Delivery of Adipose Derived Stem Cells for Healing Surgical Hernia Repairs

描述（由申请人提供）：美国每年进行超过700，000例疝修补手术，尽管最近取得了进展，但复发率仍然很高。切口或内脏疝修补术占这些手术的10万例，每年花费17亿美元，初次修补的复发率为25%，第二次修补后为44%。结合生物相容性补片以加强腹部筋膜已在很大程度上取代了外科疝修补术中的高张力疝修补技术。目前，优选的生物材料包括耐用的合成网片，其具有永久性异物的所有缺陷;不能提供足够长期支撑的可吸收网片;或生物假体，其是生物可吸收的，但以不可接受的高速率失效，导致复发性疝。因此，外科医生只能在异物和弱修复之间做出选择。我们的目标是通过使用含有脂肪源性干细胞（ASC）的生物假体来加快疝修补术后的愈合速度。ASC于2001年被鉴定，并已用于许多适应症的细胞治疗，包括骨折，心肌修复和软组织修复。它们的促愈合功能主要是通过在损伤部位分泌的旁分泌因子介导的，以促进血管形成和组织重塑。我们设想的产品原型将是一种即时护理的ASC种子生物假体，它将促进更快的愈合时间，预防感染，并留下生物修复。我们的生物假体旨在防止切口疝复发，从而减少住院随访护理，额外手术和患者痛苦。 公共卫生相关性：提高手术疝修补术后的愈合率将减少疼痛、不适和后续护理。将生物制剂引入软组织愈合代表了外科手术的潜在改进，但由于缺乏临床可行的输送机制，这些策略仍未得到充分利用。该提案将开发一种新型生物假体，用于局部保留细胞，以提高愈合率并减少切口疝修补术的复发。由于疝修补术是全球最常见的外科手术之一，在美国有超过70万例手术，因此该产品将为大量患者提供显著改善的临床结局。

DESCRIPTION (provided by applicant): Over 700,000 surgical hernia repairs are performed each year in the United States and despite recent advances, a significant rate of recurrence persists. Incisional or visceral hernia repairs account for 100,000 of these surgeries costing 1.7B annually, and have a recurrence rate of 25% for an initial repair and 44% after a second repair. The incorporation of biocompatible mesh to strengthen the abdominal fascia has largely replaced high-tension suturing techniques in surgical hernia repair. Currently, the preferred biomaterials include durable synthetic mesh, which bears all the pitfalls of a permanent foreign body; absorbable mesh which does not provide enough long-term support; or bioprosthetics, which are bioabsorbable but fail at an unacceptably high rate causing recurrent hernias. Surgeons are therefore left to choose between a foreign body and a weak repair. Our goal is to accelerate healing rates after hernia repair by using bioprosthetics containing adipose-derived stem cells (ASCs). ASCs were identified in 2001, and have been used for cell therapy in many indications including bone fractures, myocardial repair and soft tissue repair. Their prohealing function is largely mediated through paracrine factors secreted at the site of injury to promote vascularization, and tissue remodeling. The product prototype we envision will be a point-of-care ASC seeded bioprosthetic that will promote faster healing times, prevent infection, and leave a biologic repair. Our bioprosthetic is designed to prevent recurrence of incisional hernias, thereby reducing inpatient follow-up care, additional surgeries, and patient distress. PUBLIC HEALTH RELEVANCE: Improving the rate of healing after surgical hernia repair will reduce pain, discomfort and follow-up care. The introduction of biologics into soft tissue healing represents a potential improvement for surgical procedures, but due to a lack of clinically viable delivery mechanisms, these strategies remain under utilized. This proposal will develop a novel bioprosthetic for the local retention of cells to improve healing rates and reduce recurrence of incisional hernia repairs. Because hernia repair is one of the most common surgical procedures world-wide, with more than 700,000 surgeries in the United States, this product will provide substantially improved clinical outcomes for a large number of patients.