Forming porous scaffold from cellulose derivatives
View Patent ↗Scaffold comprises a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, which is crosslinked through the self-crosslinkable group. The macropores have an average pore size larger than 50 microns and are at least partially interconnected. In one method, bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase is formed. The polymer phase comprises hydroxypropylcellulose partially substituted by a substituent comprising a self-crosslinkable group, and is crosslinked through the self-crosslinkable group to form a polymer defining at least partially interconnected pores. In another method, phase separation is induced in a solution comprising a polymer precursor and water to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase. The polymer precursor comprises a self-crosslinkable group and is crosslinked through the self-crosslinkable group in the emulsion to form a polymer defining at least partially interconnected macropores.
1. A method of forming a scaffold, comprising:
forming a bicontinuous emulsion comprising a continuous aqueous phase and a continuous polymer phase, said polymer phase comprising hydroxypropylcellulose substituted by a substituent, said substituent comprising a self-crosslinkable group;
crosslinking said substituted hydroxypropylcellulose through said self-crosslinkable group in said bicontinuous emulsion to form a polymer defining interconnected pores, wherein said crosslinking comprises irradiating said emulsion with γ-ray.
2. The method of claim 1 , wherein said substituent comprises allyl isocyanate, methacrylic acid, acrylic acid, or glycidyl methacrylate.
3. The method of claim 1 , wherein said pores comprise macropores having an average pore size of larger than 50 microns.
4. The method of claim 1 , wherein said crosslinking comprises crosslinking at least about 90 wt % of said substituted hydroxypropylcellulose in said emulsion.
5. The method of claim 1 , comprising removing water from said pores by freeze-drying said polymer, wherein, after said freeze-drying, said polymer has an interconnected porosity of about 50% or higher, and said pores have an average pore size of larger than 50 microns.
6. The method of claim 1 , wherein said emulsion comprises about 80 to about 90 wt % of said aqueous phase and about 10 to about 20 wt % of said polymer phase.
7. The method of claim 1 , wherein said substituted hydroxypropylcellulose has a degree of substitution of about 2.5 or less.
8. The method of claim 1 , wherein said polymer is a gel.
9. The method of claim 1 , wherein said emulsion is formed by subjecting a solution comprising water and said substituted hydroxypropylcellulose to heat treatment at a temperature of about 313 K for about 5 minutes.
10. The method of claim 1 , wherein said substituted hydroxypropylcellulose comprises hydroxypropylcellulose allyl galactose, and said method comprises attaching a biocompatible cationic polymeric group to a side chain of said hydroxypropylcellulose allyl galactose, wherein said biocompatible cationic polymeric group comprises polylysine, polyethylene imine, or polypropyleneimine hexadecaamine.
11. The method of claim 1 , comprising attaching an arginine-glycine-aspartic acid (RGD), collagen, laminin, fibronectin, or cell growth factor to a surface of said scaffold.
12. A method of forming a scaffold, comprising:
inducing phase separation in a solution comprising a polymer precursor and water,
wherein the polymer precursor comprises a cellulose derivative, to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase, said polymer precursor comprising a self-crosslinkable group; and
crosslinking said polymer precursor through said self-crosslinkable group in said bicontinuous emulsion to form a polymer defining interconnected macropores, wherein said crosslinking comprises irradiating said emulsion with γ-ray.
13. The method of claim 12 , wherein said polymer precursor is a cellulose derivative.
14. The method of claim 13 , wherein said cellulose derivative is a methylcellulose derivative or a hydroxypropylcellulose derivative, or wherein said cellulose derivative is substituted by a substituent that comprises a self-linkable group.
15. The method of claim 14 , wherein said hydroxypropylcellulose derivative is hydroxypropylcellulose substituted by allyl isocyanate, or comprises hydroxypropylcellulose allyl galactose.
16. The method of claim 14 , wherein said substituent comprises allyl isocyanate, methacrylic acid, acrylic acid, or glycidyl methacrylate.
17. The method of claim 12 , wherein said self-crosslinkable group comprises an unsaturated double carbon-carbon bond.
18. The method of claim 12 , wherein
said polymer precursor is thermo-sensitive, and said inducing phase separation comprises heating said solution; or
said polymer precursor is pH-sensitive, and said inducing phase separation comprises changing pH of said solution.
19. The method of claim 12 , wherein said polymer is a gel.