US 20060204738A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0204738A1 Dubrow et al. (43) Pub. Date: Sep. 14, 2006 (54) MEDICAL DEVICE APPLICATIONS OF a continuation-in-part of application No. 10/661,381, NANOSTRUCTURED SURFACES filed on Sep. 12, 2003, now Pat. No. 7,056,409. Continuation-in-part of application No. 10/833,944, (75) Inventors: Robert S. Dubrow, San Carlos, CA filed on Apr. 27, 2004. (US); Lawrence A. Bock, Encinitas, Continuation-in-part of application No. 10/840,794, CA (US); R. Hugh Daniels, Mountain filed on May 5, 2004, which is a continuation-in-part View, CA (US); Veeral D. Hardev, of application No. 10/792,402, filed on Mar. 2, 2004. Redwood City, CA (US); Chunming Niu, Palo Alto, CA (US); Vijendra (60) Provisional application No. 60/549,711, filed on Mar. Sahi, Menlo Park, CA (US) 2, 2004. Provisional application No. 60/463,766, filed on Apr. 17, 2003. Provisional application No. 60/466, 229, filed on Apr. 28, 2003. Provisional application Correspondence Address: No. 60/468.390, filed on May 6, 2003. Provisional NANOSYS INC. application No. 60/468,606, filed on May 5, 2003. 2625 HANOVER ST. PALO ALTO, CA 94.304 (US) Publication Classification (51) Int. Cl. (73) Assignee: Nanosys, Inc., Palo Alto, CA (US) D04H I3/00 (2006.01) (52) U.S. Cl. .......................................................... 428/292.1 (21) Appl. No.: 11/330,722 (57) ABSTRACT (22) Filed: Jan. 12, 2006 This invention provides novel nanofiber enhanced surface Related U.S. Application Data area Substrates and structures comprising such substrates for use in various medical devices, as well as methods and uses (63) Continuation-in-part of application No. 11/090,895, for Such substrates and medical devices. In one particular filed on Mar. 24, 2005, which is a continuation-in-part embodiment, methods for enhancing cellular functions on a of application No. 10/902,700, filed on Jul. 29, 2004. surface of a medical device implant are disclosed which Continuation-in-part of application No. 10/828,100, generally comprise providing a medical device implant filed on Apr. 19, 2004, now Pat. No. 7,074.294, which comprising a plurality of nanofibers (e.g., nanowires) is a continuation-in-part of application No. 10/825, thereon and exposing the medical device implant to cells 861, filed on Apr. 16, 2004, now abandoned, which is Such as osteoblasts. Patent Application Publication Sep. 14, 2006 Sheet 1 of 19 US 2006/0204738A1 FIG. 1 Patent Application Publication Sep. 14, 2006 Sheet 2 of 19 US 2006/0204738A1 EZ"EXIB(LHVHORJd) Patent Application Publication Sep. 14, 2006 Sheet 3 of 19 US 2006/0204738A1 FIG. 2C 15.0kW X100 100m WD 12.8m FIG. 2D Nanosys Patent Application Publication Sep. 14, 2006 Sheet 4 of 19 US 2006/0204738A1 F.G. 3A Patent Application Publication Sep. 14, 2006 Sheet 5 of 19 US 2006/0204738A1 FIG. 3B Patent Application Publication Sep. 14, 2006 Sheet 6 of 19 US 2006/0204738A1 FIG. 4A Patent Application Publication Sep. 14, 2006 Sheet 7 of 19 US 2006/0204738A1 48O 492 FIG. 4B 480 492 490 FIG. 4C FIG. 4D FIG. 4E FIG. 4F Patent Application Publication Sep. 14, 2006 Sheet 8 of 19 US 2006/0204738A1 7- 5O2 O6 504 FIG. 5A Patent Application Publication Sep. 14, 2006 Sheet 9 of 19 US 2006/0204738A1 F.G. 6B Patent Application Publication Sep. 14, 2006 Sheet 10 of 19 US 2006/0204738A1 4.00E--05 3.00E+05 2.00E+05 1.00E--05 O.OOE-05 Quartz High Density High Density LOW Density Long Short Long Nanowires Nanowires Nanowires Fig. 7 Patent Application Publication Sep. 14, 2006 Sheet 11 of 19 US 2006/0204738A1 Quartz Nanowire Day 1 Fig. 8A Fig. 8B Day 4 Patent Application Publication Sep. 14, 2006 Sheet 12 of 19 US 2006/0204738A1 Week 1.) Week 22 Week 3D Week 4 N Quartz Anopore Nanowire Fig. 9 Week 1 Week 2Z Week 3D Week 4 N O Z N Quartz Nanowire Fig. 10 Patent Application Publication Sep. 14, 2006 Sheet 13 of 19 US 2006/0204738A1 Week 1 Week 22 Week 3D Week 4 N Quartz Anopore NanoWire Fig. 11A 0. 9 0.8 Week 1.) Week 22 Week 3D Week 4 N 0.7 0.6 O.5 0.4 O.3 0.2 0.1 Quartz Anopore Nanowire Fig. 11B Patent Application Publication Sep. 14, 2006 Sheet 14 of 19 US 2006/0204738A1 Week 1 xasess. 2e u x, sess Week 2 isk X3, S22 Week 3 x533 53 yar al ick Xi, see a lar Week 4 Patent Application Publication Sep. 14, 2006 Sheet 15 of 19 US 2006/0204738A1 Week 1 Week 2 Week 3 2: Kiss part Week 4 isku xta .38 in Patent Application Publication Sep. 14, 2006 Sheet 16 of 19 US 2006/0204738A1 3000 Z Osteoblasts o Fibroblasts 2500 Endothelial Cells O Smooth Muscle Cells 2000 15 O O s c.p. Ti TiGA14V CoCrMo c.p. Ti TióA14V HA Nanofiber (control) (reference)(reference) (control (coated with coated with HA) HA) Fig. 13A Patent Application Publication Sep. 14, 2006 Sheet 17 of 19 US 2006/0204738A1 8000 7000 Z Osteoblasts o Fibroblasts Endothelial Cells 6000 O Smooth Muscle Cells 5000 4000 3000 2, 2 % 3: 3 2000 2 2 2 1000 %2 %22 2 O % 2:1. 2 c.p. Ti TiéA14V CoCrMo c.p. Ti Ti5A14V HA Nanofiber (control) (reference)(reference) (control (coated with coated with HA) HA) Fig. 13B Patent Application Publication Sep. 14, 2006 Sheet 18 of 19 US 2006/0204738A1 Exis"S. 2 " . R SS Fig. 14A s ..iii. Fig. 14B Fig. 14C " .... 10am WE)16.6mit . Patent Application Publication Sep. 14, 2006 Sheet 19 of 19 US 2006/0204738A1 1sokw X3oo 10am wild 113in Fig. 16B US 2006/0204738A1 Sep. 14, 2006 MEDICAL DEVICE APPLICATIONS OF tunately, such infections are often resistant to innate immune NANOSTRUCTURED SURFACES system responses as well as to conventional antibiotic treat ments. It will be appreciated that such infections are prob CROSS-REFERENCE TO RELATED lematic not just in treatment of humans, but also in treatment APPLICATIONS of a number of other organisms as well. 0001. This application is a continuation-in-part applica 0005. A welcome addition to the art would be medical tion of U.S. patent application Ser. No. 11/090,895 filed Mar. devices having enhanced surface areas and structures/de 24, 2005, which claims priority as a continuation-in-part of vices comprising such, as well as methods of using enhanced U.S. patent application Ser. No. 10/902,700 filed Jul. 29, area surfaces in medical devices. The current invention 2004, which claims priority to U.S. Provisional Patent provides these and other benefits which will be apparent Application Ser. No. 60/549,711, filed Mar. 2, 2004. This upon examination of the following. application also claims priority as a continuation-in-part application of U.S. patent application Ser. No. 10/828, 100, SUMMARY OF THE INVENTION filed Apr. 19, 2004, which is a continuation-in-part of U.S. patent application Ser. No. 10/661,381, filed Sep. 12, 2003, 0006 The embodiments of the current invention com which claims priority to U.S. Provisional Patent Application prise various medical devices, such as clamps, valves, No. 60/463,766, filed Apr. 17, 2003; and as a continuation intracorporeal or extracorporeal devices (e.g., catheters), in-part of U.S. patent application Ser. No. 10/833,944, filed temporary or permanent implants, stents, vascular grafts, Apr. 27, 2004, which claims priority to U.S. Provisional anastomotic devices, aneurysm repair devices, embolic Application Ser. No. 60/466.229, filed Apr. 28, 2003; and as devices, and implantable devices (e.g., orthopedic and dental a continuation-in-part application of U.S. patent application implants) and the like which comprise nanostructure Ser. No. 10/840,794 filed May 5, 2004, which is a continu enhanced Surfaces. The nanostructures may comprise ation-in-part of U.S. patent application Ser. No. 10/792.402, nanofibers (including nanowires), nanotubes or nanopar filed Mar. 2, 2004, which claims priority to U.S. Provisional ticles and/or combinations thereof, and including woven and Patent Application Ser. Nos. 60/468.390, filed May 6, 2003 nonwoven fibrous mats comprising nanofibers and nano and 60/468,606 filed May 5, 2003; all of the above patents tubes. The nanostructures may be coated or uncoated, or and applications are hereby incorporated herein by reference have multiple coatings thereon. The specific coatings are in their entirety. described herein and vary depending on the desired purpose of the device or method. Such enhanced surfaces provide FIELD OF THE INVENTION many enhanced attributes to the medical devices in, on, or within which they are used including, e.g., to prevent/reduce 0002 The invention relates primarily to the field of bio-fouling, increase fluid flow due to hydrophobicity, nanotechnology. More specifically, the invention pertains to increase adhesion, biointegration, etc. medical devices containing nanostructures, composite mate 0007. In one aspect of the invention, a medical device is rials containg nanostructures, methods of making medical disclosed comprising a body structure having one or more devices containing nanostructures and methods of using Surfaces having a plurality of nanostructured components medical devices containing nanostructures. associated therewith. The medical device may comprise an intracorporeal or extracorporeal device, a temporary or BACKGROUND OF THE INVENTION permanent implant, a stent, a vascular graft, an anastomotic 0003 Medical devices including, for example, intracor device, an aneurysm repair device, an embolic device, an poreal or extracorporeal devices (e.g., catheters), temporary implantable device, a catheter, valve or other device which or permanent implants, stents, vascular grafts, anastomotic would benefit from a nanostructured surface according to the devices, aneurysm repair devices, embolic devices, and teachings of the present invention.