Ionically crosslinked hydrogels with adjustable gelation time

A biocompatible hydrogel composition, comprising:

• at least one water-soluble polymer composed of one or more monomers, the polymer being present in a predetermined concentration;
• at least one of:
• a first divalent or multivalent cation-containing compound having a Ksp at or less than 3.36×10−9;
• and a first divalent or multivalent cation-releasing compound, the at least one first divalent or multivalent cation-containing compound and the first divalent or multivalent cation-releasing compound being present in a predetermined concentration;
• and
• at least one of:
• a second divalent or multivalent cation-containing compound having a Ksp at or greater than 3.14×10−5;
• and a second divalent or multivalent cation-releasing compound, the at least one second divalent or multivalent cation-containing compound and the second divalent or multivalent cation-releasing compound being present in a predetermined concentration, wherein the Ksp of the second cation-containing compound is greater than the Ksp of the first cation-containing compound;
• wherein at least one of the monomers is selected from the group consisting of acids, monomers containing an acid group, monomers containing a derivative of an acid, and mixtures thereof, wherein the at least one monomer reacts with the divalent or multivalent cations to form ionic cross-links inter-molecularly among polymer chains to form an ionically cross-linked hydrogel composition at a gelation rate;
• wherein the hydrogel composition contains a predetermined ratio of the at least one first divalent or multivalent cation-containing compound and the first divalent or multivalent cation-releasing compound to the at least one second divalent or multivalent cation-containing compound and the second divalent or multivalent cation-releasing compound, wherein at least one of:
• the predetermined ratio;
• the first divalent or multivalent cation-containing/divalent or multivalent cation-releasing compound concentration;
• the second divalent or multivalent cation-containing/divalent or multivalent cation-releasing compound concentration;
• and the polymer concentration substantially controls the gelation rate;
• and wherein the first and second divalent or multivalent cations are selected from the group consisting of calcium, beryllium, strontium, barium, radium, aluminum, copper, zinc, osmium, and mixtures thereof.

A method for preparing an ionically cross-linked hydrogel composition, the method comprising the step of:

• selectively controlling a rate of gel formation of the hydrogel composition which comprises:
• at least one water-soluble polymer composed of one or more monomers, the polymer being present in a predetermined concentration;
• at least one of:
• a first divalent or multivalent cation-containing compound having a Ksp at or less than 3.36×10−9;
• and a first divalent or multivalent cation-releasing compound, the at least one first divalent or multivalent cation-containing compound and the first divalent or multivalent cation-releasing compound being present in a predetermined concentration;
• and at least one of:
• a second divalent or multivalent cation-containing compound having a Ksp at or greater than 3.14×10−5;
• and a second divalent or multivalent cation-releasing compound, the at least one second divalent or multivalent cation-containing compound and the second divalent or multivalent cation-releasing compound being present in a predetermined concentration;
• wherein the Ksp of the second cation-containing compound is greater than the Ksp of the first cation-containing compound;
• wherein at least one of the monomers is selected from the group consisting of acids, monomers containing an acid group, monomers containing a derivative of an acid, and mixtures thereof, wherein the at least one monomer reacts with the first and second divalent or multivalent cations to form ionic cross-links inter-molecularly among polymer chains to form an ionically cross-liked hydrogel composition at a gelation rate;
• wherein the hydrogel composition contains a ratio of first divalent or multivalent cation-containing and divalent or multivalent cation-releasing compound to second divalent or multivalent cation-containing and divalent or multivalent cation-releasing compound;
• and wherein the first and second divalent or multivalent cations are selected from the group consisting of calcium, beryllium, strontium, barium, radium, aluminum, copper, zinc, osnium, and mixtures thereof;
• wherein the controlling step is accomplished by varying at least one of:
• solubility of the first and second cation-containing compounds;
• cation concentration;
• the ratio;
• polymer concentration;
• and gelation temperature.

A hydrogel composition, comprising:

• at least one water-soluble polymer composed of one or more monomers, the polymer being present in a predetermined concentration;
• at least one of:
• a first cation-containing compound composed of calcium sulfate dihydrate (CaSO4.2H2O);
• and a first divalent or multivalent cation-releasing compound, the at least one first cation-containing compound and the first cation-releasing compound being present in a predetermined concentration;
• and
• at least one:
• of a second cation-containing compound composed of calcium carbonate (CaCO3);
• and a second divalent or multivalent cation-releasing compound, the at least one second cation-containing compound and the second cation-releasing compound being present in a predetermined concentration;
• wherein at least one of the monomers is selected from the group consisting of acids, monomers containing an acid group, monomers containing a derivative of an acid, and mixtures thereof, wherein the at least one monomer reacts with the divalent or multivalent cations to form ionic cross-links inter-molecularly among polymer chains to form an ionically cross-linked hydrogel composition.

A biocompatible hydrogel composition, consisting essentially of:

• at least one water-soluble polymer formed by polymerization of one or more monomers, the polymer being present in a predetermined concentration;
• at least one of:
• a first cation-containing compound composed of calcium sulfate dihydrate (CaSO4.2H2O);
• and a first divalent or multivalent cation-releasing compound, the at least one first cation-containing compound and the first divalent or multivalent cation-releasing compound being present in a predetermined concentration;
• and
• at least one of:
• a second cation-containing compound composed of calcium carbonate (CaCO3);
• and a second divalent or mutlivalent cation-releasing compound, the at least one second cation-containing compound and the second divalent or multivalent cation-releasing compound being present in a predetermined concentration;
• wherein at least one of the monomers is selected from the group consisting of acids, monomers containing an acid group, monomers containing a derivative of an acid, and mixtures thereof, wherein the at least one monomer reacts with the divalent or mutlivalent cations to form ionic cross-links inter-molecularly among polymer chains to form an ionically cross-linked hydrogel composition at a gelation rate;
• and wherein the hydrogel composition contains a predetermined ratio of calcium sulfate dihydrate (CaSO4.2H2O) to calcium carbonate (CaCO3), wherein the ratio of calcium sulfate dihydrate (CaSO4.2H2O) to calcium carbonate (CaCO3) substantially controls the gelation rate.