Biodegradable Piezoelectric Scaffold for Bone regeneration

用于骨再生的可生物降解压电支架

• 批准号: 9913470
• 负责人: Thanh Nguyen
• 金额: $ 21.22万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913470
• 关键词: 3-Dimensional; Acoustic Stimulation; Acoustics; Adhesives; Adipose tissue; Alginates; Area; Biocompatible Materials; Biological Assay; Bone Growth; Bone Regeneration; Bone Transplantation; Caliber; Calvaria; Cartilage; Cell Proliferation; Cell Survival; Cells; Charge; Chemicals; Clinical; Control Groups; Defect; Devices; Electric Stimulation; Electricity; Elements; Engineering; Excision; FDA approved; Film; Fracture; Future; Gene Proteins; Goals; Growth Factor; Histologic; Hydrogels; Immune; Implant; In Vitro; Infection; Mechanics; Medical; Methods; Morbidity - disease rate; Mus; Muscle; Natural regeneration; Nature; Nerve; Operative Surgical Procedures; Orthopedic Surgery procedures; Osteogenesis; Performance; Polymers; Process; Proteins; Reporting; Research Personnel; Roentgen Rays; Seeds; Site; Skin; Stains; Surface; Testing; Thick; Time; Tissue Engineering; Tissues; Ultrasonography; absorption; base; biomaterial compatibility; bone; bone engineering; bone growth factor; bone healing; cell growth; comparison group; cranium; design; healing; implantable device; in vivo; mechanical load; microCT; mineralization; mouse model; nanofiber; novel; novel strategies; osteogenic; placebo group; poly-L-lactic acid; polyvinylidene fluoride; pressure; protein expression; reconstruction; regenerative; repaired; response; scaffold; side effect; small molecule; stem; stem cell differentiation; stem cells; tissue support frame

Biodegradable Piezoelectric Scaffold for Bone Regeneration Reconstruction of large bone fractures and defects remains a big challenge in orthopaedic surgery. Replacement auto- or allo-grafts usually suffer from the problems of limited supply, donor site morbidity, infection or/and immune-rejection. Regenerative engineering strategies, employing a combination of biomaterial scaffolds, stem/osteogenic cells and growth factors/small molecules, has therefore emerged as an important area. Although bone growth factors and small molecules are powerful, many of their toxic side-effects demand for a new approach to stimulate bone growth. Electrical stimulation (ES) is an excellent alternative and many electrical stimulators have been used to treat bone fractures. However, the electrical devices still struggle with limitations; while external stimulators are not very effective, implanted devices rely on toxic and non- degradable batteries, requiring invasive removal surgery. Piezoelectric materials, a group of “smart” materials which can generate electricity under applied force, might offer compelling battery-less stimulators to electrically stimulate bone growth. Bone is also piezoelectric in nature. Under deformation, bone generates surface charge, which drives the tissue to grow against the applied force. A piezoelectric scaffold can therefore mimic natural bone in receiving mechanical loading to induce bone growth and regeneration. Here we propose for the first time a novel biodegradable and biocompatible scaffold of piezoelectric nanofibers of PLLA (Poly-L-lactide), which will be seeded with stem cells and subjected to acoustic pressure from ultrasound, to generate useful electrical charge for enhanced bone regeneration. We will assemble multiple layers of electrospun piezoelectric PLLA nanofiber films and employ adipose stem cells (ASCs) to construct the 3D piezoelectric scaffold. Accordingly, the project has two main specific aims; Aim 1 is to assess osteogenesis from ASCs seeded on the 3D biodegradable piezoelectric PLLA nanofiber scaffold under stimulation of acoustic pressure in vitro. And Aim 2 is to demonstrate the use of our constructed scaffold to heal critical-sized calvarial/skull defects in mice under stimulation of acoustic pressure. Milestone: The milestone of this project after 1 year is to find out suitable acoustic stimulation and demonstrate an enhanced osteogenesis from the stem-cells, seeded on our piezoelectric PLLA scaffold, in vitro. After 2 years, the milestone of this project is to demonstrate a significant bone ingrowth on implanted piezoelectric PLLA scaffolds to heal the calvarial defects in mice. As electrical stimulation is applicable to versatile tissues (e.g. nerve, muscle, skin, cartilage etc.), we anticipate the proposed scaffold will become a platform to construct different engineered tissues with an enhanced regenerative capability.

可生物降解的压电支架用于骨再生 大骨骨折和缺陷的重建仍然是骨科手术的巨大挑战。 替换自动或同层移植物通常遭受供应有限，供体现场发病率的问题， 感染或/和免疫反应。再生工程策略，采用 因此，生物材料支架，茎/成骨细胞和生长因子/小分子已成为一种 重要区域。 尽管骨骼生长因子和小分子很强大，但它们的许多有毒副作用都需要 刺激骨骼生长的新方法。电气模拟（ES）是一个很好的选择，许多 电刺激剂已用于治疗骨折。但是，电动设备仍在努力 限制；虽然外部刺激器不是很有效，但植入的设备依赖于有毒和非 - 可降解的电池，需要侵入性去除手术。 压电材料是一组“智能”材料，可以在施加力下发电，可能 提供引人注目的无电池刺激器以电刺激骨骼生长。骨头也是压电 自然。在变形下，骨会产生表面电荷，这驱动组织在施加的 力量。因此 生长和再生。在这里，我们首次提出了一种新型的可生物降解和生物相容性的 PLLA的压电纳米纤维的支架（聚-L-乳酸），该纳米纤维将与干细胞和 受到超声的声压力，以产生有用的电荷以增强 骨再生。我们将组装多层的电纺压力电气PLLA纳米纤维膜和 员工脂肪干细胞（ASC）构建3D压电支架。彼此之间，该项目有两个 主要目的； AIM 1是评估从3D可生物降解压电上种子的ASCS的骨气作用 在体外刺激声压力下，PLLA纳米纤维支架。目标2是证明使用 我们在刺激声的小鼠中构造的脚手架，以治愈小鼠的关键尺寸颅骨/颅骨缺陷 压力。 里程碑：1年后，该项目的里程碑是找出合适的声学刺激和 在我们的压电PLLA支架上展示了茎细胞的增强的成骨作用，在 体外。 2年后，该项目的里程碑是在植入的 压电PLLA脚手架可以治愈小鼠的颅缺陷。由于电刺激适用于 多才多艺的组织（例如神经，肌肉，皮肤，软骨等），我们预计所提出的脚手架将成为一个 构造具有增强能力的不同工程组织的平台。