Design And Evaluation Of A Novel Biodegradable Inferior Vena Cava Filter Based On 4D Printing Technology

Shape memory polymers（SMPs）are the most widely used intelligent materials,which can activate their shape conversion through thermal,magnetic and chemical stimuli.Due to the programmability and controllability of the recovery behavior of SMPs,they have received great attention from the biomedical field in recent years.Especially various implanted devices used for minimally invasive treatment in vivo.Implantation of Inferior Vena Cava Filters（IVCF）is an effective approach for the prevention of fatal pulmonary embolism in the clinic.However,most clinical Inferior Vena Cava Filters are currently made of nondegradable metals,which may lead to complications such as filter migration/embolization,filter fracture and cava perforation.Therefore,aiming at the disadvantages of clinical application of filters,a novel filter integrating biodegradability,controllable deployment and personalized customization is designed and manufactured based on 4D printing technology.Compared with the static objects created by 3D printing,4D printing allows a 3D printed structure to change its configuration or function with time in response to external stimuli.This feature makes the filter deformed into a temporary shape before implantation and implanted in a very small size.After implantation,it can be expanded into a precise filter shape by responding to body temperature stimulation,so as to reduce the injury of the surgical approach.The unique structural design can make the deployment process of the filter accurate and controllable,avoiding the occurrence of tilt and displacement.Biodegradable materials are hydrolyzed or enzymatically hydrolyzed in the human body.When the patient passes the thrombotic risk period,they are finally transformed into water and carbon dioxide and discharged out of the body,avoiding the adverse reactions caused by the presence of permanent foreign bodies,avoiding secondary surgery and reducing medical cost.This technology can realize the rapid customization of filters with different structures suitable for patients with different vessel sizes.In this work,we first use Cite Space V5.7 visualization analysis tool to measure visual analysis in the field of nearly ten years,and retrieved 1072 effective documents in the Web Of Science Core Collection database.Through the analysis of the annual issuance,the national/regional partner network,the keyword burst network,the literature co-introduction and the emergent value,it is considered that IVCF plays an important role in the prevention of fatal pulmonary embolism in the acute stage of venous thromboembolism.In the future,a new IVCF without secondary removal and with few complications should be further developed.Therefore,polyglycerol sebacate acrylate（PGSA）was synthesized and modified,and then mixed with hydroxyethyl methacrylate（HEMA）to prepare a body temperature response shape memory polymer material suitable for digital light processing printing.The transition temperature,mechanical strength and degradation performance of the materials under different ratios were studied.It is proved that when PGSA and HEMA are mixed at the mass ratio of55% : 45%,the tensile strength of the material can reach 10 MPa and the shape transition temperature is 37.8℃,which can be suitable for human body.Degradation experiments were carried out in PBS simulated body fluids at 37°C.The results showed that the in vitro degradation rate was about 11.49% at 8 weeks,and the structural integrity could be maintained.We cultured human umbilical vein endothelial cells on the material and carried out subcutaneous implantation experiments in Balb/c mice for12 weeks.The results showed that the material had good cell compatibility and histocompatibility,which was helpful for the adhesion and wrapping of vascular endothelial cells around the filter to avoid displacement.The hemocompatibility experiment was carried out with the fresh blood of healthy volunteers.The results confirmed that the material could avoid hemolysis and platelet aggregation.Finally,the filter structure is designed by blender 3D modeling software,the novel filter is 4D printed by digital light processing printer,and the in vitro deployment demonstration is carried out.In the thrombus interception experiment,the thrombus with a diameter of more than 5 mm can be effectively intercepted.Therefore,4D printing novel biodegradable IVCF can be used as a potential substitute for metal filter and provide a new strategy for the prevention of fatal pulmonary embolism.