BIOCOMPATIBLE HYDROGEL POLYMER MATRIX FOR DELIVERY OF CELLS
Provided herein are biocompatible hydrogel polymer matrices, which are prepared from biocompatible pre-formulations. The biocompatible pre-formulations comprise at least one nucleophilic compound, at least one electrophilic compound, and at least one cell. The biocompatible hydrogel polymer matrix is bioabsorbable and releases the cell at a target site, achieving a controlled delivery. The biocompatible hydrogel polymer matrix provides a solid support conducive for cell viability and functionality. The cells may grow on the hydrogel polymer surface of inside the hydrogel polymer matrix.
1 . A method of delivering a cell to a subject, the method comprising administering a fully synthetic, polyglycol-based biocompatible hydrogel polymer matrix comprising a fully synthetic, polyglycol-based biocompatible hydrogel polymer comprising at least one first monomeric unit bound through at least one amide, thioester, or thioether linkage to at least one second monomeric unit, wherein the polymer forms the matrix that encapsulates:
(a) at least one cell; and
(b) a culture medium which supports the growth of the at least one cell; and
wherein the fully synthetic, polyglycol-based biocompatible hydrogel polymer matrix provides controlled release of the at least one cell in the subject.
2 . The method of claim 1 , wherein the at least one first monomeric unit is PEG-based and fully synthetic, and wherein the at least one second monomeric unit is PEG-based and fully synthetic.
3 . The method of claim 1 , wherein the cell is selected from a mammalian cell, insect cell, protozoal cell, bacterial cell, viral cell, or fungal cell.
4 . The method of claim 3 , wherein the mammalian cell is a stem cell.
5 . The method of claim 1 , The polyglycol-based biocompatible hydrogel polymer matrix of claim 1 , wherein the culture medium comprises a growth factor.
6 . The method of claim 1 , wherein the first monomeric unit is derived from a MULTIARM-(5-50k)-SH, a MULTIARM-(5-50k)-NH2 or a MULTIARM-(5-50k)-AA monomer and the second monomeric unit is derived from a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, or a MULTIARM-(5-50k)-SS monomer.
7 . The method of claim 6 , wherein the first monomeric unit is derived from a 4ARM-5k-SH, 4ARM-2k-NH2, 4ARM-5k-NH2, 8ARM-20k-NH2, 4ARM-20k-AA, or 8ARM-20k-AA monomer, and the second monomeric unit is derived from a 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, or 4ARM-20k-SS monomer.
8 . The method of claim 1 , wherein the animal is a human.
9 . The method of claim 1 , wherein the polyglycol-based biocompatible hydrogel polymer matrix is bioabsorbed within about 14 to 180 days.
10 . The method of claim 1 , wherein the controlled release of the at least one cell to a target site of the animal's body comprises diffusion of the at least one cell from the polyglycol-based biocompatible hydrogel polymer matrix.
11 . The method of claim 1 , wherein the controlled release of the at least one cell to a target site of the animal's body is at least partially through degradation and bioabsorption of the polyglycol-based biocompatible hydrogel polymer matrix.
12 . A fully synthetic polyglycol-based biocompatible pre-formulation, comprising:
(a) at least one fully synthetic polyglycol-based first compound comprising more than one nucleophilic group;
(b) at least one fully synthetic polyglycol-based second compound comprising more than one electrophilic group;
(c) at least one cell; and
(d) a culture medium that supports growth of the at least one cell;
wherein the polyglycol-based biocompatible pre-formulation at least in part polymerizes and/or gels to form a polyglycol-based biocompatible hydrogel polymer matrix encapsulating the cell in the presence of water.
13 . The polyglycol-based biocompatible pre-formulation of claim 12 , wherein the mammalian cell is a stem cell.
14 . The polyglycol-based biocompatible pre-formulation of claim 12 , wherein the culture medium comprises a buffer.
15 . The polyglycol-based biocompatible pre-formulation of claim 12 , wherein the first compound is a MULTIARM-(5-50k)-SH, a MULTIARM-(5-50k)-NH2, a MULTIARM-(5-50k)-AA, or a combination thereof, and the second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.
16 . The polyglycol-based biocompatible pre-formulation of claim 15 , wherein the first compound is 4ARM-5k-SH, 4ARM-2k-NH2, 4ARM-5k-NH2, 8ARM-20k-NH2, 4ARM-20k-AA, 8ARM-20k-AA, and a combination thereof, and the second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-20k-SS, or a combination thereof.
17 . The polyglycol-based biocompatible pre-formulation of preceding claim 16 , wherein the first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the second compound is 4ARM-20k-SGA.
18 . The polyglycol-based biocompatible pre-formulation of claim 12 , wherein the polyglycol-based biocompatible pre-formulation gels to form a polyglycol-based biocompatible hydrogel polymer matrix in between about 20 seconds and 10 minutes.
19 . The polyglycol-based biocompatible hydrogel polymer matrix of claim 12 .
20 . (canceled)