Browsing by Subject "Acute muscle injury"

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Open Access
Investigation of the effects of bioactive peptide nanofibers on acute muscle injury regeneration
(2016-10) Eren Çimenci, Çağla
Skeletal muscle constitutes a large part of the human body. It is a hierarchically organized heterogeneous tissue and is composed of muscle fiber bundles, muscle fibers, myofibrils and myofilaments. Since muscle cells are terminally differentiated, they have limited capacity to renew themselves. Only new cells can fuse with muscle fibers and increase the size and volume of skeletal muscle. Myosatellite cells or satellite cells are small, mononuclear progenitor cells with virtually no cytoplasm. They are located in between the sarcolemma and basement membrane of terminally-differentiated muscle fibers. Satellite cells are precursors to skeletal muscle cells, and are able to give rise to satellite cells or differentiated skeletal muscle cells. They are normally found in silent state in adult muscle, but act as a reserve cell population that is able to proliferate in response to injury and give rise to regenerated muscle and to more satellite cells. Formation of the new muscular tissue is called myogenesis. During this event, satellite cells differentiate into myoblasts, and then myoblasts fuse with each other in order to form myofibers. There are many genes that regulate the myogenesis process and each of them is activated in a different step of myogenesis. Increased or decreased levels of gene expression determine the differentiation capacity. Peptide nanofibers are supramolecular structures formed via self-assembly and they are promising molecules in regenerative medicine and tissue engineering. Peptide-based molecules for tissue regeneration is a widely studied area and currently used in the treatment-investigation of many different tissues such as bone, cartilage, skin and nerve. Since laminin is one of the most abundant proteins found in the basal membrane of the skeletal muscle; in this thesis, we designed and synthesized a laminin-mimetic bioactive (LM/E-PA) molecule functionalized with bioactive groups for mimicking laminin activities and capable of accelerating satellite cell activation. Our research group had previously shown that LM/E-PA containing nanofibers can support muscle differentiation in vitro. In this thesis, the clinical relevance was demonstrated further by assessing laminin-mimetic bioactive scaffold in acute muscle injury in an in vivo rat model. Our findings revealed that this scaffold system significantly promotes satellite cell activation in skeletal muscle and accelerates regeneration following acute muscle injury. In addition, our findings show that the regeneration capacity of the skeletal muscle was increased and consequently regeneration time was reduced. This study is one of the first examples of molecular level and tissue level regeneration of skeletal muscle by using bioactive peptide nanofibers following acute muscle injury, and shows that laminin mimetic nanofiber system is a promising material for development of new therapeutic curatives for acute skeletal muscle injuries.
Open Access
Laminin mimetic peptide nanofibers regenerate acute muscle defect
(Acta Materialia Inc, 2017) Cimenci, C. E.; Uzunalli, G.; Uysal, O.; Yergoz, F.; Umay, E. K.; Güler, Mustafa O.; Tekinay, A. B.
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.