IP Library › Granted Patent US 12,245,740
Granted Patent B2
US 12,245,740 · App. 18/045,377 · Granted Mar 11, 2025

Systems and methods to repair tissue defects

Inventors: Darryl D. D'Lima (San Diego, CA); Clifford W. Colwell, Jr. (La Jolla, CA)
Assignee: SCRIPPS HEALTH
A61B1/00009A61B1/00A61B34/30A61B90/00A61F2/0805A61F2/0811A61F2/30756A61F2/3094A61L27/025A61L27/20A61L27/24A61L27/3604A61L27/3608A61L27/3612A61M5/14212A61M5/20B29C64/112B33Y10/00B33Y70/00C12N5/0654C12N5/0655A61B2017/00969A61B2090/395A61F2002/30962A61L2430/06
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 12,245,740
App. No.
18/045,377
Granted
Mar 11, 2025
Kind
B2
Abstract

Methods of bioprinting a bio-ink construct on an internal tissue defect or a chondral defect during a minimally invasive surgery on an individual in need thereof are provided, comprising: visualizing the defect; positioning a bioprinter comprising a printhead within proximity of or in contact with the defect; and ejecting a bio-ink from the printhead onto the defect to form a bio-ink layer, thereby generating a bio-ink construct. Further provided are systems for bioprinting a bio-ink construct on an internal tissue defect during a minimally invasive surgery on an individual in need thereof, comprising a control system, an endoscope, and a bioprinter comprising a printhead.

Claims (23)

1. A method of bioprinting a bio-ink construct on an internal tissue defect during a minimally invasive surgery on an individual in need thereof, comprising:

a. visualizing the internal tissue defect;

b. positioning a bioprinter comprising: a printhead, a bio-ink reservoir, and a nozzle within proximity of or in contact with the internal tissue defect, wherein the bio-ink reservoir is fluidically connected to the nozzle, and wherein the bio-ink reservoir contains a bio-ink comprising a plurality of cells and a photoinitiator; and

c. ejecting the bio-ink from the printhead onto the internal tissue defect to form a bio-ink layer, thereby generating a bio-ink construct.

2. The method of claim 1 , wherein the bio-ink construct comprises a plurality of bio-ink layers.

3. The method of claim 1 , wherein the bio-ink construct is a live tissue.

4. The method of claim 1 , wherein the printhead comprises a needle, an extended cylinder, a fluid line, a print nozzle, or a plurality of print nozzles.

5. The method of claim 1 , further comprising polymerizing the bio-ink.

6. The method of claim 1 , wherein the bioprinter further comprises a second printhead.

7. The method of claim 1 , further comprising positioning a second bioprinter comprising a second printhead within proximity of or in contact with the internal tissue defect.

8. The method of claim 1 , further comprising ejecting a second bio-ink from the second printhead of the second bioprinter onto the internal tissue defect to form a second bio-ink layer.

9. The method of claim 1 , further comprising controlling the bioprinter with a control system.

10. The method of claim 9 , wherein the control system controls a bio-ink printing parameter.

11. The method of claim 10 , wherein the bio-ink printing parameter comprises temperature, back-pressure, drops per nozzle, frequency of drop rate, number of nozzles in use, firing energy, resolution, viscosity, cell concentration, physiological temperature, speed of printing, or a combination thereof.

12. The method of claim 9 , wherein the method further comprises controlling a robotic arm operatively connected to the control system.

13. The method of claim 12 , wherein the method comprises controlling the robotic arm to perform at least one of: 1) positioning the bioprinter within proximity of or in contact with the internal tissue defect, and 2) moving the bioprinter with six degrees of freedom.

14. The method of claim 4 , wherein the method further comprises controlling and actuating a first print nozzle of the plurality of print nozzles independently of controlling and actuating a second print nozzle of the plurality of print nozzles.

15. The method of claim 1 , wherein the printhead ejects the bio-ink continuously.

16. The method of claim 1 , further comprising positioning an endoscope within proximity of the internal tissue defect.

17. The method of claim 16 , wherein the endoscope visualizes the internal tissue defect.

18. The method of claim 1 , wherein the bio-ink further comprises a component of extracellular matrix, a synthetic polymer, a natural polymer, a cross-linking agent or a combination thereof.

19. The method of claim 1 , wherein the internal tissue defect comprises a chondral defect.

20. The method of claim 19 , wherein the chondral defect comprises an osteochondral defect.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 10, 2022
From: D'LIMA, DARRYL D.; COLWELL, CLIFFORD W.
To: SCRIPPS HEALTH
Reel/Frame 061725/0849 →
Continuity (3)
Continuation 16304618
Provisional Application 62341914 · May 26, 2016
Related Publication 20230233058A1 · Jul 27, 2023
References Cited (113)
US 5425723A · Wang · 1995 [cited by applicant]
US 5526027A · Wade et al. · 1996 [cited by applicant]
US 6077251A · Ting et al. · 2000 [cited by applicant]
US 6517521B1 · Ly · 2003 [cited by applicant]
US 6733479B1 · Ott · 2004 [cited by applicant]
US 7767452B2 · Kleinsek · 2010 [cited by applicant]
US 8323881B2 · Fujisato et al. · 2012 [cited by applicant]
US 9393364B2 · Fischer, Jr. · 2016 [cited by applicant]
US 9498271B2 · Osborne et al. · 2016 [cited by applicant]
US 11369465B2 · D'Lima et al. · 2022 [cited by applicant]
US 11497831B2 · D'Lima et al. · 2022 [cited by applicant]
US 20020177822A1 · St. Cyr et al. · 2002 [cited by applicant]
US 20020177903A1 · Geistlich et al. · 2002 [cited by applicant]
US 20030049839A1 · Romero-Ortega et al. · 2003 [cited by applicant]
US 20030065400A1 · Beam et al. · 2003 [cited by applicant]
US 20030100824A1 · Warren et al. · 2003 [cited by applicant]
US 20030175410A1 · Campbell et al. · 2003 [cited by applicant]
US 20040005295A1 · Lee et al. · 2004 [cited by applicant]
US 20040193097A1 · Hofmann et al. · 2004 [cited by applicant]
US 20040237822A1 · Boland et al. · 2004 [cited by applicant]
US 20050209564A1 · Bonner et al. · 2005 [cited by applicant]
US 20050226855A1 · Alt et al. · 2005 [cited by applicant]
US 20060156978A1 · Lipson et al. · 2006 [cited by applicant]
US 20080166329A1 · Sung et al. · 2008 [cited by applicant]
US 20080294096A1 · Uber, III et al. · 2008 [cited by applicant]
US 20090117087A1 · Carroll et al. · 2009 [cited by applicant]
US 20090239302A1 · Decher et al. · 2009 [cited by applicant]
US 20100076397A1 · Reed et al. · 2010 [cited by applicant]
US 20100178274A1 · Sekiya et al. · 2010 [cited by applicant]
US 20100236481A1 · O'Brien et al. · 2010 [cited by applicant]
US 20110136162A1 · Sun et al. · 2011 [cited by applicant]
US 20110234668A1 · Hoisington et al. · 2011 [cited by applicant]
US 20120089238A1 · Kang et al. · 2012 [cited by applicant]
US 20130041380A1 · Sengun et al. · 2013 [cited by applicant]
US 20140012225A1 · Yoo et al. · 2014 [cited by applicant]
US 20150105891A1 · Golway et al. · 2015 [cited by applicant]
US 20150224291A1 · Guillemot et al. · 2015 [cited by applicant]
US 20190008998A1 · Cui et al. · 2019 [cited by applicant]
US 20220331086A1 · D'Lima et al. · 2022 [cited by applicant]
US 20230028989A1 · D'Lima et al. · 2023 [cited by applicant]
EP 1027989A2 · 2000 [cited by applicant]
EP 1232863A1 · 2002 [cited by applicant]
EP 1374941B1 · 2006 [cited by applicant]
EP 2343415A2 · 2011 [cited by applicant]
GB 2343415A · 2000 [cited by applicant]
JP 2002254654A · 2002 [cited by applicant]
JP 2010501547A · 2010 [cited by applicant]
JP 2011255513A · 2011 [cited by applicant]
JP 2016513979A · 2016 [cited by applicant]
RU 2733955C1 · 2020 [cited by applicant]
WO WO9922683A1 · 1999 [cited by applicant]
WO WO2009049823A1 · 2009 [cited by applicant]
WO WO2011066577A1 · 2011 [cited by applicant]
WO WO2011107599A1 · 2011 [cited by applicant]
WO WO2014110590A1 · 2014 [cited by applicant]
WO WO2015017579A1 · 2015 [cited by applicant]
WO WO2015066705A1 · 2015 [cited by applicant]
WO WO2015175880A1 · 2015 [cited by applicant]
WO WO2015179572A1 · 2015 [cited by applicant]
WO WO2016164566A1 · 2016 [cited by applicant]
WO WO2017040975A1 · 2017 [cited by applicant]
WO WO2017080646A1 · 2017 [cited by applicant]
WO WO2017205663A1 · 2017 [cited by applicant]
WO WO2018083010A1 · 2018 [cited by applicant]
WO WO2018185755A1 · 2018 [cited by applicant]
WO WO2021113301A1 · 2021 [cited by applicant]
Cui et al. (Journal of Visualized Experiments 2014;88:e51294:5 pages) (Year: 2014). [cited by examiner]
Pongphantarak, S. ([Online] retrieved on Sep. 3, 2024 from: (https://www.samitivejhospitals.com/article/detail/natural-orifice-transluminal-endoscopic-surgery-notes; Aug. 26, 2016; 4 pages). (Year: 2016). [cited by examiner]
Nomura et al. (Gynecology and Minimally Invasive Therapy 2013;2:85-88). (Year: 2013). [cited by examiner]
Badylak et al. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng 13 (2011): 27-53. [cited by applicant]
Bartolovic et al. The differentiation and engraftment potential of mouse hematopoietic stem cells is maintained after bio-electrospray. Analyst 135:157-164 (2010). [cited by applicant]
Bone and Joint Regeneration Technology. National Institute of Advanced Industrial Science and Technology Today. Available at https://www.aist.go.jp/Portals/0/resource_images/aist_e/research_results/publications/pamphlet… [cited by applicant]
Brinkman et al. Photo-cross-linking of type I collagen gels in the presence of smooth muscle cells: mechanical properties, cell viability, and function. Biomacromulecules 4:890-895 (2003). [cited by applicant]
Chiu et al. Functionalization of poly(L-lactide) nanofibrous scaffolds with bioactive collagen molecules. J Biomed Mater Res 83(4):1117-1127 (2007). [cited by applicant]
Cui et al. Accelerated myotube formation using bioprinting technology for biosensor applications. Biotechnol Lett 35(3):315-321 (2013). [cited by applicant]
Cui et al. Direct Human Cartilage Repair Using Three-Dimensional Bioprinting Technology. Tissue Engineering Part A 18(11-12):1304-1312 (2012). [cited by applicant]
Cui et al. Synergistic Action of Fibroblast Growth Factor-2 and Transforming Growth Factor-beta1 Enhances Bioprinted Human Neocartilage Formation. Biotechnol Bioeng 109(9):2357-2368 (2012). [cited by applicant]
Cui et al. Thermal Inkjet Printing in Tissue Engineering and regenerative Medicine. Recent Pat Drug Deliv Formul 6(2):149-155 (2012). [cited by applicant]
Gruene et al. Laser printing of stem cells for biofabrication of scaffold-free autologous grafts. Tissue Engineering: Part C Methods 17(1):79-89 (2011). [cited by applicant]
Gupta et al. In Situ Photo-Cross-Linking of Cinnamate Functionalized Poly(methyl methacrylate-co-2-hydroxyethyl acrylate) Fibers during Electrospinning. Macromolecules 37(24):9211-9218 (2004). [cited by applicant]
Haslauer et al. Collagen-PCL Sheath-Core Bicomponent Electrospun Scaffolds Increase Osteogenic Differentiation and Calcium Accretion of Human Adipose-Derived Stem Cells. J Biomater Sci Polym Ed 22(13):1695-1712 (2011). [cited by applicant]
Li et al. Carbodiimide crosslinked collagen from porcine dermal matrix for high-strength tissue engineering scaffold. Int J Biol Macromol 61:69-74 (2013). [cited by applicant]
Li et al. Electrospun polyacrylonitrile nanofiber yarn prepared by funnel-shape collector Materials Letters 79:245-247 (2012). [cited by applicant]
Matsusaki et al. Three-dimensional human tissue chips fabricated by rapid and automatic inkjet cell printing. Adv Healthcare Mater 2(4):534-539 (2013). [cited by applicant]
O'Connell et al. Development of the Biopen: a handheld device for surgical printing of adipose stem cells at a chondral wound site. Biofabrication 8(1):015019 (2016). [cited by applicant]
Pak et al., Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells. BioMed Research International 2014:436029 (2014). [cited by applicant]
PCT/US2014/011525 International Search Report and Written Opinion dated May 13, 2014. [cited by applicant]
PCT/US2017/034539 International Search Report and Written Opinion dated Sep. 8, 2017. [cited by applicant]
PCT/US2020/062805 International Search Report and Written Opinion dated Mar. 9, 2021. [cited by applicant]
Pescosolido et al. Hyaluronic acid and dextran-based semi-IPN hydrogels as biomaterials for bioprinting. Biomacromolecules 12(5):1831-1838 (2011). [cited by applicant]
Rye. Microneedle Arrays for Injection Seeding of Tissue Engineered Scaffolds. Thesis (81 pgs) (2014). [cited by applicant]
Sahoo et al. Bio-electrospraying: A potentially safe technique for delivering progenitor cells. Biotechnol Bioeng 106(4):690-698 (2010). [cited by applicant]
Schuurman et al. Bioprinting of hybrid tissue constructs with tailorable mechanical properties. Biofabrication 3(2):021001 (7 pgs.) (2011). [cited by applicant]
Shafiq et al. Decellularized human cornea for reconstructing the corneal epithelium and anterior stroma. Tissue Eng Part C Methods 18(5):340-348 (2012). [cited by applicant]
Shields et al. Mechanical Properties and Cellular Proliferation of Electrospun Collagen Type II. Tissue Engineering 10(9/10):1510-1517 (2004). [cited by applicant]
Song et al., Engineered 3D tissue models for cell-laden microfluidic channels. Analytical and Bioanalytical Chemistry 395:185-193 (2009). [cited by applicant]
Song et al. Sodium alginate hydrogel-based bioprinting using a novel multinozzle bioprinting system. Artif Org 35(11):1132-1136 (2011). [cited by applicant]
Srouji et al. 3-D Nanofibrous electrospun multilayered construct is an alternative ECM mimicking scaffold. J Mater Sci Mater Med 19(3):1249-1255 (2008). [cited by applicant]
Stankus et al. Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials. 28:2738-2746 (2007). [cited by applicant]
Tsuda. Hone Kyushu Yokuseiyaku Koho to shite no Hakotsu Saibo Keisei Yokusei Inshi OCIF/OPG, Ko-RANKL Kotai, Oyobi sono Hoka no RANKL/RANK System Modulator J. Jpn Orthop Assoc. 78(8):1-P3-5 (2005) (w/English translation… [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Mar. 16, 2021. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Mar. 22, 2019. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Mar. 30, 2020. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated May 24, 2018. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Nov. 2, 2017. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Oct. 14, 2020. [cited by applicant]
U.S. Appl. No. 14/759,398 Office Action dated Sep. 24, 2019. [cited by applicant]
Xu et al. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication 5(1):015001 (10 pgs) (2012). [cited by applicant]
Yamaguchi et al. Cell patterning through inkjet printing of one cell per droplet. Biofabrication 4(4):045005 (8 pgs) (2012). [cited by applicant]
Yan et al. Laser-assisted printing of alginate long tubes and annular constructs. Biofabrication 5(1):015002 (8 pgs) (2013). [cited by applicant]
Yu et al., Decellularized scaffolds in regenerative medicine. Oncotarget 7(36):58671-58683 (2016). [cited by applicant]
Zhang et al. Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts. Biomacromolecules 6:2583-2589 (2005). [cited by applicant]
Zhao et al. Biodegradable fibrous scaffolds composed of gelatin coated poly(epsilon-caprolactone) prepared by coaxial electrospinning. J Biomed Mater Res A 83(2):372-382 (2007). [cited by applicant]