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从二维肌管培养到三维工程化骨骼肌构建体:体外骨骼肌模型及疾病建模应用的全面综述

From 2D Myotube Cultures to 3D Engineered Skeletal Muscle Constructs: A Comprehensive Review of In Vitro Skeletal Muscle Models and Disease Modeling Applications.

作者信息

Cao Tianxin, Warren Curtis R

机构信息

Cardiovascular-Renal-Metabolic Diseases Research Department, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.

出版信息

Cells. 2025 Jun 11;14(12):882. doi: 10.3390/cells14120882.


DOI:10.3390/cells14120882
PMID:40558510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12191219/
Abstract

In recent years, the field of skeletal muscle tissue engineering has experienced significant advancements, evolving from traditional two-dimensional (2D) cell cultures to increasingly sophisticated three-dimensional (3D) engineered constructs. While 2D models have provided foundational insights into muscle cell biology, emerging 3D platforms aim to better recapitulate the complex native muscle environment, including mature muscle fibers, supportive vasculature, and native-like extracellular matrix (ECM) composition. Here, we provide a comprehensive review of current in vitro skeletal muscle models, detailing their design principles, structure, and functionalities as well as the advantages and limitations inherent to each approach. We put a special emphasis on 3D engineered muscle tissues (EMTs) developed through advanced bioengineering strategies and note that design criteria such as scaffold selection, perfusion system incorporation, and co-culture with supporting cell types have significantly enhanced tissue maturity and complexity. Lastly, we explore the application of these engineered models to disease studies, highlighting models of both mendelian muscle disorders and common polygenic diseases and the potential of these platforms for drug discovery and regenerative therapies. Although an ideal in vitro model that fully recapitulates native muscular architecture, vascularization, and ECM complexity is yet to be realized, we identify current challenges and propose future directions for advancing these bioengineered systems. By integrating fundamental design criteria with emerging technologies, this review provides a roadmap for next-generation skeletal muscle models poised to deepen our understanding of muscle biology and accelerate therapeutic innovation.

摘要

近年来,骨骼肌组织工程领域取得了重大进展,从传统的二维(2D)细胞培养发展到日益复杂的三维(3D)工程构建体。虽然二维模型为肌肉细胞生物学提供了基础见解,但新兴的三维平台旨在更好地模拟复杂的天然肌肉环境,包括成熟的肌纤维、支持性脉管系统和类似天然的细胞外基质(ECM)组成。在此,我们对当前的体外骨骼肌模型进行全面综述,详细介绍它们的设计原则、结构和功能,以及每种方法固有的优缺点。我们特别强调通过先进生物工程策略开发的三维工程肌肉组织(EMT),并指出诸如支架选择、灌注系统整合以及与支持细胞类型共培养等设计标准显著提高了组织的成熟度和复杂性。最后,我们探讨这些工程模型在疾病研究中的应用,重点介绍孟德尔肌肉疾病和常见多基因疾病的模型,以及这些平台在药物发现和再生治疗方面的潜力。尽管尚未实现完全模拟天然肌肉结构、血管化和ECM复杂性的理想体外模型,但我们确定了当前的挑战,并提出了推进这些生物工程系统的未来方向。通过将基本设计标准与新兴技术相结合,本综述为下一代骨骼肌模型提供了路线图,有望加深我们对肌肉生物学的理解并加速治疗创新。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b9/12191219/b77754e5134c/cells-14-00882-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b9/12191219/b77754e5134c/cells-14-00882-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6b9/12191219/b77754e5134c/cells-14-00882-g001.jpg

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本文引用的文献

[1]
iPSC-derived cardiomyocytes and engineered heart tissues reveal suppressed JAK2/STAT3 signaling in LMNA-related emery-dreifuss muscular dystrophy.

Redox Biol. 2025-6

[2]
Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss.

NPJ Regen Med. 2025-3-1

[3]
An automated platform for simultaneous, longitudinal analysis of engineered neuromuscular tissues for applications in neurotoxin potency testing.

Curr Res Toxicol. 2025-1-26

[4]
Development of 3D Muscle Cell Culture-Based Screening System for Metabolic Syndrome Drug Research.

Tissue Eng Part C Methods. 2025-2

[5]
Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.

Brain. 2025-5-13

[6]
3D-environment and muscle contraction regulate the heterogeneity of myonuclei.

Skelet Muscle. 2024-11-11

[7]
Mechanical Stimulation and Aligned Poly(ε-caprolactone)-Gelatin Electrospun Scaffolds Promote Skeletal Muscle Regeneration.

ACS Appl Bio Mater. 2024-10-21

[8]
Bioengineered Model of Human LGMD2B Skeletal Muscle Reveals Roles of Intracellular Calcium Overload in Contractile and Metabolic Dysfunction in Dysferlinopathy.

Adv Sci (Weinh). 2024-8

[9]
Endothelial cell signature in muscle stem cells validated by VEGFA-FLT1-AKT1 axis promoting survival of muscle stem cell.

Elife. 2024-6-6

[10]
Recent trends in 3D bioprinting technology for skeletal muscle regeneration.

Acta Biomater. 2024-6

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