1. LOGO Presenter : S.Mohammad Zargar Supervisor : Dr. Mahdikhani Faculty of Engineering Department of Biomedical Engineering

2. Treatments Surgeries and procedures for atherosclerosis include:  Angioplasty  Stent placement  Coronary Artery Bypass Grafting surgery (CABG)  Atherectomy 2

3. CABG Coronary artery bypass grafting (CABG) is a type of surgery - where arteries or veins from other areas in the body are used to bypass the narrowed coronary arteries. CABG can improve blood flow to your heart, relieve chest pain, and possibly prevent a heart attack. 3

4. Company Logo Atherectomy Unlike angioplasty and stents, which push plaque into the vessel wall, atherectomy cuts plaque from the wall of the artery. While atherectomy is usually employed to treat arteries it can be used in veins and vascular bypass grafts as well. 4

5. Angioplasty In the late 1970s, doctors began using balloon angioplasty to treat coronary arteries that got too narrow. 5

6. Company Logo Coronary Stents Because no new support is left, in a small percentage of cases, the artery will regain its previous shape or even collapse after the balloon is deflated. About 30% of coronary arteries treated with balloon angioplasty get narrower again. To solve these problems, small stents were created that could be mounted on the balloon and put into a blood vessel. The stent expands when the balloon is inflated, locks into place, and forms a permanent scaffold to hold the artery open after the balloon is deflated and removed. 6

7. BMS First-generation stents were made of bare metal. Although they almost eliminated the risk of the artery collapsing, they only modestly reduced the risk of re-narrowing. About a quarter of all coronary arteries treated with bare-metal stents would close up again, usually in about 6 months. 7

8. DES Stents coated with drugs that interrupted the re-narrowing are called drug-eluting stents. While bare-metal stents (BMS) are still utilized, drug-eluting stents (DES) now offer clinicians the ability to prevent restenosis via a different mechanism. Advantages: In clinical trials, these reduced re-narrowing cases to less than 10%. They also lowered the need for repeat procedures for people with diabetes, who have a bigger chance of their arteries getting narrow again. 8

9. First Generation DES  First-generation DES include sirolimus-eluting stents (SES; 2003) and paclitaxel-eluting stents (PES; 2004).  SES and PES revolutionized rates of restenosis after cardiac procedures. These stents were developed to prevent the proliferation of smooth-muscle cells and other cell types seen with restenosis.  PES and SES were compared in several clinical trials, most of which concluded that SES were associated with lower rates of clinical restenosis and late lumen loss. The superiority of SES may be due to differences in mechanism of action, timing of drug delivery, and cellular inflammatory response for SES and PES at sites of overlapping stents. Sirolimus Paclitaxel 9

10. Second Generation DES  Second-generation DES, including zotarolimus- and everolimus-eluting stents (ZES, EES), were approved for use in the United States in 2008.  The newer stents, EES and ZES, are thinner and more flexible and have a cobalt-chromium alloy platform, which makes them more deliverable than the first-generation stents. These stents may also be more biocompatible, thereby generating less inflammatory response and faster vessel endothelialization. Zotarolimus Everolimus 10

11. DES dual antiplatelet therapy (DAPT) Although the underlying principle of DES remains constant, each type may offer variations with respect to deliverability (ease of placement), efficacy (preventing restenosis), and safety (thrombosis rates). The use of dual antiplatelet therapy (DAPT) with stents has significantly improved outcomes in patients undergoing PCI. 11

12. in-stent thrombosis Still, there were concerns that drug-eluting stents were associated with a rare but serious complication called in-stent thrombosis. This is where a blood clot forms in a stent one or more years after it's implanted. Because this complication can be fatal, it’s important that people with drug-eluting stents take aspirin and an anticlotting drug as prescribed until a doctor tells them to stop. 12

13. Dual Antiplatelet Therapy Coronary rethrombosis and coronary restenosis are sequelae of stent placement. Coronary rethrombosis is defined as reocclusion of coronary vessels by thrombin formation, and coronary restenosis is reocclusion of coronary vessels and smooth-muscle endothelial overgrowth. These sequelae can lead to devastating events such as MI and death. DES are associated with a reduced risk of restenosis but an increased risk of rethrombosis, specifically with early discontinuation of DAPT. Dual antiplatelet therapy (DAPT) = Combination of aspirin and a P2Y12. platelet receptor inhibitor to prevent stent thrombosis after a. percutaneous coronary intervention. 2. Percutaneous coronary intervention (PCI) = reperfusion of a coronary. 13

14. Third-Generation Stents if the BVS absorbed into the vessel wall over the next year, we would expect a number of great things that the vessel might resume some or most of its normal function. A bioresorbable, biodegradable, or bioabsorbable stent is manufactured from a material that may dissolve or be absorbed in the body. 14

15. Company Logo Hot Tip 15

16. Company Logo Damaged Cardiac Tissue Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. the body’s natural response after MI is a process of fibrous remodeling that ultimately leads to scar formation instead of functional myocardium formation. This scar formation prevents the heart from functioning properly and eventually leads to complete heart failure. 16

17. Myocardial Infarction Pharmaceutical therapy Medical devices Transplantation Limitations High Invasiveness scarcity of donor organs prolonged hospitalization time Limitations thrombosis or stenosis of devices immune rejection Treatments of MI Tissue engineered organ 17

18. CV TERM As a result, there is a huge need for developing new solutions to repair or replace damaged cardiac tissues. Injectable hydrogels have emerged as a promising approach for cardiac repair in regenerative medicine. 18

19. CV RM In regenerative medicine approach, the appropriate cell types are injected to the injured myocardium. These cells can be progenitor cells or stem cells that can be differentiated into the necessary cardiac cell types or even fully differentiated cardiac cells. Some biomaterials-alone can be injected near the infarcted heart tissue to provide the mechanical support to the injured heart tissue. 19

20. Company Logo CV TE In tissue engineering, the desired cell types are grown in some natural or synthetic biomaterials or sometimes even without any biomaterials, for the in vitro formation of cardiac tissue that could be implanted around the damaged areas of heart. 20

21. Hydrogels  Hydrogels are “water-swollen polymer networks” that have a high percentage of water content identical to human tissues.  They can be injected as a liquid and be crosslinked to a gel phase using certain physical or chemical stimuli. In situ cross-linking Methods: Thermo-sensitive hydrogels photo cross-linking pH-dependent Crosslinking Ionic crosslinking 21

22. Design Parameters in synthesis of Hydrogels Biocompatible Biodegradable Bioresorbable Not triggering an immune response Contractible Elastic Able to sustain periodic contraction and relaxation Well-vascularizes 22

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