Injectable Polymers for Treating Myocardial Infarction

 
 

The injection technique of in situ cardiac tissue engineering utilizes the idea that the body is capable of healing and remodeling itself. Unlike most cells in the body, cardiomyocytes are unable to divide and proliferate. This is one the reasons why MI is a difficult to treat condition.

The first example of in situ cardiac tissue engineering was called cellular cardiomyoplasty. For this process, viable cells are transplanted into the infarct region to replace the dead cardiomyocytes. The types of cells that are transplanted are typically some sort of stem cell, such as embryonic stem cells, or mesenchymal stem cells. The problems with this technique are limited cell retention, limited transplant survival, and poor cell distribution. The survival is limited by lack of vasculature, since the cells are injected into an ischemic region of the heart.

Injectable polymer scaffolds have been a more feasible solution to treating MI with in situ cardiac tissue engineering. Injectable polymers can either be injected with or without cells. When injected without cells, the polymers serve as a method to prevent negative LV remodeling, by providing enough mechanical stress to avoid remodeling. When injected with cells, the polymers help cell survival since most cells are adherent-dependent. The polymer scaffolds can also be injected with therapeutic genes or proteins to help the infarct area.

The advantage to using injectable polymers is that it is much more minimally invasive than implanting in vitro engineered tissue. The first group to try this approach was Christman et al. The polymer scaffold they used in their study was fibrin glue.

Fibrin glue is a commercially available compound (Baxter Healthcare Corp.) that is used as a surgical sealant. It consists of two components: 1) concentrated fibrinogen & aprotinin, 2) thrombin and CaCl2. The aprotinin is a fibrinolysis inhibitor. The fibrin glue is applied via a Duploject applicator which keeps the two components in separate compartments. When the syringe is pushed, the two components mix together. The mixture stays as a liquid for several seconds and then solidifies into a gel matrix.












(http://www.baxterbiosurgery.com/us/) An image of the dual-syringe applicator used for the commercially available fibrin glue (Tisseel VH fibrin sealant).


Other studies have been conducted with other injectable polymers such as Matrigel and collagen biopolymers. Matrigel (BD Biosciences Discovery Labware) is a commercial available biopolymer that is a basement membrane extract of collagen, proteoglycans, and laminin. Each of these polymers remain in liquid form until injected into the myocardium.

 

Injectable Polymer Scaffolds