Evaluation of extracellular matrix gel for adhesion prevention and tissue healing intendon surgery

细胞外基质凝胶预防粘连和组织愈合意向手术的评价

• 批准号: 10482261
• 负责人: Peter Alexander Smith
• 金额: $ 25.66万
• 依托单位: TYBR HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10482261
• 关键词: Abdomen; Address; Adhesions; Adopted; Adoption; Affect; Anatomy; Animal Model; Architecture; Articular Range of Motion; Biomechanics; Cadaver; Cell physiology; Cells; Characteristics; Chemotaxis; Chronic; Cicatrix; Clinical; Collaborations; Collagen; Confined Spaces; Data; Defect; Development; Devices; Doctor of Philosophy; Economic Burden; Engineering; Evaluation; Extracellular Matrix; Feedback; Fibroblasts; Film; Flexor; Foxes; Gel; Growth; Hand; Hand Injuries; Health; Health Care Costs; Human; Hydration status; Hydrogels; Immune response; Impairment; In Vitro; Individual; Injury; Instruction; Intervention; Investigation; Lead; Liquid substance; Measures; Mechanics; Medical Device; Medicine; Methods; Modeling; Morbidity - disease rate; Motion; Movement; Mus; Nerve; Operative Surgical Procedures; Orthopedic Surgery; Orthopedics; Oryctolagus cuniculus; Paper; Patients; Pelvis; Peritoneum; Physicians; Physiological; Positioning Attribute; Postoperative Period; Pre-Clinical Model; Prevention; Prevention Measures; Procedures; Quality of life; Recovery; Rehabilitation therapy; Repeat Surgery; Safety; Science; Signal Transduction; Solid; Surgeon; Techniques; Technology; Tendon Injuries; Tendon structure; Thinness; Tissues; Trauma; Universities; Upper Extremity; Validation; Virginia; achilles tendon; base; biomaterial compatibility; biomechanical test; chronic pain; commercialization; cost; design; disability; economic impact; healing; improved; in vivo; injured; joint function; joint mobilization; joint stiffness; limb injury; musculoskeletal injury; novel; novel strategies; opioid use; patient response; prevent; repaired; research and development; response; restoration; scaffold; tissue injury; tissue repair; translational scientist; usability; wound healing

Project Summary Approximately 32M musculoskeletal injuries in the US cost nearly $322B annually (1). The high economic burden is due in part to post-operative scar formation (i.e., adhesions), which is the leading cause of disability following tendon surgery (4, 5). We are developing a sprayable adhesion barrier derived from extracellular matrix (ECM Spray), which serves as a mechanical barrier and elicits a healing response from the patient’s own body to prevent adhesions from forming. Around 1.5M patients suffer flexor tendon injuries each year and as many as 30-40% of these individuals will subsequently have limited range of motion due to adhesions (6). Current options to mitigate adhesions are limited and flawed, and there is an unmet need for a technology which can safely and effectively prevent adhesion formation to maintain normal joint function after tendon injury. ECM Spray is thermally responsive, forming a thin film hydrogel over the tissue where applied and prevents adhesions by acting as a mechanical barrier between adjacent tissues. Application of ECM Spray as the last step of a surgical procedure resulted in >70% reduction on post-operative adhesions in abdominal and pelvic animal models of adhesion formation. A major limitation of currently available orthopedic tendon protectors / adhesion barriers is that they are bulky sheets unable to conform to the region of the repaired flexor tendon and therefore impair tendon movement / gliding. Newer thin sheet products are available, but surgeons describe them as performing like “wet toilet paper” because they disintegrate upon hydration. ECM Spray is applied as a liquid, rather than a sheet, to conform to the repaired flexor tendon and surrounding flexor tendon sheath. Past attempts at developing sprayable adhesion barriers have been unsuccessful, in part because of impaired tissue healing after application. While it remains unknown what impact ECM Spray will have upon tendon healing, we have shown that ECM Spray acts as an inductive scaffold to support constitutive repair of the peritoneum. Based upon these data, the objective of the present study is to determine ECM Spray’s safety, efficacy, and usability in orthopedic surgery following flexor tendon injury. In Aim 1, we will characterize tenocyte cellular response to ECM Spray, which will determine if ECM is biocompatible and supportive of tenocyte and synoviocyte growth. In Aim 2, we will determine if ECM Spray effective for reducing tendon adhesion formation without compromising the biomechanics of healing tendons. In Aim 3, we will demonstrate usability in human anatomy, which is critical to surgeon adoption and commercialization. Results from this safe-by-design approach will lead to key research and development milestones necessary for use of ECM Spray in orthopedic surgery and could ultimately improve the lives of the millions affected each year by adhesion-related morbidity.

项目摘要 美国大约3200万肌肉骨骼损伤每年近322B美元（1）。高经济 负担部分归因于术后疤痕形成（即粘附），这是残疾的主要原因 肌腱手术后（4，5）。我们正在开发一个可衍生自细胞外基质的粘附屏障 （ECM喷雾），它是机械障碍，并引起患者自己身体的治愈反应 为了防止粘附形成。每年约有150万患者遭受屈肌肌腱损伤，多数 这些人中有30-40％随后由于广告而导致的动作范围有限（6）。当前选项 减轻依从性是有限且缺陷的，并且对可以安全和可以安全的技术有未满足的需求 ECM喷雾有效地防止粘附形成以维持肌腱损伤后正常关节功能。 热反应迅速，在施加的组织上形成薄膜水凝胶，并通过 充当相邻组织之间的机械障碍。 ECM喷雾剂作为手术的最后一步 过程导致腹部和骨盆动物模型的术后粘附降低> 70％ 粘附形成。当前可用的骨科肌腱保护器 /粘附屏障的主要局限性是 它们是笨重的床单，无法符合修复的屈肌肌腱的区域 肌腱运动 /滑行。提供了较新的薄纸产品，但外科医生将其描述为表演 就像“湿厕纸”一样，因为它们在水合时会分解。 ECM喷雾剂被用作液体，而不是 板，符合修复的屈肌肌腱和周围的屈肌鞘。过去的尝试 开发可喷涂的粘附屏障一直没有成功，部分原因是组织愈合受损 应用。虽然尚不清楚ECM喷雾对肌腱愈合会产生什么影响，但我们已经显示 该ECM喷雾充当电感支架，以支持腹膜的本构修复。基于这些 数据，本研究的目的是确定ECM喷雾的安全性，效率和可用性 屈肌肌腱损伤后的手术。在AIM 1中，我们将表征Tenocyte细胞对ECM喷雾的反应， 这将确定ECM是否具有生物相容性并支持Tenocyte和滑膜细胞生长。在AIM 2中，我们 将确定ECM喷雾是否有效减少肌腱粘附形成而不损害 愈合肌腱的生物力学。在AIM 3中，我们将证明人类解剖学的可用性，这对 外科医生采用和商业化。这种安全设计方法的结果将导致关键研究 以及在骨科手术中使用ECM喷雾所需的发展里程碑，并最终可以改善 每年与广告有关的发病率都会影响数百万人的生活。