“…Therefore, these results also support the previous described interaction between the PCL matrix and DIP. The same behavior has also been reported using a different polymer matrix, thermoplastic polyurethane (TPU), with DIP [ 1 ], or other drug compounds, such as levofloxacin and 17-β-estradiol [ 36 , 37 ]. Fig.…”
Section: Resultssupporting
confidence: 56%
“…AM, also known as 3D printing, is an increasingly growing manufacturing technology that provides the ability to fabricate structures of precise geometries from 3D model by the deposition of material in a layer-by-layer fashion. This technology has been previously investigated for the manufacture of multiple 3D devices medical devices including surgical meshes [ [36] , [37] , [38] ], subcutaneous Implants [ 39 ], wound dressings [ 40 , 41 ] or catheters [ 42 , 43 ] among others, showcasing the versatility of this technique for biomedical applications. In addition, cardiovascular prosthesis containing a small percentage of antimicrobial compounds to prevent infections have been performed using 3D printing technology [ 1 ].…”
Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.
“…Therefore, these results also support the previous described interaction between the PCL matrix and DIP. The same behavior has also been reported using a different polymer matrix, thermoplastic polyurethane (TPU), with DIP [ 1 ], or other drug compounds, such as levofloxacin and 17-β-estradiol [ 36 , 37 ]. Fig.…”
Section: Resultssupporting
confidence: 56%
“…AM, also known as 3D printing, is an increasingly growing manufacturing technology that provides the ability to fabricate structures of precise geometries from 3D model by the deposition of material in a layer-by-layer fashion. This technology has been previously investigated for the manufacture of multiple 3D devices medical devices including surgical meshes [ [36] , [37] , [38] ], subcutaneous Implants [ 39 ], wound dressings [ 40 , 41 ] or catheters [ 42 , 43 ] among others, showcasing the versatility of this technique for biomedical applications. In addition, cardiovascular prosthesis containing a small percentage of antimicrobial compounds to prevent infections have been performed using 3D printing technology [ 1 ].…”
Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.
“…In order to solve some of the limitations presented by polymeric materials, drugs can be added to obtain polymeric devices with enhanced properties. Drugs such as antibiotics, anticancer drugs or anticoagulant agents, among many others, were combined with polymers for this purpose [ 1 , 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The combination of antibiotics and polymers has been extensively studied for the development of anti-infective materials [ 16 , 17 , 18 ].…”
Small-diameter synthetic vascular grafts are required for surgical bypass grafting when there is a lack of suitable autologous vessels due to different reasons, such as previous operations. Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for this revascularization technique. Therefore, the development of biodegradable vascular grafts capable of providing a localized and sustained antithrombotic drug release mark a major step forward in the fight against cardiovascular diseases, which are the leading cause of death globally. The present paper describes the use of an extrusion-based 3D printing technology for the production of biodegradable antiplatelet tubular grafts for cardiovascular applications. For this purpose, acetylsalicylic acid (ASA) was chosen as a model molecule due to its antiplatelet activity. Poly(caprolactone) and ASA were combined for the fabrication and characterization of ASA-loaded tubular grafts. Moreover, rifampicin (RIF) was added to the formulation containing the higher ASA loading, as a model molecule that can be used to prevent vascular prosthesis infections. The produced tubular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet and antimicrobial activity and cytocompatibility. The results suggested that these materials were capable of providing a sustained ASA release for periods of up to 2 weeks. Tubular grafts containing 10% (w/w) of ASA showed lower platelet adhesion onto the surface than the blank and grafts containing 5% (w/w) of ASA. Moreover, tubular grafts scaffolds containing 1% (w/w) of RIF were capable of inhibiting the growth of Staphylococcus aureus. Finally, the evaluation of the cytocompatibility of the scaffold samples revealed that the incorporation of ASA or RIF into the composition did not compromise cell viability and proliferation at short incubation periods (24 h).
“…Curcumin released was around 61 μg compared to 75 mg used for filament extrusion. Considered the small loss of curcumin during HME, around 80% was incorporated into grafts; as previously reported [17,36], curcumin might be interacting with TPU due to TPU hydrophobic nature, limiting drug release; therefore, curcumin will continue to release also after the 2 weeks. Using material such as TPU, drug could remain in the graft for a longer period if grafts remain permanently in the patient body.…”
Section: In Vitro Release Of Curcumin From Vascular Graftsmentioning
Abstract3D printing has provided a new prospective in the manufacturing of personalized medical implants, including fistulas for haemodialysis (HD). In the current study, an optimized fused modelling deposition (FDM) 3D printing method has been validated, for the first time, to obtain cylindrical shaped fistulas. Printing parameters were evaluated for the manufacturing of fistulas using blank and 0.25% curcumin-loaded filaments that were produced by hot melt extrusion (HME). Four different fistula types have been designed and characterized using a variety of physicochemical characterization methods. Each design was printed three times to demonstrate printing process accuracy considering outer and inner diameter, wall thickness, width, and length. A thermoplastic polyurethane (TPU) biocompatible elastomer was chosen, showing good mechanical properties with a high elastic modulus and maximum elongation, as well as stability at high temperatures with less than 0.8% of degradation at the range between 25 and 250 °C. Curcumin release profile has been evaluated in a saline buffer, obtaining a low release (12%) and demonstrating drug could continue release for a longer period, and for as long as grafts should remain in patient body. Possibility to produce drug-loaded grafts using one-step method as well as 3D printing process and TPU filaments containing curcumin printability has been demonstrated.
Graphical abstract
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