Project 1

Project 1

<!-- [if !supportLists]-->1.      <!--[endif]-->Market survey about coronary stents

The coronary stent market is globally estimated to grow at a compounded annual growth rate of 3.3% from 2022 to 2023. It is estimated at USD 8.8 billion in 2021. The major drivers of the market are risk factors like cardiovascular diseases, diabetes, obesity, complex lesions and others. The rising prevalence of cardiovascular diseases like stroke, heart attack, and the growing geriatric population drives the market significantly.

The unprecedented rise in coronary artery disease incidence is predicted to boost the demand for an effective coronary stent device for treatment.

North America dominates the coronary stent market. The key players in the market include

<!-- [if !supportLists]-->·         <!--[endif]-->Abbott

<!-- [if !supportLists]-->·         <!--[endif]-->Medtronic

<!-- [if !supportLists]-->·         <!--[endif]-->Boston scientific corporation

<!-- [if !supportLists]-->·         <!--[endif]-->Terumo corporation

<!-- [if !supportLists]-->·         <!--[endif]-->Biotronic

<!-- [if !supportLists]-->2.      <!--[endif]-->Indian coronary stent market

Currently, Indian coronary stent market value is estimated at USD 1303.5 million in 2023 and is expected to grow at a compounded growth rate of 13.2% during the forecast period 2023-2030.

Drivers of Indian coronary stent market:

<!-- [if !supportLists]-->·         <!--[endif]-->Preference of use of stents over bypass surgeries by patients,

<!-- [if !supportLists]-->·         <!--[endif]-->Research and development activities conducted across India and

<!-- [if !supportLists]-->·         <!--[endif]-->Prevalence of CVD

<!-- [if !supportLists]-->·         <!--[endif]-->Addition of coronary stent in the list of essential medicines in 2022

Reference: https://www.fortunebusinessinsights.com/industry-reports/coronary-stents-market-100065

https://www.coherentmarketinsights.com/market-insight/india-coronary-stents-market-3484

 

<!-- [if !supportLists]-->3.      <!--[endif]-->Literature summary of application, development, and current challenges in the development of cardiac stent

Coronary artery disease occludes the coronary artery that supplies blood to the heart due to the formation of plaque or deposition of cholesterol.

Traditionally, coronary artery bypass surgery was the only method to treat CAD. The concept of angioplasty where balloon is inserted to the artery and blasted at the occluded site was the revolutionizing factor to treat CAD.

Plane balloon angioplasty was gradually improved with stent placement. The major milestones in treating CAD and subsequently coronary stents is mentioned below.

Year	Event description	Person
1964	Using a prosthetic device in coronary angioplasty concept development	Dotter and Judkins
1977	First coronary angioplasty procedure in an awake patient	Andreas Gruntzig
1986	First implantation of stent in human coronary arteries	Sigwart and Peul
1994	FDA-approved use of stents for treatment of CAD in case of failed balloon angioplasty	FDA
1999	First drug eluting stent was implanted	Eduardo Sousa
2002-04	Approval of Cypher and Taxus stents	EME and FDA
2011	Approval of bioresorbable vascular scaffold in Europe	EME

 

<!-- [if !supportLists]-->4.      <!--[endif]-->Development of Drug-eluting stents

The placement of bare metallic stents faced required patient to stay on anti-coagulant therapy which resulted in major blood loss and increased hospital stays. Also, restenosis is another major problem where there is tissue ingrowth through the metallic stents.

To overcome the above-mentioned challenges, drug-eluting stents are developed. These stents have various compounds that target inflammation, platelet activation, thrombosis.

Coating bare metallic stents with anti-proliferative drugs like sirolimus or paclitaxel substantially reduced in-stent restenosis. This is one of the successful trials.

<!-- [if !supportLists]-->5.      <!--[endif]-->Development Challenges

<!-- [if !supportLists]-->·         <!--[endif]-->Drug eluting stents presented more risk of stent thrombosis. It involves the formation of clots around the stent which leads to sudden blockages and heart attacks.

<!-- [if !supportLists]-->·         <!--[endif]-->Restenosis: re-narrowing down of stented artery due to growth of scar tissue results in decreased blood flow

<!-- [if !supportLists]-->·         <!--[endif]-->In-stent restenosis: a type of restenosis that occurs within the stent itself due to tissue ingrowth or inflammation

<!-- [if !supportLists]-->·         <!--[endif]-->Stent migration: migration of stent would not serve the intended purpose

<!-- [if !supportLists]-->·         <!--[endif]-->Inflammation: the immune response starting off with inflammation could potentially lead to complications and even failure at times

<!-- [if !supportLists]-->·         <!--[endif]-->Dual antiplatelet therapy: the necessity to be on blood thinning agents would increase the risk of bleeding

<!-- [if !supportLists]-->·         <!--[endif]-->Cost: the therapy and the product development are expensive which is a serious problem in developing nations

<!-- [if !supportLists]-->·         <!--[endif]-->Design complexity: stents that are flexible yet strong, easy to deploy and capable of conforming to different vessel dimensions like size and shape are very challenging

<!-- [if !supportLists]-->·         <!--[endif]-->Durability and longevity: material design that can withstand stresses for a long period if time are essential as it is a percutaneous procedure and requires operation.

<!-- [if !supportLists]-->·         <!--[endif]-->Biocompatibility: though it is written at last here, this is the primary challenge faced as all the materials used should be biocompatible so that it does not trigger any immune response.

 

<!-- [if !supportLists]-->6.      <!--[endif]-->Project hypothesis

My hypothesis for stent design is as below

‘A drug-eluting stent with nanoparticulate coatings with braided metal structure.’

Novelty is in the manufacturing process, materials used and nanoparticulate coatings.

Key features of the proposed cardiac stent

<!-- [if !supportLists]-->·         <!--[endif]-->Longevity and durability

<!-- [if !supportLists]-->·         <!--[endif]-->Biocompatible

<!-- [if !supportLists]-->·         <!--[endif]-->Radiopaque

<!-- [if !supportLists]-->·         <!--[endif]-->Easy deployment

Material selection and justification

Metallic scaffold-Nitinol

<!-- [if !supportLists]-->·         <!--[endif]-->Nitinol is an alloy of nickel and titanium

<!-- [if !supportLists]-->·         <!--[endif]-->Nitinol is a shape-memory alloy. It can be thermally activated thus preventing balloon for deployment.

<!-- [if !supportLists]-->·         <!--[endif]-->Easy deployment can be achieved as it used mechanical pullback catheter.

<!-- [if !supportLists]-->·         <!--[endif]-->The material properties offer flexibility and strength

<!-- [if !supportLists]-->·         <!--[endif]-->The presence of titanium makes it biocompatible.

<!-- [if !supportLists]-->·         <!--[endif]-->It is as radiopaque as stainless steel making it visible in X-ray scans

Polymer-free coating

<!-- [if !supportLists]-->·         <!--[endif]-->Any -limus analogous drug can be used like everolimus

<!-- [if !supportLists]-->·         <!--[endif]-->In polymer-free drug eluting stents (PF-DES), drug is directly bonded to the metallic stent scaffold

<!-- [if !supportLists]-->·         <!--[endif]-->Specific titania nanotube structure is used as it demonstrated higher cytocompatibility and hemocompatibility

Reference: https://doi.org/10.3390/biomimetics8010072

<!-- [if !supportLists]-->7.      <!--[endif]-->Stent manufacturing processes

<!-- [if !supportLists]-->·         <!--[endif]-->Metallic scaffold of nitinol is manufactured by laser-cutting process.

<!-- [if !supportLists]-->o   <!--[endif]-->Laser-cutting uses high-powered laser beam onto the surface of the material. The intense heat generated by the laser vapourizes the metal from undesired part there-by leaving the required geometry

<!-- [if !supportLists]-->·         <!--[endif]-->Drug-eluting coatings in polymer-free DES is done through anodization

<!-- [if !supportLists]-->o   <!--[endif]-->Anodization is the electrochemical process converting the metal surface into anodic oxide

Reference: https://www.sciencedirect.com/science/article/pii/S0264127519304691

<!-- [if !supportLists]-->8.      <!--[endif]-->Manufacturing flowchart

<!-- [if !supportLists]-->·         <!--[endif]-->Material selection: depending up on the application and end results, materials are chosen

<!-- [if !supportLists]-->·         <!--[endif]-->Stent design: using CAD software, design parameters like strut thickness, design structure like braid or helical or coil is determined

<!-- [if !supportLists]-->·         <!--[endif]-->Fabrication: the material is prepared and is fabricated as mentioned above

<!-- [if !supportLists]-->·         <!--[endif]-->Cleaning and surface treatment: once fabricated, the design is cleaned to remove any contaminants

<!-- [if !supportLists]-->·         <!--[endif]-->Quality control: testing is performed to comply with the standards and ensure the quality

<!-- [if !supportLists]-->·         <!--[endif]-->Sterilization: the stent is sterilized and the packaged.

<!-- [if !supportLists]-->9.      <!--[endif]-->Testing methods

Coronary stents have to be tested to ensure patient safety and quality. These tests have to be conducted to demonstrate its compliance to regulatory standards. Various tests that are conducted on coronary tstents include

In vitro tests

These tests can be conducted in a laboratory setting. They include-

<!-- [if !supportLists]-->·         <!--[endif]-->Mechanical testing: to evaluate mechanical properties like flexibility, strength and crush resistance. Tests include force testing and bending tests.

<!-- [if !supportLists]-->·         <!--[endif]-->Corrosion resistance: to evaluate the ability to resist corrosion when exposed to physiological fluids

<!-- [if !supportLists]-->·         <!--[endif]-->Durability and fatigue testing: to evaluate the structural integrity over a period of time when subjected to cyclic loads, repeated bending and compression cycles.

<!-- [if !supportLists]-->·         <!--[endif]-->Drug-eluting stent testing: to determine the drug release rate and stability of drug coating over time.

<!-- [if !supportLists]-->·         <!--[endif]-->Radiopacity testing: to test the visibility when exposed to X-rays.

<!-- [if !supportLists]-->·         <!--[endif]-->Material characterization: to determine the physical and chemical composition and properties

In-vivo tests

<!-- [if !supportLists]-->·         <!--[endif]-->Animal studies: to study the desig feasibility and its safety in biological systems. Most studied animal models include pigs, rabbits and rodents.

<!-- [if !supportLists]-->·         <!--[endif]-->Biocompatibility: the interaction of stent within biological system is studied.

<!-- [if !supportLists]-->·         <!--[endif]-->Ease of deployment: to understand the complexities involved in placing the stent

<!-- [if !supportLists]-->·         <!--[endif]-->Restenosis and neointimal formation: to evaluate the effectiveness of stent in preventing re-stenosis and the extent of neointimal hyperplasia post-implantation.

<!-- [if !supportLists]-->·         <!--[endif]-->DES effectiveness: the distribution of drug and the effectiveness in inhibiting restenosis.

<!-- [if !supportLists]-->·         <!--[endif]-->Inflammatory response: evaluates the allergic reactions caused by stent

Biocompatibility studies

<!-- [if !supportLists]-->·         <!--[endif]-->Cytotoxicity studies: these studies evaluate the toxicity of stent when it interacts with the living cells

<!-- [if !supportLists]-->·         <!--[endif]-->Hemocompatibility studies: they determine if stent causes any damage to blood cells.

Pre-clinical studies: these are conducted in animal models like mice, rodents and rabbits.

Clinical studies: they are the clinical trials conducted before they release the stent into the market. It involves rigorous testing in 4 phases