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García Botero et al. Plast Aesthet Res 2018;5:15 I http://dx.doi.org/10.20517/2347-9264.2018.09 Page 3 of 8

Current treatment of venous ulcers involves the application of compression therapy, with bandages or hosiery,
along with different dressing types applied beneath the compression bandage or hosiery to enhance healing,
create a humid environment and control exudates. However, several studies have reported non-significant
differences when applying dressing types regarding time of healing and numbers of healed ulcers .
[2]
The advancement of new biotechnologies has focused on the development of alternative therapies such
as growing tissue in vitro, production of recombinant growth factors and tissue engineering. The use of
autologous-derived products from the patient’s blood, along with collagen or fibrin matrices, with or without
cultured cells and autologous growth factors, has been suggested as an alternative therapy for treatment
of chronic ulcers . In vitro studies with animal models have reported a beneficial effect of growth factors,
[9]
specifically platelet-derived growth factor (PDGF), fibroblast growth factor and granulocyte-macrophage
colony-stimulating factor, on the proportion of healed ulcers [10-12] .

Fibrin matrices are a cost-effective option for ulcer management. Their source is from the blood of the same
patient and they provide scaffolding for tissue growth, migration and cell regeneration. The beneficial effects
of the fibrin matrix may be enhanced when it is used in conjunction with growth factors that stimulates cell
proliferation.

The objective of the present review is to evaluate the available evidence for effective management of venous
leg ulcers with autologous fibrin matrix with or without growth factors.

METHODS
We did a systematic review of studies evaluating the use of fibrin matrices with or without growth factors for
the management of chronic venous ulcers in lower limbs. All studies were included without date restrictions.
Articles searched in MEDLINE and EMBASE databases were performed in English. Available systematic
reviews were searched in COCHRANE, and preliminary results and ongoing clinical trials were searched at
ClinicalTrial.gov. The MESH terms corresponding to “fibrin” and “matrix”, and “venous ulcer” were used in
the search. The article searched was restricted to human reports. The LILACS database was used for searches
in Spanish and Portuguese languages. Intervention was defined as the application of any autologous fibrin
matrix (from the same patient with or without growth factors, for the treatment of venous ulcers in lower
limbs).

Criteria for inclusion
The criteria for inclusion were studies evaluating patients with peripheral vascular disease of venous origin,
who exhibited venous ulcers in lower limbs and received treatment with fibrin matrices with or without
growth factors. Patients with chronic venous ulcers unhealed after 8 weeks of standard medical treatment.

Criteria for exclusion
Studies involving patients with ulcers of arterial origin or “mixed etiology” (defined as: ulcers from a
combination of arterial and venous origin, venous insufficiency in pregnant women), patients with chronic
osteomyelitis, diabetes with ulcers in the lower limbs, Marjolin’s ulcers (ulcerating squamous cell carcinoma),
malignant or terminal disease with an incidence of ≥ 5 years, thermic, electric or radiation burns on the
ulcerated area, vasculitis, chronic liver diseases, autoimmune diseases treated with immunosuppressant’s,
chemotherapy or radiotherapy, and diseases that affect wound healing, such as kidney insufficiency (patients
in dialysis or receiving therapy following a kidney transplant), were excluded.

Also, studies of patients with concomitant use of others substances or products different than those evaluated
in the present review, and those focused on compression instead of dressing therapy for the treatment of
venous ulcers were excluded from the present literature review.
[13]