Resorbable, amino acid-based poly(ester urea)s scaffold for vascular graft tissue engineering

Patent metadata

Field	Value
Publication number	US-10537660-B2
Application number	US-201415032809-A
Country	US
Kind code	B2
Filing date	Oct 29, 2014
Priority date	Oct 29, 2013
Publication date	Jan 21, 2020
Grant date	Jan 21, 2020

Abstract

Embodiments relate to amino acid-based poly(ester urea)s with amino acid residues selected L-leucine, L-isoleucine, L-valine or combinations thereof. The amino acid-based poly(ester urea)S may optionally include a second amino acid residue selected from proteinogenic amino acids and non-proteinogenic amino acids. The amino acid-based poly(ester urea)s are particular useful for the preparation of vascular grafts. Due to the biocompatibility of the amino acid-based poly(ester urea)s, vascular grafts prepared from amino acid-based poly(ester urea)s with small internal diameters (i.e. less than 5 mm) may be prepared and inserted into a patient or animal, and provide a substantial decrease in the risk of failure compared to conventional polymers used in vascular grafts.

First claim

What is claimed is:

1. An amino acid-based poly(ester urea) comprising
a first amino acid residue selected from the group consisting of L-leucine, isoleucine, L-valine and combinations thereof attached to a hydrocarbylene group having from 10 to 12 carbon atoms through an ester group; and
a second amino acid residue defined by the formula:

where R is a pendent functional group, wherein said second amino acid residue is attached to a hydrocarbylene group having from 10 to 12 carbon atoms through an ester group.

2. The amino acid-based poly(ester urea) of claim 1 , where the pendent functional group is an oxygen atom connected to a alkyl or aryl group containing an alkyne group, an alkene group, an azide group, a benzyl protected phenol group, a ketone group or a strained cyclooctyne.

3. The amino acid-based poly(ester urea) of claim 1 , where the amino acid-based poly(ester urea) comprises the following formula:

where each J is individually a L-leucine, L-isoleucine, or L-valine side chain, at least one X 2 is a proteinogenic amino add or non-proteinogenic amino acid side chain defined by the formula:

where R is a pendent functional group; each n is individually about 10 to 12 units; m
is from about 10 to about 500 units; and o is from about 10 to about 500 units.

4. An amino acid-based poly(ester urea) vascular graft having a tubular structure comprising an amino acid-based poly(ester urea), said amino acid-based poly(ester urea)comprising:
a first amino acid residue selected from L-leucine, L-isoleucine, L-valine or combinations thereof attached to a hydrocarbylene group having from 10 to 12 carbon atoms through an ester group; and
a second amino acid residue defined by the formula:

where R is a pendent functional group, wherein said second amino acid residue is attached to a hydrocarbylene group having from 10 to 12 carbon atoms through an ester group.

5. The poly(ester urea) vascular graft of claim 4 , where the amino acid-based poly(ester urea) is defined by the following formula:

where each J is individually a L-leucine, L-isoleucine, or L-valine side chain, each n is about 10 to 23 units, m is from about 10 to about 500 units; o is about 10 to about 500 units; at least one X 2 is a proteinogenic amino acid or non-proteinogenic amino acid side chain defined by the formula:

where R is a pendent functional group.

6. The poly(ester urea) vascular graft of claim 5 , where R is a pendent functional group comprising an oxygen atom connected to an alkyl or aryl group containing an alkyne group, an alkene group, an azide group, a benzyl protected phenol group, a ketone group or a strained cyclooctyne.

7. The poly(ester urea) vascular graft of claim 4 , There the poly(ester urea) is electrospun.

8. The poly(ester urea) vascular graft of claim 4 , where the vascular graft has an internal diameter of about 0.05 mm to about 20 mm.

9. A method of preparing an amino acid-based poly(ester urea) vascular graft comprising
(i) providing a charged solution of amino acid-based poly(ester urea) wherein said amino acid-based poly(ester urea) is defined by the following formula;

where each J is individually a L-leucine, L-isoleucine, or L-valine side chain, at least one X 2 is a proteinogenic amino acid or non-proteinogenic amino acid side chain defined by the formula:

where R is a pendent functional group; each n is individually about 10 to 12 units; m is from about 10 to about 500 units; and o is from about 10 to about 500 units;
(ii) providing a grounded mandrel coated with a dissolvable coating;
(iii) electrospinning the charged solution of amino acid-based poly(ester urea) onto the dissolvable coating of the grounded mandrel to produce a tubular structure,
(iv) dissolving the dissolvable coating; and
(v) removing the tubular structure from the mandrel.

10. The method of claim 9 , where the dissolvable coating is a water soluble sugar.

11. The method of claim 9 , wherein said pendent functional group (R) is an oxygen atom connected to a alkyl or aryl group containing an alkyne group, an alkene group, an azide group, a benzyl protected phenol group, a ketone group or a strained cyclooctyne.

Assignees

• Univ Akron

Inventors

• Becker Matthew
• Reneker Darrell
• Gao Yaohua

Classifications

• D01D5/003

  the material being a polymer solution or dispersion (D01D5/0053 takes precedence) · CPC title

• A61L2400/12

  Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces · CPC title

• A61L27/507

  for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062) · CPC title

• D01F6/84

  from copolyesters · CPC title

• D01F6/68

  from polyaminoacids or polypeptides · CPC title