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

MAP：一种可流动、精密设计且可调节的组织支架，利用超多孔几何形状来控制炎症并促进糖尿病伤口的再生愈合

• 批准号: 10015273
• 负责人: Stephanie Deshayes
• 金额: $ 83.69万
• 依托单位: TEMPO THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015273
• 关键词: Acute; Address; Adoption; Allografting; Alpha Particles; Amputation; Animal Model; Area; Automobile Driving; Bandage; Biocompatible Materials; Biological; Biological Factors; Biomedical Engineering; Brain; Breast; Caliber; Cells; Characteristics; Chemicals; Chronic; Clinical; Clinical Data; Clinical Research; Colon; Complications of Diabetes Mellitus; Cost Savings; Data; Development; Devices; Diabetic Foot Ulcer; Engineering; Environment; Epithelial; Epithelium; Evaluation; Exposure to; Family suidae; Formulation; Geometry; Granulation Tissue; Growth Factor; Healthcare; Heart; Histologic; Hydrogels; Impaired healing; Impaired wound healing; Impairment; Inflammation; Inflammatory Response; Injury; Institutional Review Boards; Investigation; Light; Lower Extremity; Malignant Neoplasms; Mechanics; Metaphor; Microspheres; Modeling; Multiple Wounds; Natural regeneration; Outpatients; Pathway interactions; Patient-Focused Outcomes; Patients; Performance; Phase; Porifera; Porosity; Process; Prostate; Recurrence; Reporting; Research; Risk; Safety; Shapes; Site; Skin; Skin Substitutes; Streptozocin; Structure; Surface; Techniques; Technology; Testing; Therapeutic; TimeLine; Tissue Grafts; Tissues; Translating; Treatment Cost; Variant; Vascularization; Visit; Work; Wound models; acute wound; animal tissue; base; biomaterial compatibility; chronic wound; clinical development; clinically relevant; cost; cost effective; diabetic; diabetic patient; diabetic ulcer; diabetic wound healing; foot; good laboratory practice; healing; improved; improved outcome; infection rate; limb amputation; mortality; next generation; novel; particle; performance tests; post-market; pre-clinical; pressure; regenerative; safety study; scaffold; scale up; tissue regeneration; tissue support frame; wound; wound bed; wound care; wound dressing; wound environment; wound healing; wound treatment

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.

摘要/摘要 慢性糖尿病足溃疡 (DFU) 是全球范围内的一项重大医疗负担，费用高达 11 美元 2014 年仅在美国就产生了 10 亿美元。目前的处理能力受到以下因素的限制：(i) 无法采用标准湿法处理 干包扎技术来治愈这些伤口，以及（ii）先进治疗方法的高成本，例如组织- 基于或活细胞生物工程的皮肤替代品。这些治疗方法的高昂费用限制了 直到伤口变成慢性后才报销。美国每年约有 150 万新发和持续 DFU 病例 被记录下来。在一生中，脚部有伤口的糖尿病患者有 20% 的机会发生下肢损伤 在美国截肢。据报道，5 年后 DFU 患者的死亡率为 55% 至 74%，其中 高于前列腺癌、乳腺癌和结肠癌等癌症。 这种巨大的临床需求和缺乏具有成本效益的产品创造了巨大的市场机会，可以 通过生物材料疗法来解决，其功效与先进的皮肤替代品相同，但代价是伤口 敷料。低产品成本和易用性将推动早期（急性）阶段的报销和采用 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，改善患者的治疗效果并降低付款人的成本。直到 现在，还没有低成本的治疗方法可以融入伤口床并促进伤口愈合。 无需细胞或生物制剂即可再生。 为了满足这一市场需求，Tempo Therapeutics 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。 MAP 让我们能够赋能 具有独特几何支架结构的合成化学制剂。我们的 MAP 材料具有流动性 （易于使用）填充多种形状和尺寸的伤口，并转化为超多孔海绵状 暴露于 LED 白光后伤口部位的网络。超孔隙几何形状促进快速组织 与领先的脱细胞相比，向内生长、早期血管化和更快的伤口上皮化 基于组织的基质，炎症反应最小。 Tempo 开发了我们的第一个产品 MAP 伤口基质，用于治疗急性健康伤口，并已 最近通过直接 De Novo 向 FDA 提交了一份监管申请，其中包含安全性和性能数据。 Tempo 已完成产品生产的初步规模化，并正在准备上市后临床数据 2019年开始努力。 在拟议的直接进入第二阶段的工作中，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受损的问题。我们将采用专门的伤口愈合受损模型 糖尿病猪，按照良好实验室规范 (GLP) 进行，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证实。 MAP 的最佳配方在 将选择缓慢愈合的环境并刺激组织再生进行安全分析和 研究设备豁免 (IDE) 将在提案结束时提交。