The significance of three-dimensional (3D) bioprinting in the domain of regenerative medicine and tissue engineering is readily apparent.

Photobiomodulation therapy (PBMT) emerged as a significant non-invasive method of stimulating regeneration of the skeletal muscle tissue. This review considers the pathophysiologic and molecular mechanisms of muscle repair, with a focus on the imperative of inflammation resolution, activation of satellite cells, mitochondrial ATP generation, and angiogenesis, with consideration of the role of PBMT. We systematically evaluate preclinical and clinical studies, highlighting the translational gaps caused by differences between controlled experimental models and the complex, heterogeneous nature of human muscle injuries. Variability in PBMT parameters-such as wavelength, fluence, and pulse mode-and the lack of standardized protocols are identified as major barriers to consistent therapeutic outcomes. Furthermore, we discuss the effects of PBMT in acute and chronic muscle injury models and provide an in-depth analysis of laser parameters to elucidate dose-response relationships. Future directions for research involve the application of real-time biofeedback devices, the utilization of artificial intelligence-based individualized therapeutic approaches, as well as the integration of photobiomodulation therapy with nanotechnology, biomaterials, and multiple mechanical stimulation methods. In concusion, while PBMT has significant potential for muscle regeneration therapies, its clinical application requires more complete mechanistic validation, rigorous standardization, and interdisciplinary technological development.

Intrafusal fibres are a specialised cell population in skeletal muscle, found within the muscle spindle. These fibres have a mechano-sensory capacity, forming part of the monosynaptic stretch-reflex arc, a key component responsible for proprioceptive function. Impairment of proprioception and associated dysfunction of the muscle spindle is linked with many neuromuscular diseases. Research to-date has largely been undertaken in vivo or using ex vivo preparations. These studies have provided a foundation for our understanding of muscle spindle physiology, however, the cellular and molecular mechanisms which underpin physiological changes are yet to be fully elucidated. Therefrom, the use of in vitro models has been proposed, whereby intrafusal fibres can be generated de novo. Although there has been progress, it is predominantly a developing and evolving area of research. This narrative review presents the current state of art in this area and proposes the direction of future work, with the aim of providing novel pre-clinical and clinical applications.

Skeletal muscle is an insulin sensitive tissue and accounts for approximately 80% of post‐prandial glucose disposal. This study describes the effects of insulin, delivered for 72 h, to skeletal muscle myoblasts during differentiation or to skeletal muscle myotubes. After chronic treatment, cultures were acutely stimulated with insulin and analyzed for total and phosphorylated Akt (Ser⁴⁷³), mRNA expression of metabolic and myogenic markers and insulin‐stimulated glucose uptake. Skeletal muscle cells differentiated in the presence of insulin chronically, reduced acute insulin stimulated phosphorylation of Akt Ser⁴⁷³. In addition, there was a reduction in mRNA expression of Hexokinase II (HKII), GLUT4 and PGC‐1α. Insulin‐stimulated glucose uptake was attenuated when cells were differentiated in the presence of insulin. In contrast, myotubes exposed to chronic insulin showed no alterations in phosphorylation of Akt Ser⁴⁷³. Both HKII and GLUT4 mRNA expression were reduced by chronic exposure to insulin; while PGC‐1α was not different between culture conditions and was increased by acute insulin stimulation. These data suggest that there are differential responses in insulin signalling, transcription, and glucose uptake of skeletal muscle cells when cultured in either the presence of insulin during differentiation or in myotube cultures.

Statins are currently the most prescribed hypercholesterolemia-lowering drugs worldwide, with estimated usage approaching one-sixth of the population. However, statins are known to cause pleiotropic skeletal myopathies in 1.5% to 10% of patients and the mechanisms by which statins induce this response, are not fully understood. In this study, a 3D collagen-based tissue-engineered skeletal muscle construct is utilised as a screening platform to test the efficacy and toxicity of a new delivery system. A hyaluronic acid derived nanoparticle loaded with simvastatin (HA-SIM-NPs) is designed and the effect of free simvastatin and HA-SIM-NPs on cellular, molecular and tissue response is investigated. Morphological ablation of myotubes and lack of de novo myotube formation (regeneration) was evident at the highest concentrations (333.33 μM), independent of delivery vehicle (SIM or HA-SIM-NP). A dose-dependent disruption of the cytoskeleton, reductions in metabolic activity and tissue engineered (TE) construct tissue relaxation was evident in the free drug condition (SIM, 3.33 μM and 33.33 nM). However, most of these changes were ameliorated when SIM was delivered via HA-SIM-NPs. Significantly, homogeneous expressions of MMP2, MMP9, and myogenin in HA-SIM-NPs outlined enhanced regenerative responses compared to SIM. Together, these results outline statin delivery via HA-SIM-NP as an effective delivery mechanism to inhibit deleterious myotoxic side-effects.

Non-invasive promotion of myogenic regulatory factors (MRF), through photobiomodulation therapy (PBMT), may be a viable method of facilitating skeletal muscle regeneration post-injury, given the importance of MRF in skeletal muscle regeneration. The aim of this systematic review was to collate current evidence, identifying key themes and changes in expression of MRF in in vivo models. Web of Science, PubMed, Scopus and Cochrane databases were systematically searched and identified 1,459 studies, of which ten met the inclusion criteria. MyoD was most consistently regulated in response to PBMT treatment, and the expression of remaining MRFs was heterogenous. All studies exhibited a high risk of bias, primarily due to lack of blinding in PBMT application and MRF analysis. Our review suggests that the current evidence base for MRF expression from PBMT is highly variable. Future research should focus on developing a robust methodology for determining the effect of laser therapy on MRF expression, as well as long term assessment of skeletal muscle regeneration.