# US 10,245,353 B2 · Hydrophilic electrospinning biological composite stent material used for tissue regeneration and preparation method and application thereof

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- Number: US 10,245,353 B2
- Document ID: US10245353B2
- Status: Granted
- Kind: B2
- Application number: 15/037,507
- Filed: 2013-11-19
- Published: 2016-09-29
- Granted: 2019-04-02
- Earliest claimed: 2013-11-19
- Assignees: Shanghai P & P Biotech Co., Ltd
- Applicants: Shanghai P & P Biotech Co., Ltd
- Inventors: Hongbing He; Ling Su; Zhang Liu; Li Yang
- Web page: https://patentgrep.com/patent/US10245353B2

## CPC

- A61L 31/046: {Fibrin; Fibrinogen}
- A61L 31/041: {Mixtures of macromolecular compounds}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- D01D 5/0007: {Electro-spinning (non-woven fabrics produced by electro-spinning D04H1/728)}
- D01F 1/10: Other agents for modifying properties
- D01F 6/625: {derived from hydroxy-carboxylic acids, e.g. lactones}
- D01F 6/84: from copolyesters
- A61L 2300/404: Biocides, antimicrobial agents, antiseptic agents
- A61L 2430/06: for cartilage reconstruction, e.g. meniscus
- A61L 2430/10: for reconstruction of tendons or ligaments
- A61L 2430/22: for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
- D10B 2401/022: hydrophylic
- D10B 2509/06: Vascular grafts; stents
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D01F: CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D10B: INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES

## Abstract

A hydrophilic electrospinning biological composite scaffold material used for tissue regeneration and a preparation method and an application thereof are provided. Fibrinogen, L-arginine or an aqueous solution of hydrochloride thereof and a P(LLA-CL) solution are blended and an electrospinning technology is used to prepare the biological composite scaffold material. The biological composite scaffold material has an equilibrium contact angle that is less than 55°, is hydrophilic and has a good application prospect in repairing body tissue defects.

## Claims

### Claim 1

A hydrophilic electrospinning biological composite scaffold material, wherein it is prepared by blending an aqueous solution of fibrinogen and L-arginine or hydrochloride thereof with a P(LLA-CL) solution using an electrospinning technique, wherein the hydrophilic electrospinning biological composite scaffold material has an equilibrium contact angle, and the equilibrium contact angle thereof is less than 55°.

### Claim 2 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the fibrinogen is derived from fibrinogen of mammals.

### Claim 3 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein in the aqueous solution of fibrinogen and L-arginine or hydrochloride thereof, the mass ratio of fibrinogen to L-arginine or hydrochloride thereof is 1.2:1-12.5:1.

### Claim 4 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the mass ratio of polylactic acid to polycaprolactone in the P(LLA-CL) is 20:80-95:5.

### Claim 5 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the aqueous solution of fibrinogen and L-arginine or hydrochloride thereof comprises solvents selected from the group consisting of pure water, water for injection, salt solutions, buffers and cell culture media.

### Claim 6 (depends on 5)

The hydrophilic electrospinning biological composite scaffold material according to claim 5, wherein the salt solutions are selected from sodium chloride solution and potassium chloride solution; the buffers are selected from phosphate buffer, Tris-HCl buffer, glycine buffer and D-Hank's solution; and the cell culture media are selected from DMEM medium, 1640 medium and MEM medium.

### Claim 7 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the aqueous solution of fibrinogen and L-arginine or hydrochloride thereof comprises one or more solvents selected from the group consisting of hexafluoroisopropanol, trichloromethane, dimethylformamide, tetrahydrofuran, chloroform and acetone.

### Claim 8 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein after the aqueous solution of fibrinogen and L-arginine or hydrochloride thereof is blended with the P(LLA-CL) solution, the mass ratio of fibrinogen to P(LLA-CL) is 0.2:1-2.1:1.

### Claim 9 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein after contacting with an aqueous solution, the total volume shrinkage ratio is not more than 20% and the porosity is not less than 30%.

### Claim 10 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the aqueous solution of Fibrinogen and L-arginine or hydrochloride thereof is further loaded with antibacterial substances which are one or more substances selected from penicillins, cephalosporins, carbapenms, aminoglycosides, tetracyclines, macrolides, glycosides, sulfonamides, quinolones, nitroimidazoles, lincosamides, phosphonomycin, chloromycetin, polymyxin B and bacitracin.

### Claim 11 (depends on 10)

The hydrophilic electrospinning biological composite scaffold material according to claim 10, wherein the penicillins are selected from penicillin, ampicillin and carbenicillin; the cephalosporins are selected from cephalexin, cefuroxime sodium, ceftriaxone and cefpirome; the carbapenms are thiomycin; the aminoglycosides are selected from gentamicin, streptomycin and kanamycin; the tetracyclines are selected from tetracycline and chlortetracycline; the macrolides are selected from erythromycin and azithromycin; the glycosides are vancomycin; the sulfonamides are selected from sulfadiazine and trimethoprim; the quinolones are selected from pipemidic acid and ciprofloxacin; the nitroimidazoles are selected from metronidazole and tinidazole; and the lincosamides are selected from lincomycin and clindamycin.

### Claim 12 (depends on 10)

The hydrophilic electrospinning biological composite scaffold material according to claim 10, wherein the antibacterial substances is released not less than 30% of total load amount within 15 minutes after the implantation of the scaffold material.

### Claim 13 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the biological composite scaffold material is membranous and has a thickness of 10-1500 μm.

### Claim 14 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the biological composite scaffold material is tubular, and the tube wall thereof has a thickness of 1-1500 m and the internal diameter thereof is 2-200 mm.

### Claim 15 (depends on 1)

The hydrophilic electrospinning biological composite scaffold material according to claim 1, wherein the biological composite scaffold material is columnar, and the diameter thereof is 2-20 mm.

### Claim 16 (depends on 1)

A method of preparing the hydrophilic electrospinning biological composite scaffold material according to claim 1, comprising:
blending an aqueous solution of fibrinogen and L-arginine or hydrochloride with a P(LLA-CL) solution and subjecting the obtained solution to electrospinning by using an electrospinning technique, to prepare the biological composite scaffold material.

### Claim 17 (depends on 16)

The method according to claim 16, wherein in the electrospinning technique, the parameters for an electrospinning machine are set as follows: electrospinning distance of 10-30 cm; electrospinning voltage of 15-70 kV; and solution flow rate of 2-400 ml/h.

### Claim 18 (depends on 16)

The method according to claim 16, wherein the method further comprises performing the sterilization of the prepared biological composite scaffold material by using 15-35 KGy ionizing radiation.

### Claim 19 (depends on 1)

Application of the hydrophilic electrospinning biological composite scaffold material according to claim 1, for using as the material for the repair of body tissue defects or using for the preparation of the material for repairing body tissue defects, the application comprising implanting the repair material in the body of a subject in need thereof.

### Claim 20 (depends on 19)

The application according to claim 19, wherein the biological composite scaffold material is membranous and used in the preparation of repair materials for the treatment of meninges defects, abdominal defects, pelvic organ prolapse, atrium defects, ventricular septum defects, pericardium defects, tendon or ligament rupture, or parenchymatous organ rupture.

### Claim 21 (depends on 19)

The application according to claim 19, wherein the biological composite scaffold material is tubular and used to prepare repair materials for repairing tubular organ defects, and the tubular organ comprises one or more selected from nerve conduit, esophagus, trachea, stomach, intestinal tract, biliary tract, ureter, bladder, vagina, artery and vein.

### Claim 22 (depends on 19)

The application according to claim 19, wherein the biological composite scaffold material is columnar and used to prepare repair materials for repairing the rupture or defect of ligament, achilles tendon or cartilage.

### Claim 23 (depends on 2)

The hydrophilic electrospinning biological composite scaffold material according to claim 2, wherein the mammals are humans, pigs, cattle, sheep or horses.

### Claim 24 (depends on 13)

The hydrophilic electrospinning biological composite scaffold material according to claim 13, wherein the biological composite scaffold material has a thickness of 50-500 μm.

### Claim 25 (depends on 14)

The hydrophilic electrospinning biological composite scaffold material according to claim 14, wherein the tube wall has a thickness of 50-500 μm.