Novel functionalized and patterned surfaces for cardiovascular applications
- Autores: Romain Hugues Marie Schieber
- Directores de la Tesis: Marta Pegueroles Neyra (dir. tes.), Frank T. Mücklich (codir. tes.)
- Lectura: En la Universitat Politècnica de Catalunya (UPC) ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: José María Manero Planella (presid.), Francisco Javier González Fernández (secret.), Guido Falk (voc.)
- Programa de doctorado: Programa de Doctorado Erasmus Mundus en Ciencia e Ingeniería de Materiales Avanzados / Advanced Materials Science and Engineering por la Universidad Politécnica de Catalunya; Linköpings Universitet(Suecia); Luleå Tekniska Universitet(Suecia); Universität des Saarlandes(Alemania) y Université de Lorraine(Francia)
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Nowadays, cardiovascular diseases are mainly treated by implantation of a metallic or polymeric mesh, called stent, which maintains the artery widely open. This technique shows very good clinical results, however, it exists non negligible cases of in stent restenosis (ISR) and late stent thrombosis (LST) during the first year after stent implantation. These complications are mainly due to a delayed recovery of the endothelium after stent implantation, which also involves smooth muscle cells (SMCs) over-proliferation and platelet aggregation. Stent surface modification to modulate a specific cell lineage response has not been comprehensively explored. In particular, surface nano topography, biofunctionalization or chemical features may be applied to increase endothelial cells (ECs) adhesion and/or migration, and to control platelet agglomeration.
The overall aim of this thesis was to obtain novel modified surfaces for stents implants with the ability to induce accelerated reendothelialization and controlled platelet aggregation in order to avoid ISR and LST. On CoCr alloy, as the gold standard material for bare metal stents (BMSs), two different strategies were evaluated, generation of linear patterns by direct laser interference patterning (DLIP) and, immobilization of biomolecules. On poly(L-lactic acid) (PLLA), as a material for bioresorbable stents (BRSs), endothelialization was enhanced by surface functionalization with NaOH etching, plasma treatment and cutinase enzyme hydrolysis.
CoCr alloy surfaces were successfully modified with a linear pattern of different periodicities and depths. Afterwards, Arg-Gly-Asp (RGD) and Tyr Ile Gly Ser Arg (YIGSR) peptides were covalently immobilized to the surfaces through silanization. Early ECs adhesion was improved on the peptide functionalized surfaces, especially for YIGSR compared to RGD. High depth nano patterned surfaces generated ECs alignment within the topographical lines and enhanced EC migration. Noteworthy, the combined use of both strategies, topography and biofunctionalization, synergistically accelerated the ECs migration and proliferation. Also, platelet adhesion and aggregation decreased in all patterned surfaces compared to smooth CoCr probably due to changes in wettability and oxide layer characteristics. Cellular studies provided evidence of the potential of DLIP topographies and YIGSR biofunctionalization to foster endothelialization without enhancement of platelet adhesion, which will be of high importance when designing new stents.
Concerning polymeric biodegradable materials, PLLA films were obtained by solvent casting in chloroform and, oxygen plasma, NaOH solution or cutinase enzyme treatments were used to functionalize the PLLA films and create surface hydroxyl and carboxyl groups without compromising biocompatibility. A higher amount of functional groups and an improved ECs adhesion was observed by oxygen plasma and cutinase enzyme hydrolysis compared to NaOH etching. Plasma or cutinase enzyme functionalized PLLA films presented a degradation rate similar to a peripheral commercial stent. Finally, 3D printed PLLA BRSs were obtained by solvent-cast direct write technique. Consequently, the combined use of the solvent cast direct write technique and plasma or enzyme functionalization holds a great potential to fabricate 3D printed PLLA BRSs with the capacity to accelerate the surface endothelialization.
Overall, the present thesis offers a comprehensive view of the effectiveness of modifying CoCr alloy and PLLA films with specific topographies or functionalization strategies to enhance surface endothelialization while preventing restenosis and thrombosis.
