First Results on Three Patients Treated with Topical Recombinant Human Erythropoietin (rhEPO) to Improve Wound Healing in Diabetic Foot Ulcers

Abstract Background Adipose-derived mesenchymal stem cells (ADSCs) are an important focus in regenerative medicine. However, the biological function of ADSCs in the wound repair of diabetic foot ulcers (DFUs) remains unclear. This study aimed to determine the underlying mechanisms of ADSCs involved in the wound healing of DFUs. Methods The cell surface markers cluster of differentiation 34 (CD34), stromal cell antigen 1 (Stro-1), cluster of differentiation 90 (CD90) and cluster of differentiation 105 (CD105) on ADSCs were identified by flow cytometry. Oil Red O staining and Alizarin Red S staining were performed to identify the multipotential differentiation of ADSCs into adipocytes and bone. The levels of Methyltransferase-like 3 (METTL3), vascular endothelial growth factor C (VEGF-C) and insulin-like growth factor 2 binding protein 2 (IGF2BP2) were assessed by RT-qPCR. CCK-8, Transwell and tubule formation assays were conducted to assess lymphatic endothelial cell (LEC) viability, migration and tubule formation ability, respectively. RIP and RNA pulldown assays were conducted to assess the interaction between IGF2BP2 and VEGF-C. The levels of VEGF-C, VEGFR3, LYVE-1 and IGF2BP2 proteins were assessed by Western blotting. The levels of VEGF-C in LECs were measured by ELISA. Results Our findings illustrated that ADSCs accelerate LEC proliferation, migration and lymphangiogenesis via the METTL3 pathway and regulate VEGF-C expression via the METTL3/IGF2BP2-m6A pathway VEGF-C-mediated lymphangiogenesis via the METTL3/IGF2BP2-m6A pathway in DFU mice. Conclusion ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing in DFUs, indicating that ADSCs may be regarded as a promising therapeutic strategy to promote wound healing in DFUs.

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Attack of the NETs! NETosis primes IL-1β-mediated inflammation in diabetic foot ulcers

Clinical Science ◽

10.1042/cs20200240 ◽

2020 ◽

Vol 134 (12) ◽

pp. 1399-1401

Author(s):

Man K.S. Lee ◽

Gopalkrishna Sreejit ◽

Prabhakara R. Nagareddy ◽

Andrew J. Murphy

Keyword(s):

Wound Healing ◽

Diabetic Foot ◽

Healing Process ◽

Foot Ulcers ◽

Wound Healing Process ◽

Inflammasome Activation ◽

Diabetic Foot Ulcers ◽

Nlrp3 Inflammasome Activation ◽

Improve Wound Healing ◽

Insight Into

Abstract In volume 133 issue 4 of Clinical Science, Liu et al. showed that neutrophils release extracellular traps (NETs) in the setting of diabetes which acts as a stimulus for NLRP3 inflammasome activation in macrophages to promote IL1β-dependent exacerbation of inflammation. They also provide evidence to show that degrading NETs improves the wound healing process. These findings provide an insight into how NETs communicate with other cells in the vicinity (e.g. macrophages) to exacerbate the inflammatory response. Most importantly, they provide novel avenues to improve wound healing process such as diabetic foot ulcers (DFUs) by targeting NETs.

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A study of effectiveness of topical recombinant human platelet derived growth factor for wound healing in patients with chronic diabetic foot ulcers at tertiary health care center

Medpusle International Journal of Surgery ◽

10.26611/1061028 ◽

2019 ◽

Vol 10 (2) ◽

pp. 62-64

Author(s):

Shirish Maskepatil ◽

◽

Sanjay Prabu Warad ◽

Keyword(s):

Health Care ◽

Wound Healing ◽

Growth Factor ◽

Diabetic Foot ◽

Human Platelet ◽

Care Center ◽

Platelet Derived Growth Factor ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Health Care Center

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The Mesenchymal Stem Cell-Derived Exosomal Long Noncoding RNA H19 Promotes Wound Healing in Diabetic Foot Ulcers by Up-Regulating PTEN via MicroRNA-152-3p

SSRN Electronic Journal ◽

10.2139/ssrn.3408040 ◽

2019 ◽

Author(s):

Bo Li ◽

Song Luan ◽

Jing Chen ◽

Yue Zhou ◽

Tingting Wang ◽

...

Keyword(s):

Wound Healing ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Diabetic Foot ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Foot Ulcers ◽

Diabetic Foot Ulcers

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Punch Grafting for the Management of Hard-to-Heal Diabetic Foot Ulcers: A Prospective Case Series

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211031085 ◽

2021 ◽

pp. 153473462110310

Author(s):

Marta García-Madrid ◽

Irene Sanz-Corbalán ◽

Aroa Tardáguila-García ◽

Raúl J. Molines-Barroso ◽

Mateo López-Moral ◽

...

Keyword(s):

Wound Healing ◽

Clinical Outcomes ◽

Diabetic Foot ◽

Donor Site ◽

Case Series ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Wound Debridement ◽

Prospective Case Series

Punch grafting is an alternative treatment to enhance wound healing which has been associated with promising clinical outcomes in various leg and foot wound types. We aimed to evaluate the clinical outcomes of punch grafting as a treatment for hard-to-heal diabetic foot ulcers (DFUs). Six patients with chronic neuropathic or neuroischemic DFUs with more than 6 months of evolution not responding to conventional treatment were included in a prospective case series between May 2017 and December 2020. All patients were previously debrided using an ultrasound-assisted wound debridement and then, grafted with 4 to 6 mm punch from the donor site that was in all cases the anterolateral aspect of the thigh. All patients were followed up weekly until wound healing. Four (66.7%) DFUs were located in the heel, 1 (16.7%) in the dorsal aspect of the foot and 1 (16.7%) in the Achilles tendon. The median evolution time was 172 (interquartile range [IQR], 25th-75th; 44-276) weeks with a median area of 5.9 (IQR; 1.87-37.12) cm2 before grafting. Complete epithelization was achieved in 3 (50%) patients at 12 weeks follow-up period with a mean time of 5.67 ± 2.88 weeks. Two of the remaining patients achieved wound healing at 32 and 24 weeks, respectively, and 1 patient showed punch graft unsuccessful in adhering. The median time of wound healing of all patients included in the study was 9.00 (IQR; 4.00-28.00) weeks. The wound area reduction (WAR) at 4 weeks was 38.66% and WAR at 12 weeks was 88.56%. No adverse effects related to the ulcer were registered through the follow-up period. Autologous punch graft is an easy procedure that promotes healing, achieving wound closure in chronic DFUs representing an alternative of treatment for hard-to-heal DFUs in which conservative treatment has been unsuccessful.

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Therapeutic Properties of Honey for the Management of Wounds; Is There a Role in the Armamentarium of Diabetic Foot Ulcer Treatment? Results From In vitro and In vivo Studies

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211026819 ◽

2021 ◽

pp. 153473462110268

Author(s):

Ioanna A. Anastasiou ◽

Ioanna Eleftheriadou ◽

Anastasios Tentolouris ◽

Georgia Samakidou ◽

Nikolaos Papanas ◽

...

Keyword(s):

Wound Healing ◽

Diabetic Foot ◽

Diabetic Animal ◽

Cochrane Library ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Diabetic Wound ◽

Diabetic Wound Healing ◽

Therapeutic Properties

Diabetic foot ulcers are one of the most dreadful complications of diabetes mellitus and efforts to accelerate diabetic wound healing are of paramount importance to prevent ulcer infections and subsequent lower-limb amputations. There are several treatment approaches for the management of diabetic foot ulcers and honey seems to be a safe and cost-effective therapeutic approach on top of standard of care. The aim of this review was to summarize the therapeutic properties of honey and the data regarding its possible favorable effects on diabetic wound healing. A literature search of articles from 1986 until April 2021 was performed using MEDLINE, EMBASE, and the Cochrane Library to assess for studies examining the therapeutic wound healing properties of honey, it's in vitro effect, and the efficacy and/or mechanism of action of several types of honey used for the treatment of diabetic animal wounds. Honey has antioxidant, anti-inflammatory, and antibacterial properties and in vitro studies of keratinocytes and fibroblasts, as well as studies in diabetic animal models show that treatment with honey is associated with increased re-epithelialization and collagen production, higher wound contraction, and faster wound healing. The use of honey could be a promising approach for the management of diabetic foot ulcers.

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Surgical Treatment of Diabetic Foot Ulcers Complicated by Osteomyelitis with Gentamicin-Loaded Calcium Sulphate-Hydroxyapatite Biocomposite

Journal of Clinical Medicine ◽

10.3390/jcm10020371 ◽

2021 ◽

Vol 10 (2) ◽

pp. 371

Author(s):

Kor H. Hutting ◽

Wouter B. aan de Stegge ◽

Jaap J. van Netten ◽

Wouter A. ten Cate ◽

Luuk Smeets ◽

...

Keyword(s):

Wound Healing ◽

Surgical Treatment ◽

Treatment Regimen ◽

Diabetic Foot ◽

Prospective Trial ◽

Calcium Sulphate ◽

Foot Ulcers ◽

Ulcer Recurrence ◽

Diabetic Foot Ulcers ◽

Cox Regression Analysis

Diabetic foot ulcers, complicated by osteomyelitis, can be treated by surgical resection, dead space filling with gentamicin-loaded calcium sulphate-hydroxyapatite (CaS-HA) biocomposite, and closure of soft tissues and skin. To assess the feasibility of this treatment regimen, we conducted a multicenter retrospective cohort study of patients after failed conventional treatments. From 13 hospitals we included 64 patients with forefoot (n = 41 (64%)), midfoot (n = 14 (22%)), or hindfoot (n = 9 (14%)) ulcers complicated by osteomyelitis. Median follow-up was 43 (interquartile range, 20–61) weeks. We observed wound healing in 54 patients (84%) and treatment success (wound healing without ulcer recurrence) in 42 patients (66%). Treatment failures (no wound healing or ulcer recurrence) led to minor amputations in four patients (6%) and major amputations in seven patients (11%). Factors associated with treatment failures in univariable Cox regression analysis were gentamicin-resistant osteomyelitis (hazard ratio (HR), 3.847; 95%-confidence interval (CI), 1.065–13.899), hindfoot ulcers (HR, 3.624; 95%-CI, 1.187–11.060) and surgical procedures with gentamicin-loaded CaS-HA biocomposite that involved minor amputations (HR, 3.965; 95%-CI, 1.608–9.777). In this study of patients with diabetic foot ulcers, complicated by osteomyelitis, surgical treatment with gentamicin-loaded CaS-HA biocomposite was feasible and successful in 66% of patients. A prospective trial of this treatment regimen, based on a uniform treatment protocol, is required.

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