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US007575759B2

(12) United States Patent

Murphy et al.

(io) Patent No.: (45) Date of Patent:

US 7,575,759 B2 Aug. 18, 2009

(54) TISSUE ENGINEERING SCAFFOLDS

(75) Inventors: William L. Murphy, Chicago, IL (US);

Robert G. Dennis, Ann Arbor, MI (US);
David J. Mooney, Dexter, MI (US)

(73) Assignee: The Regents of the University of
Michigan, Ann Arbor, MI (US)

( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 620 days.

(21) Appl.No.: 10/330,578

(22) Filed: Dec. 27, 2002

(65) Prior Publication Data

US 2004/0026811 Al Feb. 12, 2004

Related U.S. Application Data

(60) Provisional application No. 60/345,775, filed on Jan. 2, 2002.

(51) Int. CI.

A61F 2/00 (2006.01)

(52) U.S. CI 424/423

(58) Field of Classification Search None

See application file for complete search history.

(56) References Cited

U.S. PATENT DOCUMENTS

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4,902,511 A * 2/1990 Kronman 424/423

5,514,378 A * 5/1996 Mikosetal 424/425

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6,103,255 A * 8/2000 Leveneetal 424/426

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6,333,029 Bl 12/2001 Vyakarnam et al 424/93.1

6,337,198 Bl* 1/2002 Leveneetal 435/174

6,436,426 Bl * 8/2002 Liao et al 424/426

7,309,232 B2* 12/2007 Rutherford et al 433/226

2002/0005600 Al * 1/2002 Ma 264/49

OTHER PUBLICATIONS

"Humidity". Dictionary.com. Accessed online on Feb. 16, 2007. <http://dictionary.reference.com/browse/humidity>.* Murphy et al. Salt Fusion: An approach to improve pore interconnectivity within tissue engineering scaffolds. Feb. 2002. Tissue Engineering, vol. 8, No. 1. pp. 43-52.*

Aldini, N.N., et al., "Effectiveness of a bioabsorbable conduit in the repair of peripheral nerves," Biomaterials 17:959-962 (1996). Carrier et al., "Cardiac tissue Engineering: Cell seeding, cultivation parameters, and tissue construct characterization," Biotech Bioeng 64:580-589 (1999).

Chaignaud, B.E., et al., "The history of tissue engineering using synthetic biodegradable polymer scaffolds and cells," In: Atala,A., Mooney, D.J., eds. Synthetic biodegradable polymer scaffolds. Boston, MA: Birkhauser, 1997, pp. 1-14.

(Continued)

Primary Examiner—M P Woodward

Assistant Examiner—Casey S Hagopian

(74) Attorney, Agent, or Firm—Medlen & Carroll, LLP

(57) ABSTRACT

The present invention relates to methods and compositions for the production of scaffolds, such scaffolds to be used for a variety of purposes, including tissue engineering. More specifically, the present invention relates to the use of fused crystals, such as fused salt crystals to form a framework. The methods for producing the scaffolds of this invention improve the porosity, interconnectivity and ease of manufacture as compared to prior art methods.

16 Claims, 15 Drawing Sheets

Page 2

OTHER PUBLICATIONS

Dennis et al., Excitability and isometric contractile properties of mammalian skeletal muscle constructs engineered in vitro, In Vitro Cell Dev Biol-Animal 36:327-335 (2000).

Evans, G.R.D., et al, "In vivo evaluation of poly (L-lactic acid) porous conduits for peripheral nerve regeneration," Biomaterials 20:1109-1115 (1999).

Evans, G.R.D., et al., "Tissue engineered conduits: the use of bioderadablepoly(D,L-latic-co-glycolic acid) scaffolds in peripheral nerve regeneration," In: Stark, G.E., Horch, R., Tanczos, E., Eds.. Biological Matrices and Tissue Reconstruction. Berlin:Springer, (1998) pp. 225-235.

Freed et al., "Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers," JBiomed Mater Res 27:11-23 (1993).

Harris, L.D., et al., "Open pore biodegradable matrices formed with gas foaming," JBiomed Mater Res 42:396-402, (1998). Hutmacher, D.W., "Scaffolds in tissue engineering bone and cartilage," Biomaterials 21:2529-2543 (2000).

Ishaug-Riley et al., "Ectopic bone formation by marrow stromal osteoblast transplantation usinpoly (DL-lactic-co-glycolic acid) foams implanted into the rat mesentery," J Biomed Mater 36:1-8 (1997).

Kaufmann, P.M., et al., "Highly porous polymer matrices as a threedimensional culture system for hepatocytes," Cell Transplant 6:463468, (1997).

Kim et al., "Engineering smooth muscle tissue with a predefined structure," /Biomed Mater Res 41:322-332 (1998). Lu et al., "The importance of new proccessing techniques in tissue engineering," MRS Bull 21:28-32 (1996).

Ma, RX. and Choi, J., "Biodegradable polymer scaffolds with welldefined interconnected spherical pore network," TissueEng 7:23-33, (2001).

Mikos,A.G., etal. "Preparation and characterization of poly (L-lactic acid) foams" Polymer 35:10680-1077 (1994). Murphy, W.L. and Mooney, D.J., "Controlled delivery of inductive proteins, plasmid DNA and cells from tissue engineering matrices," / Periodontal Res 34:413-419 (1999).

Murphy, W.L. et al, "Growth of continuous bone-like mineral within porous poly (lactide-co-glycolide) scaffolds in vitro," / Biomed Mater Res 50:50-58 (2000).

Murphy, W.L., et al., "Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds fortissue engineering,"Biomaterials 21:2521-2527 (2000). Oberpenning et al., "De novo reconstitution of a functional mammalian urinary bladder by tissue engineering," Nat Biotech 7:149-155 (1999).

Shea, L.D., et al., "DNA delivery from polymer matrices for tissue engineering," Nat Biotech 17:551-554 (1999). Sheridan, M., et al. "Bioabsordable polymer scaffolds for tissue engineering capable of sustained growth factor delivery," / Control Rel 64:91-102 (2000).

Valentini, R.F., et al., "Collagen and laminin containing gels impede peripheral nerve regeneration through semipermeable nerve guidance channels," Exp Neurol 98:350-356 (1987). Van Vlack, L.H. "Elements of materials science and engineering," 4ed. Addison-Wesley Publishing Company, Reading, MA, pp. 120 &316, (1980).

van Wachem et al., "Absence of muscle regeneration after implantation of a collagen matrix seeded with myoblasts," Biomaterials 20:419-426(1999).

* cited by examiner

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