IP Library › Granted Patent US 12,702,827
Granted Patent B2
US 12,702,827 · App. 17/736,432 · Granted Aug 11, 2026

Cartilage treatment

Inventors: Yossi Gross (Moshav Mazor, IL); Yuval Mandelbaum (Gat-Rimon, IL)
Assignee: Discure Technologies Ltd
A61N1/326A61N1/05A61N1/08
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Quick Facts
Patent No.
US 12,702,827
App. No.
17/736,432
Filed
May 4, 2022
Granted
Aug 11, 2026
Kind
B2
Art Unit
3792
USPC
607/50
Abstract

Apparatus is provided for treating hyaline cartilage of a subject, the apparatus including a chondral implant, which includes a first exposed electrode surface and which is configured to be implanted in osteochondral tissue of the subject. A second exposed electrode surface is configured to be implanted in a body of the subject. Control circuitry is configured to promote regeneration of the hyaline cartilage by driving the first and the second exposed electrode surfaces to drive nutrients toward the first exposed electrode surface. Other embodiments are also described.

Claims (43)

1 . Apparatus for treating hyaline cartilage of a subject, the apparatus comprising:

a chondral implant, which comprises a first exposed electrode surface and which is configured to be implanted in osteochondral tissue of the subject;

a second exposed electrode surface, which is configured to be implanted in a body of the subject; and

control circuitry, which is configured to promote regeneration of the hyaline cartilage by cyclically:

driving the first and the second exposed electrode surfaces to electroosmotically drive fluid containing nutrients toward the first exposed electrode surface for periods of time having a duration of at least 3 minutes, and

providing rest periods during which the nutrient-containing fluid is not electroosmotically driven toward the first exposed electrode surface.

2 . The apparatus according to claim 1 , wherein the first exposed electrode surface has a surface area of 1-30 cm2.

3 . The apparatus according to claim 1 , wherein the control circuitry is configured to configure the first exposed electrode surface to be a cathode and the second exposed electrode surface to be an anode.

4 . The apparatus according to claim 1 , wherein the chondral implant comprises a synthetic scaffold, and wherein the first exposed electrode surface comprises an electrically-conductive material of the synthetic scaffold.

5 . The apparatus according to claim 4 , wherein the electrically-conductive material comprises carbon fiber.

6 . The apparatus according to claim 5 , wherein the carbon fiber is hollow carbon fiber.

7 . The apparatus according to claim 4 , wherein the electrically-conductive material comprises a biocompatible bioresorbable conductive porous material.

8 . The apparatus according to claim 4 , wherein the electrically-conductive material is shaped as a thin layer.

9 . The apparatus according to claim 1 , wherein the chondral implant comprises one or more synthetic materials that are configured to stimulate the hyaline cartilage regeneration.

10 . The apparatus according to claim 9 , wherein the chondral implant comprises a synthetic scaffold that is configured to stimulate the hyaline cartilage regeneration.

11 . The apparatus according to claim 10 , wherein the first exposed electrode surface is coupled to the synthetic scaffold, and wherein the chondral implant is configured to be implanted such that the first exposed electrode surface is located deeper within the osteochondral tissue than the synthetic scaffold.

12 . The apparatus according to claim 11 , wherein the synthetic scaffold is shaped as a thin layer.

13 . The apparatus according to claim 10 , wherein the synthetic scaffold comprises a layer of fibrin glue.

14 . The apparatus according to claim 10 , wherein the synthetic scaffold is biphasic.

15 . The apparatus according to claim 1 , wherein the chondral implant further comprises a tissue graft that is configured to stimulate the hyaline cartilage regeneration.

16 . The apparatus according to claim 15 , wherein the first exposed electrode surface is coupled to the tissue graft, and the chondral implant is configured to be implanted such that the first exposed electrode surface is located deeper within the osteochondral tissue than the tissue graft.

17 . The apparatus according to claim 1 , wherein the chondral implant is configured to be implanted in a chondral defect of the hyaline cartilage.

18 . The apparatus according to claim 17 , wherein the chondral implant comprises an osteochondral plug that is configured to stimulate the hyaline cartilage regeneration in the chondral defect.

19 . The apparatus according to claim 18 , wherein the first exposed electrode surface is located in a transition zone of the osteochondral plug between a chondral layer of the osteochondral plug and a subchondral bone layer of the osteochondral plug.

20 . The apparatus according to claim 18 , wherein the osteochondral plug comprises naturally-derived cartilage.

21 . The apparatus according to claim 18 , wherein the osteochondral plug comprises a biocompatible, artificial material.

22 . The apparatus according to claim 1 , wherein the control circuitry is configured to provide the rest periods having respective durations of at least 1 minute.

23 . Apparatus for treating hyaline cartilage of a subject, the apparatus comprising:

a chondral implant, which comprises a first exposed electrode surface and which is configured to be implanted in osteochondral tissue of the subject;

a second exposed electrode surface, which is configured to be implanted in a body of the subject; and

control circuitry, which is configured to promote regeneration of the hyaline cartilage by driving the first and the second exposed electrode surfaces to drive nutrients toward the first exposed electrode surface, by applying a voltage between the first and the second exposed electrode surfaces.

24 . The apparatus according to claim 23 , wherein the control circuitry is configured to drive the first and the second exposed electrode surfaces to electroosmotically drive fluid containing the nutrients toward the first exposed electrode surface.

25 . The apparatus according to claim 24 , wherein the control circuitry is configured to cyclically:

drive the first and the second exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid toward the first exposed electrode surface, and

provide rest periods during which the nutrient-containing fluid is not electroosmotically driven toward the first exposed electrode surface.

26 . The apparatus according to claim 23 , wherein the voltage is 0.1-1.1 V.

27 . Apparatus for treating hyaline cartilage of a subject, the apparatus comprising:

a chondral implant, which comprises a first exposed electrode surface and which is configured to be implanted in osteochondral tissue of the subject;

a second exposed electrode surface, which is configured to be implanted in a body of the subject; and

control circuitry, which is configured to promote regeneration of the hyaline cartilage by cyclically:

driving the first and the second exposed electrode surfaces to electroosmotically drive fluid containing nutrients toward the first exposed electrode surface, and

providing rest periods during which the nutrient-containing fluid is not electroosmotically driven toward the first exposed electrode surface,

wherein the control circuitry is configured to sense a voltage between the first and the second exposed electrode surfaces during each of the rest periods, and upon detection of a reduction of the sensed voltage to below a threshold value, again begin electroosmotically driving the nutrient-containing fluid toward the first exposed electrode surface.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 2, 2024
From: RAINBOW MEDICAL LTD.
To: DISCURE TECHNOLOGIES LTD.
Reel/Frame 065991/0623 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 4, 2022
From: GROSS, YOSSI; MANDELBAUM, YUVAL
To: RAINBOW MEDICAL LTD.
Reel/Frame 059813/0016 →
Continuity (2)
Continuation 17402911 · Aug 16, 2021
Related Publication 20230047627A1 · Feb 16, 2023
References Cited (219)
US 3842841A · Brighton · 1974 [cited by examiner]
US 4026304A · Levy · 1977 [cited by examiner]
US 4044774A · Corbin et al. · 1977 [cited by applicant]
US 4360031A · White · 1982 [cited by applicant]
US 4503863A · Katims · 1985 [cited by applicant]
US 4506673A · Bonnell · 1985 [cited by examiner]
US 4602638A · Adams · 1986 [cited by applicant]
US 4710174A · Moden et al. · 1987 [cited by applicant]
US 4738250A · Fulkerson et al. · 1988 [cited by applicant]
US 5088977A · Sibalis · 1992 [cited by applicant]
US 5121754A · Mullett · 1992 [cited by applicant]
US 5433739A · Sluijter et al. · 1995 [cited by applicant]
US 5529574A · Frackelton · 1996 [cited by applicant]
US 5792100A · Shantha · 1998 [cited by applicant]
US 5911223A · Weaver et al. · 1999 [cited by applicant]
US 5938690A · Law et al. · 1999 [cited by applicant]
US 6041252A · Walker et al. · 2000 [cited by applicant]
US 6146380A · Racz et al. · 2000 [cited by applicant]
US 6161047A · King et al. · 2000 [cited by applicant]
US 6360750B1 · Gerber et al. · 2002 [cited by applicant]
US 6567702B1 · Nekhendzy et al. · 2003 [cited by applicant]
US 6591138B1 · Fischell et al. · 2003 [cited by applicant]
US 6602248B1 · Sharps et al. · 2003 [cited by applicant]
US 6620155B2 · Underwood et al. · 2003 [cited by applicant]
US 6832115B2 · Borkan · 2004 [cited by applicant]
US 6941172B2 · Nachum · 2005 [cited by applicant]
US 6997941B2 · Sharkey et al. · 2006 [cited by applicant]
US 7013177B1 · Whitehurst et al. · 2006 [cited by applicant]
US 7069083B2 · Finch et al. · 2006 [cited by applicant]
US 7120489B2 · Shalev et al. · 2006 [cited by applicant]
US 7155287B2 · Gavronsky · 2006 [cited by applicant]
US 7174221B1 · Chen et al. · 2007 [cited by applicant]
US 7217351B2 · Krumme · 2007 [cited by applicant]
US 7223227B2 · Pflueger · 2007 [cited by applicant]
US 7270659B2 · Ricart et al. · 2007 [cited by applicant]
US 7317947B2 · Wahlstrand et al. · 2008 [cited by applicant]
US 7398121B2 · Matsumura et al. · 2008 [cited by applicant]
US 7509171B2 · DiMauro · 2009 [cited by applicant]
US 7640062B2 · Shalev · 2009 [cited by applicant]
US 7831306B2 · Finch et al. · 2010 [cited by applicant]
US 7860569B2 · Solberg et al. · 2010 [cited by applicant]
US 8060207B2 · Wallace et al. · 2011 [cited by applicant]
US 8190248B2 · Besio et al. · 2012 [cited by applicant]
US 8366615B2 · Razavi · 2013 [cited by applicant]
US 8423148B1 · Lytinas · 2013 [cited by examiner]
US 8457761B2 · Wariar · 2013 [cited by applicant]
US 8577469B2 · Gross · 2013 [cited by applicant]
US 8676348B2 · Gross · 2014 [cited by applicant]
US 8740982B2 · Lee · 2014 [cited by applicant]
US 9131980B2 · Bloom · 2015 [cited by applicant]
US 9616221B2 · Gross · 2017 [cited by applicant]
US 9724513B2 · Lane et al. · 2017 [cited by applicant]
US 9731122B2 · Gross · 2017 [cited by applicant]
US 10398884B2 · Lad et al. · 2019 [cited by applicant]
US 10765527B2 · Chin et al. · 2020 [cited by applicant]
US 20020151948A1 · King et al. · 2002 [cited by applicant]
US 20020183683A1 · Lerner · 2002 [cited by applicant]
US 20030130707A1 · Gan et al. · 2003 [cited by applicant]
US 20030158589A1 · Katsnelson · 2003 [cited by applicant]
US 20030216792A1 · Levin et al. · 2003 [cited by applicant]
US 20030225331A1 · Diederich et al. · 2003 [cited by applicant]
US 20040002746A1 · Ryan et al. · 2004 [cited by applicant]
US 20040019381A1 · Pflueger · 2004 [cited by applicant]
US 20040049180A1 · Sharps et al. · 2004 [cited by applicant]
US 20040083002A1 · Belef et al. · 2004 [cited by applicant]
US 20040116977A1 · Finch et al. · 2004 [cited by applicant]
US 20040186576A1 · Biscup et al. · 2004 [cited by applicant]
US 20040210209A1 · Yeung et al. · 2004 [cited by applicant]
US 20050010205A1 · Hovda et al. · 2005 [cited by applicant]
US 20050021104A1 · DiLorenzo · 2005 [cited by applicant]
US 20050119650A1 · Sanders et al. · 2005 [cited by applicant]
US 20050137646A1 · Wallace et al. · 2005 [cited by applicant]
US 20050137647A1 · Wallace et al. · 2005 [cited by applicant]
US 20050159790A1 · Shalev · 2005 [cited by applicant]
US 20050187589A1 · Wallace et al. · 2005 [cited by applicant]
US 20050203599A1 · Garabedian et al. · 2005 [cited by applicant]
US 20050203600A1 · Wallace et al. · 2005 [cited by applicant]
US 20050203602A1 · Wallace et al. · 2005 [cited by applicant]
US 20050222647A1 · Wahlstrand et al. · 2005 [cited by applicant]
US 20050277996A1 · Podhajsky et al. · 2005 [cited by applicant]
US 20060030895A1 · Simon et al. · 2006 [cited by applicant]
US 20060106430A1 · Fowler et al. · 2006 [cited by applicant]
US 20060224223A1 · Podhajsky et al. · 2006 [cited by applicant]
US 20060293723A1 · Whitehurst et al. · 2006 [cited by applicant]
US 20070000784A1 · Paul et al. · 2007 [cited by applicant]
US 20070073402A1 · Vresilovic et al. · 2007 [cited by applicant]
US 20070162086A1 · Dilorenzo · 2007 [cited by applicant]
US 20070213700A1 · Davison et al. · 2007 [cited by applicant]
US 20070233202A1 · Wallace et al. · 2007 [cited by applicant]
US 20070255338A1 · Wahlstrand · 2007 [cited by applicant]
US 20070276201A1 · Lee et al. · 2007 [cited by applicant]
US 20080009927A1 · Vilims · 2008 [cited by applicant]
US 20080119907A1 · Stahmann · 2008 [cited by applicant]
US 20080177392A1 · Williams et al. · 2008 [cited by applicant]
US 20080260542A1 · Nishikawa et al. · 2008 [cited by applicant]
US 20090030399A1 · Raiszadeh · 2009 [cited by applicant]
US 20090062885A1 · Brighton et al. · 2009 [cited by applicant]
US 20090112278A1 · Wingeier et al. · 2009 [cited by applicant]
US 20090125080A1 · Montgomery · 2009 [cited by applicant]
US 20090126813A1 · Yanagisawa et al. · 2009 [cited by applicant]
US 20090131850A1 · Geiger · 2009 [cited by applicant]
US 20090216113A1 · Meier et al. · 2009 [cited by applicant]
US 20090312816A1 · Gross · 2009 [cited by applicant]
US 20100057204A1 · Kadaba et al. · 2010 [cited by applicant]
US 20100100185A1 · Trieu et al. · 2010 [cited by applicant]
US 20100131067A1 · Metcalf, Jr. et al. · 2010 [cited by applicant]
US 20100217369A1 · Gross · 2010 [cited by applicant]
US 20100324441A1 · Hargrove et al. · 2010 [cited by applicant]
US 20110046540A1 · Alterman et al. · 2011 [cited by applicant]
US 20110054518A1 · Carbunaru et al. · 2011 [cited by applicant]
US 20110125158A1 · Diwan et al. · 2011 [cited by applicant]
US 20110160638A1 · Mauge et al. · 2011 [cited by applicant]
US 20110160797A1 · Makous et al. · 2011 [cited by applicant]
US 20120041562A1 · Shachar et al. · 2012 [cited by applicant]
US 20120053659A1 · Molnar et al. · 2012 [cited by applicant]
US 20120100607A1 · Duntsch et al. · 2012 [cited by applicant]
US 20120191159A1 · Willeford · 2012 [cited by applicant]
US 20120203307A1 · Schroeppel et al. · 2012 [cited by applicant]
US 20120276501A1 · Terkel · 2012 [cited by examiner]
US 20130066392A1 · Simon et al. · 2013 [cited by applicant]
US 20130102952A1 · Gross · 2013 [cited by applicant]
US 20130166006A1 · Williams · 2013 [cited by applicant]
US 20130289385A1 · Lozano et al. · 2013 [cited by applicant]
US 20130289599A1 · Yeung et al. · 2013 [cited by applicant]
US 20140058189A1 · Stubbeman · 2014 [cited by applicant]
US 20140088672A1 · Bedenbaugh · 2014 [cited by applicant]
US 20140207224A1 · Simon · 2014 [cited by applicant]
US 20140257168A1 · Gill · 2014 [cited by applicant]
US 20140324128A1 · Gross · 2014 [cited by applicant]
US 20150011927A1 · Hua · 2015 [cited by applicant]
US 20150119898A1 · Desalles et al. · 2015 [cited by applicant]
US 20160144164A1 · Sedighiani · 2016 [cited by applicant]
US 20160220699A1 · O'Heeron · 2016 [cited by applicant]
US 20160331970A1 · Lozano · 2016 [cited by applicant]
US 20160354541A1 · Crawford et al. · 2016 [cited by applicant]
US 20170000536A1 · Tacktill · 2017 [cited by examiner]
US 20170007823A1 · Gross · 2017 [cited by applicant]
US 20170120053A1 · Fostick et al. · 2017 [cited by applicant]
US 20170274207A1 · Gross · 2017 [cited by applicant]
US 20180071523A1 · Gross et al. · 2018 [cited by applicant]
US 20180207004A1 · Yeung et al. · 2018 [cited by applicant]
US 20220241078A1 · Hermsen · 2022 [cited by examiner]
JP 2004321242 · 2004 [cited by applicant]
JP 2007501067 · 2007 [cited by applicant]
WO 9405369 · 1994 [cited by applicant]
WO 0152931 · 2001 [cited by applicant]
WO 0185027 · 2001 [cited by applicant]
WO 2001085094 · 2001 [cited by applicant]
WO 2005011805 · 2005 [cited by applicant]
WO 2006090397 · 2006 [cited by applicant]
WO 2008007369 · 2008 [cited by applicant]
WO 2017072769 · 2017 [cited by applicant]
WO 2020263088 · 2020 [cited by examiner]
Karran September E et201 al., 1 “The Amyloid cascade hypothesis for AD,” Nature Reviews Drug Discovery, vol. 10; 698-71. [cited by applicant]
De La Torre JC, “Vascular Basis of Alzheimer's Pathogensis,” Ann NY Acad Sci. 977:196-215 (Nov. 2002). [cited by applicant]
Weller RO et al, “Perivascular Drainage of Amyloid-b Peptides from the Brain and Its Failure in Cerebral Amyloid Angiopathy and Alzheimer's Disease,” Brain Pathology 18 (Apr. 2008) 253-266. [cited by applicant]
Brief PubMed search for metal ions in Alzheimers. [cited by applicant]
An Office Action dated Sep. 27, 2016, which issued during the prosecution of U.S. Appl. No. 14/926,705. [cited by applicant]
An International Search Report and a Written Opinion both dated Aug. 7, 2008, which issued during the prosecution of Applicant's PCT/IL2007/000865. [cited by applicant]
An Office Action dated Mar. 29, 2013, which issued during the prosecution of U.S. Appl. No. 12/373,306. [cited by applicant]
An Office Action dated Oct. 31, 2011, which issued during the prosecution of U.S. Appl. No. 12/373,306. [cited by applicant]
An Office Action dated Oct. 1, 2012, which issued during the prosecution of U.S. Appl. No. 12/373,306. [cited by applicant]
Notice of Allowance dated Jul. 24, 2013, which issued during the prosecution of U.S. Appl. No. 12/373,306. [cited by applicant]
An Office Action dated Apr. 11, 2013, which issued during the prosecution of U.S. Appl. No. 13/663,757. [cited by applicant]
Notice of Allowance dated Oct. 28, 2013, which issued during the prosecution of U.S. Appl. No. 13/663,757. [cited by applicant]
Elixmann IM et al., “In-vitro evaluation of a drainage catheter with integrated bioimpedance electrodes to determine ventricular size,” Biomed Tech 2013; 58 (Suppl. 1) Sep. 2013 (2 pages total). [cited by applicant]
An Office Action dated Aug. 31, 2015, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
An Applicant Initiated Interview Summary dated Dec. 14, 2015, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
An Office Action dated Feb. 3, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
Notice of Allowance dated Dec. 9, 2016, which issued during the prosecution of U.S. Appl. No. 14/794,739. [cited by applicant]
An Applicant Initiated Interview Summary dated Feb. 25, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
An Office Action dated Jun. 15, 2016, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
An International Search Report and a Written Opinion both dated Oct. 20, 2016, which issued during the prosecution of Applicant's PCT/IL2016/050728. [cited by applicant]
An Office Action dated Sep. 21, 2016, which issued during the prosecution of U.S. Appl. No. 14/794,739. [cited by applicant]
An International Search Report and a Written Opinion both dated Jan. 26, 2017, which issued during the prosecution of Applicant's PCT/IL2016/051161. [cited by applicant]
Notice of Allowance dated Jul. 14, 2017, which issued during the prosecution of U.S. Appl. No. 13/872,794. [cited by applicant]
An Office Action dated May 26, 2017, which issued during the prosecution of U.S. Appl. No. 15/453,290. [cited by applicant]
An International Preliminary Report on Patentability dated Apr. 7, 2009, which issued during the prosecution of Applicant's PCT/IL2007/000865. [cited by applicant]
Loutzenhiser, “Membrane Potential measurements in renal afferent and efferent arterioles: actions of Angiotensin II”, AJP—Renal Physiol Aug. 1, 1997 vol. 273 No. 2 F307-F314. [cited by applicant]
U.S. Appl. No. 60/830,717, filed Jul. 12, 2006. [cited by applicant]
Dao-Sheng Liu et al., “Activation of Na+ and K+ Pumping Modes of (Na,K)-ATPase by an Oscillating Electric Field,” The Journal of Biological Chemistry, vol. 265. No. 13, May 5, 1990. (pp. 7260-7267). [cited by applicant]
Robert F. Service .. “Electric fields deliver druas into tumors.” http://news.sciencemaa.ora. Feb. 4, 2015. (5 Pages Total). [cited by applicant]
Vernengo J, “Injectable Bioadhesive Hydrogels for Nucleus Pulposus Replacement and Repair of the Damaged Intervertebral Disc: A Thesis,” Drexel University (Jan. 2007). [cited by applicant]
Urban JPG et al., “The nucleus of the intervertebral disc from development to degeneration,” American Zoologist 40(1): 53-61 (2000). [cited by applicant]
Cheung KMC et al., “Intervertebral disc regeneration by use of autologous mesenchymal stem cells, an experimental model in rabbits,” Abstract from the SRS 2004 Annual Meeting. [cited by applicant]
Freemont TJ et al., “Degeneration of intervertebral discs: current understanding of cellular and molecular events, and implications for novel therapies,” Expert Reviews in Molecular Biology, Mar. 29, 2001 (Cambridge Uni… [cited by applicant]
An Office Action dated Sep. 12, 2011, which issued during the prosecution of U.S. Appl. No. 12/373,306. [cited by applicant]
An Office Action dated Jul. 24, 2017, which issued during the prosecution of U.S. Appl. No. 14/982,187. [cited by applicant]
An International Search Report and a Written Opinion both dated Mar. 10, 2017, which issued during the prosecution of Applicant's PCT/IL2016/051363. [cited by applicant]
An Office Action dated Mar. 25, 2019, which issued during the prosecution of U.S. Appl. No. 15/742,245. [cited by applicant]
An Office Action together with the English translation dated Aug. 19, 2020, which issued during the prosecution of Japanese Patent Application No. 2018-521586. [cited by applicant]
An Office Action dated Apr. 25, 2018, which issued during the prosecution of U.S. Appl. No. 15/637,330. [cited by applicant]
An Office Action dated Nov. 20, 2020, which issued during the prosecution of U.S. Appl. No. 16/353,407. [cited by applicant]
An Office Action dated Jan. 22, 2020, which issued during the prosecution of U.S. Appl. No. 15/771,551. [cited by applicant]
An Office Action dated Nov. 29, 2019, which issued during the prosecution of U.S. Appl. No. 15/969,411. [cited by applicant]
An International Search Report and a Written Opinion both dated May 23, 2019, which issued during the prosecution of Applicant's PCT/IL2019/050284. [cited by applicant]
An Office Action dated Jul. 29, 2019, which issued during the prosecution of U.S. Appl. No. 15/618,325. [cited by applicant]
An Office Action dated Mar. 6, 2020, which issued during the prosecution of U.S. Appl. No. 15/618,325. [cited by applicant]
Sawyer PN et al., “Measurement of streaming potentials of mammalian blood vessels, aorta and venacava, in vivo,” Biophysical journal vol. 6,5 (1966): 641-51. doi: 10.1016/50006-3495(66)86683-3. [cited by applicant]
Acupuncture Injection Therapy _ Pain Arthritis Relief Center, first viewed Sep. 2020. [cited by applicant]
“Researchers developing biomaterial to treat spinal disc degeneration,” Medical Press, Jun. 13, 2019 (2019-06-biomaterial-spinal-disc-degeneration). [cited by applicant]
AvistaTM MRI xx cm 8 Contact Lead Kit: Directions for Use, Boston Scientific, Apr. 2016 (91063583-01_RevC_Avista_MRI_Lead_DFU_en-USA_S). [cited by applicant]
Akbarzadeh, Abolfazl, et al. “Liposome: classification, preparation, and applications.” Nanoscale research letters 8.1 (2013): 1-9. [cited by applicant]
Herrlich, Simon, et al. “Drug release mechanisms of steroid eluting rings in cardiac pacemaker lead electrodes.” Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE. IEEE… [cited by applicant]
Freemont, A. J., et al. “Nerve In-Growth Into Painful Intervertebral Discs is Mediated By Nerve Growth Factor Roduced By Endothelial Cells of Local Blood Vessels.” Orthopaedic Proceedings. vol. 84. No. SUPP_II. The Brit… [cited by applicant]
Dolor, Aaron, et al. “Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.” PloS one 14.4 (2019): e0215218. [cited by applicant]
Bowles, Robert D., and Lori A. Setton. “Biomaterials for intervertebral disc regeneration and repair.” Biomaterials 129 (2017): 54-67. [cited by applicant]
Kang, James D. “Commentary on “Gene Therapy Approach for Intervertebral Disc Degeneration: An Update”.” Neurospine 17.1 (2020): 15-16. [cited by applicant]
Liang, C., et al. “New hypothesis of chronic back pain: low pH promotes nerve ingrowth into damaged intervertebral disks.” Acta Anaesthesiologica Scandinavica 57.3 (2013): 271-277. [cited by applicant]
Lee, Ho-Jin, et al. “Effectiveness of continuous hypertonic saline infusion with an automated infusion pump for decompressive neuroplasty: a randomized clinical trial.” The Korean journal of pain 32.3 (2019): 196. [cited by applicant]
An Office Action dated Feb. 16, 2021, which issued during the prosecution of U.S. Appl. No. 16/558,987. [cited by applicant]
Takeoka, Yoshiki, Takashi Yurube, and Kotaro Nishida. “Gene therapy approach for intervertebral disc degeneration: An update.” Neurospine 17.1 (2020): 3. [cited by applicant]
Sobajima, S., et al. “Gene therapy for degenerative disc disease.” Gene therapy 11.4 (2004): 390-401. [cited by applicant]
Sato, Kimiaki, Kensei Nagata, and Teruyuki Hirohashi. “Intradiscal pressure after repeat intradiscal injection of hypertonic saline: an experimental study.” European Spine Journal 11.1 (2002): 52-56. [cited by applicant]
Meisel, Hans-Joerg, et al. “Cell therapy for treatment of intervertebral disc degeneration: a systematic review.” Global spine journal 9.1_suppl (2019): 39S-52S. [cited by applicant]
A Notice of Allowance dated May 7, 2021, which issued during the prosecution of U.S. Appl. No. 16/332,606. [cited by applicant]
An Office Action dated Jul. 27, 2021, which issued during the prosecution of U.S. Appl. No. 17/306,209. [cited by applicant]
An Office Action dated Oct. 28, 2021, which issued during the prosecution of U.S. Appl. No. 17/402,911. [cited by applicant]
Maurice Philippson, “Principles of the Electrical Resistance of Living Tissue,” Bull. CI. Sci. Acad. R. Belg., ser. 5, vol. 7, No. 7, pp. 387-403, Jul. 1921 (Translated by James C. M. Hwang and Olivia Peytral-Rieu. J. C… [cited by applicant]