Body temperature-triggered, in situ forming biomaterials and devices

Patent metadata

Field	Value
Publication number	US-2019282735-A1
Application number	US-201716349186-A
Country	US
Kind code	A1
Filing date	Nov 14, 2017
Priority date	Nov 14, 2016
Publication date	Sep 19, 2019
Grant date	—

Abstract

Provided herein are thermoresponsive polymer materials and methods of preparation and use thereof. In particular, materials are provided that cure upon exposure to physiologic conditions (e.g., human body temperature) and find use in, for example, orthopedic surgery, bone tissue engineering, and the repair of bone injuries and defects.

First claim

1 . A composition comprising an acrylated or methacrylated polymer and a thermoresponsive initiator compound, wherein an increase in temperature above a threshold temperature results in radical formation from the thermoresponsive initiator compound, and the radical formation initiates curing of the acrylated or methacrylated polymer into a cured polymer.

2 . The composition of claim 1 , wherein the acrylated or methacrylated polymer is a liquid and/or is soluble in water and/or organic solvent.

3 . The composition of claim 1 , wherein the cured polymer is a solid and/or is insoluble in water and/or organic solvent.

4 . The composition of claim 1 , wherein the acrylated or methacrylated polymer is a biodegradeable and/or biocompatible polyester.

5 . The composition of claim 1 , wherein the acrylated or methacrylated polymer is a citric acid-based polyester.

6 . The composition of claim 5 , wherein the citric acid-based polyester comprises citric acid and linear aliphatic diol monomers.

7 . The composition of claim 6 , wherein the citric acid-based polyester comprises a poly(diol citrate).

8 . The composition of claim 7 , wherein the diol is a linear aliphatic diol, X carbons in length, wherein X is between 2 and 20, and comprising OH groups on the 1 and X carbons.

9 . The composition of claim 7 , wherein the diol is selected from the group consisting of 1,4-butanediol, 1,6-hexanediol, 1,8-octanediol, 1,10-decanediol, 1,12-dodecanediol, 1,14-quattuordecanediol, and 1,16-sedecimanediol.

10 . The composition of claim 5 , wherein at least 10% of the citric acid monomers of the acrylated or methacrylated polymer display a methacrylate or acrylate.

11 . The composition of claim 10 , wherein at least 50% of the citric acid monomers of the acrylated or methacrylated polymer display a methacrylate or acrylate.

12 . The composition of claim 11 , wherein at least 90% of the citric acid monomers of the acrylated or methacrylated polymer display a methacrylate or acrylate.

13 . The composition of claim 1 , wherein the thermoresponsive initiator compound is a diazo compound.

14 . The composition of claim 1 , wherein the thermoresponsive initiator compound is selected from the group consisting of 65, V-70, V-40, V-50, V-59, VA-044, VA-057, VA-061, VA-086, and BPO.

15 . A composition comprising a cured polymer composition prepared by the thermally-induced curing of the composition of one of claims 1 - 14 .

16 . The composition of claim 15 , wherein thermally-induced curing occurs at a temperature between 32 and 43° C.

17 . A composite material comprising the composition of one of claims 1 - 14 and one or more additional structural components.

18 . The composite material of claim 17 , wherein the additional structural components comprise at least 10 wt % of the composite material.

19 . The composite material of claim 17 , wherein the one or more additional structural components comprises a biodegradable and/or biocompatible polymer.

19 . The composite material of claim 17 , wherein the one or more additional structural components comprises a bioceramic.

21 . The composite material of claim 20 , wherein the bioceramic comprises hydroxyapatite (HA) and/or tricalcium phosphate beta (β TCP).

22 . A composition comprising a cured composite material prepared by the thermally-induced curing of the composite material of one of claims 17 - 21 .

23 . A composition comprising an acrylated or methacrylated poly(diol citrate) polymer and a thermoresponsive diazo initiator compound, wherein an increase in temperature above a threshold temperature results in radical formation from the thermoresponsive diazo initiator compound, and the radical formation initiates curing of the acrylated or methacrylated poly(diol citrate) polymer into a cured poly(diol citrate) polymer, wherein the acrylated or methacrylated polymer is a liquid and the cured polymer is a solid.

24 . A composite material comprising the composition of claim 23 and a bioceramic material.

25 . The composite material of claim 24 , wherein the bioceramic comprises hydroxyapatite (HA) and/or tricalcium phosphate beta (β TCP).

26 . A method comprising administering a composition of one of claims 1 - 15 and 23 to a bone defect or fracture and allowing the composition to cure.

27 . Use of a composition of one of claims 1 - 15 and 23 to repair a bone defect or fracture.

Assignees

• Univ Northwestern

Inventors

• Ameer Guillermo A

Classifications

• A61L27/46 Primary

  with phosphorus-containing inorganic fillers · CPC title

• A61L2430/02

  for reconstruction of bones; weight-bearing implants · CPC title

• A61L27/16

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

• A61L2300/802

  Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title