Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures

利用线和手术缝线,通过电流体控制将生物活性分子递送至基于明胶甲基丙烯酰水凝胶的软组织模型中

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Abstract

The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 ± 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 ± 0.40 μm/s) than larger molecules such as dextran (2.26 ± 0.55 μm/s with 4 kDa) or BSA (0.33 ± 0.07 μm/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

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