Specialized Pro-resolving Mediators (SPMs) & scar tissue formation after cleft-lip surgical repair

专业解决调解员 (SPM)

• 批准号: 10093009
• 负责人: Evangelos Papathanasiou
• 金额: $ 13.69万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093009
• 关键词: Academic Training; Acute; Affect; Aftercare; Animal Experiments; Animal Model; Appearance; Area; Award; Basic Science; Biochemical; Biomedical Engineering; Burn injury; Child; Childhood; Cicatrix; Cleft Lip; Cleft Palate; Cleft lip with or without cleft palate; Clinical; Clinical Research; Clinical Trials; Congenital Abnormality; Defect; Dental Research; Dentists; Effectiveness; Ensure; Environment; Esthetics; Exudate; FDA approved; Failure; Family; Fibrosis; Foundations; Funding; Future; Goals; Growth; Head; Hearing; Histologic; Human; Hypertrophic Cicatrix; Immunology; Impairment; Inflammation; Inflammatory; Inflammatory Response; Intervention Studies; Kinetics; Lead; Life; Link; Lip structure; Mediating; Mediator of activation protein; Mentors; Modeling; Mouth Diseases; Movement; Natural regeneration; Operative Surgical Procedures; Oral; Oryctolagus cuniculus; Outcome; Pathway interactions; Patients; Personal Satisfaction; Pharmaceutical Preparations; Phase; Play; Postoperative Complications; Postoperative Period; Preparation; Prevention; Process; Quality of life; Regenerative Medicine; Regenerative capacity; Regimen; Regulation; Research; Resolution; Risk Factors; Role; Safety; Science; Scientist; Signal Transduction; Solid; Speech; Talents; Therapeutic; Tissue Engineering; Tissues; Topical application; Training; Translational Research; Trauma; Validation; base; career; clinical application; craniofacial tissue; design; drug development; effectiveness evaluation; expectation; experience; lipid mediator; novel; novel strategies; novel therapeutics; oral biology; oral tissue; orofacial; post-trauma; pre-clinical; preclinical trial; prevent; programs; psychosocial; receptor; repaired; skills; social integration; soft tissue; success; therapeutic target; tissue injury; wound; wound healing

PROJECT ABSTRACT/SUMMARY Cleft lip with or without cleft palate is the most common congenital malformation of the head and the third most common birth defect. The impact of cleft lip on quality of life for the child and the family can be se- vere, affecting the child's appearance, speech, hearing, growth, psychosocial well-being and social integration. Surgical repair of the lip is the only treatment and is usually performed during the first year of life. However, hypertrophic scar (HTS) formation is a frequent postoperative complication that impairs soft tissue form, func- tion or movement and multiple lip revision surgeries are required throughout childhood for optimum esthetics and function. Uncontrolled and prolonged inflammation plays a major role in tissue injury, tissue scarring, and fibrosis. There is a critical need for new therapeutic regimens to help patients prone to scar tissue formation after lip repair and revision surgeries. The objective of this proposal is to evaluate a new approach to promote wound healing and limit scarring based on endogenous specialized pro-resolving lipid mediators (SPMs), termed Resolvins. The overarching hypothesis is that resolvins applied topically will minimize hypertrophic scarring after cleft lip repair surgery by promoting resolution of inflammation. The problem will be approached in two phases: the actions of resolvins in prevention of lip scarring will be determined in an animal model, fol- lowed by initial human studies that will generate hypotheses for future human clinical application. The specific aims are: 1a) Characterize the inflammatory/lipid mediator profile of hypertrophic scars after cleft lip defect re- pair in an FDA approved animal model; 1b) Using the rabbit model, we will determine the impact of a well characterized specialized pro-resolving lipid mediator (RvE1) on scar formation and inflammatory/lipid media- tors in wound healing after cleft lip defect repair; 2) Characterize the human inflammatory/lipid mediator profile of cleft lip wound exudate and correlate it with scarring in patients undergoing cleft lip repair surgery. These aims also provide a mentored training experience for Dr. Evangelos Papathanasiou, a talented junior dentist-scientist with a strong background in Immunology and Oral Biology. Dr. Papathanasiou's career goal is to integrate advances in drug development, tissue engineering and clinical research in order to develop new bio-engineered approaches for the regeneration of oral and craniofacial tissues and discover novel treat- ments for oral diseases. Dr. Papathanasiou with his mentors, Dr. Carroll Ann Trotman and Dr. Thomas Van Dyke, has assembled a team of highly experienced collaborators with active funded research programs and with commitment to his success, and to ensure an optimal training and research environment and successful outcomes of the proposed research. The expected outcome of this K08 award is to help Dr. Papathanasiou build a strong foundation for a career as an independent scientist in Clinical Translational Dental Research and to lead future human clinical trials of novel endogenous specialized pro-resolving lipid mediators for accelerat- ing wound healing and minimizing fibrosis and scarring.

项目摘要/总结 唇裂伴或不伴腭裂是最常见的头部和面部先天性畸形。 第三种最常见的出生缺陷。唇裂对孩子和家庭生活质量的影响可以分为以下几个方面： 影响儿童的外貌、言语、听力、成长、心理健康和社会融入。 唇部手术修复是唯一的治疗方法，通常在出生后的第一年进行。然而， 肥厚性疤痕（HTS）的形成是一种常见的术后并发症，会损害软组织的形态、功能 为了获得最佳的美观效果，整个童年时期都需要进行唇部修复或运动以及多次唇部修复手术 和功能。不受控制和长期的炎症在组织损伤、组织疤痕和组织损伤中起着重要作用。 纤维化。迫切需要新的治疗方案来帮助容易形成疤痕组织的患者 嘴唇修复和翻修手术后。该提案的目的是评估一种新方法来促进 基于内源性专门的促溶解脂质介质（SPM）的伤口愈合和限制疤痕形成， 称为解决方案。总体假设是，局部应用消退素将最大限度地减少肥大 通过促进炎症消退来消除唇裂修复手术后的疤痕。问题将会被解决 分两个阶段：将在动物模型中确定消退素预防唇部疤痕的作用，如下： 最初的人类研究得出的结论将为未来的人类临床应用产生假设。具体的 目标是： 1a) 表征唇裂缺损修复后肥厚性疤痕的炎症/脂质介质特征。 在 FDA 批准的动物模型中配对； 1b) 使用兔子模型，我们将确定一口井的影响 表征了对疤痕形成和炎症/脂质介质的专门促溶解脂质介质（RvE1） 唇裂缺损修复后伤口愈合的扭转因素； 2) 表征人类炎症/脂质介质特征 唇裂伤口渗出液的变化，并将其与接受唇裂修复手术的患者的疤痕相关联。 这些目标还为 Evangelos Papathanasiou 博士（一位才华横溢的人）提供了指导培训经验。 初级牙医科学家，具有深厚的免疫学和口腔生物学背景。帕帕塔纳西乌博士的职业生涯 目标是整合药物开发、组织工程和临床研究的进步，以开发 用于口腔和颅面组织再生的新生物工程方法，并发现新的治疗方法 口腔疾病的治疗。 Papathanasiou 博士与他的导师 Carroll Ann Trotman 博士和 Thomas Van 博士 Dyke 组建了一支由经验丰富的合作者组成的团队，他们积极资助研究项目和 致力于他的成功，并确保最佳的培训和研究环境以及成功 拟议研究的结果。 K08奖项的预期成果是帮助Papathanasiou博士 为临床转化牙科研究领域的独立科学家职业生涯奠定坚实的基础 领导未来新型内源性专业促脂质调节剂的人体临床试验，以加速 促进伤口愈合并尽量减少纤维化和疤痕。