FORMING POROUS SCAFFOLD FROM CELLULOSE DERIVATIVES
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 scaffold comprising:
a polymer defining macropores and comprising hydroxypropylcellulose partially substituted by a substituent, said substituent comprising a self-crosslinkable group, said partially substituted hydroxypropylcellulose being crosslinked through said self-crosslinkable group, said macropores having an average pore size of larger than 50 microns and being at least partially interconnected.
2 . The scaffold of claim 1 , wherein said polymer has an interconnected porosity of about 50% or higher.
3 . The scaffold of claim 1 or claim 2 , wherein said polymer has a total porosity of about 80% or higher.
4 . The scaffold of any one of claims 1 to 3 , wherein said macropores have a pore size distribution peaking at above 50 microns.
5 . The scaffold of any one of claims 1 to 3 , wherein said macropores have a pore size distribution peaking at about 90 microns.
6 . The scaffold of any one of claims 1 to 3 , wherein said macropores have a pore size distribution peaking at about 100 microns.
7 . The scaffold of any one of claims 1 to 6 , wherein said polymer has an equilibrium water content of about 85%.
8 . The scaffold of any one of claims 1 to 7 , wherein said polymer has a Young's modulus of about 10 to about 20 kPa in a hydrated state.
9 . The scaffold of any one of claims 1 to 8 , wherein said self-crosslinkable group comprises an unsaturated double carbon-carbon bond.
10 . The scaffold of any one of claims 1 to 9 , wherein said substituent comprises allyl isocyanate.
11 . The scaffold of any one of claims 1 to 9 , wherein said substituent comprises methacrylic acid, acrylic acid, or glycidyl methacrylate.
12 . The scaffold of any one of claims 1 to 11 , wherein said partially substituted hydroxypropylcellulose has a degree of substitution of less than about 2.5.
13 . The scaffold of any one of claims 1 to 11 , wherein said partially substituted hydroxypropylcellulose has a degree of substitution of about 2.1.
14 . The scaffold of any one of claims 1 to 13 , wherein said polymer is a gel.
15 . 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 partially substituted by a substituent, said substituent comprising a self-crosslinkable group;
crosslinking said partially substituted hydroxypropylcellulose through said self-crosslinkable group to form a polymer defining at least partially interconnected pores.
16 . The method of claim 15 , wherein said substituent comprises allyl isocyanate.
17 . The method of claim 15 , wherein said substituent comprises methacrylic acid, acrylic acid, or glycidyl methacrylate.
18 . The method of any one of claims 15 to 17 , wherein said pores comprise macropores.
19 . The method of any one of claims 15 to 18 , wherein said crosslinking comprises irradiating said emulsion with γ-ray.
20 . The method of any one of claims 15 to 19 , wherein said crosslinking comprises crosslinking at least about 90 wt % of said partially substituted hydroxypropylcellulose in said emulsion.
21 . The method of any one of claims 15 to 20 , comprising removing water from said pores by freeze-drying said polymer.
22 . The method of claim 21 , 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.
23 . The method of any one of claims 15 to 22 , 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.
24 . The method of any one of claims 15 to 23 , wherein said partially substituted hydroxypropylcellulose has a degree of substitution of about 2.5 or less.
25 . The method of any one of claims 15 to 24 , wherein said partially substituted hydroxypropylcellulose has a degree of substitution of about 2.1.
26 . The method of any one of claims 15 to 25 , wherein said polymer is a gel.
27 . The method of any one of claims 15 to 26 , wherein said emulsion is formed by subjecting a solution comprising water and said partially substituted hydroxypropylcellulose to heat treatment.
28 . The method of any one of claims 15 to 27 , wherein said heat treatment comprises heat treatment at a temperature of about 313 K for about 5 minutes.
29 . A method of forming a scaffold, comprising:
inducing phase separation in a solution comprising a polymer precursor and water, to form a bicontinuous emulsion comprising a continuous polymer phase and a continuous aqueous phase, said polymer precursor comprising a self-crosslinkable group;
crosslinking said polymer precursor through said self-crosslinkable group in said emulsion to form a polymer defining at least partially interconnected macropores.
30 . The method of 29 , wherein said polymer precursor is a cellulose derivative.
31 . The method of claim 30 , wherein said cellulose derivative is methylcellulose derivative.
32 . The method of claim 30 , wherein said cellulose derivative is a hydroxypropylcellulose derivative.
33 . The method of claim 32 , wherein said hydroxypropylcellulose derivative is hydroxypropylcellulose partially substituted by allyl isocyanate.
34 . The method of any one of claims 30 to 32 , wherein said cellulose derivative is partially substituted by a substituent that comprises a self-linkable group.
35 . The method of claim 34 , wherein said self-crosslinkable group comprises an unsaturated double carbon-carbon bond.
36 . The method of claim 34 , wherein said substituent comprises allyl isocyanate, methacrylic acid, acrylic acid, or glycidyl methacrylate.
37 . The method of any one of claims 29 to 36 , wherein said polymer precursor is thermo-sensitive, and said inducing phase separation comprises heating said solution.
38 . The method of claim 29 , wherein said polymer precursor is pH-sensitive, and said inducing phase separation comprises changing pH of said solution.
39 . The method of any one of claims 29 to 38 , wherein said crosslinking comprises irradiating said emulsion with γ-ray.
40 . The method of any one of claims 29 to 39 , wherein said polymer is a gel.