MAP: a Flowable, Precision-Engineered, and Tunable Tissue Scaffold Leveraging Hyper-Porous Geometry to Control Inflammation and Promote Regenerative Healing in Diabetic Wounds

摘要/摘要 慢性糖尿病足部溃疡(DFU)是全球医疗保健的重大负担，费用高达11美元 2014年，仅在美国就有10亿美元。目前的处理能力受到以下因素的限制：(I)不能将标准的湿法处理到 治愈这些伤口的干绷带技术以及(Ii)先进治疗方法的高昂成本，如纸巾- 基于或活细胞生物工程皮肤替代品。这些治疗的高昂成本限制了 直到受伤后的报销是慢性的。在美国，每年约有150万例新的和持续的DFU病例 都有记录在案。在他们的一生中，有足部伤口的糖尿病患者有20%的机会出现下肢 美国的截肢手术。5年后，DFU患者的报告死亡率从55%到74%不等，这是 高于前列腺癌、乳腺癌和结肠癌。 这种重大的临床需求和缺乏具有成本效益的产品创造了重大的市场机会，可以 用生物材料疗法来解决，其疗效与先进的皮肤替代品一样，但代价是伤口 冷汁制作。低产品成本和易用性将在早期(紧急)阶段推动报销和采用 这些高危糖尿病患者的伤口护理。控制炎症和促进组织向内生长的能力 可以缓解慢性伤口阶段，改善患者的预后，并降低支付者的成本。直到 现在，还没有一种低成本的治疗方法，当应用时可以整合到伤口床上并促进 没有细胞或生物制剂的再生。 为了满足这一市场需求，天宝治疗公司正在开发一套组织再生生物材料 基于我们专有的微孔退火颗粒(MAP)技术。地图使我们能够 具有独特几何支架结构的合成化学配方。我们的地图材料是可流动的 (易于使用)和填充多种形状和大小的伤口，并转化为超多孔海绵状 LED白光照射后伤口处有网状结构。超多孔性几何结构促进快速组织 与先导去细胞相比，向内生长、早期血管形成和创面再上皮化速度更快 以组织为基础的基质，炎症反应最小。 Tempo开发了我们的第一个产品，MAP Wound Matrix，用于治疗急性健康伤口，并已 最近通过Direct De Novo向FDA提交了一份监管申请，提供了安全和性能数据。 天宝已经完成了产品制造的初步规模，正在为上市后的临床数据做准备 从2019年开始的努力。 在拟议的直接转二期工作中，我们将开发基于MAP技术的第二个产品， 针对糖尿病伤口愈合不良的患者。我们将使用专门的损伤伤口愈合模型 糖尿病猪，在良好实验室操作规范(GLP)下进行测试，以测试一套三种配方变体 已经在一项初步的健康猪研究中得到了证明。MAP的最优公式在 缓慢愈合的环境和刺激组织再生将被选为安全简档和 研究设备豁免(IDE)将在提案末尾提交。

SUMMARY / ABSTRACT Chronic diabetic foot ulcers (DFUs) are a significant worldwide healthcare burden, reaching a cost of $11 billion in the US alone during 2014. The current treatment capability is limited by (i) inability of standard wet-to- dry bandaging techniques to heal these wounds and (ii) the high costs of advanced treatments such as tissue- based or living-cell bioengineered skin substitutes. The high costs of these treatments have limited reimbursement until after a wound is chronic. Each year in the US, ~1.5 million new and continuing DFU cases are documented. Over their lifetime, a diabetic patient with a foot wound has a 20% chance of lower limb amputation in the US. Reported mortality rates for DFU patients range from 55 to 74% after 5 years, which are above cancers such as prostate, breast, and colon. This significant clinical need and lack of cost-effective products creates significant market opportunity that can be addressed with a biomaterial therapy with the efficacy of an advanced skin substitute at the cost of a wound dressing. Low product cost and ease-of-use will drive reimbursement and adoption in the early (acute) phase of wound care in these at-risk diabetic patients. The ability to control inflammation and promote tissue ingrowth could mitigate the chronic wound phase, improving outcomes for patients and reducing costs to payers. Until now, there have been no low-cost treatments that when applied can integrate into the wound bed and promote regeneration without cells or biologics. To answer this market need, Tempo Therapeutics is developing a suite of tissue regeneration biomaterials based on our proprietary Microporous Annealed Particle (MAP) technology. MAP allows us to empower synthetic chemical formulations with unique geometric scaffold structure. Our MAP materials are flowable (ease of application) and fill wounds of multiple shapes and sizes and convert to a hyper-porous sponge-like network in the wound site after exposure to LED white light. The hyper-porosity geometry promotes fast tissue ingrowth, early vascularization, and faster wound re-epithelialization when compared to leading decellularized tissue-based matrices, with minimal inflammatory response. Tempo has developed our first product, the MAP Wound Matrix, for treatment of acute healthy wounds and has recently submitted a regulatory application via direct De Novo to FDA with safety and performance data. Tempo has completed initial scale-up of product manufacturing and is preparing for post market clinical data efforts beginning in 2019. In the proposed direct-to-phase II work, we will develop our second product based on the MAP technology, targeting impaired healing in diabetic wounds. We will employ specialized models of impaired wound healing in diabetic pigs, performed under Good Laboratory Practices (GLP), to test a suite of three formulation variants already demonstrated in a preliminary healthy swine study. The optimal formulation of MAP that performs in slow healing environments and stimulates tissue regeneration will be selected for safety profiling and an Investigational Device Exemption (IDE) will be submitted at the end of the proposal.