Dextrin hydrogel for biomedical applications
A hydrogel formulation of oxidized dextrin is reticulated with adipic acid dihydrazide, which may embody polysaccharides, proteins, nanogels, granular materials, bioactive molecules and cells for tissue regeneration and controlled drug delivery. A hydrogel can be injectable, highly biocompatible and biodegradable, for tissue regenerative applications, performing simultaneously as a vehicle e.g. for nanogels, granular materials and cells, and as controlled drug delivery systems, e.g. of hydrophobic molecules and therapeutic proteins.
1. A hydrogel formulation comprising a hydrogel of oxidized dextrin reticulated with adipic acid dihydrazide comprising the following structure:
wherein the hydrogel comprises a three-dimensional porous structure, and wherein the three-dimensional porous structure is capable of enclosing polysaccharides, proteins, nanogels, nanoparticles, granular materials, bioactive molecules and/or cells, and wherein the dextrin has a molecular weight between 1200 and 8000 Da.
2. The hydrogel formulation according to claim 1 , wherein the proteins comprise collagen, fibronectin, and casein.
3. The hydrogel formulation according to claim 1 , wherein the hydrogel formulation comprises proteins, and wherein the proteins are included in a percentage between 0-20% of the hydrogel formulation, by dry weight.
4. The hydrogel formulation according to claim 1 , wherein the polysaccharides comprise chitosan and hyaluronic acid.
5. The hydrogel formulation according to claim 1 , wherein the hydrogel formulation comprises polysaccharides, and wherein the polysaccharides are included in a percentage between 0-20 of the hydrogel formulation, by dry weight.
6. The hydrogel formulation according to claim 1 , wherein the hydrogel formulation is injectable.
7. The hydrogel formulation according to claim 1 , wherein the hydrogel formulation is non-toxic.
8. The hydrogel formulation according to claim 1 , wherein the hydrogel formulation is non-haemolytic.
9. The hydrogel formulation according to claim 1 , wherein the hydrogel is obtained from a dextrin with an oxidation degree between 25-35%.
10. The hydrogel formulation according to claim 1 , wherein the hydrogel comprises a continuous porous structure, with a diameter of about 1 μm.
11. The hydrogel formulation according to claim 1 , wherein the hydrogel is biodegradable, and wherein biodegradation of the hydrogel occurs by either surface erosion or bulk erosion.
12. The hydrogel formulation according to claim 1 , wherein the hydrogel is degradable, and wherein degradation of the hydrogel comprises hydrolytic degradation of covalent intermolecular bonds or enzymatic degradation through action of α-amylase present in human tissues or included in the hydrogel formulation.
13. The hydrogel formulation according to claim 1 , wherein the hydrogel is degradable, and wherein degradation occurs by bulk erosion and comprises a non-linear degradation profile accompanied by an increasing pore size.
14. Method of producing the hydrogel formulation of claim 1 , comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.
15. The method according to claim 14 , wherein the percentage of adipic acid dihydrazide used is between 3-10%, on a molar basis relative to the glucose residues of dextrin.
16. The method according to claim 14 , wherein the concentration of oxidized dextrin is between 25-30% (w/v).
17. The method according to claim 14 , wherein the gelification occurs during a gelification period of 1 to 30 minutes.
18. The method according to claim 14 , wherein a nanogel or nanoparticle is incorporated in the hydrogel.
19. The method according to claim 18 wherein the nanogel or nanoparticle is between 10-10,000 nm in size.
20. The method according to claim 18 , wherein incorporation of the nanogel or nanoparticle in the hydrogel is carried out by mixing the nanogel or nanoparticle with the oxidized dextrin, prior to addition of adipic acid dihydrazide.
21. The method according to claim 18 , wherein the nanogel or nanoparticle is incorporated in a proportion of 1-25% of the dextrin weight.
22. The method according to claim 18 , wherein the nanogel or nanoparticle is previously loaded with pharmaceuticals.
23. A method for tissue regeneration or controlled drug delivery comprising administering the hydrogel of claim 1 .
24. A biomaterial comprising the hydrogel described in claim 1 .
25. A synthetic bone substitute comprising the hydrogel of claim 1 and obtained by a method comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.
26. A system for controlled drug delivery comprising the hydrogel of claim 1 and obtained by a method comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.
27. A bone implant or bone filler comprising the hydrogel of claim 1 and obtained by a method comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.
28. A composition comprising the hydrogel of claim 1 and obtained by a method comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.
29. A medical prosthesis comprising the hydrogel of claim 1 and obtained by a method comprising:
a) oxidation of dextrin with periodate;
b) removal of unreacted periodate;
c) gelification by addition of adipic acid dihydrazide, at pH in the range 5.0-7.5.