3D-printed polymeric bioresorbable stents for cardiovascular applications
(English) Bioresorbable stents (BRS) have been envisioned as a revolution in the treatment of coronary heart disease. Ideally, stents would initially retain sufficient radial strength after implantation to prevent vessel recoil while degrading and ultimately being resorbed, thus leaving the vessel w...
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/399822 |
| Acceso en línea: | https://hdl.handle.net/2117/399822 https://dx.doi.org/10.5821/dissertation-2117-399822 |
| Access Level: | acceso abierto |
| Palabra clave: | Àrea temàtica UPC: Enginyeria biomèdica Àrees temàtiques de la UPC::Enginyeria dels materials |
| Sumario: | (English) Bioresorbable stents (BRS) have been envisioned as a revolution in the treatment of coronary heart disease. Ideally, stents would initially retain sufficient radial strength after implantation to prevent vessel recoil while degrading and ultimately being resorbed, thus leaving the vessel with a healthy endothelium. Still, the main challenge of BRS lies in simultaneously providing enough mechanical support to prevent recoil in the first months while controlling the degradation rate, minimizing strut thickness and improving BRS hemocompatibility and tissue integration. The main aim of the present PhD Thesis is the design and development of tunable novel polymeric bioresorbable stents manufactured by means of solvent-cast direct-writing (SC-DW) with reinforced mechanical properties, suitable degradation timeframe, drug release capability and enhanced biointegration. First, a novel versatile additive manufacturing fabrication strategy for BRS production by using polymeric inks and SC-DW onto a rotating cylinder is presented. Initially, poly-L-lactic acid (PLLA) was used to manufacture and characterize a variety of designs with different mesh patterns. In a second step, poly(L-lactic-co-caprolactone) (PLCL) was introduced, and inks were further modified with the addition of iodine, triiodobenzoic acid (TIBA) and barium sulfate (BaSO4) in order to produce radiopaque BRS. Microcomputed tomography was used to assess stents' radiopacity, showing that TIBA and BaSO4-containing stents presented high X-Ray attenuation values, maintained over 3 months incubation time. With the aim to gain further insight into PLLA and PLCL stents degradation, a complete study was performed by comparing chemical vs thermal accelerated degradation assays. The results showed that under alkaline conditions, stents underwent surface erosion, whereas stents immersed at 50 ºC experienced bulk degradation. Molecular weight decrease was accurately described by the autocatalyzed kinetic model, with PLCL showing a degradation rate 1.5 times higher than PLLA. Regarding sterilization, whereas EtO-sterilized stents remained structurally unaltered, ¿-irradiated stents presented severe deterioration as a result of extensive chain scission. In the following, a combination of SC-DW and electrospinning (ES) was proposed as a new approach to generate everolimus-eluting BRS for cardiovascular applications. A Design of Experiment was conducted to determine the parameters necessary for optimal homogeneous coating with high specific surface. Drug loading was achieved either encapsulated in the struts of the stent or in an electrospun PLCL membrane covering the stent. When encapsulated, everolimus release was found to be insufficient, whereas release from PLCL-coated 3D-printed stents would match the dose and timeframe required for in vivo applications. Finally, functionalization of 3D-printed PLLA and PLCL BRS with endothelial cell (EC) adhesive peptides was explored. Solid phase peptide synthesis was used to synthesize linear RGDS and YIGSR sequences, as well as a dual peptidic platform (PF) containing both motifs in a single biomolecule. Endothelial cell adhesion assays evidenced significantly increased cell number and spreading onto functionalized films with respect to control samples. Stents' hemocompatibility was evaluated upon a blood perfusion assay, with PLCL showing pronouncedly diminished platelet adhesion with reference to PLLA. In addition, functionalization with RGDS, YIGSR and the PF rendered BRS stents displaying even further reduced platelet adhesion. |
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