Articles comprising large-surface-area bio-compatible materials and methods for making and using them

Abstract

The present invention provides articles of manufacture comprising biocompatible nanostructures comprising significantly increased surface area for, e.g., organ, tissue and/or cell growth, e.g., for bone, tooth, kidney or liver growth, and uses thereof, e.g., for in vitro testing of drugs, chemicals or toxins, or as in vivo 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 drug delivery devices. The present invention provides biocompatible nanostructures with significantly increased surface area, such as with nanotube and nanopore array on the surface of metallic, ceramic, or polymer materials for enhanced cell and bone growth, for in vitro and in vivo testing, cleansing reaction, implants and therapeutics. The present invention provides optically transparent or translucent cell-culturing substrates. The present invention provides biocompatible and cell-growth-enhancing culture substrates comprising elastically compliant protruding nanostructure substrates coated with Ti, TiO2 or related metal and metal oxide films.

1 - 58 . (canceled) 
     
     
         59 . A product of manufacture, comprising:
 a substrate; and   a layer, the layer comprising a biocompatible material with a plurality of nanotubes that have a diameter of at least 100 nm and have a height of at least 100 nm.   
     
     
         60 . The product of manufacture of  claim 59 , wherein the plurality of nanotubes are arranged on a surface of the layer at a density of at least 0.2×10 8 /cm 2 . 
     
     
         61 . The product of manufacture of  claim 59 , wherein the plurality of nanotubes are vertically aligned and laterally spaced. 
     
     
         62 . The product of manufacture of  claim 59 , wherein the substrate is a radiotranslucent thermoplastic polymer and the layer is a thin film nanostructure. 
     
     
         63 . The product of manufacture of  claim 59 , wherein the biocompatible material is a biocompatible surface layer comprising any of a metal, metal alloy, titanium, titanium alloy, ceramic, titanium oxide, titanium dioxide, aluminum oxide, and any combination thereof. 
     
     
         64 . The product of manufacture of  claim 59 , wherein the substrate is a non-metallic substrate comprising any of a polymer, a thermosetting polymer, a porous polymer, a plastic material, an elastomeric polymer, a transparent thermoplastic polymer, a transparent UV-light curable polymer, a transparent glass, a polydimethysiloxane (PDMS), a polymethyl methacrylate (PMMA), polyethene, polypropene, polystyrene, poly vinyl chloride, equivalent compounds, and any combination thereof. 
     
     
         65 . The product of manufacture of  claim 59 , wherein the layer is coupled to the substrate by applying the layer onto a surface of the substrate using any of a thin-film and a thick-film coating followed by an anodization process. 
     
     
         66 . The product of manufacture of  claim 65 , wherein the applying further comprising depositing the layer onto the surface. 
     
     
         67 . The product of manufacture of  claim 65 , wherein the anodization process comprising an electrochemical anodization process followed by a heat treatment. 
     
     
         68 . The product of manufacture of  claim 67 , wherein the heat treatment crystallizes the plurality of nanotubes. 
     
     
         69 . The product of manufacture of  claim 59 , wherein the layer further comprises a micro-nano combined structure, the -nano component of the micro-nano combined structure comprising the plurality of nanotubes as set forth in  claim 59 . 
     
     
         70 . The product of manufacture of  claim 59 , wherein the layer further comprises a macro-nano combined structure, the -nano component of the macro-nano combined structure comprising the plurality of nanotubes as set forth in  claim 59 . 
     
     
         71 . The product of manufacture of  claim 70 , wherein the -macro component of the macro-nano combined structure comprises any of mesh screens, ribbons, and wire arrays. 
     
     
         72 . The product of manufacture of  claim 59 , wherein the layer includes any of growth factors, biological agents, antibiotics, genes, proteins, drugs, and magnetic nanoparticles associated with the plurality of nanotubes. 
     
     
         73 . The product of manufacture of  claim 59 , wherein the plurality of nanotubes comprises any of Ti, Ti oxide, Zr, Hf, Nb, Ta, Mo, W, their alloys, their oxides, and any combination thereof. 
     
     
         74 . The product of manufacture of  claim 59 , wherein the plurality of nanotubes are covered with TiO 2 . 
     
     
         75 . The product of manufacture of  claim 59 , wherein the plurality of nanotubes comprises an elastically compliant nanostructure. 
     
     
         76 . An implant, comprising:
 a substrate; and   a layer, the layer comprising a biocompatible material with a plurality of nanotubes that have a diameter of at least 100 nm and have a height of at least 100 nm.   
     
     
         77 . The implant of  claim 76 , wherein the implant is any of a dental implant, a spinal implant, and an orthopedic implant. 
     
     
         78 . A method for making a product of manufacture, comprising:
 providing a substrate; and   coupling a layer to the substrate, the layer comprising a biocompatible material with a plurality of nanotubes that have a diameter of at least 100 nm and have a height of at least 100 nm.