Autologous micro-fragmented adipose tissue for the treatment of diabetic foot minor amputations: a randomized controlled single-center clinical trial (MiFrAADiF)

Abstract

Background The diabetic foot ulcer (DFU) is one of the most prevalent complications of diabetes mellitus and often develops severe effects that can lead to amputation. A non-healing “minor” amputation often precedes a major amputation resulting in a negative impact on the function and quality of life of the patients. Stem cell-based therapies have emerged as a promising option to improve healing, and the adipose tissue is an abundant and easy to access source. The injection of autologous micro-fragmented adipose tissue at the amputation stump of a diabetic population undergoing a lower limb minor amputation was evaluated and compared with the standard care. Methods In this randomized controlled trial with two arms (parallel assignment) and no masking, 114 patients undergoing a lower limb minor amputation were randomized to standard of care or to micro-fragmented adipose tissue injection prepared using a minimal manipulation technique (Lipogems®) in a closed system. Clinical outcomes were determined monthly up to 6 months. Primary endpoint of the study was the evaluation of the healing rate and time after the minor amputation. Secondary endpoints included the assessment of safety, feasibility, technical success, relapse rate, skin tropism, and intensity of pain. Results At 6 months, 80% of the micro-fragmented adipose tissue-treated feet healed and 20% failed as compared with the control group where 46% healed and 54% failed ( p = 0.0064). No treatment-related adverse events nor relapses were documented, and technical success was achieved in all cases. The skin tropism was improved in the treatment group, and the pain scale did not differ between the two groups. Conclusion The results of this randomized controlled trial suggest that the local injection of autologous micro-fragmented adipose tissue is a safe and valid therapeutic option able to improve healing rate following minor amputations of irreversible DFU. The technique overcomes several stem cell therapy-related criticisms and its potential in wound care should be better evaluated and the therapeutic indications could be expanded. Trial registration ClinicalTrials.gov number: NCT03276312 . Date of registration: September 8, 2017 (retrospectively registered).

Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot

“…Studies found that SVF could secrete a variety of cytokines, differentiate into various cells such as endothelial cells, and have the potential to participate in angiogenesis in vivo. Therefore, it can improve local blood circulation and form the microenvironment that is conducive to tissue cell survival and functional maintenance [13][14][15].…”

Comparative technical analysis of lipoaspirate mechanical processing devices

“…In one work (Brzezienski & Jarrell, 2016), surgeons indifferently used the GID700 and Puregraft devices, and no comparison of clinical results is made. The identified clinical results refer to multiple fields of application: 14 papers refer to breast reconstruction (Brzezienski & Jarrell, 2016;Chiu, Fracol, Feld, Qiu, & Kim, 2019;De Fazio & Cingozoglu, 2020;Economides & Song, 2018;Gabriel et al, 2017;Lee et al, 2011;Losken et al, 2011;Mestak et al, 2014;Mestak, Mestak, Bohac, Edriss, & Sukop, 2013;Mestak & Zimovjanová, 2012;Ruan et al, 2019;Russe et al, 2015;Sforza, Andjelkov, Zaccheddu, Husein, & Atkinson, 2016;Wang et al, 2012), 5 to osteoarthritis (4 of the knee and 1 of the hip) (Barfod & Blønd, 2019;Dall'Oca et al, 2019;Jones et al, 2018;Panchal, Malanga, & Sheinkop, 2018;Schiavone Panni et al, 2019), 3 to complex anal fistula (Laureti et al, 2020;Naldini, Sturiale, Fabiani, Giani, & Menconi, 2018;Topal, Eray, Rencüzo gulları, Yalav, & Alabaz, 2019), whereas 8 studies concern different pathologies (Casarotti, Chiodera, & Tremolada, 2018;Cestaro, De Rosa, Massa, Amato, & Gentile, 2015;Cherian, Malanga, Hogaboom, Pollack, & Dyson-Hudson, 2019;Hirahara, Andersen, & Panero, 2017;Kuka et al, 2020;Lonardi et al, 2019;Saibene, Pipolo, Lorusso, Portaleone, & Felisati, 2015;Zuin et al, 2019). The interesting fact is that all the aforementioned devices are mainly used for breast reconstructions, exc...…”

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“…In a randomized controlled trial [38] the effectiveness of micro-fragmented fat tissue versus conventional treatment has been investigated in a series of patients destined for diabetic foot amputation. At 6 months, 80%, of the group treated with Lipogems MFAT healed compared to 46% of those in the group of conventional treatment.…”