Evaluating the role of photobiomodulation in human cervical remodeling in pregnancy

评估光生物调节在人类妊娠期宫颈重塑中的作用

• 批准号: 10288476
• 负责人: Christine P Hendon
• 金额: $ 24.3万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10288476
• 关键词: 3-Dimensional; Affect; Area; Attenuated; Bathing; Biological Assay; Bluetooth; Cervical; Cervical Ripening; Cervix Uteri; Cesarean section; Clinical; Collagen; Data; Deposition; Device or Instrument Development; Devices; Discipline of obstetrics; Electrical Engineering; Engineering; Etiology; Exhibits; Extracellular Matrix; Failure; Fetus; Future; Gel; Goals; Healthcare; Human; Inflammation; Inflammatory; Interstitial Collagenase; Intervention; Knowledge; Light; Matrix Metalloproteinases; Mechanics; Mediating; Mothers; Muscle relaxation phase; Opsin; Organ; Pathway interactions; Perfusion; Perinatal mortality demographics; Pessaries; Phototherapy; Play; Pregnancy; Pregnancy Rate; Premature Birth; Premature Infant; Process; Production; Protocols documentation; Relaxation; Reporting; Research; Research Personnel; Risk; Role; Smooth Muscle; Smooth Muscle Myocytes; Sphincter; Tensile Strength; Testing; Therapeutic Intervention; Time; Tissue Sample; Tissues; Translations; Uterus; Vaginal delivery procedure; Validation; Vascular Smooth Muscle; Wireless Technology; Woman; cervical remodeling; chemokine; clinical care; comorbidity; cytokine; disability; emerging adult; experimental study; exposed human population; healing; in vivo; mechanical properties; mortality; mortality risk; multidisciplinary; multiplex assay; neonatal death; nonhuman primate; novel; novel strategies; novel therapeutics; perinatal morbidity; photobiomodulation; pregnant; premature; prevent; receptor; soft tissue; wound healing

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.

抽象的： 为了使胎儿在期限内交付，子宫颈必须在适当的时间进行重塑，软化和扩张 怀孕。如果子宫颈过早地重塑，则怀孕有自发早产（SPTB）的风险 每年美国10分之一的产科困境，使婴儿处于风险增加 对于新生儿死亡，成年初期的终生合并症和/或死亡率。相反，如果子宫颈展示 宫颈重塑和扩张不足或延迟，怀孕可能会超过到期日，这会增加 围产期发病率/死亡率和对母亲风险的风险，包括剖宫产的一倍 速度。迄今为止，治疗干预措施以防止过早的宫颈重塑导致SPTB或不足 宫颈重塑导致后期怀孕是有限的，并且不完全有效。光生物调节 （PBM）使用低水平光疗法（LLLT）当前正在临床环境（如伤口愈合）中使用 已显示具有蓝光的PBM会引起血管平滑肌松弛（增加组织灌注） 红色/红外光可以调节炎症，ECM重塑和愈合组织的机械强度。 迄今为止，我们已经证明了人类子宫颈的内部OS包含大量 收缩平滑肌（这可能形成括约肌，使子宫颈在怀孕期间关闭）和 人宫颈平滑肌细胞通过分泌促炎性在宫颈ECM重塑中起作用 细胞因子和基质金属蛋白酶（MMP）。鉴于PBM可以调节平滑肌收缩力， 炎症/ECM的重塑和组织强度，在此提案中，我们旨在确定是否可以利用 光的力量并使用LLLT来增强或衰减颈椎平滑肌介导的收缩力， 促炎/ECM重塑途径和宫颈组织机械性能。此外，由于我们 多学科研究人员团队包括世界一流的工程师，具有人类软组织专业知识 力学和电气工程，我们的目标是开发一种新颖的无线内部LLLT设备（用于 随后的验证非人类灵长类动物）可以在受控时间内发射特定的光波长 时期。从拟议的研究中获得的知识具有将临床护理转化为临床护理的巨大希望 预防或逆转过早宫颈重塑的新型治疗方法导致SPTB或增强宫颈 女性的重塑/扩张。