Novel peptide-coated suture for cleft lip and palate repair

用于唇裂和腭裂修复的新型肽涂层缝合线

基本信息

批准号：
9244801
负责人：
Chia Soo
金额：
$ 54.44万
依托单位：
SCARLESS LABORATORIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9244801
关键词：
Acute Address Adolescent Adult Affect Amino Acids Animals Appearance Asians Biological Blood Vessels Bone Tissue California Chemistry Cicatrix Cleft lip with or without cleft palate Clinical Research Clinical Sciences Collagen Congenital Abnormality Cutaneous Data Defect Devices Ensure Esthetics Evaluation Family suidae Fibroblasts Freeze Drying Funding Goals Grant Growth Human Hypertrophic Cicatrix Incubators Industry Institutes International Investigation Latino Mechanics Medical Device Methods Modeling Mucous Membrane Muscle Myofibroblast Native Americans Natural regeneration Newborn Infant Operative Surgical Procedures Outcome Outcome Measure Patients Penetration Peptides Pharmacologic Substance Phase Postoperative Complications Pre-Clinical Model Privatization Procedures Process Production Protocols documentation Qualitative Methods Quality of life Reproducibility Research Infrastructure Resources Rodent Rodent Model Safety Skin Skin Tissue Small Business Innovation Research Grant Small Business Technology Transfer Research Specific qualifier value Sterility Surgeon Surgical sutures Surgical wound Tensile Strength Testing Therapeutic Thick Tissues Toxic effect Translational Research United States Food and Drug Administration United States National Institutes of Health Visual Work Wound Healing biomaterial compatibility cleft lip and palate clinically relevant commercialization cost efficient craniofacial crosslink cytotoxicity design ethnic minority population evaluation/testing fetal fibromodulin genotoxicity healing high risk implantation improved in vivo innovation irritation man manufacturing process migration nanosystems novel older patient palate repair prevent primary outcome prophylactic psychologic public health relevance repaired safety study safety testing soft tissue symposium systemic toxicity therapeutic development wound

项目摘要

DESCRIPTION (provided by applicant): Cleft lip with or without cleft palate affects one in 700 newborns annually, which is the fourth most common birth defect in the US and occurs most often in patients of Asian, Latino, and Native American descent. Cleft lip and palate (CLP) are particularly severe in ethnic minorities, and often requires multiple surgeries to address functional, esthetic, and psychological difficulties arising from missing mucosa, muscle, bone, and skin tissues in the cleft defect. To induce proper healing, the wound edges resulting from CLP revision surgeries must be approximated with medical devices such as surgical sutures. Due to the lack of tissue, action of perioral/intraoral musculature, and craniofacial growth, there is excessive tension across the wounds in CLP surgeries. One of the most serious postoperative complications of CLP surgeries is wound dehiscence (2.40%-22.76% according to various studies), which almost always leads to additional surgeries. Unfortunately, all available surgical suture devices approximate tissue in a purely mechanical, non-biological, fashion. The outcome of whether a sutured wound will heal with adequate tensile strength to prevent dehiscence or widened scars is largely dependent on surgeon and patient factors such as tension, vascularity, and local cellular activity in the approximated wound. Therefore, development of therapeutic suture devices that can accelerate fibroblast migration and increase tensile strength in high risk, high tension wounds can significantly minimize wound dehiscence and hypertrophic scarring to promote improved functional and esthetic outcomes in CLP surgeries. Towards this end, we have developed a technologically innovative suture that incorporates our discoveries from scarless fetal skin repair. Specifically, we have found that a 40-amino acid fibromodulin (FMOD) peptide, F06-C40 can significantly promote fibroblast migration and increase wound tensile strength in both rodent and pig models. We then fabricated novel, F06-C40-coated absorbable surgical sutures through a scalable, inexpensive lyophilization process. Testing of the F06-C40-coated absorbable surgical sutures showed an increase of wound tensile strength by 50% vs. control non-peptide-coated sutures in porcine models preferred by the Food and Drug Administration (FDA) for testing human cutaneous products. Thus, the goal of the current Direct-to-Phase II SBIR application is to refine the design, establish the manufacturing process, and test the safety and efficacy of the F06-C40-coated surgical suture device for the initial focus of promoting soft tissue approximation in adult CLP revision surgeries. Overall, this proposal will accomplish key efficacy, manufacture, and preliminary biocompatibility objectives to expedite F06-C40-coated surgical suture product commercialization. If successful, this product can significantly improve the quality of life of CLP patients suffering from wound dehiscence subsequent to revision surgeries. A long-term goal is to prophylactically promote wound healing in any patients requiring tensile strength establishment in regenerated tissues.

描述（由申请人提供）：每年，有或没有腭裂的唇裂会影响七百个新生儿中的一个，这是美国第四大常见的出生缺陷，最常见于亚洲人、拉丁裔和美洲原住民血统的唇裂患者。腭裂（CLP）在少数族裔中尤为严重，通常需要多次手术来解决由于裂隙缺损中粘膜、肌肉、骨骼和皮肤组织缺失而引起的功能、美观和心理困难，以诱导适当的愈合。由于缺乏组织、口周/口内肌肉组织的作用以及颅面生长，CLP 修复手术造成的伤口边缘必须用手术缝合线等医疗设备进行近似处理。 CLP 手术中伤口张力过大，CLP 手术最严重的术后并发症之一是伤口裂开（根据各种研究，为 2.40%-22.76%），这几乎总是导致额外的手术。不幸的是，所有可用的手术缝合设备。以纯粹机械、非生物的方式近似组织，缝合伤口是否会以足够的拉伸强度愈合以防止裂开或扩大的疤痕，很大程度上取决于外科医生和患者的因素，例如张力、因此，开发能够加速成纤维细胞迁移并增加高风险、高张力伤口的拉伸强度的治疗性缝合装置可以显着减少伤口裂开和肥厚性疤痕，从而促进改善功能和美观结果。为此，我们开发了一种技术创新的缝合线，其中结合了我们在无疤痕胎儿皮肤修复中的发现，具体来说，我们发现了一种 40 氨基酸纤维调节蛋白。 (FMOD) 肽，F06-C40 可以显着促进成纤维细胞迁移并增加啮齿动物和猪模型中的伤口拉伸强度，然后我们通过可扩展的、廉价的冻干工艺制造了新型的、F06-C40 涂层的可吸收手术缝合线。 -与对照非肽涂层缝线相比，C40 涂层可吸收手术缝线的伤口拉伸强度增加了 50%美国食品和药物管理局 (FDA) 首选用于测试人体皮肤产品的猪模型因此，当前直接进入 II 期 SBIR 申请的目标是完善设计、建立制造工艺并测试安全性和有效性。 F06-C40 涂层手术缝合装置的最初重点是促进成人软组织逼近总体而言，该提案将实现关键的功效、制造和初步生物相容性目标，以加快 F06-C40 涂层手术缝合线产品的商业化。如果成功，该产品可以显着改善 CLP 的生活质量。修复手术后遭受伤口裂开的患者长期目标是预防性地促进任何需要再生组织的拉伸强度的患者的伤口愈合。