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.

用于骨再生的可生物降解压电支架 大面积骨折和缺损的重建仍然是骨科手术中的一大挑战。 替代自体或同种异体移植物通常会遇到供应有限、供体部位发病率、 感染或/和免疫排斥，采用组合的再生工程策略。 因此，生物材料支架、干/成骨细胞和生长因子/小分子已成为一种 重要领域。 尽管骨生长因子和小分子很强大，但它们的许多毒副作用需要 刺激骨骼生长的新方法 电刺激 (ES) 是一种很好的替代方法。 电刺激器已被用于治疗骨折，但是，电刺激器仍然存在一些问题。 局限性；虽然外部刺激器不是很有效，但植入设备依赖于有毒和非 可降解电池，需要进行侵入性切除手术。 压电材料是一组可以在外力作用下发电的“智能”材料， 提供引人注目的无电池刺激器来电刺激骨骼生长。骨骼也是压电的。 在变形的情况下，骨骼会产生表面电荷，从而驱动组织逆着所施加的力生长。 因此，压电支架可以模仿天然骨接受机械载荷以诱导骨。 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。 PLLA（聚左旋丙交酯）压电纳米纤维支架，将接种干细胞和 受到超声波声压的作用，产生有用的电荷，以增强 我们将组装多层静电纺压电 PLLA 纳米纤维薄膜并进行骨再生。 利用脂肪干细胞（ASC）构建3D压电支架因此，该项目有两个。 主要具体目标；目标 1 是评估接种在 3D 可生物降解压电材料上的 ASC 的成骨作用 PLLA 纳米纤维支架在体外声压刺激下的用途。 我们构建的支架可在声学刺激下治愈小鼠临界尺寸的颅骨/颅骨缺损 压力。 里程碑：一年后这个项目的里程碑是找到合适的声学刺激和 证明了接种在我们的压电 PLLA 支架上的干细胞增强的成骨作用， 两年后，该项目的里程碑是证明了植入后骨的显着向内生长。 压电 PLLA 支架可治愈小鼠颅骨缺损，因为电刺激适用于该支架。 多功能组织（例如神经、肌肉、皮肤、软骨等），我们预计所提出的支架将成为 平台构建具有增强再生能力的不同工程组织。