Flaps are often used in plastic and reconstructive surgery, and random pattern flaps were the first to be described. The indications for their use are numerous and include post-traumatic loss of substance, surgical oncoplasty, pressure ulcers, etc… Although they are very versatile flaps, complications like necrosis still occur even when a pre-operatory plan is made and a good dissection is performed.
Reducing the necrosis rate is one of the most important challenges in the field of plastic surgery because over the years there has been an evolution of techniques and knowledge as well as profound changes in patients’ conditions [Citation1].
Knowledge of skin blood perfusion helps surgeons formulate ideal surgical plans. In 2016, Mohan et al. described the “hot spot-cold spot” principle in perforator flaps, asserting that every perforator has a proper vascular territory and the density of vessels is not the same throughout various areas of the body’s skin surface. The researcher explained that some areas have a high density of vessels (hot spots) and identification of these regions can aid in flap planning and execution [Citation2]. Machine-based Laser Doppler now allows for very high precision and sensitivity.
Surgeons have lot of procedures at their disposable in order to increase the rate of flap survival such as hyperbaric oxygen, vasodilators, and regenerative medicine. The angiogenic capabilities of adipose-derived stem cells and vascular stromal fractions are being actively studied in order to amplify the success rate of both graft [Citation3] and flap procedures. The first experimental study was proposed by Lu et al. in 2008 and used marked stem cells harvested from inguinal fat pads of mice in order to increase the survival rate of random skin flaps 3:1. [Citation4]
The data from studies using adipose-derived stem cells suggest that these kinds of cells contribute to neoangiogenesis by releasing growth factors (such as vascular endothelial growth factor, VEGF) that are able to increase capillary differentiation.
The main limitation in using adipose-derived stem cells (ADSCs) in humans is the lack of good follow-up with this kind of cell population. Indeed, there is a lack of evidence on their safety.
In line with this data, other researchers have demonstrated that intravenous infusions of endothelial precursors cells can increase vascularization. Over the years, many studies have shown that perfusion becomes more powerful through two mechanisms: one is the extension of microvessels from a capillary network (classic neoangiogenesis), and the second is through new vessel formation via differentiation of endothelial progenitor cells (vasculogenesis) [Citation5].
Although research on growth factors has paved the way for interesting scenarios, their use is not without risks or doubts, so they are often limited to in vitro research or animal studies.
Recently, the increase in our knowledge of ischemia/reperfusion injury has allowed us to propose the study of the effects of certain antioxidant molecules often derived from plants. In some cases the effects on the survival rates of flaps harvested from animals was amazing. Over the years, the number of studies on this topic has increased and become more varied as the interest of the scientific community has increased. We must consider that there were 191 studies on survival rates of flaps published on Pubmed in 2000, while after 10 years, 433 papers were published. This number remained stable in the following years, increasing or decreasing slightly in 2017 and 2018, respectively.
Recently, a research group studied the effects of asiacotide, an extract of an herbal medicine (Centella asiatica), on survival rates of McFarlane flaps harvested from rats [Citation6].
Asiacotide is a crystal triterpene that promotes angiogenesis and reduces oxidative damage [Citation7] and the inflammatory response through modulation of tumor necrosis factor (TNF) and interleukin-6. It also induces the expression of VEGF. These researchers found that administering asiacotide inside the McFarlane’s flap increased the survival rate through the mechanism explained above because it produced new blood vessels, thereby improving perfusion (investigated by laser flowmetry).
Another interesting effect of asiacotide was a reduction in the damage caused by reactive oxygen free radicals. During random flap transplantation, the capillary perfusion of some areas can decrease dramatically. If the blood flow is restored, the accumulated excess of free radicals can cause ischemic reperfusion injury [Citation7]. This event plays a key role in the first two days after ischemia. The following inflammation damages the cell membranes through the production of arachidonic acid and other metabolites; moreover, the recruited neutrophils can generate a large number of new oxygen radicals.
The severity of these events is significantly reduced if asiacotide is administered within the flap.
Why does the scientific community pay so much attention to this topic?
It is well known that chronic diseases are a scourge of modern medicine. While the average life expectancy is increasing, we still must fight against chronic diseases, such as diabetes, hypertension, and atherosclerosis, which compromise microcirculation and sometimes result in devastating pathological conditions that reduce the quality of life of patients.
Furthermore, the advancement of technology allows for more complex and refined surgical practices, even in frail patients.
A deeper understanding of the mechanism of response to ischemia will allow us to develop personalized therapies, and this will play a key role not only in limiting ischemia reperfusion damage but also in highly futuristic projects involving disparate branches of medicine.
Declaration of interests
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- Zhang P, Feng J, Liao Y, et al. Ischemic flap survival improvement by composition-selective fat grafting with novel adipose tissue derived product - stromal vascular fraction gel. Biochem Biophys Res Commun. 2018;495(3):2249–2256. doi: 10.1016/j.bbrc.2017.11.196.
- Mohan AT, Sur YJ, Zhu L, et al. The concepts of propeller, perforator, keystone, and other local flaps and their role in the evolution of reconstruction. Plast Reconstr Surg. 2016;138(4):710e–729e. doi: 10.1097/PRS.0000000000002610.
- Nisi G, Barberi L, Ceccaccio L, et al. Effect of repeated subcutaneous injections of carbon dioxide (CO2) on inflammation linked to hypoxia in adipose tissue graft. Eur Rev Med Pharmacol Sci. 2015;19(23):4501–4506.
- Lu F, Mizuno H, Uysal CA, Cai X, Ogawa R, Hyakusoku H. Improved viability of random pattern skin flaps through the use of adipose-derived stem cells. Plast Reconstr Surg. 2008;121(1):50–58. doi: 10.1097/01.prs.0000293876.10700.b8.
- Simman R, Craft C, McKinney B. Improved survival of ischemic random skin flaps through the use of bone marrow nonhematopoietic stem cells and angiogenic growth factors. Ann Plast Surg. 2005;54(5):546–552. doi: 10.1097/01.sap.0000158068.86576.73.
- Feng X, Huang D, Lin D, et al. Effects of asiaticoside treatment on the survival of random skin flaps in rats. J Invest Surg. 2019. 2021;34(1):107–117.
- Cuomo R, Sisti A, Grimaldi L, Nisi G, Brandi C, D'Aniello C. Ischemic damage of the flaps: new treatments. J Invest Surg. 2018;1–2. doi: 10.1080/08941939.2018.1484199.