Injectable and Moldable Composite Bone Scaffolds for Spinal Fusion

用于脊柱融合的可注射和可成型复合骨支架

基本信息

批准号：
10089684
负责人：
Lichun Lu
金额：
$ 5.05万
依托单位：
MAYO CLINIC ROCHESTER
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：
2019-04-05 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10089684
关键词：
3-Dimensional 3D Print Address Angiogenic Factor Animal Model Animals Anterior Applications Grants Arthrodesis Autologous Transplantation Biocompatible Materials Bone Growth Bone Regeneration Bone Transplantation Caring Chemistry Clinical Coupled Defect Dental Dental Models Development Devices Dorsal Encapsulated Esters Exhibits Formulation Fumarates Funding Generations Goals Gold Growth Factor Human Hydrogels Hydroxyapatites Implant In Situ Injectable Injections Institutional Review Boards Investigation Laboratories Ligaments Mandible Mechanics Medial Minimally Invasive Surgical Procedures Modality Modeling Molds Morbidity - disease rate Motion Musculoskeletal Natural regeneration Nerve Operative Surgical Procedures Oral Orthopedics Oryctolagus cuniculus Osteogenesis Otolaryngology Patients Performance Plant Roots Polymers Porosity Procedures Process Property Psoas Muscles Research Savings Shapes Sheep Site Solid Specific qualifier value Spinal Spinal Fusion Structure System Techniques Testing Time Translating Translations Transplantation United States National Institutes of Health Vascular Endothelial Growth Factors Vertebral column Viscosity Work allogenic bone transplantation base biodegradable polymer biomaterial compatibility bone bone morphogenetic protein 2 caprolactone catalyst clinically relevant controlled release craniofacial crosslink design first-in-human healing in vivo instrument maxillofacial mechanical properties member migration minimally invasive nano novel osteoinductive factor poly(propylene fumarate)pre-clinical programs reconstruction regenerative release factor repaired scaffold skeletal spine bone structure success three dimensional structure

项目摘要

Project Summary/Abstract Many clinical situations in musculoskeletal care, including spinal arthrodesis procedures, require a bone reconstruction strategy to treat contained defects (a hole in a bone), non-contained defects (a missing segment of bone), or fusion across bone generation spaces (where bone would not normally grow). Novel orthopaedic biomaterials that effect guided bone growth into biodegradable polymeric composite scaffolds are candidates to address such requirements, and the goal that has motivated the development of these materials is the augmentation and eventual elimination of current autograft and allograft bone strategies for transplantation into skeletal sites. For the past decade, our laboratory has done extensive work on three-dimensional (3-D) preformed bone scaffolds and transitioned them to clinically relevant large animal models for segmental bone defect repair. The current proposal focuses on the translation of our injectable and moldable bone scaffold work toward initial human use in spinal fusion via three integrated aims. In Aim 1, we will further optimize members of our suite of biocompatible, biodegradable, and self-crosslinkable fumarate ester polymeric biomaterial networks by inter-crosslinking of poly(propylene fumarate) (PPF) and poly(caprolactone) (PCL) via catalyst-free click chemistry (PPF/PCL). The network will incorporate osteoconductive nano-hydroxyapatite (nano-HA) and degradable hydrogel porogens that encapsulate vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2). The VEGF-containing hydrogel will degrade faster than the BMP- containing hydrogel to achieve dual, sequential delivery of angiogenic and osteoinductive factors coupled with two-stage porosity generation. The composite PPF/PCL formulations will be optimized separately for injectable and moldable bone scaffolds based on success criteria in rheological and handling properties, mechanical properties, porosity and interconnectivity, degradation rates, and growth factor release profiles. In Aim 2, we will determine the in vivo effect of the injectable and moldable PPF/PCL scaffold formulations in rabbit interbody and posterolateral spinal fusion models, respectively. Due to the fact that the gold standard, autograft bone, may incur donor site morbidity and can have a suboptimal fusion rate in some situations, spinal fusion is often considered one of the most challenging applications of bone graft substitutes, thus allowing us to critically evaluate the optimized candidate scaffold implant formulations. In Aim 3, we will assess the bone regeneration performance of PPF/PCL composite scaffolds in a large animal model of clinically relevant human surgical procedures as a translational step toward initial human use. We have selected a sheep unilateral posterior spine pedicle screw instrumented reconstruction model, consisting of either a posterior interbody fusion, a posterolateral intertransverse process fusion, or a combination of both these fusion processes at the same level, utilizing our injectable and moldable scaffold strategies to accomplish these goals.

项目摘要/摘要肌肉骨骼护理中的许多临床情况，包括脊柱关节固定程序，都需要骨头治疗包含缺陷的重建策略（骨骼中的一个孔），未牢固的缺陷（缺失段骨骼），或跨骨产生空间的融合（骨骼通常不会生长）。新颖的骨科将引导骨生长到可生物降解的聚合物复合支架的生物材料是候选者解决此类要求，以及促使这些材料开发的目标是增强和最终消除当前自体移植和同种异体骨策略以移植到骨骼部位。在过去的十年中，我们的实验室在三维（3-D）上做了广泛的工作预先形成的骨支架，并将其转变为临床上相关的大型动物模型缺陷维修。当前的提案着重于我们可注射和可塑的骨支架的翻译通过三个综合目的努力在脊柱融合中最初使用人类使用。在AIM 1中，我们将进一步优化我们的生物相容性，可生物降解和可自连接的富马酸酯聚合物聚合物的成员通过聚（富马酸丙二醇丙酸）（PPF）和聚（Caprolactone）（PCL）（PCL）的生物材料网络通过无催化剂点击化学（PPF/PCL）。该网络将结合骨导导式纳米羟基磷灰石（纳米-HA）和可降解的水凝胶孔，封装血管内皮生长因子（VEGF）和骨形态发生蛋白-2（BMP-2）。含VEGF的水凝胶的降解速度比BMP- 含有水凝胶以实现双重，顺序递送血管生成和骨诱导因子，并与两阶段的孔隙率产生。复合PPF/PCL公式将分别优化用于注射的基于流变学和处理特性的成功标准，机械性能标准的可塑骨支架性质，孔隙率和互连，降解速率和生长因子释放曲线。在AIM 2中，我们将确定兔子中可注射和可塑的PPF/PCL支架的体内效应室内和后外侧脊柱融合模型。由于黄金标准，自体移植骨骼，可能会产生供体部位的发病率，并且在某些情况下可能具有次优融合率，脊柱融合为通常被认为是骨移植替代品最具挑战性的应用之一，从而使我们批判性评估优化的候选支架植入物配方。在AIM 3中，我们将评估骨骼再生 PPF/PCL复合支架的性能在大型临床相关的人类手术模型中程序是迈向最初人类使用的转化步骤。我们选择了单侧绵羊脊柱椎弓根螺钉仪器重建模型，由后部室内融合组成后外侧跨跨过程融合，或两个在相同的融合过程的组合级别，利用我们的可注射和可塑的脚手架策略来实现这些目标。