Soft robots with autonomous adaptation for effective drug delivery amidst fibrous encapsulation
Data files
Mar 06, 2024 version files 11.52 MB
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_0.3agarose_device1_repeat_1_.csv
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_0.3agarose_device1_repeat_1_(1).csv
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_0.3agarose_device1_repeat_1_(2).csv
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_0.3agarose_device1_repeat_1_(3).csv
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_0.3agarose_device1_repeat_1_(4).csv
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_0.3agarose_device2_repeat_1_.csv
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_0.3agarose_device2_repeat_1_(1).csv
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_0.3agarose_device2_repeat_1_(2).csv
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_0.3agarose_device2_repeat_1_(3).csv
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_0.3agarose_device2_repeat_1_(4).csv
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_0.3agarose_device2_repeat_1_(5).csv
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_0.3agarose_device2_repeat_1_(6).csv
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_0.3agarose_device2_repeat_1_(7).csv
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_0.3agarose_device2_repeat_1_(8).csv
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_0.3agarose_device2_repeat_1_(9).csv
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_0.3agarose_device3_repeat_1_.csv
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_0.3agarose_device3_repeat_1_(1).csv
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_0.3agarose_device3_repeat_1_(2).csv
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_0.3agarose_device3_repeat_1_(3).csv
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_0.3agarose_device3_repeat_1_(4).csv
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_0.3agarose_device4_repeat_1_.csv
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_0.3agarose_device4_repeat_1_(1).csv
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_0.3agarose_device4_repeat_1_(2).csv
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_0.3agarose_device4_repeat_1_(3).csv
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_0.3agarose_device4_repeat_1_(4).csv
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_0.3agarose_device5_repeat_1_(1).csv
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_0.3agarose_device5_repeat_1_(2).csv
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_0.3agarose_device5_repeat_1_(3).csv
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_0.3agarose_device5_repeat_1_(4).csv
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_0.3agarose_device5_repeat_1_(5).csv
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_0.3agarose_device6_repeat_1_.csv
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_0.3agarose_device6_repeat_1_(1).csv
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_0.3agarose_device6_repeat_1_(2).csv
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_0.3agarose_device6_repeat_1_(3).csv
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_0.3agarose_device6_repeat_1_(4).csv
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_0.6agarose_device1_repeat_1_.csv
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_0.6agarose_device1_repeat_1_(1).csv
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_0.6agarose_device1_repeat_1_(2).csv
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_0.6agarose_device1_repeat_1_(3).csv
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_0.6agarose_device1_repeat_1_(4).csv
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_0.6agarose_device2_repeat_1_.csv
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_0.6agarose_device2_repeat_1_(1).csv
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_0.6agarose_device2_repeat_1_(2).csv
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_0.6agarose_device2_repeat_1_(3).csv
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_0.6agarose_device2_repeat_1_(4).csv
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_0.6agarose_device3_repeat_1_.csv
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_0.6agarose_device3_repeat_1_(1).csv
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_0.6agarose_device3_repeat_1_(2).csv
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_0.6agarose_device3_repeat_1_(3).csv
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_0.6agarose_device3_repeat_1_(4).csv
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_0.6agarose_device4_repeat_1_(2).csv
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_0.6agarose_device4_repeat_1_(3).csv
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_0.6agarose_device4_repeat_1_(4).csv
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_0.6agarose_device4_repeat_1_(5).csv
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_0.6agarose_device4_repeat_1_(6).csv
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_0.6agarose_device5_repeat_1_.csv
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_0.6agarose_device5_repeat_1_(1).csv
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_0.6agarose_device5_repeat_1_(2).csv
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_0.6agarose_device5_repeat_1_(3).csv
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_0.6agarose_device5_repeat_1_(4).csv
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_0.6agarose_device6_repeat_1_(4).csv
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_0.6agarose_device6_repeat_1_(5).csv
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_0.6agarose_device6_repeat_1_(6).csv
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_0.6agarose_device6_repeat_1_(7).csv
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_0.6agarose_device6_repeat_1_(8).csv
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_Xagarose_device_7_run1_.csv
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_Xagarose_device_7_run1_(1).csv
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_Xagarose_device_7_run1_(2).csv
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_Xagarose_device_7_run1_(3).csv
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_Xagarose_device_7_run1_(4).csv
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A1_Left_Device1_Day1_m1.csv
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A1_Left_Device1_Day1_m2.csv
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A1_Left_Device1_Day1_m3.csv
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A1_Left_Device1_Day1_m4.csv
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A1_Left_Device1_Day1_m5.csv
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A1_Right_Device2_Day1_m1.csv
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A1_Right_Device2_Day1_m2.csv
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A1_Right_Device2_Day1_m3.csv
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A1_Right_Device2_Day1_m4.csv
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A1_Right_Device2_Day1_m5.csv
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A3_Left_Device6_Day1_m1.csv
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A3_Left_Device6_Day1_m2.csv
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A3_Left_Device6_Day1_m3.csv
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A3_Left_Device6_Day1_m4.csv
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A3_Left_Device6_Day1_m5.csv
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A3_Left_Device6_Day3_m1.csv
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A3_Left_Device6_Day3_m2.csv
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A3_Left_Device6_Day3_m3.csv
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A3_Left_Device6_Day3_m4.csv
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A3_Left_Device6_Day3_m5.csv
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B1_Left_Device8_Day1_m1.csv
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B1_Left_Device8_Day1_m2.csv
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B1_Left_Device8_Day1_m3.csv
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B1_Left_Device8_Day1_m4.csv
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B1_Left_Device8_Day1_m5.csv
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B1_Right_Device7_Day1_m1.csv
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B1_Right_Device7_Day1_m2.csv
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B1_Right_Device7_Day1_m3.csv
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B1_Right_Device7_Day1_m4.csv
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B1_Right_Device7_Day1_m5.csv
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B5_Left_Device11_Day1_m1.csv
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B5_Left_Device11_Day1_m2.csv
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B5_Left_Device11_Day1_m3.csv
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B5_Left_Device11_Day1_m4.csv
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B5_Left_Device11_Day1_m5.csv
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B5_Left_Device11_Day3_m1.csv
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B5_Left_Device11_Day3_m2.csv
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B5_Left_Device11_Day3_m3.csv
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B5_Left_Device11_Day3_m4.csv
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B5_Left_Device11_Day3_m5.csv
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B5_Left_Device11_Day5_m1.csv
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B5_Left_Device11_Day5_m2.csv
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B5_Left_Device11_Day5_m3.csv
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B5_Left_Device11_Day5_m4.csv
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B5_Left_Device11_Day5_m5.csv
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B5_Right_Device12_Day1_m1.csv
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B5_Right_Device12_Day1_m2.csv
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B5_Right_Device12_Day1_m3.csv
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B5_Right_Device12_Day1_m4.csv
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B5_Right_Device12_Day1_m5.csv
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B5_Right_Device12_Day3_m1.csv
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B5_Right_Device12_Day3_m2.csv
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B5_Right_Device12_Day3_m3.csv
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B5_Right_Device12_Day3_m4.csv
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B5_Right_Device12_Day3_m5.csv
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B5_Right_Device12_Day5_m1.csv
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B5_Right_Device12_Day5_m2.csv
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B5_Right_Device12_Day5_m3.csv
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B5_Right_Device12_Day5_m4.csv
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B5_Right_Device12_Day5_m5.csv
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B7_Left_Device13_Day1_m1.csv
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B7_Left_Device13_Day1_m2.csv
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B7_Left_Device13_Day1_m3.csv
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B7_Left_Device13_Day1_m4.csv
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B7_Left_Device13_Day1_m5.csv
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B7_Left_Device13_Day3_m1.csv
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B7_Left_Device13_Day3_m2.csv
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B7_Left_Device13_Day3_m3.csv
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B7_Left_Device13_Day3_m4.csv
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B7_Left_Device13_Day5_m1.csv
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B7_Left_Device13_Day5_m2.csv
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B7_Left_Device13_Day5_m3.csv
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B7_Left_Device13_Day5_m4.csv
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B7_Left_Device13_Day5_m5.csv
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B7_Left_Device13_Day7_m1.csv
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B7_Left_Device13_Day7_m2.csv
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B7_Left_Device13_Day7_m3.csv
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B7_Left_Device13_Day7_m4.csv
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B7_Left_Device13_Day7_m5.csv
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B7_Right_Device14_Day1_m1.csv
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B7_Right_Device14_Day1_m2.csv
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B7_Right_Device14_Day1_m3.csv
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B7_Right_Device14_Day1_m4.csv
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B7_Right_Device14_Day1_m5.csv
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B7_Right_Device14_Day3_m1.csv
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B7_Right_Device14_Day3_m2.csv
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B7_Right_Device14_Day3_m3.csv
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B7_Right_Device14_Day3_m4.csv
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B7_Right_Device14_Day3_m5.csv
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B7_Right_Device14_Day5_m1.csv
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B7_Right_Device14_Day5_m2.csv
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B7_Right_Device14_Day5_m3.csv
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B7_Right_Device14_Day5_m4.csv
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B7_Right_Device14_Day5_m5.csv
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B7_Right_Device14_Day7_m1.csv
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B7_Right_Device14_Day7_m2.csv
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B7_Right_Device14_Day7_m3.csv
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B7_Right_Device14_Day7_m4.csv
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B7_Right_Device14_Day7_m5.csv
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C1_Left_Device16_Day1_m1.csv
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C1_Left_Device16_Day1_m2.csv
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C1_Left_Device16_Day1_m3.csv
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C1_Left_Device16_Day1_m4.csv
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C1_Left_Device16_Day1_m5.csv
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C1_Right_Device15_Day1_m1.csv
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C1_Right_Device15_Day1_m2.csv
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C1_Right_Device15_Day1_m3.csv
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C1_Right_Device15_Day1_m4.csv
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C1_Right_Device15_Day1_m5.csv
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C3_Left_Device17_Day1_m1.csv
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C3_Left_Device17_Day1_m2.csv
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C3_Left_Device17_Day1_m3.csv
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C3_Left_Device17_Day1_m4.csv
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C3_Left_Device17_Day1_m5.csv
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C3_Left_Device17_Day3_m1.csv
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C3_Left_Device17_Day3_m2.csv
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C3_Left_Device17_Day3_m3.csv
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C3_Left_Device17_Day3_m4.csv
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C3_Left_Device17_Day3_m5.csv
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C3_Right_Device19_Day1_m1.csv
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C3_Right_Device19_Day1_m2.csv
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C3_Right_Device19_Day1_m3.csv
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C3_Right_Device19_Day1_m4.csv
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C3_Right_Device19_Day1_m5.csv
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C3_Right_Device19_Day3_m1.csv
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C3_Right_Device19_Day3_m2.csv
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C3_Right_Device19_Day3_m3.csv
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C3_Right_Device19_Day3_m4.csv
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C3_Right_Device19_Day3_m5.csv
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C5_Left_Device18_Day1_m1.csv
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C5_Left_Device18_Day1_m2.csv
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C5_Left_Device18_Day1_m3.csv
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C5_Left_Device18_Day1_m4.csv
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C5_Left_Device18_Day1_m5.csv
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C5_Left_Device18_Day3_m1.csv
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C5_Left_Device18_Day3_m2.csv
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C5_Left_Device18_Day3_m3.csv
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C5_Left_Device18_Day3_m4.csv
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C5_Left_Device18_Day3_m5.csv
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C5_Left_Device18_Day5_m1.csv
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C5_Left_Device18_Day5_m2.csv
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C5_Left_Device18_Day5_m3.csv
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C5_Left_Device18_Day5_m4.csv
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C5_Left_Device18_Day5_m5.csv
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C5_Right_Device20_Day1_m1.csv
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C5_Right_Device20_Day1_m2.csv
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C5_Right_Device20_Day1_m3.csv
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C5_Right_Device20_Day1_m4.csv
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C5_Right_Device20_Day1_m5.csv
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C5_Right_Device20_Day3_m1.csv
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C5_Right_Device20_Day3_m2.csv
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C5_Right_Device20_Day3_m3.csv
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C5_Right_Device20_Day3_m4.csv
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C5_Right_Device20_Day3_m5.csv
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C5_Right_Device20_Day5_m1.csv
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C5_Right_Device20_Day5_m2.csv
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C5_Right_Device20_Day5_m3.csv
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C5_Right_Device20_Day5_m4.csv
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C5_Right_Device20_Day5_m5.csv
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C7_Left_Device21_Day1_m1.csv
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C7_Left_Device21_Day1_m2.csv
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C7_Left_Device21_Day1_m3.csv
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C7_Left_Device21_Day1_m4.csv
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C7_Left_Device21_Day1_m5.csv
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C7_Left_Device21_Day3_m1.csv
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C7_Left_Device21_Day3_m2.csv
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C7_Left_Device21_Day3_m3.csv
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C7_Left_Device21_Day3_m4.csv
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C7_Left_Device21_Day3_m5.csv
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C7_Left_Device21_Day5_m1.csv
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C7_Left_Device21_Day5_m2.csv
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C7_Left_Device21_Day5_m3.csv
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C7_Left_Device21_Day5_m4.csv
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C7_Left_Device21_Day5_m5.csv
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C7_Left_Device21_Day7_m1.csv
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C7_Left_Device21_Day7_m2.csv
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C7_Left_Device21_Day7_m3.csv
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C7_Left_Device21_Day7_m4.csv
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C7_Left_Device21_Day7_m5.csv
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C7_Right_Device22_Day1_m1.csv
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C7_Right_Device22_Day1_m2.csv
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C7_Right_Device22_Day1_m3.csv
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C7_Right_Device22_Day1_m4.csv
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C7_Right_Device22_Day1_m5.csv
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C7_Right_Device22_Day3_m1.csv
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C7_Right_Device22_Day3_m2.csv
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C7_Right_Device22_Day3_m3.csv
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C7_Right_Device22_Day3_m4.csv
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C7_Right_Device22_Day3_m5.csv
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C7_Right_Device22_Day5_m1.csv
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C7_Right_Device22_Day5_m2.csv
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C7_Right_Device22_Day5_m3.csv
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C7_Right_Device22_Day5_m4.csv
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C7_Right_Device22_Day5_m5.csv
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C7_Right_Device22_Day7_m1.csv
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C7_Right_Device22_Day7_m2.csv
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C7_Right_Device22_Day7_m3.csv
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C7_Right_Device22_Day7_m4.csv
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C7_Right_Device22_Day7_m5.csv
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COMSOL_FSDSR_files.zip
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Fig3_F_fitted_vs_measured.csv
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Fig3_G_Rp_at_each_day_for_each_device.csv
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Fig3_H_Rp_versus_thickness_and_volume.csv
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Figure_3_code_data_fitting.txt
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Figure_3_PartD_Thickness_and_volume_of_fibrotic_capsule_averages.csv
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Figure_3_PartD_Thickness_and_volume_of_fibrotic_capsule_single.csv
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Figure_5_code_creation_of_KNN_classifier.txt
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Figure_5_code_Image_processing.txt
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Figure_5_code_KNN_to_dictate_actuation_regimen.txt
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Figure_6_code_Find_best_actuation_regimen.txt
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README.md
Abstract
The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its consequences via soft robotic actuations. Occlusion of the FSDSR porous membrane was monitored over 7 days in a rodent model using electrochemical impedance spectroscopy. The electrical resistance of the fibrotic capsule correlated to its increase in thickness and volume. Our FibroSensing membrane showed great sensitivity in detecting changes at the abiotic/biotic interface, such as collagen deposition and myofibroblast proliferation. The potential of the FSDSR to overcome fibrous capsule formation and maintain constant drug dosing over time was demonstrated in silico and in vitro. Controlled closed-loop release of methylene blue into agarose gels (with a comparable fold change in permeability relating to 7 and 28 days in vivo), was achieved by adjusting the magnitude and frequency of pneumatic actuations following impedance measurements by the FibroSensing membrane. By sensing fibrous capsule formation in vivo, the FSDSR will be capable of probing and adapting to the foreign body response through dynamic actuation changes. Informed by real-time sensor signal, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrous capsule formation.
README: Soft robots with autonomous adaptation for effective drug delivery amidst fibrous encapsulation
The necessary raw data is included and clearly labelled with examples:
Electrical impedance measurements were taken during animal study data - A1_Left_Device1_Day1_m1 etc.
A1 - animal
Left - side of the animal device placed
Device1 - device number
Day1 - day measurement taken
m1 - technical replicate
KNN classfier - 0.3agarose device1 repeat 1(1) (etc.)
0.3agarose - concentration of agarose
device1 - device number
repeat 1 - technical replicate
Comsol model - FSDSR_FCt_75um_Day7_Porosity0.8_Passive_timeS_Cmol_mm (etc.)
75um - capsule thickness
day7 - day
porosity0.8 - porosity
passive - passive diffusion
TriActN - actuated with a triangular pressure profile followed by number N of actuations over 10 min period
RectActN - actuated with a rectangular pressure profile followed by number N of actuations over 10 min period
timeS - denotes the values in the first column of the file is time (Sec)
Cmol_mm - denotes the values in the second column of the file is the surface integral of the concentration in the region beneath the device with units (mol/mm)
Figure_3_PartD_Thickness_and_volume_of_fibrotic_capsule_averages (etc.)
diameter - diameter of capsule (mm)
thickness - thickness of capsule (mm)
volume - volume of capsule (mm^3)
R2 - Pore resistance (Ohms)
Rp - Log of fitted pore resistance (Ohms)
Code/Software
All code is intended to work in R and included here as .txt files.
The code was used in Rmarkdown documents and might contain chunks to output a graph in the final report.
The code provided cannot be used by itself as the import and averaging steps were not included. However, the code shows exactly the steps followed for each analysis, once the data had been imported and averaged.