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

据估计，2015年分别有25，000名加拿大和292，130名美国女性被诊断患有乳腺癌（BC）。在几项随机对照试验证实保乳手术（BCS）或放射性乳房肿瘤切除术的安全性和有效性后，它已取代乳房切除术成为BC的首选手术治疗。然而，在接受BCS的患者中通常观察到不良的美容效果和不规则的软组织缺损。除了损害患者的美学外观外，软组织缺损是心理困扰的主要来源。因此，对于乳房中的软组织缺陷的矫正存在很大的未满足的需求，目前使用许多关键意见临床医生认为不令人满意的其他技术以有限的成功来适应该需求。利用在过去十年中构思和研究的创新生物材料科学，主要研究者（PI）开发了ReFilx，用于矫正乳房肿瘤切除术后观察到的不规则乳房缺损。ReFilx结构具有及时的生物降解率，同时能够立即支持乳房形状和形态，允许组织长入以取代材料并保持形态。它在管理机构认为无毒的水平上被吸收为副产品。通过使用猪模型的两项初步研究，我们已经确定了满足植入标准的ReFilx制剂。在该NSERC I2I申请中，我们建议通过开发和验证ReFilx合成中涉及的原材料的规模扩大策略以及最终形成结构的制造来支持该产品的商业化。 这将通过两个关键里程碑来实现：（1）开发预聚物的规模扩大策略和（2）开发ReFilx结构的高通量和可再现制造原型。 开发和验证这些工艺将反过来加快并降低从实验室到商业生产的过渡成本。

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.******