Injectable Antimicrobial Hydrogel for Extremity Wound Management
Abstract
The long-term goal of this work is to drive clinical translation of a novel therapy for bone regeneration in infected limb injuries. Approximately 20% of battlefield wounds are bone fracture and loss at the extremities, which often (80%) are open wounds with significant peripheral tissue damage and loss. These wounds are contaminated by microbes from the local flora (skin and mucosal membranes) and from the environment (e.g., air, soil and penetrating objects). Thus, extremity wounds are considered dirty and necessitate early irrigation, debridement, and antibiotic therapy at the far-forward hospitals (leading edge of the battlefield). However, antibiotic resistance remains a significant problem at primary military medical facilities, occurring in approximately 15% of surgical patients. Moreover, the prevalence of infection in chronic wounds is reported as high as 53%. The severity and lethality of wound infection is expected to increase due to more prolonged field care management and delayed treatment as increased adversarial capabilities and weaponry impair evacuation. The microbial burden of acute and chronic wounds impairs healing and leads to infection-related complications such as sepsis, amputation, multi-organ failure and death. The two critical problems are that no treatment exists to impede infection at the battlefield and no antibiotic cocktail exists with broad-spectrum antimicrobial efficacy in infected wounds, particularly one that is efficacious against bacterial biofilms. Moreover, antibiotic therapy is limited by side effects and risk of developing antibiotic resistance and immune system damage. Our device is a new antimicrobial treatment that can be injected into wounds at the point of care to prevent bacterial colonization, eliminate infection, and promote healing. It is a hydrogel loaded with microparticles that deliver nitric oxide (NO*) in a spatiotemporally controlled manner. NO* is a natural antimicrobial produced by the human immune system. It has broad-spectrum antimicrobial action against numerous microbial components. NO* is also known to enhance bone regeneration. We have developed NO* carriers, particularly silicate microparticles, and verified their bactericidal efficacy in vitro. We have developed an injectable hydrogel, a liquid that solidifies when injected, to deliver the NO* carriers and to promote bone regeneration. The goal of this study is to compare the efficacy of hydrogels with three different NO* carriers to clear infection and to regenerate bone in a bone defect made in the femurs of rats. We will also monitor potential risks of impaired clotting and vascular leakage. This work will identify the donor formulation with bactericidal efficacy and fastest bone regeneration. It will also inform how the device works, the primary modes of action. This data on efficacy, modes, and safety is critical in the path to complete the clinical trials for our device within 10 years. We will apply it to protect the intellectual property via patent applications and to define the regulatory pathway with the FDA. No study has developed a single-dose, injectable, prolonged NO* delivery system such as ours to treat deep wound infection and promote tissue regeneration. This work addresses the FY20 PRORP Focus Area of Retention Strategies. We envision the application of our device in two theaters: (1) the point of injury in the forward battlefield as a prophylactic to prevent infection of contaminated wounds and (2) Echelon II and III facilities to eliminate infection and promote bone healing, part of a comprehensive treatment strategy for extremity wounds. This will minimize complications associated with compromised contaminated wounds and promote more rapid healing. These indications can be mirrored in the civilian population, with application in emergency rooms to treat traumatic injury and in elective care to treat chronic infections such as osteomyelitis. Once the market
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2120008
Entities
People
- Juan M Taboas
Organizations
- United States Army
- University of Pittsburgh