Methods and compositions related to physiologically responsive microneedle delivery systems

1. A device for transport of a material across a biological barrier of a subject comprising:

a plurality of microneedles each having a base end and a tip, with at least one pathway disposed at or between the base end and the tip;

a substrate to which the base ends of the microneedles are attached or integrated;

at least one reservoir which is in connection with the base ends of the microneedles array, wherein the reservoir comprises an agent delivery system, wherein the agent delivery system comprises an agent to be transported across the biological barrier, or a means for producing an agent to be transported across the biological barrier, and a means for detecting a physiological signal from the recipient, wherein said means for producing an agent to be transported across the biological barrier and said means for detecting a physiological signal both comprise viable, cultured cells; and

a signal amplifier system integrated within the microneedles, wherein the signal amplifier system comprises a component capable of amplifying the physiological signal from the recipient wherein the means for producing an agent to be transported across the biological barrier produces an agent, or changes the amount of agent produced, based on an amplified signal from the signal amplifier system.

2. The device of claim 1 , wherein the agent delivery system comprises a feedback component, such that volume or amount of the agent to be transported across the biological barrier can be altered based on the physiological signal.

3. The device of claim 2 , wherein the physiological signal from the recipient is insufficient to be detected by the feedback component without amplification from the signal amplifier system.

4. The device of claim 1 , wherein the cells are pancreatic β cells or stem cell-differentiated human pancreatic cells.

5. The device of claim 1 , wherein the reservoir is semi-permeable.

6. The device of claim 1 , wherein the reservoir comprises an alginate microgel.

7. The device of claim 1 , wherein the reservoir comprises a therapeutic, prophylactic, or diagnostic agent.

8. The device of claim 7 , wherein the agent is selected from the group consisting of peptides, proteins, carbohydrates, nucleic acid molecules, lipids, organic molecules, biologically active inorganic molecules, and combinations thereof.

9. The device of claim 8 , wherein the agent is insulin.

10. The device of claim 7 , wherein the biological substance is glucose.

11. The device of claim 1 , wherein the physiological signal is a biological substance in the subject.

12. The device of claim 11 , wherein the physiological response in the subject comprises physiological environment factors, including pH, temperature, blood glucose levels and other biomarkers.

13. The device of claim 1 , wherein the signal amplifier system comprises self-assembled polymeric nanosized vesicles.

14. The device of claim 13 , wherein the glucose signal amplifier comprises glucose oxidase, α-amylase, and glucoamylase.

15. The device of claim 1 , wherein the signal amplifier system is in the tip of the microneedle.

16. The method of claim 1 , wherein said viable, cultured cells are mammalian cells.