Treatment of venous ulcers with growth factors: systematic review and meta-analysis

Carvalho, Magali Rezende de; Silveira, Isabelle Andrade; Oliveira, Beatriz Guitton Renaud Baptista de

doi:10.1590/0034-7167-2017-0865

Cited by 17 publications

(20 citation statements)

References 34 publications

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“…Evidence to support the use of PRP to enhance the chronic VLUs healing is deficient. Recent systematic reviews and meta‐analyses and a Cochrane review made a recommendation supporting its use only in diabetic foot wounds but in other wounds, including the VLU, the conclusions were conflicting 8,12,13 . The included studies, in these reviews, enrolled different types of ulcers, with only five studies investigating the use of PRP in a pure sample of venous ulcers 10,11,15‐17 .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, most studies included wounds of different aetiologies, making the conclusion for the treatment effect on a single entity difficult. Additionally, the net number of VLUs included was relatively small to draw significant results, and the follow up periods were mostly short leaving no chance to detect any possible mid‐ or long‐term effect of this method to reduce recurrence 12,13 …”

Section: Introductionmentioning

confidence: 99%

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Autologous platelet‐rich plasma injection enhances healing of chronic venous leg ulcer: A prospective randomised study

El‐Barbary

Hassan

Elbendak

2020

International Wound Journal

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Our aim was to compare the efficacy and safety of platelet‐rich plasma (PRP) application versus PRP injection for chronic venous leg ulcer (VLU) healing compared with compression therapy as a control. From July 2018 to December 2019, 90 chronic VLU patients were randomly assigned to PRP dressings (n = 30), local PRP injections (n = 30), and compression therapy alone (n = 30). Standard compression accompanied both PRP groups. The main endpoints were ulcer healing and area reduction within 3, 6, and 12 months. Complications and ulcer recurrence were also recorded. The study included 72 (80.0%) males and 18 (20.0%) females aged 22 to 66 years, having VLUs for 1 to 11 years. PRP injection promoted healing (24/30, 80%) more than PRP application (20/30, 66.7%) and compression (14/30, 46.7%), P = .007. Healing time was significantly shorter after PRP injection compared with the other two groups. A greater area reduction was observed after PRP injection compared with compression at all follow‐up visits, P = .013, .002, and < .001, and compared with PRP application only at 3 months post‐treatment, P = .016. Recurrence and complications were comparable among the groups. PRP injection enhances the healing of chronic venous ulcers more than each of PRP application and compression therapy. All had comparable recurrence and safety.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autologous platelet‐rich plasma injection enhances healing of chronic venous leg ulcer: A prospective randomised study

El‐Barbary

Hassan

Elbendak

2020

International Wound Journal

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“…These growth factors include plateletderived growth factor, transforming growth factor, epidermal growth factor, keratinocyte growth factor, and fibroblast growth factor. A recent meta-analysis evaluating 10 studies consisting of 472 in the intervention group (growth factors) and 330 as control determined that there was moderate bias in the study design and that, although tendencies toward healing VLU were present, none reached statistical significance [172]. Further studies with sound methodology, frequency, and duration of growth factor application and proper control are required before strong recommendations can be made.…”

Section: Latest Innovations In Surgical Treatment and Drug Therapiesmentioning

confidence: 99%

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Raffetto

Ligi

Maniscalco

et al. 2020

JCM

146

114

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Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50–70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

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“…In general, minor injuries which do not affect the dermal layer, also referred to as superficial wounds, can be completely self-healing, while major injuries involving deeper dermal layers defined as full-thickness wounds heal slowly and are susceptible to the development of abnormal fibrotic scars or chronic inflammation. For large cutaneous lesions, traditional therapies such as debridement, addition of growth factors, or dressing of the wounds have been used in clinical practice [2][3][4]. Nonetheless, delayed healing, excessive fibrotic healing, and development of chronic inflammation remain great challenges.…”

Section: Introductionmentioning

confidence: 99%

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

et al. 2020

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Background: Factors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton's jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice. Methods: First, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism. Results: PF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group. (Continued on next page)Conclusions: SAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.

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Treatment of venous ulcers with growth factors: systematic review and meta-analysis

Cited by 17 publications

References 34 publications

Autologous platelet‐rich plasma injection enhances healing of chronic venous leg ulcer: A prospective randomised study

Autologous platelet‐rich plasma injection enhances healing of chronic venous leg ulcer: A prospective randomised study

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

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