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/摘要 带有或不带left裂的裂口唇是头部最常见的先天性畸形， 第三最常见的先天缺陷。唇裂对儿童和家庭生活质量的影响可能会受到影响 Vere影响孩子的外表，言语，听力，成长，社会心理健康和社会融合。 嘴唇的手术修复是唯一的治疗方法，通常在生命的第一年进行。然而， 肥厚性疤痕（HTS）形成是一种频繁的术后并发症，会损害软组织形式，功能 在整个儿童期都需要进行最佳美学 和功能。不受控制和长时间的炎症在组织损伤，组织疤痕和 纤维化。新的治疗方案至关重要，以帮助患者容易形成疤痕组织 嘴唇修复和修订手术后。该建议的目的是评估一种新方法来促进 基于内源性专业促进脂质介质（SPM）的伤口愈合和限制疤痕 被称为Resolvins。总体假设是局部应用的溶质剂将最大程度地减少肥厚性 通过促进炎症的分辨率，唇裂修复手术后疤痕。问题将被解决 在两个阶段中：在动物模型中，将在预防唇部疤痕的预防唇疤痕方面的作用， 在最初的人类研究中，该研究将为未来的人类临床应用产生假设。具体 目的是：1A）表征唇裂缺陷后肥厚性疤痕的炎症/脂质介体轮廓 配对FDA批准的动物模型； 1b）使用兔子模型，我们将确定井的影响 在疤痕形成和炎症/脂质培养基方面，特征了专门的促分解脂质介质（RVE1） 裂开唇部缺陷修复后伤口愈合中的TOR； 2）表征人类炎症/脂质介体轮廓 唇裂伤口渗出裂口并将其与接受唇裂修复手术的患者的疤痕相关。 这些目标还为埃文加罗斯（Evangelos Papathanasiou）博士提供了指导的培训经验 初级牙医科学家具有强大的免疫学和口服生物学背景。 Papathanasiou博士的职业 目标是整合药物开发，组织工程和临床研究的进步，以发展 针对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 口腔疾病的疾病。 Papathanasiou博士及其导师Carroll Ann Trotman博士和Thomas Van博士 戴克（Dyke）召集了一支经验丰富的合作者团队，由活跃的研究计划和 致力于他的成功，并确保最佳的培训和研究环境和成功 拟议研究的结果。该K08奖的预期结果是帮助Papathanasiou博士 为临床翻译牙科研究的独立科学家的职业奠定了坚实的基础 领导新的内生内源性专门分解脂质介质的未来人类临床试验。 伤口愈合，最小化纤维化和疤痕。