Laminin mimetic peptide nanofibers regenerate acute muscle defect

Date
2017
Advisor
Instructor
Source Title
Acta Biomaterialia
Print ISSN
1742-7061
Electronic ISSN
1878-7568
Publisher
Acta Materialia Inc
Volume
60
Issue
Pages
190 - 200
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Abstract

Skeletal muscle cells are terminally differentiated and require the activation of muscle progenitor (satellite) cells for their regeneration. There is a clinical need for faster and more efficient treatment methods for acute muscle injuries, and the stimulation of satellite cell proliferation is promising in this context. In this study, we designed and synthesized a laminin-mimetic bioactive peptide (LM/E-PA) system that is capable of accelerating satellite cell activation by emulating the structure and function of laminin, a major protein of the basal membrane of the skeletal muscle. The LM/E-PA nanofibers enhance myogenic differentiation in vitro and the clinical relevance of the laminin-mimetic bioactive scaffold system was demonstrated further by assessing its effect on the regeneration of acute muscle injury in a rat model. Laminin mimetic peptide nanofibers significantly promoted satellite cell activation in skeletal muscle and accelerated myofibrillar regeneration following acute muscle injury. In addition, the LM/E-PA scaffold treatment significantly reduced the time required for the structural and functional repair of skeletal muscle. This study represents one of the first examples of molecular- and tissue-level regeneration of skeletal muscle facilitated by bioactive peptide nanofibers following acute muscle injury. Significance Statement Sports, heavy lifting and other strength-intensive tasks are ubiquitous in modern life and likely to cause acute skeletal muscle injury. Speeding up regeneration of skeletal muscle injuries would not only shorten the duration of recovery for the patient, but also support the general health and functionality of the repaired muscle tissue. In this work, we designed and synthesized a laminin-mimetic nanosystem to enhance muscle regeneration. We tested its activity in a rat tibialis anterior muscle by injecting the bioactive nanosystem. The evaluation of the regeneration and differentiation capacity of skeletal muscle suggested that the laminin-mimetic nanosystem enhances skeletal muscle regeneration and provides a suitable platform that is highly promising for the regeneration of acute muscle injuries. This work demonstrates for the first time that laminin-mimetic self-assembled peptide nanosystems facilitate myogenic differentiation in vivo without the need for additional treatment.

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Book Title
Keywords
Acute muscle injury, Functional self-assembly, Hydrogel, Laminin, Peptide nanofiber, Regeneration, Cardiotoxin, Laminin, MyoD1 protein, Myogenin, Nanofiber, Peptide, Transcription factor PAX7, Animal behavior, Animal experiment, Animal model, Animal tissue, Article, Basal lamina, Cell activation, Cell differentiation, Circular dichroism, Comparative study, Controlled study, Flow kinetics, High performance liquid chromatography, Hydrogel, In vitro study, In vivo study, Liquid chromatography-mass spectrometry, Male, Muscle cell, Muscle development, Muscle disease, Muscle regeneration, Nonhuman, pH, Priority journal, Protein analysis, Protein expression, Protein function, Protein structure, Rat, Reverse transcription polymerase chain reaction, Satellite cell, Scanning electron microscopy, Synthesis, Transmission electron microscopy, Western blotting
Citation
Published Version (Please cite this version)