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).

摘要 我们的研究目标是开发一种具有生物活性的“自适应”形状记忆聚合物（SMP） 骨髓间充质干细胞联合支架修复局限性颅骨缺损 细胞（BMSCs）。自体移植物与长时间的收获程序、供体部位发病率以及 难以将移植物塑形和定位到缺损中。组织工程是一种有前途的选择， 需要一种目前未满足的需要-一种生物材料支架，其同时提供：（1）能够 保形地适合不规则缺损以增强骨整合，（2）生物活性，（3）骨诱导性 和（4）高度互连的孔和细胞迁移所必需的受控的生物降解性， 扩散和新组织积累，同时避免脆性机械性能。的意义和 这种方法的创新是一种新的“自适应”，聚多巴胺涂层SMP支架设计， 这些财产。由PI开发，建议的混合SMP支架由有机 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]。脚手架设计满足关键功能要求：（1）奥塞奥- 整合：由于其形状记忆行为，SMP支架将是“自适应的”， 通过短暂暴露于温盐水并锁定新的临时性假体， 在冷却到体温时成形。(2)生物活性和（3）骨诱导性：一种纳米细针，生物活性 将聚多巴胺涂层应用于SMP支架孔表面以支持祖细胞成骨 以及骨整合所必需的羟基磷灰石的形成。(4)互连孔，受控 生物可降解性和稳健的机械性能：SMP支架制造策略能够实现高 孔隙率和孔隙互连性，同时避免脆性机械行为。支架率 生物降解将由无机链段类型（即PDMS或PSE）和分子量（Mn）（即， 交联密度）。SMP支架的愈合潜力将在一个临界大小的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。 该小组由拟议工作所有关键领域的专家组成。Melissa Grunlan教授（PI）将 致力于制备聚多巴胺涂层SMP支架和未涂层对照（目标1-3）。Mariah教授 Hahn（Co-I）将领导体外组织工程研究，将大鼠和人BMSC纳入组织工程。 支架（目标2）。Brian Saunders教授（Co-I）将在大鼠颅骨缺损处植入细胞负载支架（Aim （3）第三章。Michael Moreno教授将致力于研究支架，天然组织和 骨移植结构（目标1-3）。将通过组织学/免疫组织化学评价愈合（Roy教授 Pool和Saunders，Co-Is）、微型CT（Saunders）和生物力学测试（Moreno）。输入将由 两名颅面整形外科医生，雷蒙德·哈什巴格和凯文·霍普金斯（顾问）。