Extremity trauma is one of the most common battlefield injuries. Through advances in early field intervention and resuscitation, such injuries have become increasingly survivable. Despite progress, extremity injuries can be devastating with complex injuries to the vasculature, bone, connective tissues, muscle, and nerves. Approximately 50% of patients with complex extremity injuries have severely impaired limb function. These injuries are commonly associated with long term complications and poor functional recovery. In fact, at the same age, military personnel have doubled the rate of post‐traumatic osteoarthritis compared to individuals in the civilian population. Severe extremity trauma with initial limb salvage leads to delayed amputation in approximately 14% of patients, typically following many months of repeated surgeries and attempts at rehabilitation. Only 20% of wounded military personnel who experience severe extremity trauma are ultimately able to return to service.
Vascular trauma to the extremities remains a major cause of morbidity and mortality among U.S. and allied warfighters, and has increased proportionately in recent conflicts. At the peak of recent conflicts, Improvised Explosive Devices (IEDs) caused more than 3,000 casualties per year, many involving extremity injury. Arterial damage, laceration and thrombosis can require vascular reconstruction to save tissues from ischemia, necrosis, and further amputation. The current standards of care for vascular reconstruction ‐ harvesting of autologous vein and synthetic grafts (e.g., Teflon/Dacron) ‐ both have important limitations. Autologous grafting is limited in patients with multiple extremity injuries, and vein harvest can lead to chronic venous insufficiency at the donor site, as well as limit future vascular surgery options in young patients (i.e., heart bypass grafting). Currently available synthetic grafts are generally considered a 2nd line option due to contraindications to use in contaminated battlefield wounds.
Optimal solutions would not only provide more durable repairs, but reduce the need for autologous tissue and number of surgical procedures.
Therefore, this program focused on the clinical, prototyping, and manufacturing needs of entities developing prototypes that can serve as permanent arterial and/or venous grafts for reconstruction and repair of traumatic injuries. The prototype must be intended for permanent vascular repair – serve as a permanent vascular graft to repair and reconstruct extremity injuries. One research project award recipient was selected from the Offerors who responded to MTEC’s Permanent Vascular Repair Request for Project Proposals (17-05-PVR).
Human Tissue Engineered Blood Vessels for Vascular Reconstruction in the Injured Warfighter
Project Team: Humacyte, Inc.
Award Amount: $649,898 (does not include proposed cost share of $3,583,458)
Project Duration: 12 Months
Project Objectives: The human acellular vessel (HAV) is a novel regenerative medicine product manufactured using a state-of-the art tissue engineering bioprocess to manufacture a human tissue blood vessel that, following surgical implantation, repopulates and remodels with the recipient’s own cells. The HAV has the potential to be an integral component in the treatment of serious and life-threatening conditions resulting from combat injuries and is being developed for the United States Warfighter. Over the project duration, Humacyte will work to complete several Chemistry, Manufacturing, and Controls (CMC) regulatory requirements in support of the submission of a Biologics License Application (BLA) to the Food and Drug Administration (FDA). Humacyte will proactively seek the advice and feedback of FDA, through additional points of contact granted under the Regenerative Medicine Advanced Therapy (RMAT) designation, to ensure alignment on critical CMC components.
• Manufacturing: Humacyte will develop and implement the protocol for comparability of the current manufacturing system to the Phase 3 manufacturing system. HAV product will be manufactured and a subset of early batches designated to the protocol will be analyzed. A comparability study summary will be completed at the end of the 12 month period of performance.
• Product stability: Protocols for both room temperature and refrigerated stability will be developed and executed; product will be manufactured to support the stability protocol, including time zero analysis. A stability study summary will be completed at the end of the 12 month period of performance.
• Biocompatibility and adventitious agent safety testing: HAV product will be produced to support biocompatibility and adventitious agent safety testing.
Year One Accomplishments:
- Completed formal stability protocol for innovative, commercial bioprocessing of human acellular vessels.
- A microbial bloom study was completed by quantitative experts on our product storage solution in support of the upcoming adventitious agent study. A protocol has been drafted to evaluate viral clearance capabilities of selected Humacyte vessel decellularization steps.
- Initial testing of full commercial scale batches has been conducted on schedule. We are continuing conversations with the FDA on qualification requirements for our innovative regenerative medicine product.