Grant: $100,000 - National Institutes of Health - Jun. 4, 2009
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Award Description: Award title: Endomyocardial catheter delivery of artificial biopolymer matrices for enhanced cell retention in cardiovascular cell based therapy. The overall purpose of this project is to identify formulations of two-component biopolymers including fibrinogen-thrombin and alginate-calcium hydrogels that would instantaneously form hydrogels with appropriate mechanical properties to increase cell retention during delivery through BioCardia's Helical Infusion Catheter and to test the safety of the delivery of these biomaterials in vivo in pig hearts. This project consists of five specific aims. Aim 1 consists of defining appropriate mechanical properties of the two part polymer matrices for injection into pig heart using a novel trilumen bipolar transendocardial delivery catheter system with a hollow coaxial helical needle to enhance cell retention. Aims 2 and 3 consist of formulating these polymer matrices based on the results of Aim 1 to optimize the delivery and retention of swine bone marrow mononuclear cells in vivo, while assessing the cell viability upon delivery through the catheter. Aim 4 assesses the two part polymer matrix biodistribution for each formulation when co-injected into pig heart tissue in vitro. Finally, preliminary safety data of the selected cell retention matrix formulation and delivery protocol in swine heart in vivo using cells labeled with neutron activated colloids and tracked over time within the heart and other vital organs such as the lungs, spleen and liver will be assessed in Aim 5. We expect to identify one or several formulations of the two-part biopolymers, which will have the required viscosities compatible with the pressure limitations of the catheter to flow through the latter without damage. The two-part biopolymers are expected to flow unobstructed through the catheter and with ease from to the end user to form hydrogels instantly at the end of the helical needle of the catheter. We also expect the cell viability to remain unchanged after injection through the catheter and the cell retention to be significantly increased after co-delivery with the biopolymers in the pig heart in the in vivo studies. Finally, we expect to be able to extend the use of our catheter as a device for the co-injection of two-component hydrogels and biotherapeutics including cells and proteins to targeted sites of injection with increased retention and consequently, better therapeutic results.
Project Description: The overall purpose of this project is to identify optimum formulations of two-component biopolymers including fibrinogen-thrombin and alginate-calcium that would instantaneously form hydrogels with appropriate mechanical properties to increase cell retention during delivery through BioCardia's Helical Infusion Catheter in pig heart. We will also co-inject the optimized two-part biopolymers with cells in swine heart in vivo to assess the preliminary safety data of the selected cell retention matrix formulation and the delivery protocol of these biomaterials in vivo in pig hearts. So far, we have completed four of the five specific aims. We have identified LVG alginate-calcium and fibrinogen-thrombin as the two most effective two-part biopolymers with the appropriate viscosities for injection into our novel trilumen bipolar transendocardial delivery catheter system. Cell viability was unchanged before and after injection of swine bone marrow mononuclear cells when mixed with the optimized formulations of the LVG alginate and fibrinogen components of these hydrogels. Cell retention after the formation of the optimal hydrogels via mixing with the second component, was also determined to be almost 100% due to the instantaneous gelation of these two-part biopolymers into a tight network. Furthermore, the two-part biopolymers mixed and gelled evenly when co-injected into pig heart tissue in vitro. Finally, in our last aim, we expect to see an increased cell retention when co-injecting the biopolymers with labeled cells in vivo in swine animal models due to rapid cell encapsulation within the hydrogels as compared to injecting labeled cells in media alone.
Infrastructure Description: The infrastructure investment which we made in hiring a new Research and Development scientist directly contributes to one of the main purposes of the Recovery Act since the grant allocation allowed the creation of a new job within our company. Furthermore, our new scientist has been able to pursue different avenues using BioCardia's Helical Infusion Catheter including the delivery of cells with two-part hydrogel-forming biopolymers to increase cell retention during delivery to the sites of injection. We believe that these studies will provide us with a baseline preliminary safety assessment of delivering these biopolymeric matrices in the heart as well as give us insight in using biomaterials as key biotherapeutic delivery vehicles in cardiovascular regeneration medicine. These could result in significant advancement in combining biotherapeutics with medical devices.
Jobs Summary: The hiring of a research and development scientist was the direct result of BioCardia Inc. being one of the recipients of the Recovery Act Funds. This new scientist was hired based on her previous expertise in the field of injectable natural and protein-engineered biomaterials as a medium for cell and biotherapeutic delivery. Consequently, she has been a valuable addition to the research and development team, providing much needed support to the evaluation and development of the helix biotherapeutic delivery aspect of BioCardia's state-of-the-art Helix biotherapeutic delivery catheter system. BioCardia Inc. has subsequently been able to explore different avenues to expand the use of its catheter system to include deliverables such as injectable biopolymers with cells to increase cell retention for cardiovascular regenerative medicine. (Total jobs reported: 1)
Project Status: More than 50% Completed
This award's data was last updated on Jun. 4, 2009. Help expand these official descriptions using the wiki below.