Skeletal Muscle Engineering for the Craniofacial Region

颅面区域骨骼肌工程

• 批准号: 10185671
• 负责人: Rishma Shah
• 金额: $ 41.62万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-03 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10185671
• 关键词: 3-Dimensional; 3D Print; Address; American; Appearance; Area; Autologous; Beauty; Biological; Biological Models; Biomedical Engineering; Biomimetics; Bioreactors; Bone Tissue; Cell Differentiation process; Cell Proliferation; Cells; Characteristics; Cheek structure; Climacteric; Cosmetics; Craniofacial Abnormalities; Custom; Defect; Development; Elements; Engineering; Extracellular Matrix; Face; Failure; Family suidae; Fatty acid glycerol esters; Filler; Financial Hardship; GDF8 gene; Goals; Growth Factor; Healthcare; Human; Human body; Hypertrophy; Implant; In Vitro; Individual; Injury; Insulin Antagonists; Insulin-Like Growth Factor I; Knowledge; Masseter Muscle; Mechanical Stimulation; Metabolic; Morphology; Mus; Muscle; Muscle Cells; Muscle Development; Muscle Fibers; Muscle satellite cell; Natural regeneration; Outcome; Patients; Population; Printing; Procedures; Property; Quality of life; Research; Resources; Skeletal Muscle; Societies; Structure; Supplementation; Surgeon; Surgical Flaps; Technology; Testing; Time; Tissue Engineering; Tissues; Vision; Work; barium chloride; cell behavior; craniofacial; craniofacial tissue; expectation; facial disfigurement; implantation; improved; in vivo; innovation; mechanical load; mechanical properties; muscle engineering; muscle form; muscle regeneration; muscular structure; novel; patient subsets; personalized approach; porcine model; postnatal; quadriceps muscle; reconstruction; regenerative; repaired; response; restoration; satellite cell; scaffold; skeletal; soft tissue; stem; subcutaneous; tissue reconstruction; translational model

PROJECT SUMMARY/ABSTRACT Facial disfigurement can have devastating effects on one’s quality of life. Approximately 0.26 million Americans per annum have reconstructive procedures, such as the use of tissue flaps, to correct congenital and acquired craniofacial defects. Management of large volumetric craniofacial muscle tissue defects remains a challenge. Up to one quarter of patients have repeat procedures due to flap failure, tissue rejection and limited availability of tissue; and there remains a subset of patients for whom treatment completely fails resulting in continued facial disfigurement, financial burden and challenges with societal integration. The ability to generate craniofacial muscle tissue containing the patient’s own cells would provide a more predictable, life-changing treatment for a serious problem. Previous work has demonstrated the importance of craniofacial muscle- derived cells and scaffolds for engineering the craniofacial skeletal muscles. The project proposes to engineer craniofacial muscle tissue by seeding 3-D printed biomimetic scaffolds with porcine craniofacial muscle-derived cells. The goals are to (1) generate new knowledge on the use of craniofacial muscle-derived cell populations for the formation of muscle tissue; (2) produce 3-D biomimetic scaffolds to support craniofacial muscle development; (3) bioengineer craniofacial muscle tissue for implantation. The vision is that permanent restoration of craniofacial soft tissue defects can be achieved by implantation of precision-engineered autologous craniofacial skeletal muscle tissue. The hypothesis is that successful craniofacial muscle tissue engineering applications will incorporate autologous craniofacial skeletal muscle-derived cells, 3-D printed biomimetic scaffolds, application of mechanical load and insulin-like growth factor 1 (IGF-1), a growth factor important for muscle cell proliferation and differentiation. The approach is to enrich porcine craniofacial muscle-derived cell populations with muscle stem cells (satellite cells) responsible for regeneration. The cells will be seeded into 3-D printed biomimetic scaffolds and subjected to load and IGF- 1 to improve regeneration and promote muscle fiber hypertrophy leading to a tissue suitable for implantation into the craniofacial region. Aim 1 is to produce 3-D printed biomimetic scaffolds and assess response of an enriched porcine craniofacial muscle-derived cell population within the scaffolds. Aim 2 is to determine response of engineered porcine craniofacial skeletal muscle tissue to mechanical stimulation and IGF-1 delivered within customized bioreactors. Aim 3 is to determine the regenerative capability of engineered porcine craniofacial skeletal muscle tissue in vitro and in vivo. This project ultimately aims to produce a functional craniofacial tissue for restoration of craniofacial soft tissue defects through the combination of three innovative elements: (1) craniofacial muscle-derived cell populations; (2) 3-D printed biomimetic scaffolds; (3) application of external factors (mechanical load and IGF-1). The outcomes of the proposed research will broadly impact skeletal muscle engineering applications for the entire human body.

项目概要/摘要 面部畸形会对一个人的生活质量产生毁灭性影响。大约 26 万美国人 每年进行重建手术，例如使用组织瓣，以纠正先天性和后天性 颅面缺陷。大体积颅面肌肉组织缺陷的处理仍然是一个挑战。 由于皮瓣失败、组织排斥和可用性有限，多达四分之一的患者需要重复手术 组织；仍然有一小部分患者的治疗完全失败，导致持续的 面部畸形、经济负担和社会融合的挑战。生成能力 含有患者自身细胞的颅面肌组织将提供更可预测的、改变生活的 治疗严重问题。先前的工作已经证明了颅面肌肉的重要性 用于工程颅面骨骼肌的衍生细胞和支架。 该项目建议通过在 3D 打印仿生支架上植入 3D 打印的仿生支架来设计颅面肌肉组织 猪颅面肌来源的细胞。目标是（1）产生关于使用的新知识 用于形成肌肉组织的颅面肌来源的细胞群； (2) 制作3D仿生 支持颅面肌肉发育的支架； (3)生物工程颅面肌组织 植入。愿景是通过以下方式实现颅面软组织缺损的永久修复： 植入精密设计的自体颅面骨骼肌组织。假设是 成功的颅面肌组织工程应用将结合自体颅面骨骼 肌肉源性细胞、3D 打印仿生支架、机械负载的应用和胰岛素样生长 因子 1 (IGF-1)，一种对肌肉细胞增殖和分化很重要的生长因子。方法是 丰富猪颅面肌来源的细胞群，其中肌肉干细胞（卫星细胞）负责 用于再生。这些细胞将被植入 3D 打印的仿生支架中，并承受负载和 IGF- 1 改善再生并促进肌纤维肥大，形成适合植入的组织 进入颅面部区域。目标 1 是生产 3D 打印仿生支架并评估 支架内富集的猪颅面肌来源的细胞群。目标 2 是确定 工程猪颅面骨骼肌组织对机械刺激和 IGF-1 的反应 在定制的生物反应器中交付。目标 3 是确定工程的再生能力 猪颅面骨骼肌组织的体外和体内。该项目的最终目标是生产一个 功能性颅面部组织通过三者结合修复颅面部软组织缺损 创新要素：（1）颅面肌源性细胞群； (2) 3D打印仿生支架； (3) 外部因素（机械负荷和 IGF-1）的应用。拟议研究的结果将 广泛影响整个人体的骨骼肌工程应用。