Diffusively permeable monolithic biomaterial with embedded microfluidic channels
The present invention relates to a monolithic biomaterial. The monolithic biomaterial has a primary network of convective flow, microfluidic channels that are embedded in a substrate, where the substrate is diffusively permeable to aqueous solutes. The present invention also relates to a method of making the monolithic biomaterial, as well as methods of using the monolithic biomaterial to facilitate healing of a cutaneous wound of a mammalian subject and of regulating cells.
1. A monolithic biomaterial comprising:
a substrate which is diffusively permeable to aqueous solutes and capable of supporting living cells when seeded in the substrate and
a primary network of convective flow, microfluidic channels embedded in the substrate, whereby aqueous solutes in the substrate will diffuse into said primary network of convective flow, microfluidic channels.
2. The monolithic biomaterial according to claim 1 , wherein said substrate comprises a hydrogel.
3. The monolithic biomaterial according to claim 2 , wherein said hydrogel is selected from the group consisting of alginate, an acrylate-based hydrogel, collagen, and a collagen-glycosamino-glycan co-precipitate.
4. The monolithic biomaterial according to claim 2 , wherein said hydrogel is seeded with a plurality of viable cells.
5. The monolithic biomaterial according to claim 4 , wherein said viable cells are of multiple cell types.
6. The monolithic biomaterial according to claim 4 , wherein said viable cells are seeded on or proximate to a wall of at least one of the microfluidic channels.
7. The monolithic biomaterial according to claim 4 , wherein said viable cells are homogeneously dispersed throughout the hydrogel.
8. The monolithic biomaterial according to claim 4 , wherein said viable cells comprise chondrocytes.
9. The monolithic biomaterial according to claim 2 , wherein said hydrogel further comprises a cross-linking compound.
10. The monolithic biomaterial according to claim 9 , wherein said hydrogel comprises alginate and the alginate and the cross-linking compound are present in a ratio of about 1:100 to 100:1, respectively.
11. The monolithic biomaterial according to claim 1 , wherein said substrate has an anatomic shape.
12. The monolithic biomaterial according to claim 1 , wherein said primary network of microfluidic channels comprises a plurality of main microfluidic channels arranged substantially parallel to one another.
13. The monolithic biomaterial according to claim 12 , wherein said primary network of microfluidic channels further comprises a plurality of subsidiary microfluidic channels arranged substantially perpendicular to said main microfluidic channels.
14. The monolithic biomaterial according to claim 1 , wherein said primary network of microfluidic channels comprises a plurality of main microfluidic channels having subsidiary microfluidic channels branching from said main microfluidic channels.
15. The monolithic biomaterial according to claim 14 , wherein said subsidiary microfluidic channels have cross-sectional dimensions that are smaller than those of the main microfluidic channels.
16. The monolithic biomaterial according to claim 1 further comprising at least one inlet portion suitable for delivering an incoming fluid into the primary network of microfluidic channels and at least one outlet portion suitable for removing an outgoing fluid from the primary network of microfluidic channels.
17. The monolithic biomaterial according to claim 1 further comprising a secondary network of microfluidic channels in the substrate, wherein said secondary network is independent from the primary network.
18. The monolithic biomaterial according to claim 17 , wherein said primary network and said secondary network are separated by a diffusively permeable material.
19. The monolithic biomaterial according to claim 17 further comprising at least one inlet portion suitable for delivering an incoming fluid into the primary and secondary network of microfluidic channels and at least one outlet portion suitable for removing an outgoing fluid from the primary and secondary network of microfluidic channels.
20. The monolithic biomaterial according to claim 1 , wherein said microfluidic channels have cross-sectional dimensions comprising between about 1×10 −1 μm to about 1×10 3 μm in width and between about 1×10 ˜ 1 μm to about 1×10 3 μm in height.