Novel peptide-coated suture for cleft lip and palate repair

 描述（由申请人提供）：唇裂伴或不伴腭裂每年影响700名新生儿中的一名，这是美国第四常见的出生缺陷，最常发生在亚洲，拉丁美洲和美洲原住民血统的患者中。唇腭裂（CLP）在少数民族中特别严重，并且通常需要多次手术来解决由于唇腭裂缺损中缺失的粘膜，肌肉，骨骼和皮肤组织而引起的功能，美学和心理困难。为了诱导适当愈合，CLP翻修手术产生的伤口边缘必须用医疗器械（如手术缝线）对合。由于缺乏组织，口周/口内肌肉组织的作用和颅面生长， 是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，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装置都以纯机械的、非生物的方式接近组织。缝合伤口是否会愈合，并具有足够的抗张强度以防止裂开或疤痕扩大，这在很大程度上取决于外科医生和患者因素，例如对合伤口中的张力、血管分布和局部细胞活性。因此，开发可加速成纤维细胞迁移并增加高风险、高张力伤口抗张强度的治疗性缝合器械可显著减少伤口裂开和增生性瘢痕形成，以促进CLP手术的功能和美学结局改善。 为此，我们开发了一种技术创新的缝合线，结合了我们在无瘢痕胎儿皮肤修复方面的发现。具体地，我们已经发现，40个氨基酸的纤调蛋白（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冻干工艺制造了新型F06-C40涂层可吸收外科缝线。F06-C40涂层可吸收性外科缝线的试验显示，在美国食品药品监督管理局（FDA）首选用于人体皮肤产品试验的猪模型中，与对照非肽涂层缝线相比，伤口抗张强度增加了50%。因此，当前直接进入II期SBIR申请的目标是优化设计，建立制造过程，并测试F06-C40涂层外科缝线器械的安全性和有效性，以促进成人软组织缝合的初始重点 CLP翻修手术。总体而言，该提案将实现关键有效性、制造和初步生物相容性目标，以加快F06-C40涂层外科缝线产品的商业化。如果成功，该产品可以显著改善CLP的生活质量 翻修手术后伤口裂开的患者。长期目标是在需要在再生组织中建立抗张强度的任何患者中主动促进伤口愈合。

 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.