A decellularized porcine placenta matrix hydrogel for management of radiation-induced proctitis

用于治疗放射性直肠炎的脱细胞猪胎盘基质水凝胶

• 批准号: 10599727
• 负责人: Jian Jian Li
• 金额: $ 40万
• 依托单位: BRIOPRYME BIOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599727
• 关键词: 3-Dimensional; Acute; Adhesions; Amifostine; Amino Acids; Animals; Anti-Inflammatory Agents; Antibiotics; Antioxidants; Area; Biological; Biological Factors; Biological Products; California; Cancer Patient; Cancer Survivor; Case Study; Cell Adhesion; Cells; Chronic; Clinical; Collagen; Colon; Colorectal; Complication; Conformal Radiotherapy; Cytoprotective Agent; Cytoskeleton; DNA Repair; Data; Devices; Dose; Dose Limiting; Dryness; Elastin; Electromagnetic Energy; Environment; Epithelial Cells; Epithelium; Euthanasia; Exhibits; Exposure to; Extracellular Matrix; Family suidae; Fibrosis; Film; Glycosaminoglycans; Growth Factor; Histologic; Hour; Hydration status; Hydrogels; Hyperbaric Oxygenation; Immune; Inflammation; Inflammatory; Injury; Intestinal Obstruction; Intestines; Irrigation; Ischemia; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of prostate; Measures; Mediating; Medical; Membrane; Modality; Modeling; Molecular; Monitor; Morphology; Motivation; Mucous Membrane; Mus; Normal Cell; Normal tissue morphology; Obstruction; Organoids; Oryctolagus cuniculus; Pathologic; Patients; Pelvis; Peptides; Phase; Placenta; Powder dose form; Proctitis; Proliferating; Proteins; Quality of life; RNA; Radiation; Radiation Dose Unit; Radiation Injuries; Radiation Oncologist; Radiation Oncology; Radiation Protection; Radiation therapy; Recommendation; Rectal Cancer; Rectum; Regimen; Reporting; Resistance; Saline; Secondary to; Self Administration; Skin; Small Business Technology Transfer Research; Stenosis; Sterility; Steroids; Structure; Sulfasalazine; Symptoms; Syndrome; Tail; Testing; Therapeutic; Thick; Thinness; Time; Tissues; Toxic effect; Transcript; Universities; Vascular blood supply; Work; absorption; acute symptom; chemokine; cohort; comparison control; cytokine; effective therapy; efficacy evaluation; enema administration; evidence base; experience; immunoreaction; improved; in vivo; innovation; intestinal epithelium; intestinal injury; irritation; matrigel; mouse model; neoplastic cell; p53-binding protein 1; persistent symptom; preservation; prevent; primary endpoint; prophylactic; radiation mitigation; radiation response; radiation-induced injury; radioprotected; rectal; reduce symptoms; repaired; research clinical testing; scaffold; stem cell proliferation; stem cell self renewal; stem cells; symptomatic improvement; treatment strategy; tumor growth; wound healing

PROJECT SUMMARY Radiation therapy is a widely used treatment modality for pelvic malignancies such as prostate and cervical cancer; however, the high doses needed to confer therapeutic benefit often inflict significant damage on the normal issue in and surrounding the radiation field. The most frequent complication of pelvic radiation is proctitis, which nearly all patients experience acutely and many experience chronically in the months and years following cessation of therapy. In its most severe form, radiation induced proctitis leads to compromise of the blood supply to the rectal wall, which results in full thickness ischemia, stenosis, and fecal obstruction. Treatment strategies follow a pragmatic approach of first-line anti-inflammatories alone or in combination with a steroid, followed by cytoprotective agents like sucralfate. While these strategies are associated with symptom relief in some cases, data are not strong enough to support widespread use, leaving clinicians without legitimate evidence-based therapies to recommend. BrioPryme Biologics, Inc. has developed a single patient/multiuse biologic device (sterile powder) derived from DeCellularized porcine placenta extracellular Matrix (DCM) that can be rehydrated at point of use and delivered directly to the anorectum as an enema irrigation. BrioPryme’s DCM hydrogel device forms a protective layer and adheres onto the mucosal membrane to relieve temporary irritations and provides a moist environment and a 3D scaffold to optimize wound healing. The DCM hydrogel device can be fully absorbed within 1-3 hours. It has demonstrated potential to reduce fibrotic progression when applied at time of injury, and is safe, non-toxic, and neutral towards tumor growth. Case studies in cancer patients that recently received repeated sessions of pelvic radiotherapy reported significant improvements in proctitis symptoms and quality of life following self-administration of DCM. Based on these promising studies, BrioPryme has partnered with University of California Davis Department of Radiation Oncology to define the molecular features of DCM- mediated repair (AIM 1) and evaluate the efficacy of DCM to alleviate radiation injury and stenosis in a mouse model of radiation-induced proctitis (AIM 2). Successful completion of the proposed work will establish efficacy of DCM for the management of skin and mucosal membrane toxicity resulting from radiotherapy and pave the way for formal clinical evaluation of this claim in cancer patients.

项目总结 放射治疗是一种广泛应用于前列腺癌和宫颈癌等盆腔恶性肿瘤的治疗方法。 然而，赋予治疗益处所需的高剂量往往会对 辐射场内和周围的正常问题。盆腔放射最常见的并发症是直肠炎， 在接下来的几个月和几年里，几乎所有的患者都会有剧烈的经历，许多人会长期经历这种情况 停止治疗。在最严重的情况下，辐射引起的直肠炎会导致血液供应的损害。 直肠壁，导致全层缺血、狭窄和粪便梗阻。治疗策略 遵循一线抗炎药物单独使用或与类固醇联合使用的务实方法，然后 硫糖铝等细胞保护剂。虽然这些策略在某些情况下与缓解症状有关， 数据不足以支持广泛使用，使得临床医生没有合法的证据支持 值得推荐的治疗方法。BrioPryme Biologics，Inc.开发了一种单患者/多用途生物设备 (无菌粉)从脱细胞的猪胎盘细胞外基质(DCM)中提取，可再水化 在使用时，并直接输送到肛门直肠作为灌肠冲洗。布里奥普里姆(氏)DCM水凝胶装置 形成一层保护层并附着在粘膜上以缓解暂时的刺激并提供 湿润的环境和3D支架，以优化伤口愈合。该DCM水凝胶装置可以完全 在1-3小时内吸收。它已被证明有潜力减少纤维化的进展，如果在 对肿瘤的生长是安全、无毒和中性的。最近对癌症患者的案例研究 接受重复盆腔放射治疗的患者报告直肠炎症状显著改善， DCM自我管理后的生活质量。基于这些有希望的研究，BrioPryme与 与加州大学戴维斯分校放射肿瘤学系共同确定DCM的分子特征- 介导性修复(AIM-1)及DCM对小鼠放射性损伤和狭窄的保护作用 放射性直肠炎模型(AIM 2)。拟议工作的成功完成将确立效力 DCM对放射治疗所致皮肤和粘膜毒性的治疗作用 对癌症患者这一说法进行正式临床评估的方法。