Protection from the effects of ionizing radiation remains a major concern of the DoD, as many military personnel work within environments with risk for radiation exposure. 3D Bioprinting provides a novel opportunity to evaluate radiation effects in a more robust (i.e. more than a single cell layer) human tissue environment. In this initial project, a model for evaluation of a variety of radiation effects on a 3D-bioprinted Blood Brain Barrier will be developed and the effects of low and high dose radiation exposures will be investigated.
Metal fragments from penetrating injuries due to ballistic or blast injuries remains a common surgical care dilemma for greater than two-thirds of the 45,000 Wounded Warriors returning from conflicts in Iraq and Afghanistan, who have retained metal fragments. Conventional surgical management recommends removal of shrapnel that is easily retrievable but to leave imbedded shrapnel in situ as extended surgery could increase the risk of infection and degrade healing outcomes by removing these fragments. In this initial project, a model for evaluation of trace metal diffusion and permeation of the Blood Brain Barrier (BBB) will be developed using 3D bioprinted BBB and the penetration of the BBB of military-relevant metals will be evaluated.
After full-thickness skin injury, healing deficiencies such as scars and repeated epidermal breakdown are partially due to the absence of hair follicles. Hair follicles contain repositories of multipotent stem cells that can be called upon to speed wound healing. Bioprinting allows for the fabrication of discreet skin architecture, including hair follicles,through exact placement of biomaterial and cell populations. In this initial project, human skin containing hair follicle primordia will be developed, printed, and tested, both as an in vitro barrier system and as an in vivo skin graft.
Many bacteria and bacterial toxins cause food and water-borne diarrheal illness, and are an acute risk to warfighters stationed overseas. While aspects of infection by toxin-producing E. Coli are understood, the mechanism of action for colonizing and crossing the intestinal barrier is still largely unknown. In this project, a gut eukaryotic/prokaryotic gut barrier tissue will be bioprinted and challenged to determine the effects of enterohemorrhagic E. coli on barrier integrity and cellular function.
Recent research has shown that mechanical injuries from sudden head impacts and exposures related to blast-related shock waves disrupts transport functions and blood brain barrier permeability (BBB). Changes in BBB permeability causes temporary opening of the barrier, allowing foreign molecules to enter the brain and leading to constant low-grade inflammation. In this project, an in vitro bioprinted human BBB model and in vivo rodent animal model will be exposed to shock waves, mimicking a TBI injury. Integrating data acquired from in vitro and in vivo approaches will permit us to develop a novel approach for understanding BBB pathology, to validate the in vitro model, as well as use the platform for the development and testing of treatments.
Zika virus (ZIKV) is associated with congenital brain abnormalities in infants born to infected mothers, and severe encephalitis in adults. ZIKV has been readily detected in the infected brain suggesting that ZIKV easily crosses the Blood Brain Barrier (BBB). The exact mechanisms of how ZIKV crosses the BBB and cause an infection in the underlying tissue is not known. In this project, bioprinted human and rhesus macaque BBB will be exposed to ZIKV to determine how ZIKV infects the BBB, its impact on the tight junction proteins, and the genomic and proteomic changes ZIKV induces in crossing the BBB. Each model (human and rhesus macaque) will also be used to study the efficacy of viral countermeasures to prevent ZIKV infection and transmission across the BBB.
Meniscal injuries represent one of the most common and disabling injuries sustained in a young, high-demand U.S. Military population. In our military population, we have observed the rate of meniscal tears to be more than ten times higher than the general civilian population and as high as 8.27 injuries per 1000 person-years. As a result, knee arthroscopy in active-duty service members is the most common orthopedic procedures performed in the DoD, with more than 8,000 meniscal procedures performed annually. To date, meniscal repair and replacement strategies have lagged behind other tissue engineering endeavors and it stands to reason that tissue-engineered meniscal bio- printed implants may provide an alternative solution for the treatment of meniscal injury. In collaboration with USMA, 4D Bio³ will create a 3D printed in vitro meniscus tissue model and subject it to physiologically relevant conditions to advance military readiness and improve long term soldier health.
The ability to move bioprinting out of sterile biology laboratories to forward-deployed positions is mission-critical to future bioprinting military operations. For this project, our partners have customized a lightweight and rugged bioprinter which will be deployed to an undisclosed, forward location for ten weeks of bioprinting and experimentation in a desert environment. The team intends to create a number of experimental prints, including plastic medical models, mesenchymal stem cells, and next-gen wound bandages. This project is a step toward bringing next-generation critical care close to the warfighter. For example, bioprinting a variety of wound-healing biologics, bandages, stents, and even bandage/biosensors on demand and at or near the point-of-care would be expected to improve healing and survival rates of the warfighter. Point-of-care bioprinting is also expected to provide significant advantages in soldier care and military applications through reduction of expensive and wasteful logistics, warehousing, refrigeration, and shipping. Bioprinting only what the soldier needs, where it is needed, and when it is needed, is expected to improve outcomes and reduce overall costs of advanced medicine for our warfighter.
There is a growing need for bioprinting subject matter experts within the DoD for the advancement of tissue engineering strategies to meet the regenerative medicine and warfighter readiness missions of the present and near future. The 4D Bio3 FabAE-si program is a pilot program for the development of a collaborative tissue engineering research and educational program between Uniformed Services University and the United States Military Academy in the field of tissue engineering, using advanced bioprinting technologies for application in sports related injuries. Through this program, cadets at USMA will learn basic and advanced techniques for 3D bioprinting through a distance learning course. The skills and knowledge learned in this course, combined with key USMA personnel, will be put to immediate use to address sports injury defects with bioprinted replacement tissue. Expansion to other military academies and DoD training entities is occurring in 2019/2020.
Resurrection of the pilot DARPA "Blood Pharming" red blood cell (RBC) program from the early 2000s with the intent of producing full range of human blood products ("whole blood") in austere environments. Using state-of-the-art biotechnology, the program will initially target the production of human RBCs and neutrophils. This effort incorporates multiple partners from various Federal agencies, as well as academia and industry.