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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要放射疗法是一种广泛使用的治疗方式，用于骨盆恶性肿瘤，例如前列腺和颈椎癌症;但是，赋予治疗益处所需的高剂量通常会对辐射场和周围的正常问题。骨盆辐射最常见的并发症是直肠炎，几乎所有患者在随后的几个月和几年中都经历了敏锐的经历和许多患者的经历停止治疗。辐射诱导的凝血炎以最严重的形式导致血液供应妥协到直肠壁，这会导致厚度缺血，狭窄和粪便对象。治疗策略遵循单独或与类固醇结合的一线抗炎药的务实方法甲氯酸盐等细胞保护剂。尽管这些策略在某些情况下与症状缓解有关，但数据不足以支持宽度的使用，使临床医生没有合法的证据疗法推荐。 Briopryme Biologics，Inc。开发了一个单一的患者/多用途生物学设备（无菌粉末）源自脱细胞猪pleceta pleceta细胞外基质（DCM）在使用点，直接作为灌溉灌溉直接传递到肛门。 Briopryme的DCM水凝胶设备形成一个受保护的层，并粘附在粘膜膜上以挽救暂时的刺激并提供潮湿的环境和3D脚手架，以优化伤口愈合。 DCM水凝胶设备可以完全在1-3小时内吸收。当在损伤，安全，无毒和对肿瘤生长的中性。癌症患者的案例研究骨盆放射疗法的反复会议报告说，直肠炎症状和 DCM自我管理后的生活质量。基于这些承诺研究，Briopryme已合作与加州大学戴维斯分校放射肿瘤学系一起定义DCM-的分子特征介导的维修（AIM 1）并评估DCM减轻小鼠辐射损伤和狭窄的效率辐射引起的直肠炎的模型（AIM 2）。成功完成拟议的工作将确立效率 DCM用于治疗皮肤和粘膜膜毒性，并由放射疗法引起的在癌症患者中对该主张进行正式临床评估的方式。