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

项目摘要/摘要 创伤性和非创伤性肌肉骨骼疾病是导致大量发病率、疼痛和 残疾，影响到运动员、士兵、在职工作人员和老年人口。这意味着主要的社会和 经济障碍，因为肌肉骨骼损伤在美国每年造成300亿美元的损失。受伤后， 目前临床上使用不同的治疗方法，包括手术应用自体或 同种异体移植。然而，并发症往往与手术修复有关，包括神经损伤， 感染、疤痕形成、组织移植物供应受限、担心免疫反应和愈合不良 损伤组织的容量。事实上，自然愈合和外科手术在修复方面效率低下。 肌肉功能受损，导致生活质量不佳。因此，一种新的治疗模式 需要肌肉骨骼组织损伤，以提供有效的、长期的治疗 病人。在这里，我们计划设计具有仿生机械性能的纳米纤维支架，以控制- 通过患者特定的富血小板血浆(PRP)释放血管生成因子和肌肉生成因子。这个 纳米纤维支架将覆盖一层含有诱导多能干细胞培养的水凝胶层 衍生成肌前体细胞(iPS-MPC)，有望分化为高度组织化 肌管。这一提案目标的实现将是工程学领域的一次范式转变 组织用于治疗肌肉疾病，并提供了一种有效的长期治疗 大多数病人。

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.