A new class of biodegradable synthetic biomaterial for seroma prevention

描述(申请人提供)：血清瘤是一种常见的术后并发症，尤其是消融和重建手术后的常见并发症。如果不及时干预，术后血清肿瘤可能会导致严重的患者并发症，包括感染、组织坏死、永久性囊性空洞、肢体活动度降低和永久性毁容。浆液瘤形成的高发生率和由此导致的患者发病率的增加导致了广泛使用引流术来治疗形成后的浆液瘤。在过去的几十年里，也开发和实施了几种临床和试验性预防治疗策略；然而，到目前为止，还没有一种预防策略显示出临床相关的疗效，血清肿瘤率仍然处于令人无法接受的高水平。因此，临床上需要一种有效的、预防性的浆液性肿瘤治疗方法。目前由STTR资助的研究工作将为一种新型生物材料的商业化奠定基础 预防浆液瘤，从而通过改善患者结局和降低患者发病率来增强患者的健康。初步研究表明，一种新型的水凝胶形式的共嵌段聚合物，由甲氧基聚乙二醇(Mpeg)嵌段和聚碳酸酯形式的二羟基丙酮(PDHA)嵌段组成，在防止血清形成方面显示出有效的效果。通过在第一阶段/第二阶段的努力中完成研究和开发任务，将汇编关于mpeg-pDHA的生物兼容性、有效性和在预防血清病方面的作用模式的令人信服的数据集。该数据集将支持mpeg-pDHA进入FDA的监管程序。已经开发了一个重要的初步数据集，证明了mpeg-pDHA水凝胶在预防血清瘤方面的临床应用。这种生物材料的主要特点是：在体外和体内生物降解(在体外24小时内和体内3天内)成为生物相容的产品，并在公认的乳腺癌根治术动物模型中成功地消除血清肿块。第一阶段的工作将集中于确定mpeg-pDHA在体内的效力范围，并使用FDA接受的体外和体内生物兼容性测试标准来评估其生物兼容性。主要任务如下：任务1-合成和表征将在第一阶段研究中使用的mpeg-pDHA聚合物。任务2-利用采集大鼠背阔肌的模型，确定体内疗效的范围。任务3-使用食品和药物管理局接受国际标准化组织10993标准，通过体外细胞毒性、遗传毒性、全身毒性和血液相容性研究，以及通过体内动物实验进行植入后的局部毒性效应来量化生物相容性。 公共卫生相关性：浆液瘤的形成是一种常见的术后并发症，它会降低患者的健康，并且没有公认的预防性治疗方法。目前STTR资助的研究工作旨在推动一种新的可生物降解材料的开发，用于预防浆液瘤，从而通过改善手术结果来改善患者的健康。

DESCRIPTION (provided by applicant): Seromas are a common post-operative complication particularly prevalent following ablative and reconstructive surgeries. Without timely intervention post-operative seromas can lead to significant patient morbidity including infection, tissue necrosis, permanent cystic cavities, reduced limb mobility and permanent disfigurement. The high incidence of seroma formation and the resulting increase in patient morbidity has led to the widespread use of drainage to treat seroma after formation. The last several decades have also seen the development and implementation of several clinical and experimental preventative treatment strategies; however, to date no preventative strategy has shown clinically relevant efficacy and seroma rates remain at unacceptably high levels. Consequently, there is a clear need for a clinically effective, preventative seroma treatment. The current STTR funded research effort will lay the foundation for the commercialization of a new class of biomaterial for the prevention of seroma, thereby enhancing patient health through improved patient outcomes and reduced patient morbidity. Preliminary studies have shown that a novel coblock polymer in hydrogel form, consisting of a methoxy polyethylene glycol (MPEG) block and a block of the polycarbonate form of dihidroxyacetone (pDHA), has shown efficacy in preventing seroma formation. Through the completion of research and development tasks during Phase I/II efforts, a compelling data set will be compiled on the biocompatibility, the efficacy and the mode of action of MPEG-pDHA in seroma prevention. This data set will support the entry of MPEG-pDHA into the FDA's regulatory process. A significant preliminary data set demonstrating the clinical utility of MPEG-pDHA hydrogels in seroma prevention has been developed. Key features of this biomaterial are: in vitro and in vivo biodegradation (within 24h in vitro and 3 das in vivo) into biocompatible products, and successful elimination of seroma in an accepted animal model of radical mastectomy. Phase I efforts will focus on determining the range of efficacy of MPEG-pDHA in vivo and on evaluating its biocompatibility using FDA accepted in vitro and in vivo biocompatibility testing standards. The key tasks are listed below: Task 1 - Synthesize and characterize the MPEG-pDHA polymers to be used during the Phase I study. Task 2 - Determine the range of efficacy in vivo using a model involving the harvesting of the rat latissimus dorsi muscle. Task 3 - Use FDA accepted ISO 10993 standards to quantify biocompatibility through in vitro cytotoxicity, genotoxicity, systemic toxicity, and hemocompatibility studies and local toxic effects after implantation through in vivo animal studies. PUBLIC HEALTH RELEVANCE: Seroma formation is a common post-operative complication that diminishes patient health and for which there are no accepted preventative treatments. The current STTR funded research effort aims to advance the development of a new biodegradable material for the prevention of seroma and thereby improve patient health through improved surgical outcomes.