Traumatic brachial plexus injuries are devastating events that frequently result in severe chronic functional impairment. At present, the main treatment methods are multiple nerve transfer and nerve transfer combined with free functional gracilis transfer. The indications for FFGT surgery include presentation beyond 9 months from injury, unavailable or failed prior local tendon or nerve grafts or transfers, and as the primary procedure for reconstruction of elbow flexion [21]. Functional gracilis transplantation can lead to muscle fibrosis due to ischemia-reperfusion injury. At the same time, there is inflammatory response in the recipient site of the transplanted muscle, leading to tissue adhesion. In clinic, some surgeons have proposed to improve operative gracilis function by using modified gracilis muscle harvesting technique (preserving the epimysium), but it is lack of animal experiments.
The preservation or recreation of a plane of differential tissue movement or gliding is vital for the maintenance of function, particularly where intricate movements are required such as in the hand and upper limb. Fascia has been used as a free graft or vascularized flap in an attempt to reconstitute a gliding surface. However, when the epimysium is disrupted the fascia adopts the pattern of a scar which spans the tissue planes and this will limit movement between these planes [22].
As we known, the endomysium, perimysium, epimysium and deep fasciae have not just a role of containment, limiting the expansion of the muscle with the disposition in concentric layers of the collagen tissue, but are fundamental elements for the transmission of muscular force, each one with a specific role [23, 24]. Where the epimysium of two muscles connects, there is frequently a connective tissue membrane that transports the vessels and the nerves destined to reach these muscles. Primarily the epimysium is subjected to mechanical tension and to forces that act orthogonally on its internal and outer surface, so the epimysium is very important for muscle contraction. There is an inflammatory microenvironment between the transferred muscle and the recipient site. Ischemia or reperfusion (I/R) injury in free muscle transfer in reconstructive surgery leads to a significant up-regulation of inflammatory parameters, infiltration of inflammatory cells, and angiogenesis [25]. Our study demonstrated that the epimysium could be used as a physical barrier to isolate the transplanted muscle from the external environment. It also could reduce the infiltration of inflammatory cells into the gracilis, reduce the formation of postoperative adhesion, and improve the gracilis function.
Moreover, FTY720, a S1PR1 agonist, has been widely used in clinical and experimental research of fibrosis. Numerous studies have shown that FTY720 can reduce lung, liver and kidney fibrosis, and scar formation [26–29]. In the muscle injury model of rats, FTY720 can effectively reduce the local inflammatory cell infiltration, and make macrophages enter M2 phase ahead of time, reduce the severity of muscle injury, improve muscle regeneration and reduce muscle fibrosis [30, 31]. Some studies showed that the application of an FTY720-loaded film increased M2 monocyte/macrophage recruitment, as well as arteriogenesis in ischemic skeletal muscle [32–34]. FTY720 can significantly reduce the degree of myocardial fibrosis and reduce the mortality of experimental animals in the model of myocardial ischemia-reperfusion [35]. In this study, FTY720 was used to further intervene the experimental animals with preserved epimysium. It was found that the infiltration of inflammatory cells in the early stage decreased between the interface between the gracilis muscle and adductor longus muscle and adductor magnus muscle in the group 3 and group 4, compared with group 2, as well as the collagen deposition, the thickness of adhesive band and the positive expression of TGF-β1.This is similar to the above results. Therefore, S1P / S1PR1 axis maybe take part in the inflammatory process of gracilis and recipient site, but it needed further study by cell experiment in vivo.
There are several limitations of this study. First, the study is based on the short-term observation of gracilis function without long-term follow-up to assess functional recovery of gracilis. Second, we use a the gracilis muscle orthotopic transplantation model instead of free gracilis transfer model in this study.