The Effect of Adipose-Derived Stem Cells and Exosome Usage on Flap Survival in Pedicled and Free Venous Flaps

Project no. 24051 · Status: Kapanmış (Yayın bekleniyor) · 2022

Summary

With the development of technology and increasing experience, reconstruction algorithms in plastic surgery have expanded. The basis of reconstruction lies in the principle of repairing the missing tissue with similar tissue. Today, the advantages and power of free flaps come to the fore in the reconstruction of many tissues. Among these areas, head and neck reconstruction, hand and upper extremity reconstruction, breast reconstruction and lower extremity reconstructions are among the areas where free flaps are frequently preferred. For example, tongue reconstruction can be performed with free flaps in a patient who has undergone glossectomy due to tongue cancer, and the patient's speech and swallowing functions can be fulfilled. In patients who have undergone mastectomy due to breast cancer, breast tissue can be regained with various free flaps and the person can feel psychologically and socially healthy. In addition, in patients with soft tissue defects in the hand, upper extremity or lower extremity for various reasons, soft tissue reconstruction can be achieved with free flaps, the underlying neurovascular structures, tendons and bones of the patient are covered, and the disability that may develop as a result of damage to these structures can be prevented. In this way, the patient, who may have lost a limb as a result of damage to these structures, is enabled to walk again or use his hands, and the person can return to social and business life. Although classical free flaps are generally lifted over an artery and vein, the blood flow scheme is classically based on the Harvesian model and is through the arterial system, capillary system and venous system. In addition to the advantages of these flaps; For example, the radial forearm flap has disadvantages such as one of the major arteries feeding the hand cannot be sacrificed, the flap may be thicker than desired, especially in reconstructions that require thin tissues such as the mouth and upper extremities, perforator dissection is required in perforator free flaps, dissection takes time and there is a risk of injury to the perforator during dissection. . Venous flaps, unlike classical flaps, do not have an arterial circulation and all blood circulation is provided only through veins. Many studies and modifications were made on these flaps, which were first described by Nakayama in 1981, and it was shown that they could be used as free flaps. Compared to classical free flaps, venous free flaps; It has many advantages such as being easy to design, not sacrificing a major artery, having minimal donor site morbidity, having no donor site restrictions as it can be designed from any region containing a vein, being able to be removed quickly and easily because it does not require deep dissection, and having thin flap options. The use of venous free flaps historically began in rats and other animals, and their clinical applicability has been demonstrated as a result of successful results. Today, free venous flaps can be used in head and neck, lower extremity, and especially hand and upper extremity reconstructions where thin and foldable tissue is desired. In return for these advantages; Since the blood circulation of these flaps is provided by venous blood, their survival and success rates are significantly lower (57.7%) and partial (%) compared to classical free flaps due to low oxygen concentrations and high toxic metabolite rates, high venous congestion rates and the frequent occurrence of ischemia/reperfusion injury. Complications such as 42.5) and/or complete necrosis (7.5%) are seen at higher rates. In the presence of ischemia in any tissue, if the dose of ischemia exceeds the tolerance of the tissue, inflammatory processes begin and if this situation continues, tissue necrosis may occur. In reperfusion injury, reactive oxygen radicals deepen inflammation and trigger apoptotic pathways, causing aggravation of ischemic damage and tissue necrosis. It is not surprising that the above-mentioned complications occur more frequently in venous flaps, where ischemia/reperfusion injury is higher than in classical flaps. Although the physiology of the survival of venous flaps has not been clearly revealed, studies have shown that plasmatic imbibition and neovascularization play an important role in this regard. To increase the survival of these flaps and increase their success rates; Although procedures such as pre-arterialization, tissue expansion, surgical or chemical delay have been used and varying degrees of success have been achieved; Discussions continue in the literature about prioritization and increasing success rates.When the literature is scanned, studies have shown that the use of ADSC and exosomes is protective against ischemia/reperfusion injury in skin flaps and classical free flaps in humans and experimental animals, reduces complication rates such as partial or full-thickness necrosis, and has positive effects on flap survival. However, no study has been found using these two agents in venous free flaps. However, although the physiology of venous flaps is not clearly understood, flap survival is lower compared to classical free flaps due to reasons such as low oxygen concentrations and high ischemia/reperfusion injury, complication rates such as partial and full-thickness necrosis are higher, and the above-mentioned effects of ADSC and exosomes are needed more. is heard. We designed our study to reduce these high complications seen in venous free flaps, thanks to the above-mentioned properties of ADSC and exosomes, and to increase flap survival rates. Our study is experimentally planned, and we aim to use ADSCs and exosomes obtained from humans in venous free flaps designed on rats. Thus, we think that the high complication rates seen in venous free flaps will decrease and flap survival will be positively affected. If our study yields positive results, we will be able to show that a reconstruction method, which has limited use despite its many advantages, can be used more successfully. Method: The research is planned experimentally and will be conducted on rats. 27 rats; They will be divided into 3 groups and there will be 9 rats in each group. After appropriate preparation in rats, a 3x3 cm venous free flap based on the superficial epigastric vein will be removed from the right groin area. Group 1 will be the control group and will be followed without any additional intervention to the venous free flaps raised on the rats. In Group 2, the effects of ADSCs on venous free flaps raised in rats will be monitored. In Group 3, the effects of ADSC-derived exosomes on venous free flaps raised on rats will be examined. Group 1: It will be the control group and the removed venous free flap will be sutured in place with 4-0 nylon suture. Group 2: Human ADSC will be applied subcutaneously to the removed venous free flap. It will then be sewn into place with 4-0 nylon suture. Group 3: Human exosome will be applied subcutaneously to the removed venous free flap. It will then be sewn into place with 4-0 nylon suture. Rats will be photographed from a macroscopically standardized position on days 1, 2, 3, 5, 7, and 10 after the operation. Rats will be euthanized on day 10, and then the flaps will be taken to the histology laboratory for histological analysis. At the end of the study, each group will be compared macroscopically and microscopically in terms of partial and full-thickness necrosis rates, complication rates and flap survival. The ADSCs to be used have previously been obtained from humans. (Human origin ADSCs for which ethical permission was obtained by the Ege University Faculty of Medicine Clinical Research Ethics Committee decision dated 02.04.2015 and numbered 15-3.2/19 in the Non-Pharmaceutical Research category)The exosomes to be used will be obtained from human fat tissue obtained from the abdominal region of a healthy volunteer by the classical liposuction method. To obtain adipose tissue-derived exosome, approximately 1 liter of adipose tissue from a healthy volunteer will be sufficient.

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