3D printed UV crosslinking masks
Current approaches in small diameter vascular grafts for coronary artery bypass surgeries fail to address physiological variations along the graft that contribute to thrombus formation and ultimately graft failure. An interlayer drug delivery system can sustain delivery of heparin through the graft with a high degree of temporal and spatial control. A heparin-loaded gelatin methacrylate interlayer sits between a biohybrid composed of decellularized bovine pericardium and poly(propylene fumarate) and UV crosslinking is controlled via 3D printed shadow masks. The masks enable control of the resultant gelMA crosslinking and properties by modulating the incident light intensity on the graft. High doses of heparin have detrimental effects on endothelial cell function. When exposed to heparin in a slower, more sustained manner consistent with the masks, endothelial cells behave similarly to untreated cells. Slower release profiles cause significantly more release of tissue factor pathway inhibitor, an anticoagulant, than a faster release profile.
1 . A method to control localized drug delivery to elicit a cell response, the method comprising:
varying light exposure in a photo-crosslinkable material to create a gradient in the crosslinking of the photo-crosslinkable material;
loading the photo-crosslinkable material with a drug; and
temporally and spatially modulating the release of the drug from the photo-crosslinkable material;
slowing the modulated release of the drug with a permeable material, wherein the permeable material comprises decellularized bovine pericardium (dECM).
2 . The method of claim 1 wherein the photo-crosslinkable material comprises gelatin methacrylate (gelMA).
3 . The method of claim 1 further comprising utilizing a barrier adjacent to the photo-crosslinkable material to substantially prevent diffusion of the drug through the barrier.
4 . The method of claim 3 wherein the barrier is hydrophobic and prevents hydrophilic drug(s) from moving therethrough.
5 . The method of claim 1 wherein the drug comprises more than one drug.
6 . The method of claim 1 further comprising modifying drug delivery to elicit different endothelial cell responses and to promote an antithrombotic environment.
7 . The method of claim 1 further comprising balancing endothelialization with a thrombotic response.
8 . A method to control localized drug delivery to elicit a cell response, the method comprising:
varying light exposure in a photo-crosslinkable material to create a gradient in the crosslinking of the photo-crosslinkable material, wherein the photo-crosslinkable material comprises gelatin methacrylate (gelMA);
loading the photo-crosslinkable material with a drug;
temporally and spatially modulating the release of the drug from the photo-crosslinkable material; and
introducing the gelMA as an interlayer into a bovine pericardium (dECM)+poly(propylene fumarate) (PPF) biohybrid vascular graft.
9 . The method of claim 8 further comprising slowing the modulated release of the drug with a permeable material.
10 . The method of claim 9 wherein the permeable material comprises decellularized bovine pericardium (dECM).
11 . A method to control localized drug delivery to elicit a cell response, the method comprising:
varying light exposure in a photo-crosslinkable material to create a gradient in the crosslinking of the photo-crosslinkable material, wherein the photo-crosslinkable material comprises gelatin methacrylate (gelMA);
loading the photo-crosslinkable material with a drug;
temporally and spatially modulating the release of the drug from the photo-crosslinkable material;
introducing the gelMA as an interlayer into a bovine pericardium (dECM)+poly(propylene fumarate) (PPF) biohybrid vascular graft; and
dosing pericardium with heparin, thereby allowing the heparin to be diffused through the dECM to provide sustained release at the surface of the biohybrid vascular graft.
12 . The method of claim 11 further comprising employing the spatial control of heparin release to address longitudinal differences along the biohybrid vascular graft.
13 . The method of claim 11 further comprising utilizing a concentration of heparin low enough to support endothelial adhesion and migration and high enough to prevent platelet adhesion.