Base material for tissue reconstruction, implantable material, and methods of preparing the same

• US 20030124168A1
• Filed: 12/30/2002
• Published: 07/03/2003
• Est. Priority Date: 07/03/2000
• Status: Abandoned Application

• Current Assignee: Nobuhiko Yui, Japan Tissue Engineering Co., Ltd. (Teijin Limited)
• Original Assignee: Japan Tissue Engineering Co., Ltd. (Teijin Limited)
• Inventors: Kato, Masakazu, Yui, Nobuhiko, Ooya, Tooru, Yamamoto, Takeyuki
• Application Number:
  US10/330,106
• Publication Number:
  US 20030124168A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 27/14 Macromolecular materials
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C08L 101/00 Compositions of unspecified macromolecular compounds
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 2533/70 Polysaccharides
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage

Abstract

Base materials for tissue regeneration which enable the tissue regeneration, have mechanical properties needed in the tissue regeneration and can disappear via degradation in vivo after the completion of the tissue regeneration; and implantable materials with the use of the same. The above-described base materials for tissue regeneration comprise polyrotaxane, wherein biocompatible groups having bulky substituents have been introduced via hydrolyzable bond into both ends of a linear molecule penetrating plural cyclic molecules, or a polyrotaxane hydrogel having a network structure formed by crosslinking the cyclic molecules to each other, the biocompatible groups to each other, or the cyclic molecules to the biocompatible groups in each polyrotaxane molecule.

Claims

1. A base material for tissue reconstruction that is mainly composed of either one of a polyrotaxane and a polyrotaxane hydrogel, where the polyrotaxane has biocompatible groups, each of which has a bulky substituent and is introduced via a hydrolytic bond to either terminal of a linear molecule with multiple cyclic molecules threaded thereon, and the polyrotaxane hydrogel has a network structure formed by crosslinking between the cyclic molecules, between the biocompatible groups, or between the cyclic molecule and the biocompatible group in adjoining molecules of the polyrotaxane.

2. A base material for tissue reconstruction in accordance with claim 1, wherein the linear molecule is any of polyethylene glycol, polypropylene glycol, copolymers of polyethylene glycol and polypropylene glycol, and polymethyl vinyl ether, and the cyclic molecule is any of α

-, β

-, and γ

-cyclodextrins.

3. A base material for tissue reconstruction in accordance with claim 1, wherein the hydrolytic bond is an ester bond.

4. A base material for tissue reconstruction in accordance with claim 3, wherein the crosslinking is any of a urethane bond, an amide bond, a carbamide bond, an ether bond, a sulfide bond, and a Schiff base linkage.

5. A base material for tissue reconstruction in accordance with claim 1, wherein the bulky substituent is either one of a group having at least one benzene ring and a group having at least one tertiary butyl.

6. A base material for tissue reconstruction in accordance with claim 1, wherein the biocompatible group is any of amino acids, oligopeptides, oligosaccharides, sugar derivatives.

7. A base material for tissue reconstruction in accordance with claim 1, wherein the linear molecule is polyethylene glycol, the cyclic molecule is α

-cyclodextrin, the hydrolytic bond is an ester bond, the biocompatible group having the bulky substituent is benzyloxycarbonyl-L-phenylalanine.

8. A base material for tissue reconstruction in accordance with claim 1, wherein the polyrotaxane or the polyrotaxane hydrogel is a porous structure.

9. A base material for tissue reconstruction in accordance with claim 1, wherein the polyrotaxane content in the polyrotaxane hydrogel has a specific weight percent determined to attain a decomposition rate suitable for an application.

10. A base material for tissue reconstruction in accordance with claim 1, wherein the polyrotaxane hydrogel has the crosslinking between the cyclic molecules, between the biocompatible molecules, or between the cyclic molecule and the biocompatible molecule via a crosslinking linear molecule, which has a preset average molecular weight determined to attain a decomposition rate or a decomposition pattern suitable for an application.

14. A base material for tissue reconstruction in accordance with claim 1, said base material for tissue reconstruction being applied for culture of any of mesenchymal cells, hepatic cells, and neurons.

15. An implantable material, comprising cells cultured on or incorporated in a base material for tissue reconstruction in accordance with claim 1.

16. A method of preparing an implantable material, said method providing an implantable material by making cells cultured on or incorporated in a base material for tissue reconstruction in accordance with claim 1.

11. A base material for tissue reconstruction that is mainly composed of a polyrotaxane hydrogel and has characteristics (a) below, the polyrotaxane hydrogel having a network structure formed by crosslinking of cyclic molecules in adjoining molecules of a polyrotaxane via a crosslinking linear molecule, where the polyrotaxane has biocompatible groups, each of which has a bulky substituent and is introduced via a hydrolytic bond to either terminal of a linear molecule with multiple cyclic molecules threaded thereon:

(a) wherein a time for complete hydrolysis of the polyrotaxane hydrogel does not depend upon a water content in the polyrotaxane hydrogel, but is extended with any of a decrease in polyrotaxane content in the polyrotaxane hydrogel, an increase in molar ratio of the crosslinking linear molecule to the cyclic molecule, and a decrease in average molecular weight of the crosslinking linear molecule.

13. A base material for tissue reconstruction in accordance with claim 11, wherein the cyclic molecule is α

-cyclodextrin, the linear molecule is polyethylene glycol, the hydrolytic bond is an ester bond, the crosslinking linear molecule is polyethylene glycol bis-amine, and the polyrotaxane hydrogel has a network structure formed by crosslinking OH groups of the α

-cyclodextrins included in adjoining molecules of the polyrotaxane via urethane bonds of NH₂ groups on both terminals of the polyethylene glycol bis-amine.

12. A base material for tissue reconstruction that is mainly composed of a polyrotaxane hydrogel and has characteristics (b) below, the polyrotaxane hydrogel having a network structure formed by crosslinking of cyclic molecules in adjoining molecules of a polyrotaxane via a crosslinking linear molecule, where the polyrotaxane has biocompatible groups, each of which has a bulky substituent and is introduced via a hydrolytic bond to either terminal of a linear molecule with multiple cyclic molecules threaded thereon:

(b) wherein a decomposition pattern shown by a graph with t/t_∞

as abscissa and M_t/M₀ as ordinate does not depend upon a content of the polyrotaxane in the polyrotaxane hydrogel but depends upon a molecular weight of the crosslinking linear molecule, where t_∞

denotes a time for complete hydrolysis of the polyrotaxane hydrogel, t denotes a time elapsed since soaking of the polyrotaxane hydrogel in water, M₀ denotes an initial weight of the polyrotaxane hydrogel in a water-swelling state, and M_t denotes a weight of the polyrotaxane hydrogel at the time t.