A new class of biodegradable synthetic biomaterial for seroma prevention

用于预防血清肿的新型可生物降解合成生物材料

• 批准号: 8395792
• 负责人: Michael Craven
• 金额: $ 23.17万
• 依托单位: IFYBER, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8395792
• 关键词: Address; Advanced Development; Animal Model; Animals; Biocompatible; Biocompatible Materials; Biodegradation; Biological Sciences; Biomedical Engineering; Clinical; Collaborations; Complication; Data; Data Set; Development; Dihydroxyacetone; Drainage procedure; Drug Formulations; Ethylene Glycols; Foundations; Funding; Future; Guidelines; Harvest; Health; Hydrogels; In Vitro; Incidence; Industry; Infection; Intervention; Investigation; Lead; Limb structure; Mission; Modeling; Morbidity - disease rate; Muscle; National Institute of Biomedical Imaging and Bioengineering; Necrosis; Operative Surgical Procedures; Outcome; Patients; Phase; Polyethylene Glycols; Polymers; Postoperative Period; Prevention; Process; Radical Mastectomy; Rattus; Reconstructive Surgical Procedures; Research; Seroma; Small Business Technology Transfer Research; Technology; Testing; Tissues; Toxic effect; Universities; biomaterial compatibility; biomaterial development; clinically relevant; commercialization; cytotoxicity; ethylene glycol; genotoxicity; human subject; implantation; improved; in vivo; manufacturing scale-up; new technology; novel; phase 1 study; physical science; polycarbonate; prevent; research and development; treatment strategy

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.

描述（由申请人提供）：血清瘤是一种常见的术后并发症，尤其是在消融和重建手术后普遍存在。不及时干预，术后血清瘤可以导致患者的明显发病率，包括感染，组织坏死，永久性囊性腔，肢体迁移率降低和永久性毁容。血清瘤形成的高发病率和导致患者发病率的增加导致形成后的排水普遍治疗血清瘤。过去的几十年还看到了几种临床和实验性预防治疗策略的发展和实施。但是，迄今为止，尚无预防策略表明临床相关的功效，血清瘤率仍然保持高水平。因此，显然需要进行临床有效的预防性血清瘤治疗。当前由STTR资助的研究工作将为新的生物材料商业化奠定基础 预防血清瘤，从而通过改善患者结局并降低患者发病率来增强患者健康。初步研究表明，一种新型的水凝胶形式的二共聚合物，该聚合物由甲氧基聚乙烯乙二醇（MPEG）块和二羟基乙酮（PDHA）的聚碳酸酯形式的块组成，在预防血清瘤形成方面具有疗效。通过在I/II阶段的工作期间完成研发任务，将汇编引人注目的数据集，内容集，汇编有关MPEG-PDHA在预防血清中的生物相容性，功效和作用方式。该数据集将支持MPEG-PDHA进入FDA的监管过程。 已经开发了一个重要的初步数据集，该数据集证明了MPEG-PDHA水凝胶在预防血清瘤中的临床实用性。这种生物材料的关键特征是：体内和体内生物降解（在24小时内体外和3个DAS在体内）中，在生物相容性产物中成功消除了自由基乳房切除术的动物模型中的血清瘤。第一阶段的努力将着重于确定MPEG-PDHA在体内的功效范围，并使用接受体外和体内生物相容性测试标准的FDA评估其生物相容性。关键任务如下列出：任务1-合成并表征在I阶段研究期间要使用的MPEG -PDHA聚合物。任务2-使用涉及收获大鼠latissimus redorsi肌肉的模型来确定体内功效的范围。任务3-使用FDA接受的ISO 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和通过体内动物研究植入后的局部毒性作用来量化生物相容性。 公共卫生相关性：血清瘤形成是一种常见的术后并发症，可减少患者健康，并且没有接受的预防性治疗。当前的STTR资助研究工作旨在推动开发一种可预防血清瘤的新型可生物降解材料，从而通过改善手术结果来改善患者健康。