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      Using 3D Bioprinted Autologous Minimally Manipulated Homologous Adipose Tissue for Limb Salvage in Treating Diabetic Foot Ulcer

      research-article
      , MD 1 , , MD 1
      Archives of Plastic Surgery
      Thieme Medical Publishers, Inc.
      adipose tissue, bioprinting, diabetic foot, limb salvage

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          Abstract

          Reconstructive surgeons face challenges when considering limb salvage methods for the treatment of diabetic foot ulcers (DFUs). In this article, we present our experience with autologous fat grafting as a viable alternative in cases where flap reconstruction is difficult. We encountered a 78-year-old female patient with a nonhealing DFU who had multiple comorbidities, including renal failure and severe peripheral arterial disease. During the initial multidisciplinary meeting, due to extensive necrosis and osteomyelitis, amputation was recommended. However, the patient expressed a strong preference for a salvage procedure and refused amputation. After careful consideration, we opted to reconstruct the patient's foot using three-dimensional bioprinted autologous minimally manipulated homologous adipose tissue. The AMHAT was engrafted well without complications such as autolysis, graft failure, or infection. After the operation, the large defect with partial bone exposure was covered with healthy granulation tissue. The size of the wound decreased to less than half its original size after 6 weeks of surgery, and it decreased to less than 25% after 12 weeks of surgery. The AMHAT may be an appealing treatment option for diabetic foot patients who are unsuitable for flap reconstruction due to comorbidities.

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          Most cited references15

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          Long-Term Prognosis of Diabetic Foot Patients and Their Limbs

          OBJECTIVE There is a dearth of long-term data regarding patient and limb survival in patients with diabetic foot ulcers (DFUs). The purpose of our study was therefore to prospectively investigate the limb and person survival of DFU patients during a follow-up period of more than 10 years. RESEARCH DESIGN AND METHODS Two hundred forty-seven patients with DFUs and without previous major amputation consecutively presenting to a single diabetes center between June 1998 and December 1999 were included in this study and followed up until May 2011. Mean patient age was 68.8 ± 10.9 years, 58.7% were male, and 55.5% had peripheral arterial disease (PAD). Times to first major amputation and to death were analyzed with Kaplan-Meier curves and Cox multiple regression. RESULTS A first major amputation occurred in 38 patients (15.4%) during follow-up. All but one of these patients had evidence of PAD at inclusion in the study, and 51.4% had severe PAD [ankle-brachial pressure index ≤0.4]). Age (hazard ratio [HR] per year, 1.05 [95% CI, 1.01–1.10]), being on dialysis (3.51 [1.02–12.07]), and PAD (35.34 [4.81–259.79]) were significant predictors for first major amputation. Cumulative mortalities at years 1, 3, 5, and 10 were 15.4, 33.1, 45.8, and 70.4%, respectively. Significant predictors for death were age (HR per year, 1.08 [95% CI, 1.06–1.10]), male sex ([1.18–2.32]), chronic renal insufficiency (1.83 [1.25–2.66]), dialysis (6.43 [3.14–13.16]), and PAD (1.44 [1.05–1.98]). CONCLUSIONS Although long-term limb salvage in this modern series of diabetic foot patients is favorable, long-term survival remains poor, especially among patients with PAD or renal insufficiency.
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            Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review.

            High mortality rates have been reported after major amputations of a lower limb secondary to diabetes and peripheral vascular disease. However, the mortality rates have varied across studies. A systematic review of the 5-year mortality after nontraumatic major amputations of the lower extremity was conducted. A data search was performed of Medline using OVID, CINHAL, and Cochrane, 365 abstracts were screened, and 79 full text articles were assessed for eligibility. After review, 31 studies met the inclusion and exclusion criteria. Overall, the 5-year mortality rate was very high among patients with any amputation (major and minor combined), ranging from 53% to 100%, and in patients with major amputations, ranging from 52% to 80%. Mortality after below-the-knee amputation ranged from 40% to 82% and after above-the-knee amputation from 40% to 90%. The risk factors for increased mortality included age, renal disease, proximal amputation, and peripheral vascular disease. Although our previous systematic review of the 5-year mortality after ulceration had much lower rates of death, additional studies are warranted to determine whether amputation hastens death or is a marker for underlying disease severity.
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              Autologous micro-fragmented adipose tissue for the treatment of diabetic foot minor amputations: a randomized controlled single-center clinical trial (MiFrAADiF)

              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).
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                Author and article information

                Journal
                Arch Plast Surg
                Arch Plast Surg
                10.1055/s-00051611
                Archives of Plastic Surgery
                Thieme Medical Publishers, Inc. (333 Seventh Avenue, 18th Floor, New York, NY 10001, USA )
                2234-6163
                2234-6171
                10 April 2024
                May 2024
                1 April 2024
                : 51
                : 3
                : 332-336
                Affiliations
                [1 ]Department of Plastic and Reconstructive Surgery, Soonchunhyang University College of Medicine, Seoul, Korea
                Author notes
                Address for correspondence Woo Jin Song, MD Department of Plastic and Reconstructive Surgery, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine 59, Daesagwan-ro, Yongsan-gu, SeoulKorea pswjsong@ 123456schmc.ac.kr
                Author information
                http://orcid.org/0009-0001-1797-080X
                http://orcid.org/0000-0002-8957-3950
                Article
                APS-23-Jun-0381-CR
                10.1055/a-2263-7957
                11081718
                58aeff9d-744e-4e45-ba02-a11eb7a76028
                The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ )

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 June 2023
                : 29 January 2024
                Funding
                Funded by: Soonchunhyang University Research Fund
                Award ID: 2023-0051
                Funding This research was supported by Soonchunhyang University Research Fund (Grant No. 2023-0051).
                Categories
                Research/Experimental
                Idea and Innovation

                Surgery
                adipose tissue,bioprinting,diabetic foot,limb salvage
                Surgery
                adipose tissue, bioprinting, diabetic foot, limb salvage

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