Novel peptide-coated suture for cleft lip and palate repair

 描述(申请人提供)：唇裂伴或不伴腭裂每年影响700名新生儿中的1例，这是美国第四大最常见的出生缺陷，最常发生在亚裔、拉丁裔和美洲原住民后裔的患者中。唇腭裂(CLP)在少数民族中尤为严重，通常需要多次手术来解决因唇腭裂缺损处缺失的粘膜、肌肉、骨和皮肤组织而引起的功能、美学和心理困难。为了促进适当的愈合，CLP翻修手术产生的伤口边缘必须用手术缝线等医疗设备接近。由于缺乏组织，口周/口内肌肉的活动，以及头面部的生长， 在中电手术中伤口过度紧张。CLP手术后最严重的并发症之一是伤口裂开(根据各种研究，2.40%-22.76%)，这几乎总是导致额外的手术。不幸的是，所有可用的外科缝合设备都以一种纯粹的机械、非生物的方式接近组织。缝合的伤口是否会以足够的抗张强度愈合，以防止裂开或扩大的疤痕，其结果在很大程度上取决于外科医生和患者的因素，如张力、血管和接近伤口的局部细胞活动。因此，在高危、高张力创面中，开发能够加速成纤维细胞迁移并增加抗张强度的治疗性缝合设备，可以显著减少伤口裂开和增生性瘢痕，从而改善CLP手术的功能和美观效果。为此，我们开发了一种技术创新的缝合线，结合了我们在无疤痕胎儿皮肤修复方面的发现。具体地说，我们发现一种由40个氨基酸组成的纤维调节蛋白(FMOD)多肽F06-C40可以显著促进成纤维细胞的迁移，并在啮齿动物和猪的模型中增加伤口的抗张强度。然后，我们通过可伸缩的、廉价的冷冻干燥过程制造了新型的、F06-C40涂层的可吸收外科缝合线。F06-C40涂层可吸收外科缝合线的测试显示，在食品和药物管理局(FDA)首选的用于测试人类皮肤产品的猪模型中，伤口抗张强度比对照非肽涂层缝合线提高了50%。因此，目前的直接到第二阶段SBIR应用的目标是改进设计，建立制造工艺，并测试F06-C40涂层外科缝合器的安全性和有效性，以促进成人软组织接近的初始焦点 中电翻修手术。总体而言，这项建议将实现关键的疗效、制造和初步生物相容性目标，以加快F06-C40涂层手术缝线产品的商业化。如果成功，这款产品可以显著提高中电的生活质量 翻修手术后伤口裂开的患者。一个长期的目标是预防性地促进任何需要在再生组织中建立抗张强度的患者的伤口愈合。

 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.