Hydrogels for vocal cord and soft tissue augmentation and repair
The present invention provides hydrogels and compositions thereof for vocal cord repair or augmentation, as well as other soft tissue repair or augmentation (e.g., bladder neck augmentation, dermal fillers, breast implants, intervertebral disks, muscle-mass). The hydrogels or compositions thereof are injected into the superficial lamina propria or phonatory epithelium to restore the phonatory mucosa of the vocal cords, thereby restoring a patient's voice. In particular, it has been discovered that hydrogels with an elastic shear modulus of approximately 25 Pa are useful in restoring the pliability of the phonatory mucosa. The invention also provides methods of preparing and using the inventive hydrogels.
1. A method of treating a subject having phonatory mucosa with decreased pliability causing diminished functional vibratory capacity and diminished phonation, the method comprising
locating a phonatory mucosa with diminished functional vibratory capacity in the subject; and
injecting into the phonatory mucosa a hydrogel material that comprises an elastic shear modulus ranging from about 15 to about 121 Pa measured at a frequency of 10 Hz in an amount effective to increase pliability of the phonatory mucosa sufficiently to allow the phonatory mucosa to vibrate and improve phonation;
wherein the hydrogel material comprises a first cross-linked synthetic polymer and a second polymer,
wherein the first cross-linked synthetic polymer comprises a cross-linked form of polyethylene glycol, polylysine, polyvinyl alcohol, or hyaluronic acid, and
wherein the second polymer is selected from the group consisting of polyethers, polyacrylates, polyesters, polyanhydrides, polyols, polypeptides, polyvinyl alcohols, proteins, polysaccharides, gelatins, elastins, collagens, celluloses, methylcelluloses, hyaluronic acid, dextrans, alginates, and derivatives thereof, and
wherein the hydrogel material comprises an interpenetrating or semi-interpenetrating network of the first and second polymers.
2. The method of claim 1 , wherein the phonatory mucosa is a part of a vocal cord of the subject.
3. The method of claim 2 , wherein the hydrogel material is injected into a superficial lamina propria of the phonatory mucosa.
4. The method of claim 1 , wherein the phonatory mucosa is part of the larynx.
5. The method of claim 1 , wherein a superficial lamina propria is missing from the phonatory mucosa.
6. The method of claim 1 , wherein the hydrogel material comprises crosslinked polyethylene glycol diacrylate (PEG-DA) and polyethylene glycol (PEG) in a ratio of about 30:70.
7. The method of claim 1 , wherein the hydrogel material has an elastic shear modulus ranging from about 15 to about 35 Pa measured at a frequency of 10 Hz.
8. The method of claim 1 , wherein the hydrogel material has an elastic shear modulus ranging from about 20 to about 30 Pa measured at a frequency of 10 Hz.
9. The method of claim 1 , wherein the hydrogel material has an elastic shear modulus ranging from about 21 to about 25 Pa measured at a frequency of 10 Hz.
10. The method of claim 1 , wherein the first cross-linked synthetic polymer comprises an acrylated polymer or a methacrylated polymer of polyethylene glycol, polylysine, polyvinyl alcohol, or hyaluronic acid.
11. The method of claim 1 , wherein
The first cross-linked synthetic polymer comprises polyethylene glycol diacrylate (PEG-DA); and
the second polymer is selected from the group consisting of polyethylene glycol (PEG), polyols, polyacrylates, polypeptides, poly(lysine), gelatins, elastins, collagens, celluloses, methylcelluloses, polysaccharides, and derivatives thereof.
12. The method of claim 11 , wherein the second polymer comprises polyethylene glycol (PEG).
13. The method of claim 12 , wherein the molecular weight of the PEG-DA is about 10 to about 20 kDa and the molecular weight of the PEG is about 10 to about 20 kDa.
14. The method of claim 11 , wherein the second polymer comprises a polysaccharide.
15. The method of claim 14 , wherein the polysaccharide is selected from the group consisting of hyaluronic acids, dextrans, and alginates.
16. The method of claim 11 , wherein the second polymer comprises a collagen.
17. The method of claim 1 , wherein the
first cross-linked synthetic polymer comprises hyaluronic acid methacrylate;
the second polymer is selected from the group consisting of polyethylene glycol (PEG), polypeptides, hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof; and
wherein the hydrogel material comprises an interpenetrating network of the polymers.
18. The method of claim 7 , wherein the phonatory mucosa is a part of a vocal cord of the subject.
19. The method of claim 18 , wherein the hydrogel material is injected into a superficial lamina propria of the phonatory mucosa.
20. The method of claim 7 , wherein the phonatory mucosa is part of the larynx.
21. The method of claim 7 , wherein the hydrogel material comprises crosslinked polyethylene glycol diacrylate (PEG-DA) and polyethylene glycol (PEG) in a ratio of about 30:70.
22. The method of claim 7 , wherein
the first cross-linked synthetic polymer comprises polyethylene glycol diacrylate (PEG-DA); and
the second polymer is selected from the group consisting of polyethylene glycol (PEG), polyols, polyacrylates, polypeptides, gelatins, elastins, collagens, celluloses, methylcelluloses, polysaccharides, and derivatives thereof.
23. The method of claim 7 , wherein the
the first cross-linked synthetic polymer comprises hyaluronic acid methacrylate; and
the second polymer is selected from the group consisting of polyethylene glycol (PEG), polypeptides, hyaluronic acid (HA), dextrans, alginates, gelatins, elastins, collagens, celluloses, methylcelluloses, and derivatives thereof.