权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Harnessing Continuous Liquid Interface 3D Printing to Improve Tumor-homing Stem Cell Therapy for Post-surgical Brain Cancer

利用连续液体界面 3D 打印改善脑癌术后肿瘤归巢干细胞疗法

基本信息

批准号：
10420701
负责人：
Shawn Hingtgen
金额：
$ 46.72万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10420701
关键词：
3-Dimensional 3D Print Advanced Development Allografting Animals Architecture Biological Assay Biophysics Blood Brain Cell Survival Chemotherapy-Oncologic Procedure Clinical Clinical Research Coculture Techniques Complex Custom Deposition Enzyme-Linked Immunosorbent Assay Excision Gelatin Genetic Engineering Glioblastoma Growth Homing Human Human Engineering Image Immune Immune system Immunocompetent Implant In Vitro Injections Kinetics Liquid substance Malignant Neoplasms Malignant neoplasm of brain Mechanics Methods Microscopic Modeling Modulus Mus Neoplasm Transplantation Operative Surgical Procedures Patients Penetration Performance Pharmaceutical Preparations Postoperative Period Primary Brain Neoplasms Printing Production Property Recurrence Residual Tumors Residual state Resolution Safety Seeds Shapes Solid Statistical Data Interpretation Stem cell transplant Surgically-Created Resection Cavity TNF-related apoptosis-inducing ligand Technology Testing Therapeutic Tissues Translating Transplantation Variant Xenograft procedure anti-cancer base bioluminescence imaging biomaterial compatibility brain tissue cancer cell cancer invasiveness cancer stem cell cancer therapy clinically relevant copolymer design first-in-human gene product hydrogel scaffold immunocytochemistry improved in vivo migration mouse model nerve stem cell novel novel therapeutics porous hydrogel preclinical study rational design response scaffold stem cell therapy stem cells tumor

项目摘要

Project Summary/Abstract Glioblastoma is the most common primary brain tumor and one of the deadliest forms of cancer. Recently, we found that biocompatible matrices significantly improve the transplant of tumor-homing neural stem cells into the post-surgical GBM cavity allowing them to deliver anti-cancer gene products that suppress tumor recurrence. Yet, the optimal scaffold figuration that maximizes tNSC transplant, migration, drug release, and subsequent GBM kill remain unknown. Using clinically relevant human tNSCs, matrices, and mouse models of GBM resection/recurrence, we have found that 3D architecture and scaffold composition markedly enhance tNSC persistence in the surgical cavity. Here in, we hypothesize that optimizing features through unique 3D printing of custom designed scaffolds will achieve superior suppression of post-surgical GBMs by tNSC therapy. Leveraging Continuous Liquid Interface Printing (CLIP), a novel continuous fabrication method with high spatial resolution, we propose to fabricate a panel of 3D matrices with different architectural, biophysical, and mechanical response features design rationally selected to improve tNSC therapy. We will define the impact of each design feature on tNSC persistence, homing and killing in vitro and in vivo, then test a final optimized matrix incorporating the most beneficial features into a single matrix using surgical resection models of patient-derived human xenografts in immune-depleted mice and syngeneic GBM allografts in immune- competent animals. We propose to undertake the following Aims: 1) Utilize CLIP to fabricate a panel of 3D printed matrices with varied design features; 2) Define the impact of 3D design features on tNSC efficacy for post-operative GBM; 3) Investigate the efficacy and safety of 3D matrix/tNSC therapy in immune-competent models of GBM resection/recurrence. The results of our study will generate a therapeutic tNSC/scaffold transplant strategy capable of robust GBM killing that can be translated for human patient testing. It will also uncover the scaffold features that regulate different aspects of tNSCs, allowing us to modulate tNSC cancer therapy through matrix design.

项目总结/文摘