Development of scale-up strategies for ReFilx: a novel soft tissue filler - I2I Phase 1

制定 ReFilx 放大策略：一种新型软组织填充剂 - I2I 第一阶段

• 批准号: 531906-2018
• 负责人: Santerre, Paul
• 金额: $ 9.04万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=664274
• 关键词: Development; scale; up; strategies; ReFilx

Approximately 25,000 Canadian and 292,130 American women were estimated to be diagnosed with breast cancer (BC) in 2015, respectively. After several randomized controlled trials confirming the safety and efficacy of breast conserving surgery (BCS) or lumpectomy with radiation, it has replaced mastectomy as the preferred surgical treatment for BC. However, poor cosmetic outcomes and irregular soft tissue defects are commonly observed in patients that undergo BCS. In addition to impairing the patients' aesthetic appearance, soft tissue defects are a main source of psychological distress. Thus, there is a large unmet need for the correction of soft tissue defects in the breast which is currently being accommodated with limited success using other technologies that many key opinion clinicians recognize as being non-satisfactory. Using innovative biomaterials science conceived and studied over the past decade, the principle investigators (PIs) have developed ReFilx for the correction of irregular breast defects observed after lumpectomy. ReFilx constructs have a timely biodegradation rate while enabling immediate support for breast shape and form, allowing tissue ingrowth to replace the material and maintain the form. It resorbs into by-products at levels recognized by regulatory agencies as being non-toxic. Through two pilot studies using a pig model, we have identified a ReFilx formulation that satisfies the implant criteria. In this NSERC I2I application, we propose to support the commercialization of this product through development and validation of scale-up strategies for the raw materials involved in ReFilx synthesis, as well as the fabrication of the final formed constructs. This will be accomplished through two key milestones: (1) develop a scale-up strategy for the pre-polymer and (2) develop prototypes for high through-put and reproducible fabrication of ReFilx constructs. Developing and validating these processes will in turn expedite and reduce the cost of transitioning from laboratory to commercial production.******

据估计，大约25,000名加拿大和292,130名美国妇女在2015年被诊断出患有乳腺癌（BC）。经过几项随机对照试验，确认了乳房保存手术（BCS）或肿块切除术的安全性和功效，它已取代了乳房切除术，成为卑诗省的首选手术治疗。然而，在接受BC的患者中，通常观察到美容结果不良和不规则的软组织缺陷。除了损害患者的美学外观外，软组织缺陷是心理困扰的主要来源。因此，对于乳房中的软组织缺陷的纠正，目前使用其他许多关键临床医生认为并不令人满意的技术来纠正乳房中的软组织缺陷。使用创新的生物材料科学在过去十年中构思和研究，主要研究人员（PIS）开发了重新校正，以纠正乳房切除术后观察到的不规则乳腺缺陷。 Refilx构建体具有及时的生物降解速率，同时可以立即对乳房形状和形式进行支撑，从而使组织向内生长更换材料并保持形式。它在监管机构认可的无毒的水平上分配副产品。通过使用PIG模型的两项初步研究，我们已经确定了满足植入物标准的recilx公式。在此NSERC I2I应用程序中，我们建议通过开发和验证Refilx合成涉及的原材料的规模策略以及制造最终形成的结构的制造，以支持该产品的商业化。 这将通过两个关键的里程碑来实现：（1）制定预聚合物的扩展策略，（2）开发用于雷克斯构建体的高贯穿和可重复制造的原型。 开发和验证这些过程将又加快并降低从实验室到商业生产的过渡成本。******