Natural Mixtures from Expired Human Platelets for Periodontal Tissue Engineering

描述（由申请人提供）：2006年美国进行了大约180万例再生牙科手术。其中，约20%使用了伤口愈合产品，如重组生长因子（RGF）或患者自身血小板浓缩物（需要使用血小板浓缩系统（PCS））。伤口愈合剂被用作加速愈合和改善患者预后的尝试-特别是在较大的再生手术和受损患者中。然而，尽管伤口愈合剂是牙周病医生和口腔外科医生用于改善患者预后的关键工具，但目前可用的产品效果不一致，而且价格昂贵。一种持续有效且更经济的产品对牙科外科专业人员来说非常重要，因为它将允许更多的采用并改善牙科再生治疗程序的结果。开发和商业化用于牙周应用的下一代伤口愈合剂是这个多阶段STTR项目的目标。Snoasis Medical提出了一种独特的生长因子来源和一种技术，可以共同产生理想的伤口愈合产品。过期的人类血小板储存单位（目前仅花费50美元）是开发此类产品的极好、低成本来源。推进这种创新方法所需要的是验证一种专有的加工方法，这种方法可以提供高产量的安全材料，并具有可量化的生物活性。因此，这个多阶段STTR项目的总体目标是表明这种新方法将产生一种成分一致的安全材料，使其在牙周再生手术中具有低成本和高性能的应用。初步的Snoasis数据表明，我们的方法可以产生生物活性优于rhPDGF的产品。为了充分确定这种方法的可行性，我们将追求以下具体目标：1)证明从过期的人类储存血小板单位中提取的提取物含有对伤口愈合和血管生成至关重要的生长因子；2)在小鼠中使用Matrigel栓试验，证明这些血小板提取物在足够的水平上表现出血管生成活性，a)在5只小鼠中以10 <g/栓的剂量在单独的栓中形成至少5条功能性毛细血管；b)对牙龈卟啉单胞菌（一种重要的牙周病原体）具有抗菌活性；c)维持FDA认为安全的热原水平（低于0.5 EU/300<g）；3)证明这些批次中的大多数具有优于rhPDGF-BB的生物活性。Snoasis将通过由STTR首席研究员Mark Roedersheimer领导的经验丰富的研发团队以及另外三名博士或医学博士级别的研究人员来实现这三个目标。预计第一阶段的成功将为后续的第二阶段项目奠定基础，该项目旨在通过在高等动物模型中测试，验证第一阶段开发的新型提取物的潜在治疗价值。第二阶段的工作将旨在产生吸引“第三阶段”商业伙伴/投资者所需的数据。

DESCRIPTION (provided by applicant): Some 1.8 million regenerative dental procedures were done in the U.S. in 2006. Of these, about 20% used a wound-healant product such as a recombinant growth factor (RGF) or concentrates of a patient's own platelets [requiring the use of a platelet concentrating system (PCS)]. Wound-healants are used as an attempt to accelerate healing and to improve patient outcomes-especially in larger regenerative procedures and in compromised patients. However, although the wound-healants are key tools for periodontists and oral surgeons to use in pursuing improved patient outcomes, the currently available products result in inconsistent efficacy and are expensive. A product that is consistently effective and much more economical would be of major importance to the dental surgery professional, as it would allow for greater adoption and improved outcomes of dental regenerative treatment procedures. Developing and commercializing that next- generation wound-healant for periodontal applications is the goal of this multi-phase STTR project. Snoasis Medical proposes a unique source of growth factors and a technique that together could lead to the ideal wound-healant product. Expired units of banked human platelets (currently costing only $50) are an excellent, low-cost source from which to develop such a product. What is needed to move forward with this innovative approach is the validation of a proprietary processing method that gives high yields of safe material that exhibits quantifiable biologic activity. Thus, the overall goal of this multi-phase STTR project is to show that this new method will yield a safe material of consistent composition that enables low-cost and high-performance application in periodontal regenerative procedures. Preliminary Snoasis data demonstrates that our method can yield a product with bioactivity superior to that of rhPDGF in vivo. To fully establish the feasibility of this approach, we will pursue the following Specific Aims: 1) Prove that extracts produced from units of expired human banked platelets contain growth factors key to wound-healing and angiogenesis; 2) Using a Matrigel plug assay in mice, prove that these platelet extracts exhibit angiogenic activity at a level sufficient to a) form a total of at least 5 functional capillaries in separate plugs placed in five mice with a dose of 10 <g/plug; b) show antibacterial activity in culture against Porphyromonas Gingivalis, a key periodontal pathogen; and c) maintain pyrogen levels considered safe by the FDA (less than 0.5 EU/300<g); and 3) Prove that a majority of these batches exhibit bioactivity superior to that of rhPDGF-BB. Snoasis will pursue these three aims with a highly experienced R&D team headed by STTR Principal Investigator Mark Roedersheimer and including three additional Ph.D.- or MD-level researchers. The anticipated Phase I success will set the stage for a follow-on Phase II project designed to validate the potential therapeutic value of the novel extracts developed during Phase I by testing them in a higher animal model. Phase II work will be designed to produce the data needed to attract "Phase III" commercial partners/investors. PUBLIC HEALTH RELEVANCE: In 2006, some 1.8 million dental procedures in the U.S. made use of a regenerative tissue product or an autograft harvested from the patient's mouth to treat serious tissue loss around teeth-with that number projected to increase at a rate of 16% over the next five years. And although it is estimated that wound- healant products are used in approximately 20% of all dental regenerative procedures, current-generation products do not fully meet the needs of periodontists and oral surgeons-often producing inconsistent results and/or proving to be very expensive (often prohibitively so). The goal of this multi-phase STTR project is to develop, validate, and commercialize the needed next-generation wound-healant that periodontists and oral surgeons can use to effectively and economically treat their patients who suffer from tissue degeneration that leads to tooth loss and threatens oral health.