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.

项目概要 美国每年约有 3200 万例肌肉骨骼损伤，造成的损失近 $322B (1)。经济水平高 负担部分是由于术后疤痕形成（即粘连）造成的，这是导致残疾的主要原因 肌腱手术后 (4, 5)。我们正在开发一种源自细胞外基质的可喷雾粘附屏障 （ECM 喷雾），作为机械屏障并引发患者自身的愈合反应 以防止形成粘连。每年约有 150 万患者遭受屈肌腱损伤，其中多达 其中 30-40% 的人随后会因粘连而导致活动范围受限 (6)。当前选项 减轻粘连的方法是有限的且有缺陷的，并且对一种能够安全且可靠地进行的技术的需求尚未得到满足。 有效防止肌腱损伤后粘连形成，维持正常的关节功能。 ECM喷雾是 热响应，在应用的组织上形成薄膜水凝胶，并通过以下方式防止粘连 作为相邻组织之间的机械屏障。 ECM喷雾作为手术最后一步的应用 在腹部和盆腔动物模型中，该手术使术后粘连减少了 70% 以上 粘附形成。目前可用的矫形肌腱保护器/粘连屏障的主要局限性是 它们是笨重的片材，无法符合修复的屈肌腱区域，因此会损害 肌腱运动/滑动。有更新的薄板产品可供使用，但外科医生将其描述为性能良好 就像“湿卫生纸”一样，因为它们在水合时会分解。 ECM Spray 以液体形式施用，而不是液体 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并未成功，部分原因是术后组织愈合受损 应用。虽然目前尚不清楚 ECM 喷雾会对肌腱愈合产生什么影响，但我们已经证明 ECM Spray 充当诱导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 Spray 在骨科领域的安全性、有效性和可用性 屈肌腱损伤后进行手术。在目标 1 中，我们将表征肌腱细胞对 ECM Spray 的反应， 这将决定 ECM 是否具有生物相容性并支持肌腱细胞和滑膜细胞的生长。在目标 2 中，我们 将确定 ECM Spray 是否能有效减少肌腱粘连形成而不影响 愈合肌腱的生物力学。在目标 3 中，我们将展示人体解剖学的可用性，这对于 外科医生的采用和商业化。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 Spray 所必需的发展里程碑，并最终可以改善 每年有数百万人的生活受到粘连相关疾病的影响。