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

专业解决调解员 (SPM)

• 批准号: 10334484
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10334484
• 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; 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 wellbeing; 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先天性头部畸形， 第三常见的出生缺陷唇裂对儿童和家庭生活质量的影响可以是 这一现象严重影响到儿童的外貌、言语、听力、成长、心理健康和社会融合。 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，在这方面， 增生性瘢痕（HTS）形成是一种常见的术后并发症， 在整个儿童时期，需要进行多次唇部矫正手术，以获得最佳的美学效果 和功能不受控制的和长期的炎症在组织损伤、组织瘢痕形成和炎症反应中起主要作用。 纤维化迫切需要新的治疗方案来帮助易于形成疤痕组织的患者 嘴唇修复和修复手术后。这项建议的目的是评估一种新的办法， 伤口愈合和限制疤痕的基础上内源性专门的前解决脂质介质（SPM）， 名为Resolvins。总体假设是，局部应用消退素将最大限度地减少肥大 通过促进炎症的消退来减少唇裂修复手术后的疤痕。这个问题将得到解决 分两个阶段：消退素在预防唇瘢痕形成中的作用将在动物模型中确定， 低于最初的人类研究，将产生未来人类临床应用的假设。具体 目的是：1a）表征唇裂缺损修复后增生性瘢痕的炎症/脂质介质谱， 1b）使用兔模型，我们将确定孔的影响 表征了瘢痕形成和炎症/脂质介质的专门促消退脂质介质（RvE 1）- 唇裂缺损修复后伤口愈合的影响因素; 2）表征人类炎症/脂质介质谱 唇裂伤口渗出物的含量，并与唇裂修复手术患者的瘢痕形成相关。 这些目标也为Evangelos Papathanasiou博士提供了一个指导性的培训经验， 具有免疫学和口腔生物学背景的初级牙医科学家。Papathanasiou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展，以开发 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博士和他的导师，卡罗尔安Trotman博士和托马斯货车博士 戴克，已经组建了一个团队，经验丰富的合作者与积极资助的研究计划， 致力于他的成功，并确保最佳的培训和研究环境和成功 建议的研究成果。这个K 08奖项的预期结果是帮助Papathanasiou博士 为作为临床转化牙科研究的独立科学家的职业生涯奠定坚实的基础， 引领未来新型内源性专门促分解脂质介质的人体临床试验， 促进伤口愈合并使纤维化和瘢痕形成最小化。