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Design and Development of Bioresorbable Drug Eluting Coronary Stents

Primary Information

Domain

Healthcare

Project No.

4129

Sanction and Project Initiation

Sanction No: F.NO.41-2-/2015-T.S.-I (PT.I, ANNE.II SL.650)

Sanction Date: 09/01/2017

Project Initiation date: 24/03/2017

Project Duration: 36

Partner Ministry/Agency/Industry

Indian Council of Medical Research (ICMR) All India Institute of Medical Sciences, Delhi (AIIMS) Innvolution Healthcare Pvt Ltd. Delhi

 

Role of partner:AIIMS will be involved in ethics committee clearance and conducting of small animal trials and future first-in-man (FIM) trials. Large animal trials of the bioresorbable stent will be done by the industry partner.

 

Support from partner:Innvolution Healthcare will be supporting the costs for clinical (large animal) trials and providing balloon catheters, guide wires, drug loading and packaging of stents for deployment.

Principal Investigator

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Prof. Naresh Bhatnagar
Indian Institute of Technology Delhi

Host Institute

Co-PIs

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Dr. Rajiv Narang
AIIMS, New Delhi

 

Scope and Objectives

Today, India is doing approximately 3 lakh Percutaneous Coronary Intervention (PCI) in a year at more than 900 Cath labs spread across India. Historically, PCI has grown @ 20% plus in last few years. The PCI per million populations in US, Europe, Japan and Australia is 2500. The same ratio is less than 100 for India. The penetration of PCI will further increase in India due to lifestyle changes. There is increasing healthcare awareness among masses, especially that cardiac diseases are the No1 killer in India. Access to services has increased now that cath labs are present in 90 Indian cities that used to be metro cities earlier. Penetration of these services to Tier 2 and 3 cities and towns are further helping to grow this market. Affordability and better penetration of health insurance is key for the growing PCI market in India. Physician skills are improving and a growing pool of young DM Cardiologists is getting trained to do PCI. Cost of hardware (stents etc) and the overall procedure has come down and it is adding to volumes at many cardiac centres. The proposed project will provide an efficient and cost effective solution for Coronary Artery Disease (CAD) by using Bioresorbable Vascular Stent (BVS) as against the current drug eluting metallic stents (DES) 1. Optimization of polymeric stent for better mechanical properties, flexibility and low crossover profile. 2. Medical grade polymer tube processing optimization suitable for stent manufacturing. 3. Validating the manufactured (using femtosecond laser cutting) bioresorbable vascular coronary stent by: -Mechanical testing -Degradation, Biocompatibility, Hemo-compatibility studies -Animal & FIM trials 4. Commercialisation and transfer of technology (TOT) of Bioresorbable Polymeric Coronary Drug Eluting Stent to provide cardiac care to large Indian population in future at an affordable cost.

Deliverables

The know-how generated from this project will be the mainstay of stenting and scaffolding industries in India and globally. Bioresorbable stents will address the clinical issues faced after angioplasties using permanent metallic stent providing peace-of-mind to the patient as the stent dissolves and normal arterial functioning is restored. Additionally, affordable commercialization of this breakthrough technology will be entirely a result of indigenous innovation and IMPRINT India. Notwithstanding the contribution to the scientific community working on cardiovascular disease as well as tissue engineering and medical device development.

 

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Scientific Output

A thorough study of cardiovascular diseases and interventional treatment strategies are being carried out for stent material selection tuned to the requirements of a plaqued artery. Characterisation studies will yield insights into the structure property relations of polymers and polymeric blends while stent cutting using cold laser technology will reveal the nuances of finishing. Indian industry is focused on metallic stents and, thus, this project will provide the foundation for a revolution in stent manufacturing. Alongside, complete numerical simulation mimicking blood flow, artery pulsation, stent recoil in crimping and deployment will lead to optimization of proper design for polymeric stents as opposed to metallic tubes. Finally, testing of mechanical and degradation properties will be conducted to qualify and attain FDA and CE certification, requiring the development of as many as 10-15 test fixtures as per ISO25539-2.

 

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Results and outcome till date

Processing window for tube manufacturing has been optimized for selected polymeric biomaterials. Mechanical properties including burst pressure, tensile and radial strength have been evaluated along with chemical and physical characterization of the materials before and after processing. Degradation behavior in a simulated in vitro environment has been studied for experimental materials. A rigorous protocol for biocompatibility testing of tubes of candidate stent materials in small animals including inflammatory response and tissue attachment is developed. Primary biocompatibility checked by surface hydrophilicity and in vitro cytotoxicity of selected materials completed to prepare for an 8 weeks study initiated to evaluate inflammatory response using histopathology and quantification of inflammatory marker in rat subcutaneous tissue.

 

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Societal benefit and impact anticipated

No company is manufacturing Bioresorbable Vascular Stents (BVS) in India at present. No work has been reported on the modified die extrusion process of biodegradable polymer stent manufacturing in India as well as in any other part of the world as this is a classified technology. Indigenizing the technology will bring down the prohibitive costs of this life saving procedure and make large strides towards affordable healthcare.

Next steps

We are soon to begin testing of our stent prototypes developed with selected material compositions, optimized tube fabrication technique and patented stent design in large animals. Evaluation of these results will lead to first-in-man trials at partner institute, AIIMS Delhi.

Publications and reports

Bhati, P., Kumar, A., Ahuja, R., & Bhatnagar, N. (2019). Evaluating the effect of manufacturing method on the radial compressive force of the bioresorbable tubes. Materials Letters, 235, 23-26.

Patents

Indian Patent Application No. 3200/DEL/2012 PCT WO/2014/091438. 12 Dec 2012 Indian Patent Application No. 201611035281

Scholars and Project Staff

Pooja Bhati (Full time PhD since July 2013) Avinash Kumar (Full time PhD since Jan 2017) Alok Srivastava (Full time PhD since Jan 2017) Ramya Ahuja (Research Associate since May 2017 & part time PhD since July 2017) Dr. Priya Vashisth (DST Inspire faculty since August 2018)

Challenges faced

1. Medical device development is a long-term project and we have reached many milestones in the last 1.5 years but would require more sustained effort and time for reaching first-in-man trials. 2. Most of the materials and equipment are monopolistic in nature and we have attempted procurement twice or even thrice for some essentials for the project but are faced with the problem of lack of interest of the industries in this business to participate in the complicated E-Tendering process and have decline to participate.

Other information

Femto Second Laser Machine costing approx. 4.5 crores is being procured by the central funds of IIT Delhi under Central Research Facilities to help this IMPRINT project to realise the final stent as a product for trials.

Financial Information

  • Total sanction: Rs. 399.89 lakhs

  • Amount received: Rs. 295.70 lakhs

  • Amount utilised for Equipment: Rs. 43.55 lakhs

  • Amount utilised for Manpower: Rs. 28.14 lakhs

  • Amount utilised for Consumables: Rs. 3.14 lakhs

  • Amount utilised for Contingency: Rs. 0

  • Amount utilised for Travel: Rs. 0.18 lakhs

  • Amount utilised for Other Expenses: 0

  • Amount utilised for Overheads: Rs. 26.20 lakhs

Equipment and facilities

 

Single Screw Extruder with Tube Dies, Simultaneous Thermal Analyzer and Fatigue testing machine for chemical and mechanical characterization of stent material and cut stents. Femto Second Laser cutting machine procurement in process.