?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.
Public Health Relevance Statement: Public Health Relevance: Cleft lip and palate (CLP) 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. 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; unfortunately, all available surgical suture devices approximate tissue in a purely mechanical, non- biological, fashion. This proposed project seeks to develop 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.
Project Terms: Acute; Address; Adolescent; Adult; Affect; Amino Acids; Animals; Appearance; Asians; Biological; biomaterial compatibility; Bone Tissue; California; Chemistry; Cicatrix; Cleaved cell; cleft lip and palate; Cleft lip with or without cleft palate; Clinical Research; Clinical Sciences; clinically relevant; Collagen; commercialization; Congenital Abnormality; cost; craniofacial; crosslink; Cutaneous; cytotoxicity; Data; Defect; design; Devices; Ensure; Esthetics; ethnic minority population; Evaluation; evaluation/testing; Family suidae; fetal; Fibroblasts; fibromodulin; Freeze Drying; Funding; genotoxicity; Goals; Grant; Growth; Healed; healing; high risk; Human; Hypertrophic Cicatrix; implantation; improved; in vivo; Incubators; Industry; innovation; Institutes; International; irritation; Latino; man; manufacturing process; Mechanics; Medical Device; meetings; Methods; migration; Modeling; Mucous Membrane; Muscle; Myofibroblast; nanosystems; Native Americans; Natural regeneration; Newborn Infant; novel; older patient; Operative Surgical Procedures; Outcome; Outcome Measure; palate repair; Patients; Penetration; Peptides; Pharmacologic Substance; Phase; Postoperative Complications; Pre-Clinical Model; prevent; primary outcome; Procedures; Process; Production; Protocols documentation; psychologic; public health relevance; Qualitative Methods; Quality of life; repaired; Research Infrastructure; Resources; Rodent; Rodent Model; Safety; safety study; safety testing; Skin; Skin Tissue; Small Business Innovation Research Grant; Small Business Technology Transfer Research; soft tissue; Specific qualifier value; Sterility; Surgeon; Surgical sutures; symposium; systemic toxicity; Tensile Strength; Testing; Therapeutic; therapeutic development; Thick; Tissues; Toxic effect; Translational Research; United States Food and Drug Administration; United States National Institutes of Health; Visual; work-study; wound; Wound Healing
