Fibrous Scaffold for Use in Soft Tissue Engineering

Abstract

The present invention relates to a fibrous scaffold for use as a substrate in soft tissue applications, in particular for preparing annulus fibrosus (AF) tissue. In aspects, the present invention also relates to an engineered biological material comprising AF tissue; constructs comprising one or more engineered biological materials; methods for producing the biological materials and constructs; and methods of using the biological materials and constructs.

What is claimed is: 
     
         1 . A fibrous scaffold for culturing soft tissues on its surface said scaffold comprising fibres comprising a blend of polyurethane polymers and oligomers wherein the oligomers increase surface energy of the scaffold and comprise polar groups that are exposed on the surface of the fibrous scaffold. 
     
     
         2 . A fibrous scaffold according to  claim 1  wherein the polar groups are selected from the group consisting of carboxylates, hydroxyls, amines and sulfonates. 
     
     
         3 . A fibrous scaffold according to  claim 1  wherein the concentration of the oligomers in the blend is less than about 5 wt %. 
     
     
         4 . A fibrous scaffold according to  claim 1  wherein the fibres are random. 
     
     
         5 . A fibrous scaffold according to  claim 1  wherein the fibres are aligned. 
     
     
         6 . A fibrous scaffold according to  claim 1  which is a nanofiber porous scaffold comprising polyurethane polymers and anionic dihydroxyl oligomers. 
     
     
         7 . A fibrous scaffold according to  claim 1  wherein the polyurethane polymers comprise hydrolysable polyurethane chains. 
     
     
         8 . A fibrous scaffold according to  claim 1  wherein the polyurethane polymers are polycarbonate urethane polymers. 
     
     
         10 . A fibrous scaffold according to  claim 1  having a fibre thickness of between about 130 to about 1500 nm. 
     
     
         11 . A process for preparing a fibrous scaffold according to  claim 1  comprising blending the polyurethane polymers and oligomers to form a polyurethane formulation wherein the concentration of the oligomers in the formulation is less than about 5 wt %, and electrospinning the formulation to form the fibrous scaffold. 
     
     
         12 . Anionic dihydroxyl oligomers produced by linking a polyether diol with a carboxylic ester in the presence of a polyisocyanate. 
     
     
         13 . Anionic dihydroxyl oligomers according to  claim 12  wherein the polyether diol is polybutylene glycol, polytetramethylene ether glycol, or a mixture thereof. 
     
     
         14 . Anionic dihydroxyl oligomers according to  claim 12  wherein the carboxylic ester is a methacrylic ester. 
     
     
         15 . Anionic dihydroxyl oligomers according to  claim 12  wherein the polyisocyanate is lysine diisocyanate, diphenylmethane diisocyanate, toluoylenediisocyanate, tolylene diisocyanate, xylene diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, cyclohexylmethane diisocyanate, methylcyclohexane diisocyanate, isopropylidene-bis(4-cyclohexyldiisocyanate) or hexamethylene diisocyanate/biuret. 
     
     
         16 . Anionic dihydroxyl oligomers according to  claim 12  characterized by one or more of the following properties:
 a) about 50% to about 70% of its side chains comprise carboxylic acid groups; 
 b) absorption bands in the about 600 cm −1  to about 4000 cm −1  region by Fourier transform infrared spectroscopy (FTIR); and 
 c) a peak corresponding to a urethane group at about 1680-1750 cm −1 , by FTIR. 
 
     
     
         17 . A polyurethane formulation comprising a blend of polyurethane polymers and anionic dihydroxyl oligomers according to  claim 12 . 
     
     
         18 . A fibrous scaffold fabricated from a polyurethane formulation according to  claim 17 . 
     
     
         19 . An engineered biological material characterized by a continuous layer of annulus fibrosus tissue on a fibrous scaffold according to  claim 1 . 
     
     
         20 . A process for producing an engineered biological material according to  claim 19  comprising:
 (a) forming a layer of isolated annulus fibrosus cells on a fibrous scaffold for culturing soft tissues on its surface said scaffold comprising fibres comprising a blend of polyurethane polymers and oligomers wherein the oligomers increase surface energy of the scaffold and comprise polar groups that are exposed on the surface of the fibrous scaffold, and; 
 (b) culturing the annulus fibrosus cells in culture media so that the annulus fibrosus cells accumulate extracellular matrix and form a continuous layer of annulus fibrosus tissue. 
 
     
     
         21 . A method of replacing or repairing damaged, degenerated or deficient intervertebral discs or portions thereof of a patient comprising implanting an engineered biological material according to  claim 19  or annulus fibrosus tissue therefrom into the site of the damaged, degenerated or deficient intervertebral disc or portions thereof, of the patient.