Photocrosslinkable oligo(poly (ethylene glycol) fumarate) hydrogels for cell and drug delivery
View Patent ↗The invention provides photocrosslinkable, injectable, biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels made from the photopolymerization of an OPF macromer with UV light and a photoinitiator. Hydrogels with varying mechanical properties and water content can be made with changes in macromer and crosslinking agent concentration in a precursor solution. The biodegradable OPF hydrogels can be injected as a fluid into a bodily defect of any shape, may incorporate various therapeutic agents, e.g., cells and/or growth factors, and may be implanted via minimally invasive arthroscopic techniques.
1. A scaffold for tissue regeneration, the scaffold comprising:
i) a biodegradable matrix comprising a hydrogel comprising oligo(poly(ethylene glycol) fumarate);
an unsaturated pyrrolidinone monomer; and
a photoinitiator; wherein the oligo(poly(ethylene glycol) fumarate) is photocrosslinked with the unsaturated pyrrolidinone monomer using the photoinitiator; and
ii) cells selected from the group consisting of chondrogenic cells and osteogenic cells.
2. The scaffold of claim 1 wherein:
the cells are encapsulated in the matrix.
3. The scaffold of claim 1 wherein:
the matrix has a surface and the cells are adhered to the surface of the matrix.
4. The scaffold of claim 3 wherein:
the cells have a spherical morphology.
5. The scaffold of claim 3 wherein:
the cells have a flattened morphology.
6. The scaffold of claim 1 wherein:
the scaffold is porous.
7. The scaffold of claim 6 wherein:
the hydrogel further comprises a porogen, wherein the oligo(poly(ethylene glycol) fumarate) is photocrosslinked with the unsaturated pyrrolidinone monomer using the photoinitiator in the presence of the porogen.
8. The scaffold of claim 6 wherein:
the scaffold has a porosity of 70% to 90%.
9. The scaffold of claim 1 wherein:
the cells are chondrogenic cells.
10. The scaffold of claim 1 wherein:
the cells are osteogenic cells.
11. The scaffold of claim 1 wherein:
the cells are suspended in collagen or a collagen derivative selected from the group consisting of gelatin and atelocollagen.
12. The scaffold of claim 1 wherein a weight ratio of oligo(poly(ethylene glycol) fumarate) to pyrrolidinone monomer before the oligo(poly(ethylene glycol) fumarate) is photocrosslinked with the unsaturated pyrrolidinone monomer using the photoinitiator is in the range of 1:0.01 to 1:0.5.
13. The scaffold of claim 1 wherein the unsaturated pyrrolidinone monomer is N-vinyl pyrrolidinone.
14. A method of making a scaffold for tissue regeneration, the scaffold comprising a biodegradable matrix comprising a hydrogel, the method comprising:
providing cells selected from the group consisting of chondrogenic cells and osteogenic cells;
providing oligo(poly(ethylene glycol) fumarate) and an unsaturated pyrrolidinone monomer, wherein a weight ratio of the oligo(poly(ethylene glycol) fumarate) to the unsaturated pyrrolidinone monomer is in the range of 1:0.01 to 1:0.5; and
photocrosslinking the oligo(poly(ethylene glycol) fumarate) and the unsaturated pyrrolidinone monomer using a photoinitiator and the cells.
15. The method of claim 14 , the method further comprising:
selecting the weight ratio of the oligo(poly(ethylene glycol) fumarate) to the unsaturated pyrrolidinone monomer to adjust mechanical properties of the scaffold.
16. The method of claim 14 , the method further comprising:
selecting the weight ratio of the oligo(poly(ethylene glycol) fumarate) to the unsaturated pyrrolidinone monomer to adjust swelling ratio and permeation of the scaffold.
17. The method of claim 14 , the method further comprising:
fabricating a three-dimensional scaffold using stereo-lithography.
18. The method of claim 14 wherein the monomer is N-vinyl pyrrolidinone.