Implantable modular hydrogel for salivary gland restoration

1. A hydrogel network comprising: a hyaluronic acid macromer crosslinked with a crosslinker, wherein the crosslinker is a multiblock copolymer, wherein the multiblock copolymer comprises an alternating copolymer of poly(ethylene glycol) (PEG) and a peptide epitope of perlecan, or an alternating copolymer of poly(acrylic acid) and a hydrophobic peptide.

2. The hydrogel network of claim 1 , wherein the multiblock copolymer comprises a multiblock copolymer of perlecan domain IV (P1nDIV) peptide alternating with PEG.

3. The hydrogel network of claim 1 , wherein the multiblock copolymer comprises a multiblock copolymer of poly(acrylic acid) alternating with a hydrophobic peptide of sequence (VPGVG) 2 .

4. The hydrogel network of claim 1 wherein the hydrogel network is biocompatible.

5. A kit comprising a hyaluronic acid macromer and a crosslinker, wherein the crosslinker is a multiblock copolymer, wherein the multiblock copolymer comprises an alternating copolymer of poly(ethylene glycol) and a peptide epitope of perlecan, or an alternating copolymer of poly(acrylic acid) and a hydrophobic peptide.

6. The kit of claim 5 wherein the hyaluronic acid macromer comprises an unsaturated double bond.

7. The kit of claim 5 wherein the hyaluronic acid macromer comprises an acrylate.

8. The kit of claim 5 further comprising hyaluronic acid hydrogel particles.

9. The kit of claim 8 wherein the hyaluronic acid hydrogel particles further comprise a growth factor.

10. The kit of claim 8 wherein the hyaluronic acid hydrogel particles are angiogenic.

11. A method of forming a hydrogel network comprising: providing a hyaluronic acid macromer; providing a crosslinker, wherein the crosslinker is a multiblock copolymer comprising an alternating copolymer of PEG and a peptide epitope of perlecan, or an alternating copolymer of poly(acrylic acid) and a hydrophobic peptide, and crosslinking the hyaluronic acid macromer with the crosslinker to form the hydrogel network.

12. The method of claim 11 , wherein the multiblock copolymer comprises a multiblock copolymer of P1nDIV peptide alternating with PEG.

13. The method of claim 11 , wherein the multiblock copolymer comprises a multiblock copolymer of poly(acrylic acid) alternating with a hydrophobic peptide of sequence (VPGVG)2.

14. The method of claim 11 further comprising encapsulating cells within the hydrogel network.

15. The method of claim 11 further comprising encapsulating hyaluronic acid hydrogel particles within the hydrogel network.

16. The method of claim 11 wherein two or more hydrogel networks are combined to form a secondary hydrogel network.

17. The method of claim 16 wherein the secondary hydrogel network is a 3D construct.

18. A method of constructing a biomimetic matrix comprising:

providing a hyaluronic acid hydrogel network comprising a hyaluronic acid macromer crosslinked with a crosslinker, wherein the crosslinker is a multiblock copolymer comprising an alternating copolymer of poly(ethylene glycol) (PEG) and a peptide epitope of perlecan, or an alternating copolymer of poly(acrylic acid) and a hydrophobic peptide;

providing hyaluronic acid hydrogel particles;

providing salivary cells; and

co-encapsulating the hyaluronic acid hydrogel particles and the salivary cells within the hyaluronic acid hydrogel network to form cell-laden microgel modules.

19. The method of claim 18 , further comprising: combining multiple cell-laden microgel modules into a secondary hyaluronic acid network to yield a 3D network.

20. The method of claim 18 wherein the cells are treated with at least one of a β-adrenergic agonist, a M3 muscarinic agonist, and combinations thereof.

21. A composition comprising: a hyaluronic acid macromer; a crosslinker comprising a multiblock copolymer comprising a copolymer of P1nDIV peptide alternating with PEG; and hyaluronic acid hydrogel particles.

22. The composition of claim 21 further comprising cells.