Research Paper on Skeletal Muscle Loss

Scaffold-Based Strategies

Biomaterials offer chemical and physical signals to transferred cells or host muscle cells to, stimulate their useful development, guard them against external body reactions, as well as regenerate muscle tissues. Biological frameworks are used in clinical tissue engineering applications and have been researched in preclinical skeletal muscle injury models.

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Collagen and fibrin are examples of the polymers used in skeletal muscle engineering. They own intrinsic bioactive signals to enhance cell behavior. Freeze-dried collagen scaffolds enabled the integration of aligned myotubes into a massive muscle imperfection, which could produce a force upon electrical stimulation. Collagen also supplies essential development factors in the wounded parts to increase muscle cell migration. Fibrin scaffolds with micro thread design were able to support the recovery of VML in mouse models.

An impediment in muscle regeneration in the musculotendinous junction. These can be partly restored in lack of implanted cells by extracellular matrix-based platforms.

Biological Scaffolds

The extracellular matrix proteins help a big deal in the regeneration and reconstruction of tissues. Repairing VML is dependent on the structural and biochemical framework. For smaller amounts of muscle loss, several tissue-derived skeletons have been tested in animal simulations and translated into the clinic for surgical application. Muscle and simultaneously generate a biological niche for recovery. The patient showed marked gains in isokinetic performance four months after surgery, and new muscle tissue at the implant site demonstrated by computer-tomography. However, allograft or xenogeneic scaffolds can still induce an adverse immune response after decellularization, and there might be a probable risk of infectious disease transmission. Therefore strategies to facilitate growth and repair of muscle tissue are very important to implement.

Surgical Techniques

Mainly includes scar tissue debridement and muscle exchange. Muscle transfer is commonly performed in a clinical position when there are vast areas of muscle loss after tumor resection, or nerve injury, trauma which impairs the irreplaceable motor function. The surgeons transplant healthy muscle from the uninfected part to restore the lost or wounded part. When Trauma and nerve injuries affect the neighboring muscles is, as a free functional muscle transfer, can be applied such as the latissimus dorsi muscle for the reestablishment of elbow flexion after injuriesautologous muscles are not found easily in a case a patient is largely affected.

Acupuncture

Acupuncture refers to Chinese medicine, which has been widely used to treat various diseases. Electrical acupuncture treatment has been revealed to destroy most Acu-LFES counteracts diabetes-induced skeletal muscle atrophy. Application of Acu-LFES for the treatment of diabetic myopathy and muscle loss resulting chronic kidney disease showed good functional improvement of the muscle.

Acupuncture improves muscle function restoration and stimulates muscle regeneration especially in chronic related diseases. However, despite everything, there are low chances of restoring muscle defect from trauma or tumor effect (Robinson, 2015).

Cell-Based Strategies

Muscle fiber regeneration is performed by cells and thus pursue this strategy for regeneration. There are cell types that known for restoring muscle loss (P. A. Kosinski, 2005)). SCs can contribute to the development of new muscle fibers. SCs transplanted into dystrophin-deficient mice yielded highly efficient regeneration of dystrophic muscle and improved muscle contractile function. vitro expansion is known for the reduction of their ability to reproduce myofibres which have affected and resulted in more force hence promoting regeneration of the muscles.

Stem-cell-based therapies provide therapeutic benefits on reversing muscle atrophy and promoting muscle regeneration. Stem cell therapy such as the umbilical-cord blood stem cell transplantation) showed positive results for treating Duchenne muscular dystrophy (Zhang, 2005). After the application of stem cells, an increase of dystrophin-positive muscular fibers was found. Biopsies of calf muscle showed growing myoblasts cells, and muscular tubes and an improvement in arms and legs during physical examination was reported.

Innervation of Regenerated Muscles

A severe stage for developing a muscle tissue after the injuries reestablishment of neuromuscular junctions to prevent the regenerated muscle from becoming atrophied. Mostly in autologous muscle transplantation, the force established after nerve stimulation is weaker, due to increased connective tissue and the failure of regeneration of some muscles. Another precarious issue is the poor reinnervation at the sites of the original NMJs, which impacts the force production. To reconstruct the NHJs in newly regenerated muscle fibers, new motor endplates are formed and nerves regenerated. The motor endplates influence muscle fiber type, alignment, and size. So far studies on the reinnervation of skeletal muscles have been limited to in vitro co-culture of muscle cells and neurons. Those results showed better contractile force in nerve-muscle constructs and then in muscle-only constructs. However, full reestablishment of new nerves and motor endplates within new muscles has proven difficult, which are further investigated.

Molecular Signaling Based Strategies

Apart from signals from the ECM, also a variety of stimulatory and inhibitory growth aspects such as IGF-1 and TGF-ss1 can drive endogenous skeletal muscle redevelopment by triggering and recruiting host stem cells. They are loaded on scaffolds for controlled delivery to the injured areas. Sustained delivery of VEGF, IGF-1, or SDF-1a was shown to enhance myogenesis and promote angiogenesis and muscle formation. Rapid release of hepatocyte growth factor (HGF) loaded on fibrin microthread frameworks encouraged rehabilitation of useful muscle tissue and enhanced the restoration of skeletal muscle in mouse models. (mmolfino, 2016) Amalgamation therapy of h-ADSCs and bFGF hydrogels led to functional recovery, revascularization, and reinnervation in lacerated muscles with negligible fibrosis.

Furthermore, PEDF peptide was reported to promote the regeneration of skeletal muscles anti-inflammatory drugs, helped to regenerate muscle tissue. (Yang, 2014)Spinal muscular atrophy is caused by transmutations in the survival neuron gene, which bring about scarcity of the ubiquitous SMN protein. Therefore, one of the strategies is to multiply the levels of full-length SMN. Nusinersen is an antisense oligonucleotide drug formulated to treat spinal muscular atrophy (SMA), which has been permitted by US FDA. It can modulate the pre-mRNA splicing of the survival motor neuron two gene and showed significant improvement of muscle function after treatment. Clinical trials on infants showed noteworthy average progresses in evolving motor indicators including sitting, walking, and motor function.

Genetically Engineered Vascularized Muscle

This form of surgical reconstruction is developing to be an important asset in current medicine. These are collected from human cells over-secreting ANGPT1 and VEGF. The described vascular cells are isolated from elderly patients and used to pre-vascularize various tissue types, ultimately constructing autologous vascularized tissues that promote neovascularization and integration within the host. The primary cells are isolated from patients with progressive arterial disease. The use of vascular cells derived from the elderly can be applied for the construction of autologous tissues for adult patients, without the issue of rejection. (Perry, L. et al., 2018) Employed gene therapy in the construction of the vascularized engineered muscle optimized and accelerated the integration process. Since the utilized vascular cells are fully differentiated with no telomerase activity, they were not likely to undergo oncogenic transformations after gene transfer. The above study facilitated the reconstruction of an abdominal wall defect in nude mice, by muscle grafts genetically modified to secrete both VEGF and ANGPT1.

This procedure, in the future, will be necessary to overcome autologous flap shortage, minimize deficiencies deeper in tissue, enhance survival of tissue transplant, and to accelerate host integration of the grafts that followed transplantation. However, further research is still required to construct larger tissues that can be used for routine procedures.

Challenges

According to Perry, L. et al. transplantation failure can occur after implantation of engineered tissue due to insufficient vascularization. This can be evidenced by tissue necrosis. Thus to enhance the survival of the implanted tissue prevascularization of thick implanted tissue is necessary.

Autologous engineered tissue products require long culturing-time, especially for the harvested cells. The procedure is also very expensive and entails many regulatory challenges.

Conclusion

Skeletal muscle loss happens in many clinical situations. Surgical methods are highly developed and can provide results for recreating muscle function. Surgery is considered high risks and high costs and even if successful, usually better function at one location.

Further more, other types of tissue-specific cells should be experimented to broaden the applicability of the methods above. Lastly, before use vascularized engineered grafts model into clinical use, comparison of endothelial cells and SMCs from numerous donors and transplantation into larger animal models will still be necessary. This requires a lot of understanding of the regeneration topic and on the developing of muscle which will require research.

References

Eckardt, A., & Fokas, K. (2003). Microsurgical reconstruction in the head and neck region: 18-year experience with 500 consecutive cases. Journal of Cranio-Maxillofacial Surgery, 31(4), 197-201.

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