The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.

The present disclosure provides engineered tissue constructs having a population of cells, such as hepatocytes and stromal cells, and methods of making and using the same (e.g., for treating a disease or disorder, such as acute liver failure, a urea cycle disorder, or hyperbilirubinemia (e.g., in a subject having Crigler-Najjar syndrome) in a human subject in need thereof).

The present application provides methods of functionalizing an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal or by culturing an organ or tissue in a bioreactor containing such nutrient. The present application also provides methods of selectively functionalizing extracellular matrix (ECM) of an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal. In some aspects, the present application provides a decellularized scaffold of a mammalian organ or tissue comprising an extracellular matrix, wherein the extracellular matrix of the decellularized scaffold is functionalized with a chemical group that is reactive in a bioorthogonal chemical reaction, such as an azide chemical group. The present application also provides biological prosthetic mesh and mammalian organs and tissues for transplantation prepared according to the methods of the application.

Methods for decellularizing organs and tissues in vitro and in vivo are provided, as are methods of maintaining organ and tissue frameworks and methods of recellularizing organs and tissues, thereby providing an approach to needed organs or tissues.

The present application provides methods of functionalizing an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal or by culturing an organ or tissue in a bioreactor containing such nutrient. The present application also provides methods of selectively functionalizing extracellular matrix (ECM) of an organ or tissue of a mammal by administering a nutrient (e.g., peracetylated N-azido galactosamine Ac4GalNAz) to the mammal. In some aspects, the present application provides a decellularized scaffold of a mammalian organ or tissue comprising an extracellular matrix, wherein the extracellular matrix of the decellularized scaffold is functionalized with a chemical group that is reactive in a bioorthogonal chemical reaction, such as an azide chemical group. The present application also provides biological prosthetic mesh and mammalian organs and tissues for transplantation prepared according to the methods of the application.

The invention provides articles of manufacture comprising biocompatible nanostructures comprising nanotubes and nanopores for, e.g., organ, tissue and/or cell growth, e.g., for bone, kidney or liver growth, and uses thereof, e.g., for in vitro testing, in vivo implants, including their use in making and using artificial organs, and related therapeutics. The invention provides lock-in nanostructures comprising a plurality of nanopores or nanotubes, wherein the nanopore or nanotube entrance has a smaller diameter or size than the rest (the interior) of the nanopore or nanotube. The invention also provides dual structured biomaterial comprising micro- or macro-pores and nanopores. The invention provides biomaterials having a surface comprising a plurality of enlarged diameter nanopores and/or nanotubes.

The instant invention provides electrospun fiber compositions comprising one or more polymers and one or more biologically active agents. In specific embodiments, the biologically active agents are nerve growth factors. In certain embodiments, the electrospun fiber compositions comprising one or more biologically active agents are on the surface of a film, or a tube. The tubes comprising the electrospun fiber compositions of the invention can be used, for example, as nerve guide conduits.

A medical device for implantation into vessels or luminal structures within the body is provided, which stimulates positive blood vessel remodeling. The medical device, such as a stent and a synthetic graft, is coated with a pharmaceutical composition consisting of a controlled-release matrix and one or more pharmaceutical substances for direct delivery of drugs to surrounding tissues. The coating on the medical device further comprises a ligand such as a peptide, an antibody or a small molecule for capturing progenitor endothelial cells in the blood contacting surface of the device for restoring an endothelium at the site of injury. In particular, the drug-coated stents are for use, for example, in balloon angioplasty procedures for preventing or inhibiting restenosis.

Methods for treating or preventing neointima stenosis are disclosed. The methods generally involve the use of a TGFβ inhibitor, a SMAD2 inhibitor, an FGF Receptor agonist, a Let-7 agonist, or a combination thereof, to inhibit endothelial-to-mesenchymal transition (Endo-MT) of vascular endothelial cells into smooth muscle cells (SMC) at sites of endothelial damage. The disclosed methods can therefore be used to prevent or inhibit neointimal stenosis or restenosis, e.g., after angioplasty, vascular graft, or stent. Also disclosed are methods for increasing the patency of biodegradable, synthetic vascular grafts using a composition that inhibits Endo-MT. A cell-free tissue engineered vascular graft (TEVG) produced by this method is also disclosed.

Compositions, systems, devices, and methods for performing precise chemical treatment of tissues are disclosed. Systems, devices, and methods for administering a chemical agent to one or more a precise regions within a tissue mass are disclosed. Compositions, systems, devices, and methods for treating targeted regions within a tissue mass are disclosed. Systems, devices, and methods for identifying, localizing, monitoring neural traffic in the vicinity of, quantifying neural traffic in the vicinity of, and mapping neural traffic near targeted regions within a tissue mass are disclosed.