Adhesive compositions with tunable porosity and acidity content and methods of use thereof

A method of preparing an adhesive composition, comprising:

• (i) providing a mixture of a multivalent metal salt, multidentate acidic organic compound, and a carbonate salt;
• (ii) contacting the mixture with an aqueous medium;
• and
• (iii) adding a pH adjusting agent to the mixture to bring a pH of the mixture to a value between 7 to 10,
• thereby preparing the adhesive composition.

A method of preparing an adhesive composition, comprising:

• (i) providing a mixture of a multivalent metal salt, multidentate acidic organic compound, and a carbonate salt;
• (ii) contacting the mixture with an aqueous medium;
• and
• (iii) adding a pH adjusting agent to the mixture to evolve a gas from the mixture,
• wherein the adhesive composition, upon curing, has a porosity between about 10% to about 50%,
• thereby preparing the adhesive composition.

A method of preparing an adhesive composition, comprising:

• (i) providing a mixture of a multivalent metal salt, multidentate acidic organic compound, and a carbonate salt;
• (ii) contacting the mixture with an aqueous medium;
• and
• (iii) adding a pH adjusting agent to the mixture to evolve a gas from the mixture,
• wherein the adhesive composition, upon curing, has a plurality of pores having a pore size of between 20 μm to 200 m,
• thereby preparing the adhesive composition.

A method of generating or regenerating bone tissue, the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby generating or regenerating bone tissue.

A method of inducing osteoblast formation, the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing osteoblast formation.

A method of treating or preventing a bone disease or disorder in a subject, the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby treating or preventing the bone disease or disorder in the subject.

A method of inducing expression of MKI67, the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%,
• thereby inducing expression of MKI67.

A method of inducing expression of Bone Morphogenetic protein-2 (BMP2), the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing expression of Bone Morphogenetic protein-2 (BMP2).

A method of inducing expression of Vascular Endothelial Growth factor (VEGF), the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing expression of Vascular Endothelial Growth factor (VEGF).

A method of inducing expression of one or both of caspase-3 and caspase-9, the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing expression of one or both of caspase-3 and caspase-9.

A method of inducing expression of Interleukin-6 (IL-6), the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto bone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing expression of Interleukin-6 (IL-6).

A method of inducing expression of tumor necrosis factor alpha (TNF-α), the method comprising:

• a) preparing an adhesive composition comprising a multivalent metal salt, an multidentate acidic organic compound, and a carbonate salt in an aqueous medium;
• b) applying the adhesive composition to a site (e.g., into or onto hone, or in between bones or bone fragments);
• and
• c) allowing the adhesive composition to harden, cure, or be resorbed by bone, the adhesive composition, upon curing, having a porosity between about 10% to about 50%;
• thereby inducing expression of tumor necrosis factor alpha (TNF-α).