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 美国每年约有3200万肌肉骨骼损伤花费近3.22亿美元（1）。高等经济 负担部分是由于术后疤痕形成（即，粘连），这是残疾的主要原因 肌腱手术后（4，5）。我们正在开发一种来自细胞外基质的可喷涂的粘连屏障 (ECM喷雾），它作为一个机械屏障，并从病人自己的身体激发愈合反应 以防止粘连形成。每年约有150万患者遭受屈肌腱损伤， 其中30-40%的患者随后会因粘连而活动受限（6）。当前选项 减轻粘连的技术是有限的和有缺陷的，并且对能够安全和 有效防止粘连形成，维持肌腱损伤后正常关节功能。ECM喷涂是 热响应，在应用的组织上形成薄膜水凝胶，并通过 作为相邻组织之间的机械屏障。ECM喷涂作为手术最后一步的应用 手术导致腹部和盆腔动物模型术后粘连减少>70%， 粘连形成目前可用的骨科肌腱保护器/防粘连屏障的主要局限性是 它们是不能与修复的屈肌腱的区域一致的大体积的片 肌腱运动/滑动。较新的薄片产品是可用的，但外科医生将其描述为执行 就像“湿厕纸”一样，因为它们在水合作用下会分解。ECM喷雾剂以液体形式使用， 片，以符合修复的屈肌腱和周围的屈肌腱鞘。过去的尝试， 开发可喷涂的粘连屏障一直是不成功的，部分原因是在植入后受损的组织愈合。 应用程序.虽然ECM喷雾对肌腱愈合的影响仍然未知，但我们已经证明， ECM喷雾剂作为一种诱导性支架来支持腹膜的组成性修复。基于这些 数据，本研究的目的是确定ECM喷雾剂在骨科手术中的安全性，有效性和可用性 屈肌腱损伤后手术。在目标1中，我们将表征腱细胞对ECM喷雾的细胞反应， 这将确定ECM是否是生物相容的并支持腱细胞和滑膜细胞生长。在目标2中， 将确定ECM喷雾是否有效减少肌腱粘连形成，而不影响 肌腱愈合的生物力学在目标3中，我们将展示人体解剖学中的可用性，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的研究 在骨科手术中使用ECM喷雾剂所需的开发里程碑，并最终可以改善 每年有数百万人的生命受到粘连相关疾病的影响。