Biohybrid composite scaffold

Patent metadata

Field	Value
Publication number	US-9421307-B2
Application number	US-201113814783-A
Country	US
Kind code	B2
Filing date	Aug 17, 2011
Priority date	Aug 17, 2010
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

A biohybrid scaffold is provided that is useful in clinical applications for abdominal wall reconstruction, pelvic floor repair, breast reconstruction, as well as other soft tissue repairs. Methods of making and using the biohybrid scaffold are provided.

First claim

We claim:

1. A method of making a biohybrid scaffold comprising:
(a) concurrently or substantially concurrently:
(1) electrospinning a biodegradable, biocompatible, elastomeric polymer composition onto a substrate; and
(2) electrospraying an ECM-derived gel composition onto the substrate, thereby producing a first layer, wherein the ECM-derived gel composition is prepared by:
(i) solubilizing decellularized tissue that has not been dialyzed by digestion with an acid protease, thereby producing a digest solution; and
(ii) raising the pH of the digest solution to between 7.2 and 7.8.

2. The method of claim 1 wherein the substrate is a mandrel.

3. The method of claim 1 wherein the biodegradable, biocompatible elastomeric polymer comprises one or more of a poly(ester urethane)urea (PEUU), a poly(ether ester urethane)urea (PEEUU), a poly(ester carbonate)urethane urea (PECUU) and a poly(carbonate)urethane urea (PCUU).

4. The method of claim 3 in which the polymer comprises polycaprolactone.

5. The method of claim 4 , in which the polycaprolactone has an Mw of 1000-5000.

6. The method of claim 4 in which the biodegradable, biocompatible elastomeric polymer comprises a copolymer of polycaprolactone, 1,4-diisocyanobutane and putrescine, wherein the Mw of polycaprolactone is ˜2000.

7. The method of claim 1 , in which the biodegradable, biocompatible elastomeric polymer composition is prepared from a polycaprolactone-polyethylene glycol-polycaprolactone triblock copolymer, an aliphatic diisocyanate and an aliphatic diamine.

8. The method of claim 7 in which the aliphatic diisocyanate is 1,4-diisocyanobutane and the aliphatic diamine is putrescine.

9. The method of claim 1 , in which the polymer is prepared from an aliphatic diisocyanate and an aliphatic diamine.

10. The method of claim 9 , in which the aliphatic diisocyanate is 1,4-diisocyanobutane and/or the diamine is putrescine.

11. The method of claim 1 , in which the ECM-derived gel composition is prepared from dermal ECM, urinary bladder ECM and/or small intestine ECM.

12. The method of claim 1 , in which the scaffold comprises >50% wt of the biodegradable, biocompatible elastomeric polymer.

13. The method of claim 1 , further comprising
(b) concurrently or substantially concurrently:
(1) electrospinning a biodegradable, biocompatible, elastomeric polymer and
(2) spraying a liquid, an aqueous liquid, or a liquid selected from the group consisting of water, a physiological salt solution, a buffer solution, a mammalian blood product and cell culture medium, onto the first layer, thereby producing a second layer.

14. A method of making a biohybrid scaffold comprising:
(a) concurrently or substantially concurrently:
(1) electrospinning a biodegradable, biocompatible, elastomeric polymer onto a substrate and
(2) spraying a liquid, an aqueous liquid, or a liquid selected from the group consisting of water, a physiological salt solution, a buffer solution, a mammalian blood product and cell culture medium, onto the substrate, thereby producing a first layer; and
(b) concurrently or substantially concurrently:

(1) electrospinning a biodegradable, biocompatible, elastomeric polymer composition onto the substrate and
(2) electrospraying an ECM-derived gel composition onto the first layer, thereby producing a second layer, wherein the ECM-derived gel composition is prepared by:
(i) solubilizing decellularized tissue that has not been dialyzed by digestion with an acid protease, thereby producing a digest solution; and
(ii) raising the pH of the digest solution to between 7.2 and 7.8.

15. The method of claim 14 , further comprising:
(c) concurrently or substantially concurrently:
(1) electrospinning a biodegradable, biocompatible, elastomeric polymer and
(2) spraying a liquid, an aqueous liquid, or a liquid selected from the group consisting of water, a physiological salt solution, a buffer solution, a mammalian blood product and cell culture medium, onto the second layer, thereby producing a third layer.

16. The method of claim 14 , in which the biodegradable elastomeric polymer of step (a) and/or step (b) is one or more of a poly(ester urethane) urea (PEUU), a poly(ether ester urethane)urea PEEUU), a poly(ester carbonate)urethane urea (PECUU) and a poly(carbonate)urethane urea (PCUU).

Assignees

• Amoroso Nicholas J
• Badylak Stephen F
• Hong Yi
• Huber Alexander
• Takanari Keisuke
• Wagner William R
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Amoroso Nicholas J
• Badylak Stephen F
• Hong Yi
• Huber Alexander
• Takanari Keisuke
• Wagner William R

Classifications

• A61L27/58 Primary

  Materials at least partially resorbable by the body · CPC title

• A61L2400/18

  Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment · CPC title

• A61L2430/34

  for soft tissue reconstruction · CPC title

• A61L27/18 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• A61L27/48

  with macromolecular fillers · CPC title