John Daristotle1 Lung Lau2 Joseph Hunter1 Shadden Zaki3 Leopoldo Torres Jr1 Priya Srinivasan2 Aristotelis Zografos3 Omar Ayyub4 Anthony Sandler2 Peter Kofinas4

1, Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States
2, Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. Center for Surgical Care, Children’s National Medical Center, Washington, District of Columbia, United States
3, Department of Materials Science and Engineering, University of Maryland, College Park, Maryland, United States
4, Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, United States

Wound closure devices prevent excessive blood loss and exposure to pathogens, whether for internal or external use. Conformal, adhesive dressings improve upon conventional wound closure devices such as sutures by minimizing collateral damage to tissue and providing a leak-proof seal. In this work, we demonstrate how solution blow spinning (SBS) can be used to spray-deliver polymer composite dressings in situ--and how the composite element delivers advanced functionality, either by (1) releasing silver ions to prevent infection or (2) by incorporating silica particles to reduce coagulation time. Both approaches utilize a body temperature-responsive biodegradable polymer blend of poly(lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) with minimal cytotoxicity.

While silver salts are frequently used as a source of antimicrobial silver ions (Ag+), their elution in commercial external wound care products is immediate and therefore their solubility is used to control Ag+ availability, often leading to exposure to unnecessarily high and cytotoxic levels. In approach (1), silver nitrate (AgNO3) is dissolved into the PLGA/PEG blowspinning solution, establishing consistent loading and elution profiles: The PLGA/PEG/Ag fibers release Ag+ quickly in a controlled manner over 24 hours, and they continue to release Ag+ over 30 days. AgNO3 concentration was tuned to 1 mg/mL to produce a dressing that inhibits microbial growth but does not affect cell viability. In a porcine burn graft donor model, PLGA/PEG/Ag can be applied once and requires few, if any, reapplications during the course of healing, and produces no delay in healing compared to a conventional polyurethane dressing. Because it is biodegradable, the polymer is incorporated into the scab and can be removed after the wound bed is reepithelialized and no longer requires a dressing.

Polymers can also be used internally as surgical sealants to prevent fluid leaks and promote hemostasis by occlusion of blood flow. However, uncharged synthetic polymers lack a mechanism to trigger the coagulation cascade. Approach (2) incorporates silica particles into PLGA/PEG to trigger the coagulation cascade via the “glass effect”, which takes advantage of the strongly negative charge present on bare silica. Composite sealants cause citrated blood to clot in scenarios where PLGA/PEG alone does not. The effect is also size-dependent: composites containing 20 nm silica particles cause blood to clot 25% faster composites with 620 nm particles. The composite sealant was tested in a liver laceration model, and achieved near-complete hemostasis within 15 minutes, while PLGA/PEG did not. Additionally, silica particles increase adhesion and can be used to modify the stiffness and extensibility of the sealant.