3D-printed scaffold device for cell transplantation
Disclosed herein is a 3D-printed, biocompatible macroporous device that houses stem cell derived β-cell (SC-β cell) clusters within a degradable fibrin gel. Cluster sizes are used that avoid severe hypoxia within 3D-printed devices and a microwell-based technique is used for resizing clusters within this range. 3D-printed devices may function for at least 12 weeks, are retrievable, and maintain structural integrity.
1. A 3D-printed device for transplanting cells into a patient, the device comprising:
a 3D-printed biocompatible polymer scaffold comprising uniform pores; and
a plurality of cells embedded in a degradable hydrogel, wherein a mixture of the plurality of cells and degradable hydrogel is housed within the pores of the 3D-printed biocompatible polymer scaffold,
wherein the plurality of cells are stem cell derived β-cells.
2. The 3D-printed device of claim 1 , wherein the plurality of cells in the device release a biologically active agent in response to a biological factor in the patient.
3. The 3D-printed device of claim 1 , wherein the pores are less than 200 μm in length or diameter.
4. The 3D-printed device of claim 1 , wherein the device has a length between about 10 mm and about 25 mm.
5. The 3D-printed device of claim 1 , wherein the device has a width between about 5 mm and about 10 mm.
6. The 3D-printed device of claim 1 , wherein the device has a thickness between about 2 mm and about 5 mm.
7. The 3D-printed device of claim 1 , wherein the biocompatible polymer comprises polylactic acid (PLA), polycaprolactone, polyvinyl alcohol (PVA), gelatin methacrylate or combinations thereof.
8. The 3D-printed device of claim 1 , wherein the degradable hydrogel comprises fibrin, collagen, alginate, triazole-thiomorpholine dioxide alginate, polyethylene glycol (PEG), PTFE, polyglycolic acid (PGA), poly-l-lactic acid (PLLA), polyhydroxyalkanoate, polycaprolactone-copolylactic acid, polylactide-coglycolide (PLGA), PDMS, polycaprolactone, gelatin methacrylate, or combinations thereof.
9. The 3D-printed device of claim 1 , wherein the implanted cells are in a cluster, wherein each pore contains one cluster of cells.
10. A 3D-printed device for transplanting cells into a patient, the device comprising:
a biocompatible polymer scaffold comprising uniform pores; and
a plurality of cells housed within the pores of the biocompatible polymer scaffold,
wherein the plurality of cells and biocompatible polymer are bioprinted to form the 3D-printed device, and wherein the plurality of cells are stem cell derived β-cells.
11. The device of claim 10 , wherein the biocompatible polymer is gelatin methacrylate.
12. A method for transplanting cells into a patient comprising:
embedding a plurality of stem cell derived β-cells into a degradable hydrogel;
implanting the degradable hydrogel with the plurality of cells into pores of a 3D-printed device; and
implanting the 3D-printed device into the patient.
13. The method of claim 12 , wherein the plurality of cells are in a cluster, wherein each pore contains one cluster of cells.
14. A method of treating a patient in need thereof, comprising,
implanting into the patient a 3D-printed device comprising a 3D-printed biocompatible polymer comprising uniform pores; a plurality of stem cell derived β-cells implanted within the pores of the 3D-printed biocompatible polymer; and a degradable hydrogel surrounding the plurality of cells,
wherein the plurality of cells in the 3D-printed device release a biologically active agent in response to a biological factor in the patient.
15. The method of claim 14 , wherein the biological factor is glucose.
16. The method of claim 14 , wherein the biologically active agent is insulin.