Incorporation of decellularized-ECM in graphene-based scaffolds enhances axonal outgrowth and branching in neuro-muscular co-cultures.

IF 2.6 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Science Progress Pub Date : 2024-07-01 DOI:10.1177/00368504241281469
Carlos Serna, Kirtana Sandepudi, Rebecca L Keate, Sophia L Zhang, Kristen Y Cotton, Alberto De La Isla, Matias Murillo, Yasmine Bouricha, Andrea A Domenighetti, Colin K Franz, Sumanas W Jordan
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Abstract

Peripheral nerve and large-scale muscle injuries result in significant disability, necessitating the development of biomaterials that can restore functional deficits by promoting tissue regrowth in an electroactive environment. Among these materials, graphene is favored for its high conductivity, but its low bioactivity requires enhancement through biomimetic components. In this study, we extrusion printed graphene-poly(lactide-co-glycolide) (graphene) lattice scaffolds, aiming to increase bioactivity by incorporating decellularized extracellular matrix (dECM) derived from mouse pup skeletal muscle. We first evaluated these scaffolds using human-induced pluripotent stem cell (hiPSC)-derived motor neurons co-cultured with supportive glia, observing significant improvements in axon outgrowth. Next, we tested the scaffolds with C2C12 mouse and human primary myoblasts, finding no significant differences in myotube formation between dECM-graphene and graphene scaffolds. Finally, using a more complex hiPSC-derived 3D motor neuron spheroid model co-cultured with human myoblasts, we demonstrated that dECM-graphene scaffolds significantly improved axonal expansion towards peripheral myoblasts and increased axonal network density compared to graphene-only scaffolds. Features of early neuromuscular junction formation were identified near neuromuscular interfaces in both scaffold types. These findings suggest that dECM-graphene scaffolds are promising candidates for enhancing neuromuscular regeneration, offering robust support for the growth and development of diverse neuromuscular tissues.

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在石墨烯基支架中加入脱细胞ECM可增强神经-肌肉共培养物中轴突的生长和分支。
周围神经和大面积肌肉损伤会导致严重残疾,因此有必要开发生物材料,通过在电活性环境中促进组织再生来恢复功能缺陷。在这些材料中,石墨烯因其高导电性而受到青睐,但其生物活性较低,需要通过生物仿生成分来增强其生物活性。在这项研究中,我们挤压打印了石墨烯-聚(乳糖-共聚乙二醇)(石墨烯)晶格支架,旨在通过加入从小鼠幼崽骨骼肌中提取的脱细胞细胞外基质(dECM)来提高生物活性。我们首先使用人类诱导多能干细胞(hiPSC)衍生的运动神经元与支持性胶质细胞共同培养的方法对这些支架进行了评估,观察到轴突生长有了显著改善。接着,我们用 C2C12 小鼠和人类原发性肌母细胞对支架进行了测试,发现 dECM 石墨烯和石墨烯支架在肌管形成方面没有明显差异。最后,我们使用一个更复杂的源自 hiPSC 的三维运动神经元球体模型与人类肌母细胞共同培养,结果表明与纯石墨烯支架相比,dECM-石墨烯支架显著改善了轴突向外周肌母细胞的扩展,并增加了轴突网络密度。在两种支架类型的神经肌肉界面附近都发现了早期神经肌肉接头形成的特征。这些研究结果表明,dECM-石墨烯支架是增强神经肌肉再生的理想候选材料,可为各种神经肌肉组织的生长和发育提供强有力的支持。
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来源期刊
Science Progress
Science Progress Multidisciplinary-Multidisciplinary
CiteScore
3.80
自引率
0.00%
发文量
119
期刊介绍: Science Progress has for over 100 years been a highly regarded review publication in science, technology and medicine. Its objective is to excite the readers'' interest in areas with which they may not be fully familiar but which could facilitate their interest, or even activity, in a cognate field.
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