IP Library Granted Patent US 12,263,270
Granted Patent B2
US 12,263,270 · App. 17/434,925 · Granted Apr 1, 2025

Acoustic extracellular matrix hydrogels and their use

Inventors: Stephen Francis Badylak (West Lafayette, IN); George S. Hussey (Cranberry Township, PA)
Assignee: University of Pittsburgh—Of the Commonwealth System of Higher Education
A61L26/0057A61L26/008A61L27/3633A61L27/52A61L2400/04
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 12,263,270
App. No.
17/434,925
Granted
Apr 1, 2025
Kind
B2
Abstract

Methods are disclosed herein for producing a mammalian acoustic extracellular matrix (ECM) hydrogel. In further embodiments, mammalian acoustic ECM hydrogels are disclosed that are produced using the disclosed methods. Also disclosed is a mammalian acoustic ECM hydrogel, wherein the hydrogel is thermoreversible. Methods of using these acoustic ECM hydrogels are also disclosed.

Claims (27)

1. A method of producing an extracellular matrix (ECM) hydrogel, comprising:

solubilizing mammalian ECM in a liquid using ultrasound frequency to produce an acoustic ECM hydrogel in a liquid phase, wherein the mammalian ECM is present at a concentration of about 25 mg/ml to about 600 mg/ml.

2. The method of claim 1 , wherein the ultrasound frequency is applied to the ECM in the liquid at a temperature between 30° C. to 43° C.

3. The method of claim 1 , wherein the ultrasound frequency is about 20 kHz to about 100 kHz.

4. The method of claim 3 , wherein the ultrasound frequency is applied to the ECM in the liquid for at least 30 seconds.

5. A method of producing an extracellular matrix (ECM) hydrogel, comprising:

solubilizing mammalian ECM in a liquid at a concentration of about 25 mg/ml to about 600 mg/ml with ultrasound at a frequency of about 20 kHz to about 100 kHz at for at least about 60 seconds at a temperature of greater than about 37° C. to produce an acoustic ECM hydrogel in a liquid phase.

6. The method of claim 5 , wherein the ultrasound frequency is applied to the mammalian ECM in the liquid for about 1 minute to about 5 minutes.

7. The method of claim 1 , wherein the mammalian ECM is lyophilized mammalian ECM.

8. The method of claim 1 , wherein the mammalian ECM is provided as pieces in the range of about 10 μm to about 2000 μm.

9. The method of claim 5 , further comprising cooling the acoustic ECM hydrogel in the liquid phase to a temperature of about 37° C. or less, thereby producing the acoustic ECM hydrogel in a gel phase.

10. The method of claim 5 , wherein the ultrasound is at a frequency of about 20 kHz.

11. The method of claim 1 , wherein the ultrasound has an amplitude of about 20 μm to about 320 μm.

12. The method of claim 1 , wherein the mammalian ECM is present at a concentration of about 25 mg/ml to about 150 mg/ml.

13. The method of claim 1 , wherein the liquid is phosphate buffered saline.

14. The method of claim 1 , wherein the ECM is a urinary bladder ECM, a small intestinal submucosal ECM, an esophageal ECM, a trachea ECM, a liver ECM or a dermal ECM.

15. The method of claim 14 , wherein the ECM is porcine ECM or bovine ECM.

16. The method of claim 1 , wherein the acoustic ECM hydrogel is gamma irradiated.

17. A method of producing an extracellular matrix (ECM) hydrogel comprising:

solubilizing mammalian ECM in a liquid using ultrasound frequency to produce an acoustic ECM hydrogel, wherein the ultrasound frequency is about 20 kHz to about 100 kHz.

18. The method of claim 17 , wherein the mammalian ECM is present at a concentration of about 25 mg/ml to about 150 mg/ml and is provided as pieces in the range of about 10 μm to about 2000 μm.

19. The method of claim 18 , wherein the ultrasound frequency is applied to the ECM in the liquid at a temperature of 30° C. to 43° C.

20. The method of claim 19 , wherein the ultrasound has an amplitude of about 20 μm to about 320 μm.

21. The method of claim 20 , wherein the ultrasound frequency is applied to the ECM in the liquid for about 30 seconds to about 5 minutes.

22. The method of claim 17 , wherein the ECM hydrogel undergoes a gel to sol transition at about 37° C.

23. The method of claim 17 , wherein the mammalian ECM is urinary bladder ECM, small intestinal submucosal ECM, esophageal ECM, tracheal ECM, liver ECM, or dermal ECM.

24. The method of claim 17 , wherein the ECM is porcine ECM or bovine ECM.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2021
From: BADYLAK, STEPHEN FRANCIS; HUSSEY, GEORGE S.
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 057344/0377 →
Continuity (3)
Provisional Application 62950565 · Dec 19, 2019
Provisional Application 62817787 · Mar 13, 2019
Related Publication 20220143265A1 · May 12, 2022
References Cited (108)
US 4902508A · Badylak et al. · 1990 [cited by applicant]
US 4956178A · Badylak et al. · 1990 [cited by applicant]
US 5281422A · Badylak et al. · 1994 [cited by applicant]
US 5352463A · Badylak et al. · 1994 [cited by applicant]
US 5372821A · Badylak et al. · 1994 [cited by applicant]
US 5554389A · Badylak et al. · 1996 [cited by applicant]
US 5573784A · Badylak et al. · 1996 [cited by applicant]
US 5645860A · Knapp, Jr. et al. · 1997 [cited by applicant]
US 5753267A · Badylak et al. · 1998 [cited by applicant]
US 5762966A · Knapp, Jr. et al. · 1998 [cited by applicant]
US 5771969A · Garay · 1998 [cited by applicant]
US 5866414A · Badylak et al. · 1999 [cited by applicant]
US 6099567A · Badylak et al. · 2000 [cited by applicant]
US 6485723B1 · Badylak et al. · 2002 [cited by applicant]
US 6576265B1 · Spievack · 2003 [cited by applicant]
US 6579538B1 · Spievack · 2003 [cited by applicant]
US 6696270B2 · Badylak et al. · 2004 [cited by applicant]
US 6783776B2 · Spievack · 2004 [cited by applicant]
US 6793939B2 · Badylak · 2004 [cited by applicant]
US 6849273B2 · Spievack · 2005 [cited by applicant]
US 6852339B2 · Spievack · 2005 [cited by applicant]
US 6861074B2 · Spievack · 2005 [cited by applicant]
US 6887495B2 · Spievack · 2005 [cited by applicant]
US 6890562B2 · Spievack · 2005 [cited by applicant]
US 6890563B2 · Spievack · 2005 [cited by applicant]
US 6890564B2 · Spievack · 2005 [cited by applicant]
US 6893666B2 · Spievack · 2005 [cited by applicant]
US 8361503B2 · Badylak et al. · 2013 [cited by applicant]
US 8394419B2 · Borden · 2013 [cited by applicant]
US 8691276B2 · Badylak et al. · 2014 [cited by applicant]
US 9226996B2 · Moro et al. · 2016 [cited by applicant]
US 9364580B2 · Moro et al. · 2016 [cited by applicant]
US 9861662B2 · Badylak et al. · 2018 [cited by applicant]
US 10004827B2 · Badylak et al. · 2018 [cited by applicant]
US 10213526B2 · Badylak et al. · 2019 [cited by applicant]
US 10729813B2 · Badylak et al. · 2020 [cited by applicant]
US 10736991B2 · Badylak et al. · 2020 [cited by applicant]
US 11213545B2 · Badylak et al. · 2022 [cited by applicant]
US 11291688B2 · Badylak et al. · 2022 [cited by applicant]
US 11389566B2 · Ramer et al. · 2022 [cited by applicant]
US 11389569B2 · Badylak et al. · 2022 [cited by applicant]
US 11406736B2 · Badylak et al. · 2022 [cited by applicant]
US 20060070631A1 · Scopton et al. · 2006 [cited by applicant]
US 20070190165A1 · Brey et al. · 2007 [cited by applicant]
US 20080260831A1 · Badylak et al. · 2008 [cited by applicant]
US 20120020932A1 · Yao et al. · 2012 [cited by applicant]
US 20130060008A1 · Wang et al. · 2013 [cited by applicant]
US 20140105856A1 · Schendel · 2014 [cited by applicant]
US 20150165091A1 · Dalecki et al. · 2015 [cited by applicant]
US 20160166735A1 · Chang et al. · 2016 [cited by applicant]
US 20170173217A1 · Badylak et al. · 2017 [cited by applicant]
US 20180200405A1 · Badylak et al. · 2018 [cited by applicant]
US 20190314552A1 · Wadsworth et al. · 2019 [cited by applicant]
CN 106456837A · 2017 [cited by applicant]
CN 108295311A · 2018 [cited by applicant]
EP 0061549A1 · 1985 [cited by applicant]
JP S48006021A · 1973 [cited by applicant]
JP S57159485A · 1982 [cited by applicant]
JP 2009528090A · 2009 [cited by applicant]
WO WO2015143310A1 · 2015 [cited by applicant]
WO WO2015164728 · 2015 [cited by applicant]
WO WO2018035491A1 · 2018 [cited by applicant]
WO WO2019246442 · 2019 [cited by applicant]
WO WO2019246444 · 2019 [cited by applicant]
WO WO2019246447 · 2019 [cited by applicant]
Becton Dickinson, BD Biosciences, BD Extracelular Matrix Proteins, BD ECM Product Reference Guide, https://www.bd.com/resource.aspx?idx=17649, 2011. [cited by examiner]
Hussey et al, “Ultrasonic cavitation to prepare ECM hydrogels,” [cited by applicant]
Zoulim, “Inhibition of hepatitis B virus gene expression: A step towards functional cure,” [cited by applicant]
Ventura et al., “In-vitro and in-vivo evaluation of hemostatic potential of decellularized ECM hydrogels,” [cited by applicant]
Garvin and VanderBurgh, “Controlling collagen fiber microstructure in three-dimensional hydrogels using ultrasound,” [cited by applicant]
Hussey et al, “Ultrasonic cavitation to prepare ECM hydrogels,” [cited by applicant]
Li et al., “Ultrasonic irradiation in the enzymatic extraction of collagen,” [cited by applicant]
Luan, “Separation and Characterization of Protein Components in Bovine Tendon Acellular Matrix Materials,” [cited by applicant]
Shen et al., “Preparation and characterization of a gene-activated matrix mimicking extracellular matrix,” [cited by applicant]
Freytes et al., “Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix,” [cited by applicant]
International Search Report and Written Opinion from parent PCT Application No. PCT/US2020/022433 13 pages (mailed May 29, 2020). [cited by applicant]
Kornmuller et al., “Fabrication of extracellular matrix-derived foams and microcarriers as tissue-specific cell culture and delivery platforms,” [cited by applicant]
Uriel et al., “Extraction and assembly of tissue-derived gels for cell culture and tissue engineering,” [cited by applicant]
Ventura et al., “In-vitro and in-vivo evaluation of hemostatic potential of decellularized ECM hydrogels,” [cited by applicant]
Wang et al., “Sonication-induced gelation of silk fibroin for cell encapsulation,” [cited by applicant]
Adams et al., “Equine bone marrow-derived mesenchymal stromal cells (BMDMSCs) from the ilium and sternum: Are there differences?” [cited by applicant]
Badylak et al., “Resorbable bioscaffold for esophageal repair in a dog model,” [cited by applicant]
Badylak et al., “Esophageal reconstruction with ECM and muscle tissue in a dog model,” [cited by applicant]
Badylak et al., “Small intestinal submucosa as a large diameter vascular graft in the dog,” [cited by applicant]
Brown et al., “Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials,” [cited by applicant]
Dziki et al., “Solubilized Extracellular Matrix Bioscaffolds Derived from Diverse Source Tissues Differentially Influence Macrophage Phenotype,” [cited by applicant]
El-Fiqi et al. “Collagen hydrogels incorporated with surface-aminated mesoporous nanobioactive glass: improvement of physicochemical stability and mechanical properties is effective for hard tissue engineering,” [cited by applicant]
Frenguelli et al, “Hepatic differentiation of human induced pluripotent stem cells (iPSC) using 3D human liver extracellular matrix hydrogel,” [cited by applicant]
Huleihel et al., “Macrophage phenotype in response to ECM bioscaffolds,” [cited by applicant]
Hussey et al., “Extracellular matrix-based materials for regenerative medicine,” [cited by applicant]
Kakushima et al., “Endoscopic submucosal dissection for gastrointestinal neoplasms,” [cited by applicant]
Keane et al., “Tissue-specific effects of esophageal extracellular matrix,” [cited by applicant]
Kim et al., “Application of ultrasonic treatment to extraction of collagen from the skins of sea bass Lateolabrax japonicus,” [cited by applicant]
Lange et al., “Pilot study of a novel vacuum-assisted method for decellularization of tracheae for clinical tissue engineering applications,” [cited by applicant]
Loneker et al., “Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in-vitro,” [cited by applicant]
Mase et al., “Clinical application of an acellular biologic scaffold for surgical repair of a large, traumatic quadriceps femoris muscle defect,” [cited by applicant]
Medberry et al., “Hydrogels derived from central nervous system extracellular matrix,” [cited by applicant]
Reing et al., “The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds,” [cited by applicant]
Saldin et al., “Extracellular matrix hydrogels from decellularized tissucs: Structure and function,” [cited by applicant]
Sicari et al., “The promotion of a constructive macrophage phenotype by solubilized extracellular matrix,” [cited by applicant]
Spang et al., “Extracellular matrix hydrogel therapies: In vivo applications and development,” [cited by applicant]
Thornton ct al., “Healing in the gastrointestinal tract,” [cited by applicant]
Tosh et al., “Determination of the maximum gelation temperature in gelatin gels,” [cited by applicant]
Uraoka et al., “Submucosal injection solution for gastrointestinal tract endoscopic mucosal resection and endoscopic submucosal dissection,” [cited by applicant]
Uriel et al., “The role of adipose protein derived hydrogels in adipogenesis,” [cited by applicant]
Voytik-Harbin et al., “Small intestinal submucosa: A tissue-derived extracellular matrix that promotes tissue-specific growth and differentiation of cells in vitro,” [cited by applicant]
Wolf., “Polypropylene surgical mesh coated with extracellular matrix mitigates the host foreign body response,” [cited by applicant]
Wu et al., “Experimental Study on Lung Extracellular Matrix Hydrogel for Treating Radiation-Induced Lung Injury in Rats,” [cited by applicant]