Mesenchymal cell-binding composite material for tissue restoration

Patent metadata

Field	Value
Publication number	US-12458731-B2
Application number	US-201615753272-A
Country	US
Kind code	B2
Filing date	Aug 17, 2016
Priority date	Aug 17, 2015
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

The presently disclosed composition and methods are provided for a nanofiber-hydrogel composite containing adipose cell binding moieties. A method for healing a soft tissue defect can include applying an adipose cell-binding composite material to a soft tissue defect in combination with exogenous adipose-derived cells or endogenous cells recruited from the surrounding tissue.

First claim

What is claimed is:

1 . A soft tissue device, comprising:
a mesenchymal cell-binding moiety covalently linked to a scaffold complex, and comprising a plurality of pores present on or within a surface of the device, wherein the pores are present at a concentration of at least 50 pores per cm 2 of the surface, and wherein at least 80% of the pores have an average pore diameter is at least 5 microns, wherein: a. the mesenchymal cell-binding moiety comprises an amino acid sequence selected from among CMLAGWIPC (SEQ ID NO: 2), CWLGEWLGC (SEQ ID NO: 4), CSWKYWFGEC (SEQ ID NO: 5), CGQWLGNWLC (SEQ ID NO: 6) or CKGGRAKDC (SEQ ID NO: 7); and b. the scaffold complex comprises a polymeric fiber having a mean diameter of from 100 nm to 8000 nm covalently linked to a hydrogel material, wherein the ratio of fiber to hydrogel material is from 1:10 to 10:1 on a component-mass basis, wherein:
i. the hydrogel material comprises a hyaluronic acid, or a derivative thereof; and
ii. the polymeric fiber comprises a biocompatible biodegradable polyester, wherein the polymeric fiber comprises maleimide groups and the surface density of the maleimide groups on the polymeric fiber is from 10 nmol/mg of fibers to 160 nmol/mg of the fiber.

2 . The device of claim 1 , wherein the soft tissue device is an adipose tissue device.

3 . The device of claim 1 , configured as a sheet having a first dimension and a second dimension independently at least twice as great in length as a third dimension, or configured as a sheet having a first dimension no greater than at least twice as great in length as a second dimension.

4 . The device of claim 1 , configured to be subdermally implantable or subdermally injectable.

5 . The device of claim 1 , further comprising a human tissue aspirate obtained from a liposuction or other surgical procedure.

6 . The device of claim 1 , further comprising a human stem cell or progenitor stem cell.

7 . The device of claim 1 , wherein the polymeric fiber comprises an electrospun polycaprolactone fiber.

8 . The device of claim 1 , wherein the hydrogel material comprises a processed tissue extracellular matrix derivable from adipose tissue.

9 . The device of claim 1 , further comprising a crosslinking moiety present in an amount effective to introduce bonding between the polymer fiber and hydrogel material.

10 . The device of claim 1 , further comprising a cross-linking moiety present in an amount effective to induce cross-linking between the polymeric fiber and hyaluronic acid.

11 . The device of claim 1 , wherein the mesenchymal cell-binding moiety comprises an adipose-binding peptide comprising the amino acid sequence CMLAGWIPC (SEQ ID NO: 2).

12 . The device of claim 1 wherein the mesenchymal cell-binding moiety comprises an amino acid sequence from CWLGEWLGC (SEQ ID NO: 4), CSWKYWFGEC (SEQ ID NO: 5), CGQWLGNWLC (SEQ ID NO: 6) or CKGGRAKDC (SEQ ID NO: 7).

13 . The device of claim 1 wherein the mesenchymal cell-binding moiety does not specifically bind to at least one of CD11b, CD14, CD19, CD79α, CD34, CD45, or HLA-DR.

14 . The device of claim 1 wherein the mesenchymal cell-binding moiety comprises an amino acid sequence from CSWKYWFGEC (SEQ ID NO: 5) or CGQWLGNWLC (SEQ ID NO: 6).

15 . The device of claim 1 wherein the mesenchymal cell-binding moiety is covalently linked to the polymeric fiber.

16 . A soft tissue device, comprising:
a mesenchymal cell-binding moiety covalently linked to a scaffold complex, and comprising a plurality of pores present on or within a surface of the device, wherein the pores are present at a concentration of at least 50 pores per cm 2 of the surface, and wherein at least 80% of the pores on the surface have an average pore diameter is at least 5 microns, wherein:
a. the mesenchymal cell-binding moiety comprises an amino acid sequence selected from among CMLAGWIPC (SEQ ID NO: 2), CWLGEWLGC (SEQ ID NO: 4), CSWKYWFGEC (SEQ ID NO: 5), CGQWLGNWLC (SEQ ID NO: 6) or CKGGRAKDC (SEQ ID NO: 7); and
b. the scaffold complex comprises a polymeric fiber having a mean diameter of from 100 nm to 8000 nm covalently linked to a hydrogel material, wherein the ratio of fiber to hydrogel material is from 1:10 to 10:1 on a component-mass basis, wherein:
i. the hydrogel material comprises a hyaluronic acid, or a derivative thereof; and
ii. the polymeric fiber comprises a biocompatible biodegradable polyester, and the mesenchymal cell-binding moiety is covalently linked to the polymeric fiber.

17 . The device of claim 16 wherein the polymeric fiber comprises maleimide groups.

18 . The device of claim 16 wherein the mesenchymal cell-binding moiety comprises the amino acid sequence CMLAGWIPC (SEQ ID NO: 2).

19 . The device of claim 16 wherein the mesenchymal cell-binding moiety comprises an amino acid sequence from CWLGEWLGC (SEQ ID NO: 4), CSWKYWFGEC (SEQ ID NO: 5), CGQWLGNWLC (SEQ ID NO: 6) or CKGGRAKDC (SEQ ID NO: 7).

20 . The device of claim 16 wherein the mesenchymal cell-binding moiety does not specifically bind to at least one of CD11b, CD14, CD19, CD79α, CD34, CD45, or HLA-DR.

21 . A soft tissue device, comprising:
a mesenchymal cell-binding moiety covalently linked to a scaffold complex, wherein:
a. the mesenchymal cell-binding moiety comprises an amino acid sequence selected from among CMLAGWIPC (SEQ ID NO: 2), CWLGEWLGC (SEQ ID NO: 4), CSWKYWFGEC (SEQ ID NO: 5), CGQWLGNWLC (SEQ ID NO: 6) or CKGGRAKDC (SEQ ID NO: 7); and
b. the scaffold complex comprises a polymeric fiber having a mean diameter of from 100 nm to 8000 nm covalently linked to a hydrogel material, wherein: the hydrogel material comprises a hyaluronic acid, or a derivative thereof.

Assignees

• Univ Johns Hopkins

Inventors

• Martin Russell
• Mao Hai-Quan
• Reddy Sashank
• Sacks Justin
• Li Xiaowei
• Cho Brian Honewee

Classifications

• A61L2400/06

  Flowable or injectable implant compositions · CPC title

• A61L27/58

  Materials at least partially resorbable by the body · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L27/38

  containing added animal cells (organs or tissue containing native cells A61L27/36) · CPC title