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.
Highlights
The delivery of bioactive molecules with control over spatial distribution remains a challenge
Www.nature.com/scientificreports bioanalysis[8,9,10,11,12,13,14], and embedded in a hydrogel as a network for chemotaxis studies[15] or multilayer feeding of cell cultures[16]. This capillary action subsequently drives the fluid along the thread, and it is directly related to the material hydrophilicity on the surface
Gelatin methacryloyl (GelMA) presents several interesting advantages, as it is denatured collagen and is a photopolymerizable hydrogel[23,24,25,26,27]
Summary
The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. 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. We use GelMA based hydrogels as tissue models to demonstrate an effective way to control the delivery and spatial distribution of biomolecules. We demonstrated the use of electrofluidics – precise control and manipulation of fluids at the microscale by the use of an external electric field – on threads to deliver biomolecules into and throughout a gel, via control of an applied electric field, to provide a simple approach involving no moving parts or pumps
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