BionanomatrixTM Applications in Development

Application Formulation Discovery Preclinical IND-Enabl. Clinical Market Partners
Arteriovenous fistula Gel, NO $1.3B by 2032
Cardiovascular stents Coating, NO $15.6B by 2030
Flow diverters Coating, NO $1.3B by 2032
Angioplasty balloons Coating, sirolimus+NO $3.3B by 2028
Direct pulp capping Coating, NO $1.9B by 2031
Knee Replacement Coating, NO $14.5B by 2032

Arteriovenous Fistula Market Outlook 2022-2032, Future Market Insights
Cardiovascular Stent Market Research Future, December 2022
Flow Diverter Market Outlook 2022-2032, Future Market Insights
Angioplasty Balloon Market - Growth, Trends, COVID-19 Impact, and forecasts (2023-2028)
Dental Cavity Filling Material Market - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2022-2031
Knee Replacement Market - Global Market Insights, Report ID: GM12804, 2022

Arteriovenous fistula (AVF) Gel

More Than 500,000 U.S. Patients Have End Stage Renal Disease (ESRD), And Over 80% Of Them Utilize Hemodialysis.

Problems with vascular access needed for hemodialysis are among the most frequent reasons for hospitalization of patients with ESRD. The direct cost of vascular access establishment and repair exceeds $700 million per year in the US. A significant problem for dialysis patients is the development of a functioning and durable vascular access, preferably an arteriovenous fistula (AVF). After creation, about 60% of AVFs fail to mature successfully for dialysis use. This is due to inadequate vasodilation and smooth muscle cell hyperplasia at the distal venous anastomosis. The Endomimetics Bionanomatrix gel is being developed for use as a coating of the AVF at the time of creation, recruiting endothelial cells and enhancing appropriate vasodilation, both necessary for proper maturation. Additionally, Endomimetics’ Bionanomatrix gel limits smooth muscle cell proliferation, which is also of benefit in that smooth muscle proliferation plays a significant role in AVF non-maturation. Endomimetics’ Bionanomatrix gel is undergoing preclinical evaluation in collaboration with a group at the University of Alabama at Birmingham.

Coronary Stents

Stents are the most common cardiovascular implants used in the treatment of cardiovascular diseases. The coronary stent market exceeded USD 10.31 billion by 2021. That market increased from USD 7.16 billion in 2016, at a compound annual growth rate (CAGR) of 7.6% from 2016 to 2021. Unfortunately, with stent deployment, there is inevitable injury to the endothelium, triggering a cascade of issues such as restenosis and thrombosis. In-stent narrowing (restenosis) often associated with bare metal stents, late stent thrombosis (a blood clot forming in a blood vessel) and inflammatory responses associated with drug-eluting stents all contribute significantly to complications, and even deaths, that can occur with stent implants. The endothelium is the lining of the blood vessels that is a thin layer of endothelial cells and underlying nanofibrillar basement membrane. It modulates vascular tone by release of factors such as nitric oxide. Endomimetics’ Bionanomatrix coating provides a pro-healing environment, enhancing healing of the endothelial lining, inhibiting blood clot formation, and limiting restenosis. Endomimetics has evaluated the coating in an established animal model of restenosis. After 28 days in a balloon injury rabbit iliac artery model, commercial bare metal stents (BMS) developed neointimal hyperplasia, and drug-eluting stents (DES) showed incomplete endothelial coverage and inflammation. However, the Endomimetics’ Bionanomatrix coated stent exhibited complete reendothelialization, reduced inflammation, and reduced neointimal hyperplasia.”

Flow Diverters For Brain Aneurysm

About 3% of the general population, or an estimated 6 million people in the US, has an intracranial aneurysm. Ruptured intracranial aneurysms are fatal in about 40% of cases, and 4 out of 7 persons who survive have significant disabilities. Most intracranial aneurysm patients are treated using minimally invasive, endovascular therapy with microcoils placed into the aneurysm cavities.

However, coil embolization therapy shows high rates (~30%) of subacute and chronic aneurysm recurrence, causing retreatment with its attendant risk of stroke. In the past 10 years, intraluminal flow diversion devices have been successfully used in aneurysm therapy. The flow diversion aneurysm treatment market is poised to grow by USD 1.64 billion by 2024, progressing at a compound annual growth rate (CAGR) of over 8% during that time frame. The most feared risk is that of rupture, leading to devastating consequences. These flow diverters have compact, metallic mesh structures and are placed within the parent artery, across the neck of the aneurysm, to divert flow and achieve aneurysm occlusion. Recent case series have demonstrated high rates of long-term aneurysm occlusion using these flow diverters. The most serious concern for the use of flow diverter therapy is clot formation on the diverter with subsequent stroke. Thus, all patients treated with flow diverter devices require long-term antiplatelet therapy – a minimum of 3 months post-procedure. If the aneurysm occlusion process could be accelerated and thrombus formation in the artery minimized, this could shorten the need for antiplatelet therapy and decrease embolic and bleeding risks. Recent studies strongly suggest that complete endothelialization of any occlusion device is essential for durable occlusion, but such endothelialization is prolonged with standard flow diverter technology. The Endomimetics’ Bionanomatrix is currently being evaluated both in vitro and in vivo. We anticipate that the Bionanomatrix coating on flow diverters can enhance healing, thereby promoting durable occlusion of aneurysms.

Drug Coated Balloon

The management of vascular stenosis (narrowing of the arteries and veins) has undergone major advances over the past decades, yet challenges remain. Bare metal stents (BMS) were plagued by unacceptably high rates of in-stent restenosis (ISR). Although drug-eluting stents (DES) were developed primarily to reduce neointimal hyperplasia, rates of ISR remain at least 5-15%. Furthermore, the use of stents remains controversial in certain situations, including within vessels with small diameters, long lesions, bifurcations, repeated ISR, and in segments of peripheral artery disease (PAD). It is estimated that 8.5 million people in the U.S. alone have PAD, which can lead to further morbidities including lifestyle limiting claudication, amputation, and stroke. In certain locations in the legs, stents carry a significant risk of stent fracture. Stent fracture rates can approach 37%, often resulting in restenosis or total vessel occlusion. The use of drug-coated balloons (DCB) has emerged as an attractive alternative to treat both PAD and ISR lesions without leaving behind a permanent stent prosthesis. DCBs are angioplasty balloons coated with an anti-proliferative drug to prevent restenosis. Endomimetics, LLC has developed a novel dual-action coating for drug-coated balloons that could reduce neointimal hyperplasia and restenosis and enhance re-endothelialization and vascular healing in patients that have PAD. The global drug-coated balloons (DCBs) market is expected to reach above USD 1.5 billion by 2025 with a high double-digit growth rate of around 15% over the forecast period.

Direct Pulp Capping

Endomimetics is developing a novel bioactive Direct Pulp Capping (DPC) material using Endomimetics’ Bionanomatrix to better treat dental caries and other dental ailments. Conventional DPC materials have shown high solubility, low sealing capacity, weak physical properties, uncontrolled pulp necrosis, and unpredictable clinical success. Although recent bioceramic materials have been developed to improve clinical outcomes with moderate clinical success, bioactive function to induce the formation of a mineralized barrier (reparative dentin) without pulp necrosis, antimicrobial/anti-inflammatory capacity, physical-mechanical properties (i.e., sealing capacity, pH control, discoloration, and setting time), and cost effectiveness of these DPC materials still needs to be improved. To address the current limitations and improve the capacity to maintain pulp vitality, the development of a novel bioactive DPC material is proposed, utilizing the innovative coating technology of the Bionanomatrix.

Knee arthroplasty

Problems with vascular access needed for hemodialysis are among the most frequent reasons for hospitalization of patients with ESRD. The direct cost of vascular access establishment and repair exceeds $700 million per year in the US. A significant problem for dialysis patients is the development of a functioning and durable vascular access, preferably an arteriovenous fistula (AVF). After creation, about 60% of AVFs fail to mature successfully for dialysis use. This is due to inadequate vasodilation and smooth muscle cell hyperplasia at the distal venous anastomosis. The Endomimetics Bionanomatrix gel is being developed for use as a coating of the AVF at the time of creation, recruiting endothelial cells and enhancing appropriate vasodilation, both necessary for proper maturation. Additionally, Endomimetics’ Bionanomatrix gel limits smooth muscle cell proliferation, which is also of benefit in that smooth muscle proliferation plays a significant role in AVF non-maturation. Endomimetics’ Bionanomatrix gel is undergoing preclinical evaluation in collaboration with a group at the University of Alabama at Birmingham.

Future Applications Under Development

  • Pacemaker and AICD leads
  • Biodegradable scaffolds
  • Silicone implants
  • Obesity treatment
  • Orthopedic devices
  • Atrial Septal Defect (ASD)
  • Peripheral vascular stents
  • Vascular Septal Defect (VSD) occluders
  • Stent grafts
  • Transcatheter Heart Valves