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

项目摘要 放射治疗是一种广泛使用的治疗盆腔恶性肿瘤，如前列腺和宫颈癌 癌症;然而，赋予治疗益处所需的高剂量通常会对患者造成严重损害。 辐射场内和周围的正常问题。盆腔放疗最常见的并发症是直肠炎， 几乎所有的患者都会急性发作，许多患者会在随后的数月或数年内慢性发作 停止治疗。在其最严重的形式，辐射诱发的直肠炎导致妥协的血液供应 直肠壁，导致全层缺血、狭窄和粪便阻塞。治疗策略 遵循一线抗炎药单独或与类固醇联合使用的务实方法， 细胞保护剂如硫糖铝。虽然这些策略在某些情况下与症状缓解有关， 数据不足以支持广泛使用，使临床医生没有合法的循证医学证据。 推荐的疗法BrioPryme Biologics，Inc.开发了一种单患者/多次使用的生物器械 （无菌粉末）来源于脱细胞猪胎盘细胞外基质（DCM），可再水化 在使用时直接输送到肛门直肠作为灌肠冲洗。BrioPryme的DCM水凝胶装置 形成保护层并粘附在粘膜上以减轻暂时的刺激， 潮湿的环境和3D支架来优化伤口愈合。DCM水凝胶装置可以完全地 在1-3小时内吸收。它已被证明有潜力减少纤维化进展时，应用于时间 并且对肿瘤生长是安全、无毒和中性的。癌症患者的案例研究， 接受盆腔放射治疗的患者报告直肠炎症状显著改善， DCM自我给药后的生活质量。基于这些有希望的研究，BrioPryme已经与 与加州戴维斯大学放射肿瘤学系合作，确定DCM的分子特征- 介导的修复（AIM 1），并评估DCM减轻小鼠放射损伤和狭窄的疗效 放射诱导的直肠炎模型（AIM 2）。成功完成拟议的工作将建立效力 扩张型心肌病用于治疗放疗引起的皮肤和粘膜毒性， 在癌症患者中对这种说法进行正式临床评估的方法。

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.