Bioactive, "Self-fitting" Shape Memory Polymer (SMP) Scaffolds to Treat Cranial Bone Defects

生物活性“自贴合”形状记忆聚合物 (SMP) 支架可治疗颅骨缺损

• 批准号: 9240216
• 负责人: Melissa Grunlan
• 金额: $ 38.8万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9240216
• 关键词: Address; Allografting; Animal Model; Animals; Area; Autologous; Autologous Transplantation; Behavior; Biocompatible Materials; Biodegradation; Biomechanics; Body Temperature; Bone Marrow; Bone Regeneration; Bone Substitutes; Bone Tissue; Bone Transplantation; Calvaria; Cell Adhesion; Cell Differentiation process; Cell Separation; Cells; Cephalic; Clinical; Complication; Defect; Deposition; Development; Diffusion; Engineering; Ethers; Evaluation; Exposure to; Extracellular Matrix; Formulation; Future; Goals; Gold; HA coating; Harvest; Histologic; Histology; Human; Hybrids; Hydroxyapatites; Immunohistochemistry; Implant; In Vitro; Infiltration; Investigation; Lead; Marrow; Melissa; Memory; Mesenchymal; Mesenchymal Stem Cells; Modeling; Modulus; Molecular Weight; Morbidity - disease rate; Nature; Nutrient; Operative Surgical Procedures; Osseointegration; Osteoblasts; Osteogenesis; Plastic Surgeon; Polymers; Porosity; Positioning Attribute; Procedures; Property; Rattus; Research; Saline; Shapes; Silicon; Site; Stem cells; Surface; Testing; Thick; Tissue Engineering; Tissues; Work; base; biomaterial compatibility; bone; bone cell; bone healing; caprolactone; cell motility; craniofacial; crosslink; density; design; healing; in vivo; innovation; mechanical behavior; mechanical properties; member; microCT; mineralization; nanoscale; osteogenic; polydimethylsiloxane; regenerative; repaired; scaffold; tissue regeneration

ABSTRACT Our research goal is the development of a bioactive, “self-fitting” shape memory polymer (SMP) scaffold to repair confined cranial defects by associated bone marrow-derived mesenchymal stem cells (BMSCs). Autografts are associated with lengthy harvesting procedures, donor site morbidity as well as difficulties in shaping and positioning the graft into the defect. Tissue engineering is a promising alternative but requires a currently unmet need - a biomaterial scaffold which simultaneously provides: (1) the ability to conformally fit into an irregular defect to enhance osseointegration, (2) bioactivity, (3) osteoinductivity and (4) highly interconnected pores and controlled biodegradability necessary for cell migration, nutrient diffusion and neotissue accumulation while avoiding brittle mechanical properties. The significance and innovation of this approach is a new “self-fitting”, polydopamine-coated SMP scaffold design that achieves all of these properties. Developed by the PI, the proposed hybrid SMP scaffolds are comprised of an organic segment [poly(ε-caprolactone), PCL] and an inorganic silicon-containing segment [polydimethylsiloxane, PDMS or poly(silyl ether), PSE]. The scaffold design meets key functional requirements: (1) Osseo- integration: The SMP scaffold will be “self-fitting” as a result of its shape memory behavior, enabling conformal fitting into an irregular defect by brief exposure to warm saline and locking of the new temporary shape upon cooling to body temperature. (2) Bioactivity and (3) Osteoinductivity: A nanothick, bioactive polydopamine coating will be applied to the SMP scaffold pore surfaces to support progenitor cell osteogenesis as well the formation of hydroxyapatite necessary for osseointegration. (4) Interconnected Pores, Controlled Biodegradability, and Robust Mechanical Properties: The SMP scaffold fabrication strategy enables high porosities and pore interconnectivity while avoiding brittle mechanical behavior. The rate of scaffold biodegradation will be controlled by inorganic segment type (i.e. PDMS or PSE) and molecular weight (Mn) (i.e. crosslink density). The healing potential of SMP scaffolds will be evaluated in a critical size-rat calvarial model using histological testing, micro-CT and biomechanical testing. The team is comprised of experts in all key areas of the proposed work. Prof. Melissa Grunlan (PI) will lead efforts to prepare polydopamine-coated SMP scaffolds and uncoated controls (Aims 1-3). Prof. Mariah Hahn (Co-I) will lead in vitro tissue engineering studies with rat- and human-BMSCs incorporated into the scaffolds (Aim 2). Prof. Brian Saunders (Co-I) will implant cell-laden scaffolds into rat calvarial defects (Aim 3). Prof. Michael Moreno will lead efforts to study biomechanical properties of scaffolds, native tissues and bone-graft constructs (Aims 1-3). Healing will be evaluated by histology/immunohistochemistry (Prof. Roy Pool and Saunders, Co-Is), micro-CT (Saunders) and biomechanical tests (Moreno). Input will be provided by two craniofacial plastic surgeons, Drs. Raymond Harshbarger and Kevin Hopkins (consultants).

抽象的 我们的研究目标是开发生物活性的“自配合”形状记忆聚合物（SMP） 通过相关的骨髓衍生的间充质茎来修复狭窄的颅骨缺损的脚手架 细胞（BMSC）。自体移植与冗长的收获程序，供体部位的发病率以及 将草塑形和定位为缺陷的困难。组织工程是一种承诺的替代品，但 需要目前未满足的需求 - 一个仅提供的生物材料支架：（1） 共形适合不规则的缺陷以增强骨整合，（2）生物活性，（3）骨诱导性 （4）细胞迁移所需的高度相互连接的孔和受控的生物降解性，营养素 扩散和新动物的积累，同时避免脆弱的机械性能。意义和 这种方法的创新是一种新的“自构”，多胺涂层的SMP脚手架设计，可实现所有目标 这些属性。由PI开发，提出的杂种SMP支架是有机的 段[poly（ε-辅助酮），PCL]和含无机硅的段[聚二甲基硅氧烷， PDMS或Poly（Silyl Ether），PSE]。脚手架设计符合关键功能要求：（1）Osseo- 集成：SMP脚手架将由于其形状记忆行为而成为“自构” 短暂暴露于温暖的盐水和新临时性的锁定中，将结合拟合到不规则的缺陷中 冷却至体温后形状。 （2）生物活性和（3）骨诱导：一种纳米，生物活性 聚多巴胺涂层将应用于SMP支架孔表面以支持祖细胞成骨的发生 以及骨整合所需的羟基磷灰石的形成。 （4）互连的孔，受控 生物降解性和鲁棒机械性能：SMP脚手架制造策略可实现高 孔隙率和孔相互连接，同时避免了脆弱的机械行为。脚手架的速度 生物降解将由无机段类型（即PDMS或PSE）和分子量（MN）控制（即 交联密度）。 SMP脚手架的愈合潜力将在临界尺寸鼠标模型中评估 使用组织学测试，微CT和生物力学测试。 该团队已完成拟议工作的所有关键领域的专家。 Melissa Grunlan教授（PI）将 领先的努力来制备涂有多巴胺的SMP支架和未涂层的对照（AIMS 1-3）。玛丽亚教授 Hahn（Co-​​I）将通过纳入大鼠和人类-BMSC进行体外组织工程研究 脚手架（目标2）。布莱恩·桑德斯（Brian Saunders）教授（CO-I）将植入含细胞的支架植入大鼠钙毛线缺陷中（AIM 3）。迈克尔·莫雷诺（Michael Moreno）教授将领导研究脚手架，天然组织和 骨移植构建体（目标1-3）。愈合将通过组织学/免疫组织化学评估（Roy教授 游泳池和桑德斯，Co-IS），Micro-CT（Saunders）和生物力学测试（Moreno）。输入将由 两名颅面整形外科医生，博士。 Raymond Harshbarger和Kevin Hopkins（顾问）。