Dextran is a branched-chain polysaccharide that has been used in medicine for many decades. It is available in two forms, the more common “Dextran 40,” commonly 10% dextran, and “Dextran 70,” commonly 6% and 32% dextran.
Most of the medicinal uses of dextran involve intravenous administration of Dextran 40. Due to its high molecular weight it is an excellent osmotic agent. Therefore, it is administered intravenously where it acts as a volume expander during hemorrhagic shock. It is used in this application for both civilian and combat trauma.1,2 It also can be used during elective surgery for volume expansion.
Intravenous administration of Dextran 40 exerts an antithrombotic effect on platelets, endothelium and red blood cells by reducing aggregation and adhesiveness. Intravascular clots are less likely to form in the presence of dextran.This property of dextran has made it useful as a prophylactic agent for deep venous thrombosis (DVT) in surgical patients. It also is used to maintain patency of vessels in procedures that require microanastomosis.
Typical intravenous dosages of dextran are a liter or more on the first day followed by a half a liter for several days.
In addition to intravenous administration, dextran has been used topically. Gynecological surgeons have used Dextran 70 as an agent of choice when distending the abdomen and pelvis during laparoscopic and hysteroscopic surgery. Dextran 70 is superior to barriers such as Gelfoam and Surgicel for preventing post-surgical adhesions.3 It also appears to be superior to normal saline.4,5
Generally, from 250 ml to 1 liter of dextran 70 is used for irrigation of the abdomen and pelvis.
The other common topical use of dextran is as a component of ophthalmologic solutions, where it acts as a soothing agent and lubricant. Dosages are measured in drops.
FibriSEAL is a hemostatic dressing primarily composed of a dry powder of the clotting proteins fibrinogen and thrombin embedded within a solid dextran dressing. There are other minor components to the dressing that act as preservatives and stabilizers.
Dextran was chosen for a number of reasons. First, as a molecule, it is amenable to the process of electrospinning. Electrospinning creates dry nanofibers of dextran that can be configured into any desired size or shape. The resulting product, called a “dextran mat,” is highly porous on a nano scale. The pores of the mat are small enough to contain the protein powder, yet large enough to readily admit water.
Secondly, dextran is highly soluble in water, so when water, or blood, contacts the mat it quickly dissolves the mat and liberates the proteins. The dry protein powder solubilizes rapidly, which allows the two clotting proteins to interact, resulting in a stable, tenacious clot. The process is very rapid, and at the stage of clot formation the dextran has been removed from the area of application.6
Finally, dextran is the ideal dressing material for FibriSEAL because of its safety profile. The dextran dosages used in the FibriSEAL dressings are a fraction of the recommended intravenous use, or the topical intra-abdominal use. The dose of dextran in FibriSEAL is proprietary, but is several orders of magnitude less per dressing than what is used intravenously in treatment of shock, DVT prophylaxis, or abdominal irrigation.
In summary, electrospun dextran is the ideal dressing material in FibriSEAL because it is safe, it dissolves rapidly, and it does not leave a trace.
FibriSEAL could become an ideal platform for the delivery of pharmaco-therapeutic agents. It is possible to embed dry forms of drugs in the FibriSEAL dressing. For example, antibiotics could be embedded in the dressing, along with fibrinogen and thrombin. The antibiotic would then become embedded in the clot and could elute into the tissues over a period of time, delivering antibiotics directly to a wound. Similarly, it is possible that some chemotherapeutic agents used in cancer treatment could also be embedded in the dressing for local delivery of higher concentrations than could be delivered by intravenous or other methods.
FibriSEAL is a platform nanotechnology that will have many applications, not only in hemostasis, but as a delivery system for a myriad of medications. (Nanotechnology is the engineering of functional systems at the molecular scale dealing with dimensions and tolerances of less than 100 nanometers, especially the manipulation of individual atoms and molecules.)
