Analysis Of Material Biomechanics Parameters Based On Aging For The Design Of Fully Biodegradable Polymer Scaffolds

Fully Biodegradable endovascular scaffold can be degraded and absorbed by the body after the completion of blood flow reconstruction to restore vasomotor contraction.The good vascular repair potential makes it have broad application prospects.The elderly is the main susceptible group of cardiovascular diseases,and vascular aging is the most important age-related change.With the development of vascular diseases,a series of susceptible environments,such as high inflammatory basis,endothelial dysfunction,vascular sclerosis occurs.On the other side,due to the degradable activity of the biodegradable scaffold,it is significantly different from the traditional inert metal scaffold in the complex process of interaction with blood vessels.Mainly lies in the changes in hemodynamics and vascular force biology during the degradation of the scaffold,and the effects of degradation products on blood vessels.Changes in the mechanical environment and degradation products are based on the characteristics of the material itself,which can cause adverse reactions in blood vessels to a large extent,such as acute thrombosis,severe restenosis,and complications such as re-atherosclerosis.Due to the completely different physiological states of blood vessels at different ages,arteries in the elderly are characterized by dysfunction and higher levels of inflammation.The fully degradable intravascular scaffold material has biodegradable activity,and the interactions with the body are also very different compared to the inert metal scaffold.However,few studies have put forward the relevant evaluation of bioabsorbable scaffold based on the characteristics of vascular environment of different ages.And few studies have proposed relevant design parameters according to the vascular environment of different ages,including degradation rate and mechanical changes in the scaffolds which are the key factors that are expected to solve the undesirable problems in the clinical application of fully degradable endovascular scaffolds.The 3-D printed fully degradable PLLA endovascular scaffold has now shown great advantages at the animal level,and clinical trials on the scaffold have also been carried out,indicating that the scaffold has reliable material biomechanical properties.While the age-related research on the scaffold has not yet been involved.Based on this,in order to optimize the design of age-based personalized biodegradable scaffold,this paper focuses on the interaction between the scaffold and blood vessels of different ages.PLLA scaffolds were implanted into the abdominal aorta of aged and young SD rats.The purpose is to analyze the age parameters related to the design of biodegradable scaffold from the perspective of material biomechanics.And to provide experimental basis and guidance for coating drug,coating design,and scaffold structure et al.The main research contents and conclusions are as follows:(1)Scaffold restenosis and late lumen loss are more serious in aged rats after PLLA scaffold implantation.After scaffold implantation at 1 weeks,severe acute thrombosis occurred in aged rats.The expression of thrombus marker--thrombomodulin TM and marker for inflammation-CD68 increased significantly.Within half a year of scaffold implantation,the level of inflammation in aged rats was always high.OCT imaging observation combined with HE staining results showed that the neointimal area of aged rats increased significantly 4 weeks after scaffold implantation,and ISR and late lumen loss are serious.(2)Reendothelialization process and barrier function of aged rats recovered slowly.In vivo evans blue staining showed that after 24 weeks of scaffold implantation,the endothelial barrier function of the two groups basically recovered,while the reendothelialization process and endothelial function recovery of the aged rats were slower than that of the young rats.The expression of CD31 and e NOS was weak.And the aging marker protein-γ-H2 AX increased in a time-dependent manner.(3)Slow scaffold degradation and poor vascular remodeling occurred in aged rats.PLLA scaffold implantation resulted in a significant decrease of collagen fibers and elastic fibers in the vascular media of aged rats in the early stage,and began to recover positively after 12 weeks,but the speed was slow.Vascular remodeling of aged rats was slow,and the change trend of collagen fibers in the vascular media was the same as MMP-2 and MMP-9.After 24 weeks of scaffold implantation,the scaffold in the young rats showed degradation,the scaffold strut profile became smaller and the degradation debris was formed.However,the scaffold strut of the old rats was still thick,and there was no obvious degradation.In conclusion,the speed of vascular repair and scaffold degradation are closely related to age.(4)Scaffold implantation induces significant hemodynamics changes in the blood vessels of aged rats which might cause restenosis.In this paper,a hemodynamic model was established based on OCT image data,and the changes of hemodynamic characteristics after scaffold implantation in different age vessels were analyzed based on Doppler ultrasound results.At 24 weeks after scaffold implantation,the wall shear stress of scaffold segment in aged rats was significantly reduced,and the risk of restenosis was high.At this time,the lumen loss of proximal and distal end of scaffold was serious,the expression of γ-H2 AX in distal end increased significantly,and the expression of e NOS was significantly different from that in young rats.The results of in vitro mechanical loading test showed that under low shear stress,the expression of γ-H2 AX increased in a time-dependent manner,and the integrity of endothelial cells decreased.Through the analysis of age-related material biomechanical parameters for design of fully degradable polymer scaffolds,we proposed that large-dose anti-proliferative drugcoated scaffolds can be prepared to solve the problem of severe restenosis and late lumen loss in elderly rats.Preparation of scaffold coatings of drugs that promote endothelial cell proliferation might solve the problem of slow recovery of reendothelialization and barrier function in elderly rats.Reduction of the scaffold thickness might solve the problems of slow degradation of scaffolds and poor vascular remodeling in elderly blood vessels.Individualized scaffolds for elderly blood vessels can also be designed from the perspective of enhancing the radial stiffness and axial flexibility,such as optimizing the thickness of the scaffold strut and scaffold structure.In conclusion,this paper deeply analyzed the response of PLLA scaffolds in blood vessels of different ages from the three aspects of vascular tissue,materials and mechanics in both animal and cell level.And the age-related parameters of the fully degradable polymer scaffold design have also been analyzed.Finally,from the perspective of material biomechanics,it provided reference opinions for the design of personalized PLLA scaffolds for the elderly,and enriched the evaluation indicators of PLLA scaffolds.