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International Journal of Bioprinting                      Coronary and peripheral artery disease. State of the art.



            and mechanical properties of polymers such as a PLGA,   PCL and graphene and loaded with niclosamide and
            PCL,  PCLA    (poly(L-lactide-co-ε-caprolactone)) [87-92] .    inositol phosphate reported good anticoagulation and
            For the particular case of mechanical reinforcement, the   antirestenosis performance. The comparison of the
            homogeneous dispersion of carbon nanotubes is crucial to   3D-printed stent with and without graphene helps discern
            ascertain optimal mechanical strength . Consequently,   the influence of the inorganic ingredient on the stent
                                            [92]
            there is no direct relationship between the amount of   performance. The presence of 4% of graphene increased
            CNT and the mechanical improvement, since very high   the Young’s modulus of PCL and demonstrated better
            concentration could lead to heterogeneous dispersion,   resistance under artery wall pressure after deployment. By
            which hinders the mechanical performance of the    the same token, PCL–graphene stent had a better control
            nanocomposite.                                     of niclosamide and inositol phosphate release.
               Graphene (GR) has demonstrated to be a useful      One of the limitations of 3DP for the production
            ingredient to improve both mechanical properties of   of VS lies in the fact that most of the materials used are
            VS  and control drug  release  from  drug-eluting  VS.  The   polymeric, but not all of them are able to be deployed
            literature regarding 3DP and GR is currently scarce, but   inside the vessels. In this regard, shape memory polymers
            there are clear indications of the usefulness of graphene   (SMP), also known as “smart” or “intelligent materials” are
            as an ingredient to improve the mechanical and biological   currently on the spotlight, not only for 3DP in general ,
                                                                                                           [97]
            properties of stents. Carbon is one of the materials with   but also in the production of VS. In fact, smart materials
            higher  hemocompatibility  due  to  chemical  inertness,   such as shape memory alloys (such as nitinol) have already
            minimal platelet activation and favorable conformational   been used to fabricate VS, and most of them have been
            changes . Coating is the most common strategy to add   commercialized.  SMP  are  polymeric  smart  materials
                  [93]
            GR to VS [94-96] . Nitinol VS coated with GR had improved   with the ability to change their shape while subjected to
            biological  properties  compared  to  its  counterpart .   some triggers such as temperature, electromagnetic fields,
                                                        [94]
            Briefly, GR coating inhibited platelet activation and was   photo-activation, electro-activation, contact  with water
            fully biocompatible with smooth muscle cells. Likewise,   (swelling), pH  medium changes,  etc.  Disregarding  the
            excellent bio- and hemocompatibility was reported for   triggering stimulus, all these smart materials are used in
            a coated stainless steel VS . In this occasion, a coating   a two-step manner [97,98] . The “programming step” is the
                                 [96]
            mixture containing poly(3,4-ethylenedioxythiophene)   shape-memory creation process, where the permanent,
            polystyrene sulfonate (PEDOT:PSS), graphene oxide   original shape is changed to a secondary (temporary) one by
            (GO), and heparin was deposited over the stainless steel VS   subjecting the material to external stress forces (mechanical
            (SUS316) by electrochemical polymerization. This process   stress). Under these circumstances, the SMP acquires a
            gave rise to a stent with high hydrophilic nature, which   desirable shape and maintains it after stress removal. Then,
            can  prevent  platelet  adhesion  following  implantation.   after the exposure of the shaped structure to other non-
            GO contributed the most to this effect, while the role of   mechanical triggers (e.g., heat, light, pH change), it is able
            heparin was the minimum. The authors hypothesized   to recover the original, permanent shape by reverting the
            that the negative charge of GO created a repulsing force   shape it acquires during the application of mechanical
            against plasma proteins and platelets (also with a negative   forces. Hence, SMP have the ability to store mechanical
            net charge) . On the opposite side, GR has also been   stress and release it under non-mechanical stimuli.
                     [96]
            shown to be a useful coating in BRS stents. Magnesium   Depending on the nature of the material, the mechanism
            alloy stents are BRS VS with good mechanical properties.   of shape modification is different. For the particular case
            Nonetheless, these stents suffers from a rapid degradation   of SMP, they share the presence of “permanent netpoints”
            and   insufficient  biocompatibility.  Layer-by-layer  or “permanent links” in their internal network structure
            deposition method was recently used to coat magnesium   and “temporary links” or “switches.” The permanent links
            alloy VS with GR functionalized with chitosan . The   are responsible for the permanent shape, the so-called
                                                    [95]
            authors stated that the resultant bioactive multilayer   “memory effect,” and therefore, these netpoints are not
            coating  endowed  magnesium alloy with  excellent  in   affected by mechanical deformation. On the other hand,
            vitro degradation resistance. Additionally, good blood   switches are formed during mechanical stress due to the
            compatibility (reduced hemolysis and platelet adhesion)   conformational freedom of some of the polymer chains. The
            and improved expression of vascular endothelial growth   deformation obtained during the programming step can
            factor (VEGF) and nitric oxide were ascribed to the GR-  be stabilized by the formation of these “temporary links”
            based coating.                                     within the polymer structure. When it comes to thermal-
               The study of Misra  et  al. is one of the few dealing   sensitive  polymers,  the  difference  between  permanent
            with 3DP, graphene, and VS . A BRS stent made of   links and temporary links lies in the existence of more than
                                    [70]

            Volume 9 Issue 2 (2023)                        242                     https://doi.org/10.18063/ijb.v9i2.664
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