Methods of generating cross-linked protein foams in situ

Inventors

Attar, Ishay

Assignees

Biochange Ltd

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Publication Number

US-11439663-B2

Patent

Publication Date

2022-09-13

Expiration Date


Abstract

In one embodiment, the present invention provides a composition, wherein the composition is a porous scaffold, wherein the pores of the scaffold are from 2 to 500 microns, the composition comprising: a) a cross-linkable protein selected from the group consisting of collagen and gelatin; b) a cross-linker which induces cross-linking of the cross-linkable protein; and c) a liquid.

Core Innovation

The patent describes cross-linkable protein foam or scaffold compositions made by combining a hygroscopic cross-linkable gelatin with at least one cross-linker and a liquid. The hygroscopic cross-linkable gelatin is provided as a powder having a particle size between 5 to 200 microns, and the composition is cross-linked to form a porous scaffold in situ or in vitro. The porous scaffold is defined as a closed cell foam or a foam.

The formed foam has a pore size of from 2 microns in diameter to 500 microns in diameter. The patent further characterizes the micronized cross-linkable protein as hygroscopic and describes rapid hydration and solubilization in use contexts. It also describes a cross-linker such as transglutaminase and optional motifs such as RGD for cell attachment.

A primary problem being addressed is treatment of a tissue defect by forming a porous scaffold in situ at a site where a patient is in need of treatment of the tissue defect. The disclosed approach forms a closed cell foam scaffold at the tissue defect site by introducing the hygroscopic cross-linkable gelatin powder into a cross-linker-containing liquid and crosslinking the composition at the site, and it also supports forming a porous foam scaffold after cross-linking a composition introduced to cells in vitro.

Claims Coverage

The document includes two independent claims. Across both, the core coverage centers on hygroscopic cross-linkable gelatin provided as a 5–200 micron powder, a cross-linker in specified concentration range, and a resulting foam having 2–500 micron pore size.

In situ closed cell foam porous scaffold from hygroscopic cross-linkable gelatin powder

A composition comprising hygroscopic cross-linkable gelatin in 0.5 wt % to 25 wt %, at least one cross-linker in 0.0001 wt % to 25 wt %, and a liquid; the gelatin is introduced as a powder having a particle size between 5 to 200 microns; the composition is introduced in a patient at a site where the patient is in need of treatment of a tissue defect; crosslinking occurs at the site to form a porous scaffold in situ; the porous scaffold is a closed cell foam having a pore size of from 2 microns in diameter to 500 microns in diameter.

In vitro porous foam scaffold from hygroscopic cross-linkable gelatin powder

A composition comprising hygroscopic cross-linkable gelatin in 0.5 wt % to 25 wt %, at least one cross-linker in 0.0001 wt % to 25 wt %, and a liquid; the gelatin is introduced as a powder having a particle size between 5 to 200 microns; the composition is introduced to cells in vitro where the composition is cross-linked to form a porous scaffold; the porous scaffold is a foam having a pore size of from 2 microns in diameter to 500 microns in diameter.

Both independent claims require hygroscopic cross-linkable gelatin and a cross-linker in specified weight ranges, with the gelatin provided as 5–200 micron powder and the resulting scaffold defined as a foam or closed cell foam having 2–500 micron pore size; the difference is in situ crosslinking in a patient at a tissue defect site versus crosslinking after introduction to cells in vitro.

Stated Advantages

Documented Applications

Wound repair; bone regeneration/bone defect treatment.

Bulking agents for urinary incontinence and fecal incontinence.

Lung volume reduction for emphysema via anti-surfactant and fibroblast attachment/collagen synthesis.

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