Hyaluronan based biodegradable scaffolds for tissue repair

• US 5,939,323 A
• Filed: 05/28/1997
• Issued: 08/17/1999
• Est. Priority Date: 05/28/1996
• Status: Expired due to Term

• Current Assignee: Brown University
• Original Assignee: Brown University
• Inventors: Kim, Hyun D., Valentini, Robert F.
• Primary Examiner(s): Witz, Jean C.
• Assistant Examiner(s): HANLEY, SUSAN MARIE
• Application Number:
  US08/864,709
• Time in Patent Office: 811 Days
• Field of Search: 435/395, 623/16, 623/18, 623/66, 623/11, 623/22, 433/173, 433/201.1, 536/55.1, 424/426, 424/443, 424/489, 424/490, 424/901
• US Class Current: 435/395
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/30767 Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30064 Coating or prosthesis-covering structure made of biodegradable material
• CPC Class Codes: A61F 2002/30199 Three-dimensional shapes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/0063 Three-dimensional shapes
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C12N 2533/70 Polysaccharides
• CPC Class Codes: C12N 2533/80 Hyaluronan
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06

Abstract

A hyaluronic acid derivitized scaffold and method of forming are disclosed. The scaffolds are useful for various medical purposes such as tissue repair, tissue reconstruction and wound healing. In order to enhance these processes the scaffolds may be engineered to incorporate biologically active molecules such as BMP.

Claims

1. A method for forming a substrate having interconnected pores for cell growth, comprising:

dissolving a water-insoluble ester derivative of hyaluronic acid in a first solvent,

forming a mixture of the first solvent, the water-insoluble ester derivative of hyaluronic acid and a pore forming agent that is insoluble in the first solvent,

contacting the mixture with a second solvent, wherein the water-insoluble ester derivative of hyaluronic acid is insoluble in the second solvent but the pore forming agent is soluble in the second solvent, whereby the first solvent and the pore forming agent are extracted from the mixture to form a porous scaffold of the water-insoluble ester derivative of hyaluronic acid, and

drying the scaffold under vacuum from a wet state at a temperature between 4°

C. and 37°

C.

2. The method of claim 1, wherein the pore forming agent is sized so as to leave voids sufficient to permit cell ingrowth into the scaffold when the pore forming agent is extracted from the mixture.

3. The method of claim 2 wherein the scaffold is dried at ambient temperatures.

4. The method of claim 1, wherein the water-insoluble ester derivative of hyaluronic acid is a covalent conjugate of hyaluronic acid esterified with a benzyl moiety.

5. The method of claim 1 further comprising coating the scaffold with a bioerodable polymer.

6. The methods of claim 1 further adding a compound selected from the group consisting of drugs, growth factors, peptides, proteins, cytokines, oligonucleotides, antisense oligonucleotides, DNA and polymers.

7. The method of claim 6, wherein the compound is added by coating the porous scaffold with the compounds.

8. The method of claim 6, wherein the compound is added by covalent attachment to the porous scaffold.