IP Library › Granted Patent US 12,420,085
Granted Patent B2
US 12,420,085 · App. 17/693,938 · Granted Sep 23, 2025

Synergistic therapies for inter vertebral disc degeneration

Inventors: Yuval Mandelbaum (Gat-Rimon, IL); Yossi Gross (Moshav Mazor, IL); Yehuda Zadok (Kiryat Ono, IL)
Assignee: Discure Technologies Ltd
A61N1/0551A61K9/0004A61K9/0009A61K35/12A61K35/28A61K35/30A61K47/02A61K47/26A61N1/32A61N1/325
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,420,085
App. No.
17/693,938
Granted
Sep 23, 2025
Kind
B2
Abstract

A method for treating an intervertebral disc of a subject is provided, the method including delivering a growth factor to a nucleus pulposus of the intervertebral disc. At least one intra-pulposus exposed electrode surface is implanted in the nucleus pulposus. At least one extra-pulposus exposed electrode surface is implanted in a body of the subject outside the nucleus pulposus. The growth factor is supported by activating control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive nutrient-containing fluid into the nucleus pulposus. Other embodiments are also described.

Claims (19)

1. A method for treating an intervertebral disc of a subject, the method comprising:

delivering a growth factor to a nucleus pulposus of the intervertebral disc by injecting the growth factor through a hollow needle;

implanting at least one intra-pulposus exposed electrode surface in the nucleus pulposus;

implanting at least one extra-pulposus exposed electrode surface in a body of the subject outside the nucleus pulposus; and

supporting the growth factor by activating control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive nutrient-containing fluid into the nucleus pulposus.

2. The method according to claim 1 , wherein delivering the growth factor to the nucleus pulposus comprises injecting the growth factor into the nucleus pulposus through the hollow needle.

3. The method according to claim 1 , wherein delivering the growth factor to the nucleus pulposus comprises delivering the growth factor to the body of the subject outside the nucleus pulposus such that the growth factor moves into the nucleus pulposus.

4. The method according to claim 3 , wherein delivering the growth factor to the body of the subject outside the nucleus pulposus comprises delivering the growth factor to an annulus fibrosus of the intervertebral disc such that the growth factor moves into the nucleus pulposus.

5. The method according to claim 3 , wherein delivering the growth factor to the nucleus pulposus comprises, while at least some of the growth factor is outside the nucleus pulposus, activating the control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the growth factor into the nucleus pulposus.

6. The method according to claim 1 , wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to apply, between the intra-pulposus exposed electrode surface and the extra-pulposus exposed electrode surface, a mean voltage insufficient to cause electrolysis.

7. The method according to claim 1 , wherein the nutrient-containing fluid includes oxygen, and wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the oxygen-containing fluid into the nucleus pulposus.

8. The method according to claim 1 , wherein the nutrient-containing fluid includes glucose, and wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the glucose-containing fluid into the nucleus pulposus.

9. The method according to claim 1 , wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to intermittently drive, during a plurality of sessions, the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus.

10. The method according to claim 9 , wherein an average duration of non-activation periods between sequential ones of the sessions is at least 12 hours.

11. The method according to claim 9 , wherein the plurality of sessions includes at least 10 sessions.

12. The method according to claim 9 , wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to intermittently drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus during one or more of the sessions during each 24-hour period.

13. The method according to claim 12 , wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to intermittently drive the intra-pulposus and the extra-pulposus exposed electrode surfaces to electroosmotically drive the nutrient-containing fluid into the nucleus pulposus during exactly one of the sessions during each 24-hour period.

14. The method according to claim 9 , wherein the plurality of sessions extends over at least one week.

15. The method according to claim 1 , wherein supporting the growth factor comprises supporting the growth factor by activating the control circuitry to apply direct current between the intra-pulposus and the extra-pulposus exposed electrode surfaces.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 5, 2024
From: MANDELBAUM, YUVAL; GROSS, YOSSI; ZADOK, YEHUDA
To: DISCURE TECHNOLOGIES LTD.
Reel/Frame 067627/0735 →
Continuity (2)
Continuation 17306209 · May 3, 2021
Related Publication 20220347464A1 · Nov 3, 2022
References Cited (212)
US 4044774A · Corbin et al. · 1977 [cited by applicant]
US 4360031A · White · 1982 [cited by applicant]
US 4503863A · Katims · 1985 [cited by applicant]
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 8457761B2 · Wariar · 2013 [cited by applicant]
US 8577469B2 · Gross · 2013 [cited by applicant]
US 8676348B2 · Gross · 2014 [cited by examiner]
US 8740982B2 · Lee · 2014 [cited by applicant]
US 9005289B1 · Simionescu et al. · 2015 [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 11376021B2 · Marino · 2022 [cited by examiner]
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 · 2004 [cited by examiner]
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 · 2006 [cited by examiner]
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 20110066192A1 · Frasier 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 20110270399A1 · Yurek 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 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 20160220699A1 · O'Heeron · 2016 [cited by applicant]
US 20160331970A1 · Lozano · 2016 [cited by applicant]
US 20160354541A1 · Crawford et al. · 2016 [cited by applicant]
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]
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]
Non-Final Office Action dated Oct. 28, 2021 issued in U.S. Appl. No. 17/402,911. [cited by applicant]
Non-Final Office Action dated Jul. 27, 2021 issued in U.S. Appl. No. 17/306,209. [cited by applicant]
Karran September E et201 al., 1 “The Amyloid cascade hypothesis for AD,” Nature Reviews Drug Discovery, vol. 10; 698-712. [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 August 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. 12/663,306. [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]
Avista™ 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]