Elsevier

Acta Biomaterialia

Volume 9, Issue 7, July 2013, Pages 7093-7114
Acta Biomaterialia

Review
Recent advances on the development of wound dressings for diabetic foot ulcer treatment—A review

https://doi.org/10.1016/j.actbio.2013.03.033Get rights and content

Abstract

Diabetic foot ulcers (DFUs) are a chronic, non-healing complication of diabetes that lead to high hospital costs and, in extreme cases, to amputation. Diabetic neuropathy, peripheral vascular disease, abnormal cellular and cytokine/chemokine activity are among the main factors that hinder diabetic wound repair. DFUs represent a current and important challenge in the development of novel and efficient wound dressings. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, remove wound exudate and promote tissue regeneration. However, no existing dressing fulfills all the requirements associated with DFU treatment and the choice of the correct dressing depends on the wound type and stage, injury extension, patient condition and the tissues involved. Currently, there are different types of commercially available wound dressings that can be used for DFU treatment which differ on their application modes, materials, shape and on the methods employed for production. Dressing materials can include natural, modified and synthetic polymers, as well as their mixtures or combinations, processed in the form of films, foams, hydrocolloids and hydrogels. Moreover, wound dressings may be employed as medicated systems, through the delivery of healing enhancers and therapeutic substances (drugs, growth factors, peptides, stem cells and/or other bioactive substances). This work reviews the state of the art and the most recent advances in the development of wound dressings for DFU treatment. Special emphasis is given to systems employing new polymeric biomaterials, and to the latest and innovative therapeutic strategies and delivery approaches.

Introduction

Diabetes mellitus is one of the most prevalent chronic diseases: in 2010, it was estimated that 285 million adults worldwide had diabetes and this figure is expected to rise to 439 million by 2030 [1], [2]. In North America and Europe, the number of adults with diabetes is expected to increase by 42.4% and 20%, respectively, and a major burst in Africa is predicted, with the number of adults with diabetes expected to increase by 98.1% from 2010 to 2030 [1], [2] (Fig. 1). The main factors responsible for the increase in the number of patients with diabetes are the growth and aging of the population and changes in lifestyle [1], [3]. Diabetes mellitus is a metabolic disorder characterized by high levels of glucose in serum and by changes in carbohydrate, lipid and protein metabolism which are caused by alterations in insulin secretion, in insulin action or in both of these processes [4]. Diabetes can be classified into type 1, type 2 and gestational diabetes. Type 1, insulin-dependent diabetes mellitus (IDDM), or juvenile-onset diabetes, is characterized by pancreatic β-cell destruction, leading to absolute insulin deficiency and, consequently, to the total dependence on exogenous insulin to sustain life [4], [5]. The incidence of type 1 diabetes is usually higher under the age of 15 though only 20-50% of patients are diagnosed before this age. In addition, the Caucasian population tends to present a higher risk for type 1 diabetes when compared to all other ethnic groups [6]. Type 2 diabetes mellitus, also known as non-insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes, is characterized by insulin resistance which may be combined with relatively reduced insulin secretion levels. Type 2 diabetes affects approximately 90% of all diabetic patients and its main risk factors are high plasma glucose concentrations in the fasting state and after an oral glucose load, being overweight and a sedentary lifestyle [7]. However, this type of diabetes can be delayed or prevented by a proper nutrition regime and by regular physical exercise [8], [9]. Finally, gestational diabetes or impaired glucose intolerance, which is first diagnosed during pregnancy, is defined as carbohydrate intolerance during gestation [10]. Gestational diabetes affects approximately 14% of pregnancies and is also an important risk factor for type 2 diabetes in women [11], [12].

In addition and among other problems, diabetic patients are more likely to develop obesity [13], [14], [15], [16], coronary heart disease, stroke [17], [18], [19], diabetic nephropathy [20], [21], [22], [23], diabetic retinopathy [24], [25], [26], [27] and diabetic neuropathy [28], [29], [30], [31]. These diseases are largely responsible for the observed high mortality rates in diabetic patients.

Section snippets

Diabetic foot ulcers (DFUs) and impaired wound healing

Wound healing is a complex process that involves the simultaneous actuation of soluble mediators, blood cells, extracellular matrix (ECM) and parenchymal cells. This process can be divided into several phases: homeostasis/coagulation, inflammation, proliferation (granulation tissue formation), re-epithelialization and remodeling [32], [33]. These phases are not typically associated with a rigorous and well-defined period of time and may overlap [30], [34], [35], [36]. The transition between

Types and main characteristics of wound dressings

Natural skin is considered the perfect wound dressing and therefore an ideal wound dressing should try to replicate its properties [66]. Historically, wound dressings were first considered to play only a passive and protective role in the healing process. However, in recent decades wound treatment has been revolutionized by the discovery that moist dressings can help wounds heal faster [67], [68]. Furthermore, a moist wound environment is also an important factor to induce the proliferation and

Future trends and perspectives

DFUs are a frequent complication of diabetes that may lead to severe and persistent infection and, in extreme cases, to lower-extremity amputation. Therapeutics usually involves the use of dressings, aiming to enhance the life quality of DFU patients, to alleviate pain, to deliver drugs and to reduce odors. The necessity to develop and improve the efficacy of wound dressings, particularly suitable for DFU treatment, has been a challenge for both researchers and clinicians. An ideal dressing

Acknowledgements

This work was financially supported by COMPETE and Fundação para a Ciência e Tecnologia (FCT-MES) under contracts, PTDC/SAU-BEB/71395/2006, PTDC/SAU-MII/098567/2008, PTDC/SAU-FAR/121109/2010, PEst-C/SAU/LA0001/2011, by EFSD/JDRF/Novo Nordisk European Programme in Type 1 Diabetes Research and Sociedade Portuguesa de Diabetologia. L.I.F.M. and A.M.A.D. acknowledge FCT-MES for their fellowships SFRH/BD/60837/2009 and SFRH/BPD/40409/2007, respectively.

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