A Bioscaffold for Repair of Congenital Defects

用于修复先天性缺陷的生物支架

• 批准号: 6338057
• 负责人: Alan Robert Spievack
• 金额: $ 10万
• 依托单位: ACELL, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338057
• 关键词: biodegradable product; biotechnology; congenital disorders; diaphragm; dogs; extracellular matrix; hernia; tissue engineering; tissue support frame; urinary bladder

DESCRIPTION (Verbatim from the Applicant's Abstract): This Phase I SBIR application seeks support to develop and evaluate a naturally-occurring extracellular matrix (ECM) bioscaffold material for tissue engineering applications; specifically, the repair and/or restoration of congenital defects in which lost or missing tissue is the limiting factor for surgical reconstruction. Porcine derived ECM harvested from the urinary bladder (UBM) represents a cellular biodegradable scaffold material that supports cell attachment, migration, proliferation and differentiation, and wound healing. Processed single sheets of UBM and other ECMs have shown excellent remodeling capabilities in both pre clinical animal studies and early human clinical studies. With SBIR Phase I support, we propose to develop a multilaminate sheet form of UBM with the appropriate mechanical and biologic properties that allow for post surgical tissue growth and thus obviate the need for repeat surgeries as the patient matures. An experimentally-created diaphragmatic hernia will be used as the model of a congenital defect. There are three specific aims. First, we will determine the manufacturing method required to develop a prototype multilaminate UBM device with the mechanical strength that exceeds by a factor of 2 the normal mammalian diaphragm. Secondly, we will evaluate the effect of two different methods of sterilization, gamma irradiation and ethylene oxide, upon the mechanical strength of the prototype UBM device. The third specific aim will evaluate the utility of the sterilized multilaminate UBM device in a dog pilot study in which an experimentally-created diaphragmatic hernia will be repaired in 10-weekold dogs and evaluated over time until the point of physical maturity. Currently, there are limited options for the surgical repair/reconstruction of body structures that require surgical repair as a result of congenital abnormalities. The proposed studies are critical in the decision-making process of determining whether or not to pursue development of this product. Each objective/specific aim has well-defined criteria for success, and the proposed studies will be conducted by an experienced and knowledgeable tissue engineering research team. A time line for the proposed work is provided, and the technology involves an innovative tissue engineering approach in a medical field with significant unmet needs. PROPOSED COMMERCIAL APPLICATION: The use of UBM-ECM for the tissue engineering applications that involve the restoration of missing tissue as a result of congenital anomalies is in many ways an orphan market. Most biomaterials currently available for such use are inadequate beause they do not "grow" as the infant grows and, thus, repeat surgical procedures are required. Many currently available materials result in scar tissue formation with extensive morbidity. The development of new materials for these applications is not cost effective for many large companies due to the relatively small number of patients requiring this material each year. However, these patients desperately need a better alternative to existing materials, and successful development of this product could lead to broader surgical applications.

描述（逐字摘自申请人摘要）：第一阶段 SBIR 应用程序寻求支持来开发和评估自然发生的 用于组织工程的细胞外基质（ECM）生物支架材料 应用程序；具体来说，修复和/或恢复先天性缺陷 其中组织丢失或缺失是手术的限制因素 重建。从膀胱中采集的猪源性 ECM (UBM) 代表支持细胞的细胞可生物降解支架材料 附着、迁移、增殖和分化以及伤口愈合。 加工后的 UBM 和其他 ECM 单片显示出出色的重塑性 临床前动物研究和早期人类临床能力 研究。在 SBIR 第一阶段的支持下，我们建议开发多层板 UBM 形式具有适当的机械和生物特性，允许 用于术后组织生长，从而避免重复手术的需要 随着患者的成熟。实验制造的膈疝将 用作先天性缺陷的模型。具体目标有三个。第一的， 我们将确定开发原型所需的制造方法 机械强度超过一倍的多层 UBM 装置 2 正常哺乳动物隔膜。其次，我们要评估一下效果 两种不同的灭菌方法，伽马射线照射和环氧乙烷， 原型 UBM 设备的机械强度。第三具体 目标将评估灭菌多层 UBM 装置在 狗的试点研究，其中实验性创造的膈疝将被 在 10 周大的狗身上进行修复，并随着时间的推移进行评估，直到达到身体状况为止 到期。目前，手术的选择有限 修复/重建需要手术修复的身体结构 先天性畸形的结果。拟议的研究至关重要 决定是否继续发展的决策过程 这个产品。每个目标/具体目标都有明确的标准 成功，并且拟议的研究将由经验丰富且 知识渊博的组织工程研究团队。拟议的时间表 提供工作，该技术涉及创新的组织工程 方法在具有重大未满足需求的医疗领域。 拟议的商业应用： UBM-ECM 在涉及修复的组织工程应用中的应用 由于先天性异常而导致的组织缺失在很多方面都是一个孤儿市场。 目前可用于此类用途的大多数生物材料都不够充分，因为它们不 随着婴儿的成长而“成长”，因此需要重复外科手术。 许多 目前可用的材料导致疤痕组织形成，并具有广泛的发病率。 这 对于许多大型企业来说，为这些应用开发新材料并不具有成本效益 由于每年需要这种材料的患者数量相对较少。 然而，这些患者迫切需要现有材料的更好替代品，并且 该产品的成功开发可能会带来更广泛的外科应用。