(22c) A Wearable Microfiber Biomaterial Incorporates Optical Nanosensors and Enables Wireless Monitoring of Oxidative Stress

Reactive oxygen species (ROS) are a family of signaling molecules continuously generated, transformed, and consumed by all aerobic organisms. Wound healing is one of the most dynamic biological process featuring ROS-linked cellular signaling throughout the entire process. Additionally, basal concentrations of ROS aid in the fight against invading microorganisms into open wounds. The excessive and uncontrolled production of ROS contributes to the sustaining and deregulation of inflammation processes, which play a central role in the pathogenesis of chronic non-healing wounds. Physiologically, hydrogen peroxide (referred herein as peroxide) and superoxide serve as intracellular ROS messengers stimulating key phases of wound healing including cell recruitment, production of cytokines, and angiogenesis. Of note, peroxide acts as the principal secondary messenger in wound healing and is present at low concentrations (100–250 µM) in normal wounds. Increased peroxide concentration is a biomarker for chronic wounds in which biofilm-making pathogens can grow significantly faster than normal acute wounds. Due to the short half-life of peroxide, detection and quantification of their concentrations are difficult in vivo and in patients. Thus, peroxide levels in wounds have generally been determined indirectly through analysis of downstream oxidation products of lipids, proteins, or DNA.

Single-Walled Carbon Nanotubes (SWCNTs) with engineered wrappings have recently been developed and utilized in various disparate fields ranging from additives that strengthen material composites to biomedical applications including targeted drug delivery, optical biosensing, and biological imaging. Of significant interest, SWCNTs exhibit intrinsic photoluminescence (fluorescence) that is photostable, tunable, and sensitive to its local environment. The electronic band gap energies of SWCNTs are dependent on their chiral identity and are differentially and reversibly oxidized, enabling the ratiometric detection of local redox environments.

With revolutionary advances in nanotechnology and biomaterials in the recent years, an extensive range of smart wound care biomaterials have been developed which incorporate components such as growth factors and/or antimicrobial agents such as iodine or silver. Electrospun micro/nanofibers are one of the novel classes of wound dressings as they mimic the chemical and mechanical environment of the 3D extracellular matrix. Micro/nanofiber-based wound dressings have been designed to enhance cell migration, prevent inflammation and infection and inhibit scar formation on wounds. Herein, we developed a process to construct wearable textiles incorporating the DNA-wrapped SWCNT nanosensors through a one-step co-axial electrospinning method. We then developed an optical microfibrous biomaterial with a “core-shell” morphology that encapsulates fluorescent SWCNT nanosensors. We chose Polycaprolactone (PCL) as the shell material as it is an FDA-approved polymer which has been extensively studied for tissue engineering and wound healing applications. Our optical biomaterial was able to ratiometrically detect peroxide in the wound biological range (20-500 uM). The ratiometric characteristic of the sensor will significantly facilitate the future in vivo and clinical applications as it transduces an absolute signal which is not dependent on excitation source distance and exposure time. Moreover, the optical nature of the biomaterial will enable the wireless detection without a need to disturb the wound dressing. We revealed that the signal from the biomaterial does not significantly decay over time as the fluorescence of SWCNTs is non-photobleachable. We also quantified the absolute weight of SWCNT nanosenors in the biomaterial over time using confocal -Raman microscopy and indicated that the nanosensors do not leak out of the fibers over time, mitigating any toxicological concerns related to SWCNTs. Our optical biomaterial was integrated into other common wound dressing materials such as hydrogels and commercialized bandages, showing the compatibility of this platform with other existing wound dressings. Thus, our wearable microfiber biomaterial enables wireless monitoring of oxidative stress directly from the wound site.