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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.

项目总结/文摘