Phase 1
Advanced Therapeutics - Cardiac Progenitor Cells (CPCs):
A major hurdle to successful clinical translation of cardiac cell therapy is poor cell survival, engraftment and retention in the infarct damaged heart. The AMCARE consortium hypothesise that enhanced efficacy can be achieved by increasing the retention of stem cells in the damaged myocardium or heart tissue following delivery, reducing potentially the effective dose, increasing the safety by reducing the risk of unwanted side effects as well decreasing the costs of cell therapy treatment.
Phase 2
Device Coupling- New Technologies for Distinct Myocardial Delivery - Smart HA-Based Biomaterial Systems
The objective of AMCARE is to utilise Contipro’s proprietary technology of HA gel production, whereby HA-based hydrogels will be used to provide a surrogate extra-cellular matrix for administered cells to both enhance cellular cohesion and retention at the damage site after delivery. AMCARE partner Contipro have developed a platform that can produce hydrogels with tuneable mechanical and viscoelastic properties - from viscous gel-like materials.
Hyaluronic Acid- Derivative Based Hydrogels
One of the HA derivatives that will be tested in the AMCARE programme patented by Contipro can produce materials with a wide range of viscoelastic properties. These HA gels have increased elasticity which allow these materials to withstand elastic and cyclical changes seen in the heart following injection into the myocardium.
HA hydrogel Delivery system
For homogenous hydrogel preparation Contripro have developed a two-way applicator with implemented static mixer (without this mixer, the gels are not homogenous and it is very difficult to standardize their mechanical properties). This HA-derivative based hydrogel is currently being used for vocal cord augmentation or as scaffolds for cells implementation for cartilage tissue engineering. The combination of this applicator and crosslinking reaction enables homogenous incorporation of cells into HA-based hydrogels without any negative influence on their viability.
The AMCARE partners also plan to develop a HA-based cardiac patch platform that can be manufactured using the HA-derivative materials detailed above into a preformed sheet for epicardial delivery to the heart. For the CardioPatch the plan is to use fibres based on hydrophobically modified or UV-crosslinkable hyaluronan because of their increased hydrolytic stability. These fibres meet all biocompatibility and biodegradability conditions. Construction of the fabric will be designed to obtain optimum geometrical and mechanical properties (porosity, mechanical properties, swelling, biodegradation time).
HA-based cardiac patch
To aid delivery the patch will consist of a polyurethane (PU) base layer. This layer serves as the adhesive layer to the pneumatic unit of the delivery device, and the knitted HA-based fibre mesh (CardioPatch) lies on top of the PU layer to face the injured myocardium.
Minimally Invasive Surgical Devices and Biomaterial Coupling
AdjuCor has developed its proprietary Sustained Pressure Regulated Epicardial Delivery System (SPREDS) to optimize delivery. This approach will allow applying the CardioPatch loaded with therapeutic agents and ensure a durable and sustainable contact with the infarcted area from the epicardial surface. SPREDS is an innovative, minimally invasive epicardial cell delivery system for patients with acute myocardial infarction.
The combination of AMCAREs novel medical devices (C-CathGel & SPREDS) and advanced biomaterial formulations (CardioPatch and CardioGel) allows for a tailored approach according to a patient-specific clinical need. The image above demonstrates the main design features of the potential C-CathGel endocardial catheter, which will be entered through the femoral/radial artery and placed within the ventricle.
Phase 3
Achieving Clinical Translation
After establishing the therapeutic benefit of the ideal HA based multimodal approach to regenerate the heart, a translational reality stage will be carried out to aid clinical realisation. A large animal study will be carried out in an acute model of myocardial infarction under GLP and industrial standards. By carrying out this thorough preclinical testing, it will enable movement along the regulatory approval pathway and enhance speedy translation by adding attractiveness and value to the developed therapeutic products and delivery device(s). To coincide with advanced preclinical assessment the AMCARE consortium will also engage in programmes in production and scale-up, regulatory compliance alignment, and ethics.
the AMCARE Project