution is formed of an aqueous culture medium including additives, inorganic salts and nutrients. The additives preferably include amino acids including but not limited to L-Arg, L-Cys, Gly, L-His, L-Ile, L-Lys, L-Leu, L-Met, L-Phe, L-Ser, L-Try, L-Try, and L-Val. The inorganic salts preferably include calcium chloride, sodium chloride, magnesium sulphate, sodium bicarbonate, sodium phosphate. The nutrients preferably include glucose, choline, folic acid, nicinamide, riboflavin, which are known to maintain cell culture. Examples include Dulbecco's Modified Eagle Medium DMEM or Minimal Essential Medium MEM with or without serum. The culture medium contains additives to reduce, inhibit, or mitigate lipid oxidation, lipotoxicy, lipid-induced responses, and lipid inflammation.

Abstract: A method is used for preparing a product for use in repairing a lesion or defect at a tissue site in a human or animal patient body. The method includes obtaining tissue from a donor human or animal body and freezing the obtained tissue. The method further includes pulverizing the frozen tissue and suspending the pulverized tissue in a fluid. The method further includes homogenizing the tissue suspension and precipitating tissue particles from the homogenized tissue suspension. The method further includes re-suspending the precipitated tissue particles and lyophilizing the tissue re-suspension to provide the product to be used in repairing the lesion or defect.

Abstract: Disclosed herein are compositions and methods for cell therapy comprising an engineered cell. The present invention is directed to a composition for treating a subject having or suspected of having a disease, the composition comprising a modified cell comprising a modified endogenous gene, wherein an endogenous gene or fragment thereof is replaced with a transgene using a CRISPR/Cas9 system to generate the modified endogenous gene, the modified cell having an altered response to a cell signal or stimulus.

Abstract: A scaffold is provided which facilitates integration of both bone and cartilage at an osteochondral lesion, thereby acting as a tissue engineered interface or tissue engineered junction between the two different tissues. The method and systems for engineering this interface may be acellular or may be loaded with cells prior to use.

Abstract: Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPA1 and/or TRPV4 inhibitor. Further provided are compositions including a TRPA1 and/or TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application.

Abstract: Described herein are compositions and methods for treatment and prevention of low back pain. The compositions include vectors comprising nucleotide sequences encoding one or more CRISPR-Cas system guide RNAs and a RNA-directed nuclease. The methods include modulating expression of a gene in a cell using said compositions, introducing a CRISPR-Cas system into a cell comprising one or more vectors comprising said compositions, inducing site-specific DNA cleavage in a cell, and treating a subject having lower back pain, and lower back pain caused by degenerative disc disease using the compositions disclosed herein.

Abstract: A method has been developed for repairing a cartilage lesion. The method includes bringing a three-dimensional porous substrate into direct contact with prepared bone. The three-dimensional porous substrate is fixedly coupled to a three-dimensional scaffold such that the substrate supports the scaffold. The three-dimensional porous substrate comprises at least three layers of woven fibers. The substrate is configured to be inserted into bone tissue including cartilage lesions such that the substrate and the scaffold replace the bone tissue including the cartilage lesions. The substrate and scaffold are further configured such that after the substrate and the scaffold have replaced the bone tissue including the cartilage lesions, the substrate and scaffold promote growth and integration of new bone tissue into the implant.

Abstract: A live tissue storage solution is formed of an aqueous culture medium including additives, inorganic salts and nutrients. The additives preferably include amino acids including but not limited to L-Arg, L-Cys, Gly, L-His, L-Ile, L-Lys, L-Leu, L-Met, L-Phe, L-Ser, L-Try, L-Try, and L-Val. The inorganic salts preferably include calcium chloride, sodium chloride, magnesium sulphate, sodium bicarbonate, sodium phosphate. The nutrients preferably include glucose, choline, folic acid, nicinamide, riboflavin, which are known to maintain cell culture. Examples include Dulbecco's Modified Eagle Medium DMEM or Minimal Essential Medium MEM with or without serum. The culture medium contains additives to reduce, inhibit, or mitigate lipid oxidation, lipotoxicy, lipid-induced responses, and lipid inflammation.

Abstract: Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPA1 and/or TRPV4 inhibitor. Further provided are compositions including a TRPA1 and/or TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application.

Abstract: Provided are methods of treating and/or preventing dermatological disorders. Provided are methods of reducing skin inflammation, reducing pain, and/or reducing itch in a subject in need thereof. The methods may include administering to the subject an effective amount of a TRPA1 and/or TRPV4 inhibitor. Further provided are compositions including a TRPA1 and/or TRPV4 inhibitor compound in combination with a carrier, vehicle, or diluent that is suitable for topical application.