Elastic biopolymer and use as a tissue adhesive

Patent metadata

Field	Value
Publication number	US-12090246-B2
Application number	US-202017064390-A
Country	US
Kind code	B2
Filing date	Oct 6, 2020
Priority date	Aug 8, 2014
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

The present invention provides an improved tissue adhesive to repair defects in soft tissue. Following ASTM standard tests, crosslinked methacryloyl-substituted gelatin hydrogels of the present invention (GelSEAL) were shown to exhibit adhesive properties, i.e. wound closure strength, shear resistance and burst pressure, that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in rats proved GelSEAL to effectively seal large lung leakages without additional sutures or staples, presenting improved performance as compared to fibrin and poly(ethylene glycol) glues. Furthermore, subcutaneous implantation in rats revealed high biocompatibility of GelSEAL as evidenced by low inflammatory host response. Advantageously, the tissue adhesives of the present invention are low cost and easy to produce, making them a promising substance to be used as a sealant for fluid leakages in soft tissue, as well as an easily tunable platform to further optimize the adhesive characteristics.

First claim

What is claimed is:

1. A composition comprising a crosslinked methacryloyl-substituted gelatin hydrogel and a pharmaceutically acceptable carrier, wherein the crosslinked methacryloyl-substituted gelatin hydrogel has a degree of methacryloyl substitution between 50% and 90% and a concentration between 20% and 40% (w/v) in the pharmaceutically acceptable carrier.

2. The composition of claim 1 , further comprising:
(i) a hemostatic agent selected from blood coagulation factors, prothrombin, thrombin, silicate nanoparticles, and any combination thereof, or
(ii) an antibacterial agent selected from silver nanoparticles, copper oxide nanoparticles, antibiotic drugs, nanoparticle-carried antibiotic drugs, penicillins, cephalosporins, penems, carbapenems, monobactams, aminoglycosides, sulfonamides, macrolides, tetracyclins, lincosides, quinolones, chloramphenicol, vancomycin, metronidazole, rifampin, isoniazid, spectinomycin, trimethoprim, sulfamethoxazole, chitosan, and any combination thereof.

3. The composition of claim 1 , wherein the methacryloyl-substituted gelatin hydrogel further comprises dopamine conjugated to the gelatin.

4. A tissue adhesive comprising the composition of claim 1 .

5. The tissue adhesive of claim 4 , having a wound closure strength of >10 kPa, or a shear resistance strength of >200 kPa, or a burst pressure of >5 kPa.

6. The tissue adhesive of claim 4 , having a wound closure strength of >20 kPa.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Khademhosseini Ali
• Annabi Nasim
• Assmann Alexander

Classifications

• A61L2300/418

  Agents promoting blood coagulation, blood-clotting agents, embolising agents · CPC title

• A61L24/0031

  Hydrogels or hydrocolloids · CPC title

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• A61L2400/04

  Materials for stopping bleeding · CPC title

• A61L2300/104

  Silver, e.g. silver sulfadiazine · CPC title