An Update in Reconstructive Surgery

This article refers to:

Therapeutic Effects against Tissue Necrosis of Remote Ischemic Preconditioning Combined with Human Adipose-Derived Stem Cells in Random-Pattern Skin Flap Rat Models

Residual defects are generally observed after tumor resection, chronic osteogenic infection, and traumatic injuries or in congenital deformities. Reconstructive surgery for critical size defects is still considered a challenge due to poor revascularisation of grafted tissue. An additional challenge is low vascularity seen after radiotherapy in cases of tumor, which affects tissue repair. This could be due to poor tissue perfusion called ischemic-reperfusion injury or ischemia [1]. This can occur either in soft tissue-like skin and subcutaneous tissue resulting in tissue necrosis of the flap or affecting hard tissue-like bone during reconstruction, resulting in infection, resorption, malunion, and disfigurement.

Using vascularized composite tissue graft is the gold standard technique, but it is a lengthy procedure that requires expert surgeons and has a risk of donor site morbidity and a high complication rate of 30-40% [2]. As a preventive measure to avoid ischemia-reperfusion injury, many studies have suggested stem cell therapies, drug treatment, and inhibition of proinflammatory cytokines. Using hyperbaric oxygen was proposed to increase tissue perfusion as a protective measure for flap surgery [1]. Negative-pressure wound therapy (NPT) has been tested in clinical trials to assess the effect of this therapy on incisions and surrounding soft tissue healing [3]. At the preclinical level, NPT showed reduced scar thickness, increased collagen and vascularity at incision sites, and increased mechanical wound properties [4]. It was reported that NPT increased blood flow and angiogenesis, decreased wound size, and induced cell proliferation [5]. Improved clinical outcomes after NPT was used in soft tissue sarcomas in irradiated subjects have been reported [3]. NPT was also reported as useful for healing open infected wounds in fractured femur bone [6]. Remote ischemic preconditioning (rIPC) was recently tested to prevent ischemia reperfusion injury in soft tissue flaps by performing cycles of 5 min of occlusion and 5 min of reperfusion using a tourniquet in the hind limb of a rat. rIPC was used with or without human adipose-derived stem cell (hADSC) therapy in a rat model [7]. In this experiment, three groups were tested and a fourth group was used as a control (no intervention). The first group of animals was subjected to rIPC only, the second group was seeded with hADSCs, and the third group was subjected to both rIPC and hADSCs. A comprehensive qualitative and quantitative analysis was conducted including imaging, immunohistochemistry, and histopathology. The study concluded that the simultaneous use of rIPC and hADSC treatments appeared to reduce skin flap necrosis and activate the neovascularisation process [7]. These encouraging results should convince surgeons and scientists to conduct randomized clinical trials and assess the outcomes.

Bone bioengineering using biomaterials bioactive molecules and autogenous stem cells have been studied extensively and variable rates of success were reported [8–10]. Other studies investigated various methods of inducing angiogenesis and arteriogenesis that are essential for the bone regeneration process [11, 12]. The application of vascular endothelial growth factors (VEGF), angiogenic proteins, and hypoxia-inducible factor-1a to improve vascularity at surgical sites have also been reported [13–15].

Using skeletal muscle as a supporting scaffold to induce bone regeneration and provide the required vascularity was recently introduced [16–20]. More advanced surgical techniques were advocated to overcome limited vascularity at surgical defects, “the recipient site,” by utilizing local skeletal muscle flaps to induce bone formation due to its reliable adequate blood supply source [17, 19, 21]. Muscle has the propensity to induce bone formation because of its intrinsic osteogenic potential when exposed to osteogenic stimuliincluding bone matrix substitutes and bone morphogenic proteins (BMP) [22]. Although these promising results are milestones in regenerative medicine, they still have certain limitations; for example, the use of skeletal muscle flaps is associated with the risk of donor site morbidity and graft availability, similar to that associated with the use of vascularized free flaps. Alternetively, decellularised muscle flaps, stem cells, and biomaterials were tested for bone augmentation in an animal model [23].

In summary, to improve the outcomes of reconstructive surgery by cultivating vascularity and inducing robust neovascularisation, this brief commentary summarized an update of different techniques used in multiple clinical applications. Tissue engineering applications using biomimetic scaffolds with microenvironmental and inductive extracellular cues that can preserve host cell properties when implanted in vivo were presented at clinical and preclinical levels. Further development and refinement of this approach are required before its clinical use in maxillofacial bone reconstruction.

Disclosure statement

No potential conflict of interest was reported by the author(s).