Microengineered scaffolds carrying patient-specific cells and growth factors for treatment of volumetric muscle loss

携带患者特异性细胞和生长因子的微工程支架，用于治疗体积肌肉损失

• 批准号: 10254311
• 负责人: Ali Tamayol
• 金额: $ 36.31万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254311
• 关键词: 3-Dimensional; Address; Affect; Allogenic; Autologous; Biocompatible Materials; Biologic Characteristic; Biological; Biological Process; Biomimetics; Blood Platelets; Blood Vessels; Cells; Cicatrix; Clinic; Complex; Data; Disease; Down-Regulation; Economics; Elderly; Electrospinning; Engineering; Engraftment; Extracellular Matrix; Family suidae; Gelatin; Generations; Growth Factor; Human; Hydrogels; Immune response; Impairment; Implant; In Vitro; Infection; Injury; Lead; Mechanics; Modality; Morbidity - disease rate; Mus; Muscle; Muscle Fibers; Muscle function; Musculoskeletal; Musculoskeletal Diseases; Myopathy; Natural regeneration; Nude Mice; Operative Surgical Procedures; Pain; Patients; Peptides; Plasma; Polymers; Population; Procedures; Process; Production; Protocols documentation; Quality of life; Recovery of Function; Regenerative capacity; Secondary to; Signal Transduction; Site; Skeletal Muscle; Soldier; Surgical sutures; Testing; Therapeutic; Tissue Engineering; Tissue Grafts; Tissues; Traumatic injury; Treatment Factor; Vascularization; base; cell growth; cellular engineering; cost; disability; functional restoration; healing; implantation; improved; in vivo; induced pluripotent stem cell; injured; mechanical properties; mouse model; muscle engineering; muscle regeneration; muscle strength; muscular structure; musculoskeletal injury; myogenesis; nanofiber; nerve injury; novel strategies; physical property; poly(glycerol-sebacate); precursor cell; recruit; release factor; repaired; scaffold; social; stem cell growth; subcutaneous; two-dimensional; volumetric muscle loss

Project Summary/Abstract Traumatic and non-traumatic musculoskeletal disorders are responsible for substantial morbidity, pain and disability, affecting athletes, soldiers, active working people and elder population. This implies major social and economic hurdles, as musculoskeletal injuries represent a cost of $30 billion in U.S. each year. After injury, different therapeutic approaches are currently used in the clinics, including surgical application of autologous or allogeneic grafts. Nevertheless, complications are often associated to surgical repair including nerve injury, infection, scarring, limitations of tissue graft supply, concerns with immunological response and poor healing capacity of injured tissue. Indeed, natural healing and surgical procedures are inefficient in restoring functionality of injured muscles, resulting in a poor quality of life. Thus, a new paradigm for the treatment of musculoskeletal tissue damage is needed that can provide an effective, and long-term therapy for most patients. Here, we plan to engineer nanofibrous scaffolds with biomimetic mechanical properties that control- releases angiogenic and myogenic factors eluted through patient specific platelet-rich plasma (PRP). The nanofibrous scaffolds will be coated with a layer of hydrogel containing culture of induced pluripotent stem cells derived myogenic precursor cells (iPS-MPCs), which are expected to differentiate into highly organized myotubes. The accomplishment of the aims of this proposal will be a paradigm shift in engineering muscle tissues towards their use in treating muscular disorders and provides an effective and long-term therapy for most patients.

项目总结/摘要 创伤性和非创伤性肌肉骨骼疾病是造成大量发病率、疼痛和 残疾，影响到运动员、士兵、积极工作的人和老年人。这意味着重大的社会和 经济障碍，因为肌肉骨骼损伤代表美国每年300亿美元的成本。受伤后， 目前在临床上使用不同的治疗方法，包括自体或 同种异体移植然而，并发症通常与手术修复相关，包括神经损伤， 感染、瘢痕形成、组织移植物供应受限、免疫反应和愈合不良的问题 受伤组织的能力。事实上，自然愈合和外科手术在恢复方面效率低下。 受伤的肌肉功能，导致生活质量差。因此，一个新的范例，为治疗 肌肉骨骼组织损伤是必要的，可以提供一个有效的，长期的治疗， 患者在这里，我们计划设计具有仿生机械特性的纳米纤维支架， 释放通过患者特异性富血小板血浆（PRP）洗脱的血管生成和肌生成因子。的 纳米纤维支架将被一层含有诱导多能干细胞培养物的水凝胶覆盖 来源的肌源性前体细胞（iPS-MPC），预期其分化为高度组织化的 肌管这一建议的目标的实现将是工程肌肉的范式转变 本发明提供了一种用于治疗肌肉疾病的有效和长期的治疗方法， 大多数病人