ABSTRACT: In order for a fetus to deliver at term, the cervix must remodel, soften and dilate at the appropriate time in pregnancy. If the cervix remodels prematurely, the pregnancy is at risk for spontaneous preterm birth (sPTB), an obstetric dilemma that affects 1 in 10 pregnancies in the U.S. each year and places babies at increased risk for neonatal death, lifelong comorbidities and/or mortality in early adulthood. Conversely, if the cervix exhibits deficient or delayed cervical remodeling and dilation, the pregnancy may go past the due date which increases the risk for perinatal morbidity/mortality and risks to the mother, including a doubling in the cesarean delivery rate. To date, therapeutic interventions to prevent premature cervical remodeling leading to sPTB or inadequate cervical remodeling leading to post-term pregnancies are limited and not entirely effective. Photobiomodulation (PBM) using low level light therapy (LLLT) is currently being used in clinical settings such as wound healing as PBM with blue light has been shown to induce vascular smooth muscle relaxation (increasing tissue perfusion) and red/infrared light can modulate inflammation, ECM remodeling and mechanical strength of healing tissues. To date, we have demonstrated that the internal os of the human cervix contains a significant amount of contractile smooth muscle (that likely forms a sphincter which keeps the cervix closed during pregnancy) and human cervical smooth muscle cells play a role in cervical ECM remodeling by secreting proinflammatory cytokines and matrix metalloproteinases (MMPs). Given that PBM can modulate smooth muscle contractility, inflammation/ECM remodeling and tissue strength, in this proposal, we aim to determine if we can harness the power of light and use LLLT to enhance or attenuate cervical smooth muscle mediated contractility, proinflammatory/ECM remodeling pathways and cervical tissue mechanical properties. In addition, since our team of multidisciplinary investigators includes world class engineers with expertise in human soft tissue mechanics and electrical engineering, our goal is to develop a novel, wireless intravaginal LLLT device (for subsequent validation non-human primates) that can emit specific wavelengths of light for controlled time periods. The knowledge obtained from the proposed studies hold great promise for translation to clinical care as novel treatments to prevent or reverse premature cervical remodeling leading to sPTB or to augment cervical remodeling/dilation in women at term.

NARRATIVE: This proposal aims to determine if photobiomodulation using low level light therapy can be used to attenuate or enhance cervical remodeling and function during human pregnancy. This research will provide a potential novel therapeutic option and a safe, non-invasive low level light therapy device that will decrease the rate of spontaneous preterm birth due to premature cervical failure and the rate of post-term pregnancies due to deficient cervical remodeling and dilation at term.