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一种具有生物活性的“自贴合”形状记忆聚合物（SMP） 通过相关骨髓间充质干细胞修复局限性颅骨缺损的支架 自体移植物与冗长的收获程序、供体部位发病率以及相关。 组织工程是一种有前途的替代方案，但在将移植物成形和定位到缺损处方面存在困难。 需要一种目前尚未满足的需求——一种生物材料支架，它同时提供：（1）能够 适形地贴合不规则缺损以增强骨整合，(2) 生物活性，(3) 骨诱导性 (4) 细胞迁移、营养物质所需的高度互连的孔隙和受控的生物降解性 扩散和新组织积累，同时避免脆性机械性能的意义和。 这种方法的创新之处在于一种新的“自装配”、聚多巴胺涂层的 SMP 支架设计，可实现所有 由 PI 开发的混合 SMP 支架由有机材料组成。 链段[聚(ε-己内酯)，PCL]和无机含硅链段[聚二甲基硅氧烷， PDMS 或聚（甲硅烷基醚），PSE]。支架设计满足关键功能要求：（1）Osseo-。 集成：SMP 支架由于其形状记忆行为而将“自我拟合”，从而使 通过短暂暴露于温盐水中并锁定新的临时材料，保形贴合到不规则缺损处 冷却至体温后形状（2）生物活性和（3）骨诱导性：纳米厚的生物活性。 聚多巴胺涂层将应用于 SMP 支架孔表面以支持祖细胞成骨 (4) 相互连通的孔隙，受控 生物降解性和稳健的机械性能：SMP 支架制造策略可实现高 孔隙率和孔隙互连性，同时避免脆性机械行为。 生物降解将由无机链段类型（即 PDMS 或 PSE）和分子量 (Mn)（即 SMP 支架的愈合潜力将在临界尺寸大鼠颅骨模型中进行评估。 使用组织学测试、显微 CT 和生物力学测试。 该团队由 Melissa Grunlan 教授（PI）的所有关键领域的专家组成。 导致制备聚多巴胺涂层的 SMP 支架和未涂层的对照（目标 1-3）。 Hahn (Co-I) 将领导体外组织工程研究，将大鼠和人类 BMSC 纳入 Brian Saunders 教授（Co-I）将把充满细胞的支架植入大鼠颅骨缺损中（目标 2）。 3) Michael Moreno 教授将领导支架、天然组织和生物力学特性的研究。 骨移植结构（目标 1-3）将通过组织学/免疫组织化学进行评估（Roy 教授）。 Pool 和 Saunders，Co-Is）、微型 CT（Saunders）和生物力学测试（Moreno）将提供。 两位颅面整形外科医生，雷蒙德·哈什巴格 (Raymond Harshbarger) 博士和凯文·霍普金斯 (Kevin Hopkins) 博士（顾问）。