Role of Skeletal Muscle Tissue in Plastic Surgery: A Comprehensive Review

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Skeletal Muscle in Surgical Treatments

Surgical treatments used to treat volumetric muscle loss (VML) are muscle transposition and scar tissues debridement (Klinkenbergetal., 2013). Autologous muscle transfer is performed when there is a large section of muscle loss after trauma, nerve injury, or tumour resection that impairs the irreplaceable motor function in a clinical situation (Stevanovicetal., 2016). Surgeons transplant healthy skeletal muscle tissue from donor sites not affected by the injury for the restoration of damaged, impaired, or lost function.

When there are no adjacent muscles available due to high level of severe trauma or nerve injuries, autologous muscle implantation should be combined with neurorrhaphy for the formation of a free functional muscle transfer (Estrella & Montales, 2016). The free functional muscle transfer is, therefore, applied to treat VML.

The common autologous muscles are gracilis muscle and latissimusdorsi muscle. According to Stevanovicetal. (2016), transfer of latissimusdorsi muscle is efficient and safe to restore elbow flexion after injuries. In an instance where a synovial sarcoma has affected the right minimus and gluteusmedius muscles, the impacted function of hip abduction should be reconstructed through free neurovascularlatissimusdorsi muscle replacement (Barrera-Ochoa etal.

, 2017). Free gracilis muscle transfer is used to restore elbow flexion after pan-brachial injuries. This muscle transfer is also used to treat Pelvic floor muscle weakness and Facial palsy reconstruction (Rozen, 2017; Maldonado etal., 2017). Lin etal. (2007) explains that functional muscle flaps lead to decent functional results, although they can cause inadequate innervation and substantial donor site morbidity. In addition, while approximately 10% of the reconstructive surgeries are resulting in graft failure because of complications, such as necrosis and infection (Bianchietal., 2009). However, when patients are severely injured, getting donors for autologous muscles for grafting is difficult; therefore, limiting the use of skeletal muscle tissue engineering.

The Use of Skeletal Muscle in Anti-Fibrotic Therapy

In anti-fibrotic therapy, transforming growth factor-beta 1 (TGF-β1) at high levels are playing essential roles in the fibrotic cascade which occurs at the beginning of muscle injuries (Li etal., 2004). For this reason, the neutralization of the transforming growth factor-beta 1 expression in damaged or injured skeletal muscle prevents the formation of scar tissue. The utilization of anti-fibrotic agents, which activate TGF-β1 to signal pathways to improve the muscle healing process and reduce muscle fibrosis, therefore, leading to repair of injuries (Fukushimaetal., 2001). Losartan, which is an angiotensin II receptor competitor, is responsible for neutralizing the impact of TGF-β1 and decrease fibrosis. The ability of losartan has made anti-fibrotic treatment to be considered as an effective therapy, which led to its approval by the United States Food and Drug Administration (FDA) for use in clinical applications (Tanigutietal., 2011). Suramin was also approved by the FDA for clinical use because it blocks TGF-β1 pathways and lessens muscle fibrosis, resulting from repairing of injured tissues (Tanigutietal., 2011).

The Role of Skeletal Muscle in Scaffolds

Biomaterials provide both physical and chemical cues for transplantation cells. According to Cezar and Mooney (2015), biomaterials ensure that transplanted cells enhance their survival, protect themselves from the foreign body responses, promote their functional maturation, and regenerate muscle tissues and recruit host cells. In different clinical tissue engineering applications, biological scaffolds have been used to treat injuries, as well as having been studied in skeletal muscle volumetric muscle loss injury pre-clinical models in the past decades (Cezar & Mooney, 2015). The scaffolds comprised of synthetic polymers, EMC, or natural polymers, and they are attempting to create a conducive microenvironment to control resident's cells behaviour.

Synthetic polymers, including PLA, PLGA and PGA are used in surgical treatments for the repair of injuries. Guexetal. (2013) mention that myoblasts implanted on electrospun with aligned nano-fibre orientation result into aligned myotubes. Synthetic scaffolds are engineered for the facilitation of growth factors to promote muscle regeneration. Yang etal. (2014) postulated that the primary disadvantages include poorer cell affinity and the risking of stimulating foreign body responses by the polymer.

The regeneration of muscle tissues and repair of injuries can be improved by ensuring that scaffolds' microenvironment is replicating native tissues to facilitate the restoration of neotissue. The effective approach to repair VML is to transplant muoinductivedecellularized scaffold that attracts the cells required for myogenesis from the host. Muscle-derived called EMC scaffolds are being investigated if they can temporarily restore and fill the morphological defect (Merritt, Cannon & Hammers, 2010). The ECM can be filled with a bone-marrow from mesenchymal stem cells (MSCs) after implantation. Merritt, Cannon and Hammers (2010) specify that the enriched extracellular matrix gains more blood vessels and restores more myofibers than normal EMC (Vannozzi, Ricotti & Santaniello, 2017).

Natural polymers are used in skeletal muscle engineering to repair injuries in plastic surgery. These polymers include fibrin, alginate, and collagen (Walters & Stegemann, 2014). The polymers are possessing intrinsic bioactivesignalling cues that enhance behavioural cells. Alginate gels with the difficulty of 13-15 kPA increase myoblast differentiation and proliferation (Grasmanetal., 2015). Free collagen scaffolds assist the assimilation of aligned myotubes into a muscle defect capable of generating force upon electrical integration. Collagen can also supply growth factors, which increase muscle cell movement. Beieretal. (2004) explain that fibrin gels stimulate myoblast survival and differentiation into myofibers when integrated into tissues.

The musculotendinous junction is a barrier in muscle regeneration following an injury. This barrier can be partial restored in the absence of transplanted cells by MCM-based platforms, withstanding half of the contralateral site force after resection in a mammalian model. The newly created muscle cells showed adherence to 3-D polyurethane-based porous scaffolds that have low stiffness and large roughness values (Grasmanetal., 2015).

Healing Process of Muscle Injuries

Healthy skeletal muscle tissue has the ability to repair itself after an injury in the presence of mature muscle cells referred to as satellite cells (SCs). The injury causes the disruption of muscle tissues homeostasis, which creates sequential involvement of numerous players in three main phases, as shown in figure 1.

In figure one above, there different numbers presenting different phases of the healing process. Number 1 and 2 represent degeneration or inflammation phase. This phase is described by necrosis and rupture of the myofibres, a significant inflammatory reaction, and formation of a hematoma. Number 3 represents a regeneration phase. In this phase, damaged tissue's phagocytosis is followed by myofibers regeneration that leads to satellite cells activation (Laumonier & Menetrey, 2016). The number 4 and 5 illustrate remodelling phase, and it involves maturation of restored myofibers that leads to recovery of muscle functional ability and also the formation of scar tissues and fibrosis (Laumonier & Menetrey, 2016).