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.

生物可降解压电骨再生支架 大面积骨骨折和骨缺损的重建是骨科手术的一大挑战。 自体或同种异体移植物的替代通常存在供应有限，供体部位发病， 感染或/和免疫排斥。再生工程策略，采用以下组合 因此，生物材料支架、干/成骨细胞和生长因子/小分子已经成为一种新的生物材料。 重要领域。 虽然骨生长因子和小分子是强大的，但它们的许多毒副作用需要一种有效的治疗方法。 刺激骨骼生长的新方法。电刺激（ES）是一种很好的替代方法， 电刺激器已经被用于治疗骨折。然而，电子设备仍然在与 局限性;虽然外部刺激不是很有效，但植入设备依赖于有毒和无毒的 可降解电池，需要侵入性移除手术。 压电材料是一组“智能”材料，可以在外力作用下发电， 提供引人注目的无电池刺激器，以电刺激骨骼生长。骨也是压电的， 自然在变形下，骨产生表面电荷，其驱动组织逆着所施加的力生长。 力因此，压电支架可以模拟天然骨接受机械载荷以诱导骨形成， 生长和再生。在这里，我们首次提出了一种新的生物可降解和生物相容性 PLLA（聚-L-丙交酯）压电纳米纤维支架，将接种干细胞， 受到来自超声波的声压，以产生有用的电荷，用于增强 骨再生我们将组装多层电纺压电PLLA薄膜， 采用脂肪干细胞（ASC）构建三维压电支架。因此，该项目有两个 主要具体目的：目的1是评估种植在3D可生物降解压电材料上的ASCs的成骨作用 聚乳酸支架在声压刺激下的体外降解。目标2是展示 我们构建的支架在声刺激下愈合小鼠的临界大小的颅骨/颅骨缺损， 压力 里程碑：1年后该项目的里程碑是找到合适的声学刺激， 证明了在我们的压电PLLA支架上接种的干细胞的骨生成增强， 体外2年后，该项目的里程碑是证明植入物上有显著的骨长入 压电PLLA支架修复小鼠颅骨缺损。由于电刺激适用于 多功能组织（如神经、肌肉、皮肤、软骨等），我们预计，拟议中的脚手架将成为一个 构建具有增强再生能力的不同工程组织的平台。