Oxygen-eluting scaffolds for cranial bone regeneration

用于颅骨再生的氧气洗脱支架

基本信息

批准号：
10586040
负责人：
Warren L Grayson
金额：
$ 45.91万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586040
关键词：
3D Print Address Adipose tissue Adoption Anatomy Autologous Transplantation Biocompatible Materials Blood Vessels Bone Matrix Bone Regeneration Bone Transplantation Calvaria Cell Fraction Cell Separation Cell Survival Cell Transplantation Cells Cephalic Cessation of life Clinical Complex Computer Models Cues Data Defect Development Diameter Economic Burden Encapsulated Endothelial Cells Esthetics Fatty acid glycerol esters Feedback Fibrin Fluorescence Formulation Fracture Harvest Hindlimb Human Hydrogels Hypoxia Image Implant In Situ In Vitro Injury Lasers Microspheres Minerals Modeling Monitor Morphogenesis Multi-modal optical imaging Multimodal Imaging Mus Natural regeneration Operative Surgical Procedures Optics Osteogenesis Oxygen Patients Perfusion Permeability Phenotype Point of Care Technology Polymers Polyvinyl Alcohol Porosity Powder dose form Process Radial Rattus Regenerative capacity Shapes Signal Transduction Site Stem cell transplant Structure Technology Testing Thick Tissue Engineering Tissues Transplantation Treatment Efficacy Vascular remodeling Vascularization bioactive scaffold bioscaffold bone clinical translation controlled release craniofacial craniofacial bone design efficacy validation healing hemodynamics hyperbaric chamber in vivo in vivo optical imaging insight long bone manufacture meter multimodality next generation non-invasive monitor novel osteogenic point of care polycaprolactone pressure progenitor response restoration scaffold scale up simulation spatiotemporal standard of care stem cell survival stem cells tissue regeneration wound

项目摘要

Each year, there are approximately 200,000 craniofacial fractures requiring bone transplantation in the US with an economic burden of $2B. These injuries often require multiple complex surgeries, which do not achieve adequate functional or aesthetic restoration. To address this limitation, the field of tissue engineering has employed advanced approaches that combine a patient’s own cells with customized bioactive scaffolds to induce regeneration. For efficacious clinical translation of tissue engineering strategies, it is crucial to develop them as point-of-care technologies in which the harvesting of cells, their packaging into scaffolds, and immediate transplantation into the defect site will take place within a single surgical procedure. A major hurdle of this strategy is that the hypoxic wound microenvironment impedes the ability of surviving cells to orchestrate regeneration. To overcome this limitation, we propose to design scaffolds capable of delivering oxygen (O2) along with the cells. Specifically, we will embed O2-eluting microtanks (µtanks) – hollow, polymeric microspheres capable of ‘storing’ O2 at elevated pressures and slowly releasing it into the cellular microenvironment – into scaffolds comprised of polycaprolactone (PCL) and decellularized bone matrix (DCB) that are 3D-printed in precise, anatomic shapes. To effectively design O2-eluting, PCL-DCB-µtank scaffolds and track the enhanced viability and therapeutic efficacy of transplanted stromal vascular fraction (SVF) cells harvested from lipoaspirate, we will utilize multimodal in vivo optical imaging. This will provide quantitative data on the in vivo microenvironmental factors that impact stem cell survival and tissue regeneration following transplantation and uniquely inform the design process leading to more effective, next-generation biomaterial scaffolds. We hypothesize that the delivery of oxygen using our microtank technology for up to four days will enhance stem cell survival, vascularization and bone formation within the defect and that by non-invasively monitoring the effects of oxygen delivery via a cranial window, we can optimize the design of the scaffold. In Specific Aim 1, we will manufacture 10-50 µm diameter biodegradable polyvinyl alcohol microtanks, incorporate them into the struts of the 3D-printed scaffolds, and validate the spatiotemporal O2 gradients within the scaffolds in response to varying the microtank concentrations and loading pressures. In Specific Aim 2, we will integrate experimental data of O2 concentrations most favorable to vascular morphogenesis/osteogenic differentiation of SVF with numerical simulations to predict the scaffold designs that provide favorable spatiotemporal O2 gradients to promote tissue regeneration. In Specific Aim 3, we will utilize non-invasive, multimodal imaging to dynamically monitor transplanted cells and vascular assembly in PCL-DCB-µtank scaffolds and use this to enhance scaffold design. We will test the optimal designs in a scaled-up, stringent, vasculature-limited model of bone regeneration. The complementary tissue engineering/imaging strengths will provide unprecedented insight into bone regeneration and produce novel platform biomaterial technologies.

每年，大约有200,000个颅面骨折，需要在美国进行骨骼移植经济燃烧为$ 2B。这些伤害通常需要多次复杂的手术，而这些手术无法实现足够的功能或审美恢复。为了解决这一限制，组织工程领域具有采用的高级方法将患者自己的细胞与定制的生物活性脚手架结合在一起诱导再生。对于组织工程策略的有效临床翻译，发展至关重要它们是保健技术，在其中收集细胞，包装到脚手架中，以及立即移植到缺陷部位将在单个手术过程中进行。一个重大障碍这种策略的是，低氧伤口微环境阻碍了幸存细胞编排的能力再生。为了克服这一限制，我们建议设计能够输送氧气的支架（O2）与细胞一起。特别是，我们将嵌入O2洗脱微型车辆（µTanks） - 空心，聚合物能够在高压压力下“存储” O2并将其缓慢释放到细胞中的微球微环境 - 进入脚手架的多碳酸酯（PCL）和脱细胞骨基质（DCB）精确的解剖形状是3D印刷的。为了有效设计O2洗脱，PCL-DCB-µTank支架并跟踪移植基质血管分数（SVF）细胞的生存能力和治疗效率我们将从脂肪酸中收获，我们将利用多模式在体内光学成像中。这将提供定量数据关于影响干细胞存活和组织再生的体内微环境因子移植并独特地告知设计过程，导致更有效，下一代生物材料脚手架。我们假设使用我们的微型技术最多四天的氧气递送将增强缺陷内的干细胞存活，血管化和骨形成，并通过非侵入性通过颅窗监视氧递送的效果，我们可以优化脚手架的设计。在特定的目标1，我们将生产直径10-50 µm可生物降解的聚乙烯基醇微粉，将它们纳入3D打印脚手架的支柱，并验证时空O2梯度脚手架响应于改变微型浓度和加载压力。在特定的目标2中，我们将整合最有利于血管形态发生/成骨的O2浓度的实验数据 SVF用数值模拟的分化，以预测提供有利的脚手架设计时空O2梯度促进组织再生。在特定的目标3中，我们将利用无创的多模式成像以动态监测PCL-DCB-μTank中的移植细胞和血管组装脚手架并使用它来增强脚手架设计。我们将在缩放，严格的，严格的，脉管限制的骨再生模型。完整的组织工程/成像强度将提供对骨再生的前所未有的见解，并生产新型的平台生物材料技术。