The second leading cause of battlefield deaths is internal bleeding from traumatic injury. A team of researchers from Texas A&M University and the Massachusetts Institute of Technology are collaborating on development of a new, injectable material designed to buy wounded soldiers survival time by stanching blood loss from internal injuries.
The potential life-saver is a biodegradable gelatin substance embedded with nano-sized discs of silicate material that speed up coagulation. Injected at the wound site, this material conforms to the shape of the injury and speeds up blood clotting by up to 77 percent in some instances according to research team member and Texas A&M assistant professor of biomedical engineering Akhilesh Gaharwar. The research team’s findings have been published in the American Chemical Society journal ACS Nano and are supported by the U.S. Army Research Office.
The ACS Nano paper, entitled “Shear-Thinning Nanocomposite Hydrogels for the Treatment of Hemorrhage,” (ACS Nano, 2014, 8 (10), pp 98339842 DOI: 10.1021/nn503719n) is coauthored by Dr. Gaharwar, Reginald K. Avery, Alexander Assmann, Arghya Paul, Gareth H. McKinley, Ali Khademhosseini, and Bradley D. Olsen, variously of Texas A&M University, College Station, TExas; the Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; the Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston; the Center for Biomedical Engineering, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Cambridge, Massachusetts; the Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology; the David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; the Department of Biological Engineering, Massachusetts Institute of Technology; the Department of Mechanical Engineering, Massachusetts Institute of Technology; and the Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
The researchers note that while several surgical approaches to achieving hemostasis on the battlefield have been developed and commercialized, such as use of fibrin glue and tissue adhesives, these approaches are difficult to employ in the field and can’t be used for incompressible wounds.
As an alternative, the coauthors present a treatment based on shear-thinning nanocomposite hydrogels composed of synthetic silicate nanoplatelets and gelatin as injectable hemostatic agents. They report that these materials have been demonstrated to decrease in vitro blood clotting times by up to 77 percent, and are able to form stable clot-gel systems. In vivo testing indicates that these nanocomposites have been shown to be biocompatible and capable of promoting hemostasis in an otherwise lethal liver laceration.
Although it’s still in the early days development-wise, Dr. Gaharwar suggests that in future the biomaterial will be preloaded into syringes that soldiers can carry into combat on their persons. Soldiers experiencing penetrating, incompressible injuries located where it is difficult or impossible to apply pressure needed to effect clotting will be able to inject the material directly into the wound site where it will accelerate coagulation and buy the time needed to get to a medical facility for treatment.
“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” Dr. Gaharwar says in a Texas A&M Engineering release. “Our materials combination of injectability, rapid mechanical recovery, physiological stability and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”
Unlike some injectable solutions, which are used at risk of their migrating to other parts of the body and forming unintended and potentially harmful clots, this nanocomposite material designed by Dr. Gaharwar and his research colleagues solidifies at the wound site and begins promoting coagulation in the targeted area immediately. Moreover, it accomplishes this without requiring applied pressure, distinguishing it from other types of hemostasis inducing wound treatments such as tourniquets, patches and chemical sealants.
“In today’s forms of warfare, most penetrating injuries, which today are the result of explosive devices, rupture blood vessels and create internal hemorrhages through which a person is constantly losing blood,” Dr. Gaharwar notes. “You can’t apply pressure inside your body, so you have to have something that can quickly clot the blood without needing pressure.”
In order to engineer such a material, Dr. Gaharwar and his colleagues focused on modifying a category of biodegradable materials called hydrogels that are used in a range of biomedical applications because of their compatibility with the body and its processes. By inserting two-dimensional nanoplatelets into the hydrogel, the Texas A&M/MIT research team was able to modify and optimize the hydrogel materials’ mechanical properties so that it could be injected into a wound site and regain its shape once inside the body, a quality necessary for it to lock itself in place.
Use of two-dimensional materials represents a new direction in biomedical engineering, Dr. Gaharwar explains. These ultrathin substances have a large surface area but a thickness of a few nanometers or less analogous to a sheet of paper but on a much smaller scale. While a sheet of paper is roughly 100,000 nanometers thick; Dr. Gaharwar’s nanoplatelets are just one nanometer thick, and he and his colleagues employ two-dimensional, disc-shaped particles known as synthetic silicate nanoplatelets whose structure, composition and arrangement result in each particle carrying both positive and negative charges which Dr. Gaharwar explains cause the platelets to interact with the hydrogel and causing it to temporarily change its viscosity when mechanical force is applied, sort of like ketchup squeezed from a bottle. This change allows the hydrogel to be injected and regain its shape inside the body.
“In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting,” Dr. Gaharwar says, noting that animal models have shown clot formation occurring in about one minute compared with five minutes without the presence of nanoparticles.
“These 2D, silicate nanoparticles are unprecedented in the biomedical field, and their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies and immune engineering,” Dr.Gaharwar concludes.
The TAMU Engineering release reports that the research team is encouraged by results so far and plans to further enhance the biomaterial so it will be able to initiate regeneration of damaged tissues through formation of new blood vessels, creating a two-pronged wound treatment that not only provides damage control but also assists the body’s natural healing process.
Dr. Akhilesh K. Gaharwar’s Nanomaterials and Tissue Engineering (iNanoTE) Laboratory focuses on designing, developing and integrating biomimetic nanostructures and stem cells for functional tissue engineering that have potential for clinical translation.
Dr. Gaharwar’s research spans diverse fields, including materials science, chemistry, stem cells biology and microfabrication of polymeric biomaterials and nanocomposites. Specifically, his laboratory specializes in developing biomimetic nanomaterials with native interface tissue-like gradient in physical and chemical properties; integrating advanced micro- and nano- fabrication technologies to mimic native interface tissue architecture; and directing stem cell behavior to obtain regionalized tissue constructs in vitro and in vivo. This integrated approach synergizes a range of seemingly disparate disciplines including medical science, polymer chemistry, micro-fabrication, and stem cell biology in order to address some of the complexity associated with engineering functional tissue interfaces in ways otherwise not possible.
The lab’s current projects include designing bioactive nanomaterials for regenerating damaged tissue interfaces; developing vascularized networks; and devising new therapeutic strategies, especially in musculoskeletal applications.
Dr. Gaharwar talks about his work with nanoplatelet hydrogels in a video that can be viewed at:
Texas A&M University Department of Biomedical Engineering
Massachusetts Institute of Technology
Texas A&M University Department of Biomedical Engineering