Dermal Equivalent Research Articles

Optimization of conteining dermal coverages production for burn wound treatment at in vivo model

Aim. The aim was to estimate the influence of cell suspension quality on the therapeutic efficiency of cell-containing dermal coverages in animal model in vivo. Methods. We carried out the application of gel wound coverages with different quality of cellular compound on the third degree burns of ICR line mice. In the negative control group animals were treated with fresh medium-containing gel, and in positive control – by gel containing high quality cell suspension. Photo fixation of burn wound status was carried out once a day. The results were estimated by ANOVA approach. Results. There was a statistically significant difference of burn wounds development and healing between positive control and both experimental groups. The decreasing of alive cell fraction in prepared gel within 5 hours has been shown as well. Conclusions. It has been shown the dependence of wound healing properties of coatings containing cells on the cell compound quality, in particular, from the viability and integrity of cells. These results are important for developing of clinical protocols using such cell‑containing dermal equivalents.
 Keywords: burn wound, dermal equivalent, stem cells, skin substitute, tissue engineering.

Impact of Cell Density and Collagen Concentration on the Electromagnetic Properties of Dermal Equivalents in the Terahertz Band

In this paper, the measurement of collagen gels and dermal equivalents (DEs) with three kinds of fibroblast cell densities and collagen concentrations is performed, respectively, using terahertz time-domain spectroscopy (THz-TDS) in transmission mode. With the objective to reduce the thickness uncertainty, an algorithm to extract material parameters and sample thickness of thin samples simultaneously is employed. The statistical mean and standard deviation of the refractive indexes and absorption coefficients in a THz band from 0.2 to 1.5 THz are presented. It is shown that the refractive indexes of DEs drop by around 10%, whereas the absorption coefficients decrease by 20% when cell density increases by one order from 0.1 to 1 $ \text{M/mL}$ . In addition, the complex refractive indexes of DEs with 3-mg/mL collagen are higher than those with 2 $\text{mg/mL}$ , whereas the THz optical parameters of DEs with 2.5 mg/mL are the lowest. The obtained results indicate that the difference in the intrinsic biological features, initial cell density, and collagen concentration changes the tissue hydration, which in turn brings changes to the electromagnetic properties.

Biocomposites Based on Degradable Materials as Biotechnological Dermal Equivalents

Biocomposites Based on Degradable Materials as Biotechnological Dermal Equivalents

Multimodal label-free imaging of living dermal equivalents including dermal papilla cells

BackgroundDespite the significant progress in the development of skin equivalents (SEs), the problem of noninvasively assessing the quality of the cell components and the collagen structure of living SEs both before and after transplantation remains. Undoubted preference is given to in vivo methods of noninvasive, label-free monitoring of the state of the SEs. Optical bioimaging methods, such as cross-polarization optical coherence tomography (CP OCT), multiphoton tomography (MPT), and fluorescence lifetime imaging microscopy (FLIM), present particular advantages for the visualization of such SEs.MethodsIn this study, we simultaneously applied several visualization techniques for skin model examination. We investigated the structure and quality of dermal equivalents containing dermal papilla (DP) cells and dermal fibroblasts (FBs) using CP OCT, MPT, and FLIM. Both the energy metabolism of the cell components and the structuring of the collagen fibrils were addressed.ResultsBased on the data from the fluorescence lifetimes and the contributions of protein-bound NAD(P)H, a bias toward oxidative metabolism was indicated, for the first time, in both the DP cells and FBs on day 14 of SE cultivation. The CP OCT and MPT data also indicated that both DP cells and FBs structured the collagen gel in a similar manner.ConclusionIn this study, multimodal label-free imaging of the structure and quality of living dermal equivalents was implemented for the first time with the use CP OCT, MPT, and FLIM of NAD(P)H. Our data suggest that the combination of different imaging techniques provides an integrated approach to data acquisition regarding the structure and quality of dermal equivalents, minimizes the potential disadvantages of using a single method, and provides an ideal information profile for clinical and research applications.

Red light accelerates the formation of a human dermal equivalent.

Development of biomaterials' substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm-2) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.

Morphological characteristics of experimental ischemic wound healing after application of autoand hetero-fibroblasts and dermal equivalent

Цель. Изучить морфологическое строение, коллагенообразование и ангиогенез в биоптатах новообразованного эпидермиса и дермы на 19-е сутки их восстановления в экспериментальной ишемизированной ране после введения ауто- и гетерофибробластов, а также после трансплантации дермального эквивалента с гетерофибробластами.
 Методы. Исследование выполнено на 28 белых половозрелых мышах линии С57/В1 в возрасте до 1 года. Вокруг и в дно хирургической экспериментальной кожной раны в лопаточной области вводили 0,4 мл взвеси фибробластов и дермальный эквивалент в количестве 1,33 млн клеток. Биоптат заливали в парафин, окрашивали гематоксилином и эозином и по Вейгерту-Ван-Гизону.
 Результаты. Наиболее существенно на регенераторный гистогенез влияет введение аутофибробластов, когда фиксируется наибольшая толщина эпидермиса, наиболее активны ангиогенез и коллагенообразование. Вместе с тем, самым дифференцированным эпидермис становится после трансплантации в рану дермального эквивалента с гетерофибробластами.
 Вывод. Благоприятное воздействие дермального эквивалента с гетерофибробластами отличается от воздействия взвеси аутофибробластов всего на несколько процентов: толщина эпидермиса - на 4,29%, площадь коллагеновых волокон - на 2,66%, площадь кровеносных сосудов - на 4,04%, что делает такие различия недостоверными.

Laminin peptide YIGSR enhances epidermal development of skin equivalents

Since the use of animal experimentation is restricted with regard to cosmetic materials, alternative in vitro models such as skin equivalents (SEs) are needed. Laminin is one of the major non-collagenous glycoproteins. The pentapeptide YIGSR (Tyr-Ile-Gly-Ser-Arg) is a functional motif of laminin that binds to the laminin receptor. In the present study, we examined whether YIGSR could improve the reconstruction of SEs. YIGSR has no effects on monolayer cell proliferation of CCD25-Sk fibroblasts or HaCaT keratinocytes. Interestingly, YIGSR decreased TGF-β1 levels, although it promoted type Ι collagen synthesis in CCD25-Sk cells. In HaCaT cells, YIGSR decreased the expression of involucrin and loricrin, which are differentiation markers. Furthermore, YIGSR increased levels of proliferating cell nuclear antigen (PCNA), p63, and integrin α6, and decreased involucrin in SE models. In addition, two models containing YIGSR (mixed with dermal equivalents or added into media) did not show any differences in expression levels of PCNA, p63, integrin α6, and involucrin. Therefore, YIGSR is a useful agent for reconstruction of SEs, independent of its method of application. These results indicate that YIGSR stimulates epidermal proliferation and basement membrane formation while inhibiting keratinocyte differentiation of SEs. Taken together, these results indicate that YIGSR promotes the reconstruction of SEs, potentially via decreased TGF-β1 levels and consequent inhibition of epidermal differentiation.

Recapitulation of Native Dermal Tissue in a Full-Thickness Human Skin Model Using Human Collagens.

Full-thickness skin models comprise a three-dimensional dermal equivalent based on an animal-derived collagen matrix that harbors fibroblasts and an epidermal equivalent formed by keratinocytes. The functionality of both equivalents is influenced by many factors, including extracellular matrix composition and resident cell type. Animal-derived collagens differ in amino acid composition and physicochemical properties from human collagens. This composition could alter the functionality of the dermal equivalent and epidermal morphogenesis with the barrier formation in full-thickness models (FTMs). By replacement of animal-derived collagen for human collagen, we generated and characterized the animal material-free human collagen full-thickness models (hC-FTMs) that better mimic native dermal tissue. An isolation procedure to obtain soluble collagen from human abdominal dermis was developed. Both FTMs and hC-FTMs were generated with primary human fibroblasts and keratinocytes. Immunohistochemical analyses with biomarkers for the dermal matrix composition, basement membrane (BM) formation, epidermal proliferation, differentiation, and activation were performed. The stratum corneum (SC) lipid composition was studied with liquid chromatography-mass spectrometry. Lipid lamellar organization was determined by small-angle X-ray diffraction. The FTMs and hC-FTMs exhibit many similarities, including the dermal matrix structure, BM formation, epidermal basal layer proliferation, and execution of differentiation programs. The SC contains a similar number of corneocyte layers and the same level of lipids. The ceramide chain length distribution and ceramide subclass profile showed only minor differences. Subsequently, this led to an unaltered lamellar organization. The animal material-free hC-FTM is generated successfully using collagens isolated from human abdominal dermis. Utilization of human collagens revealed that (epi-)dermal morphogenesis and lipid barrier formation resembled that of original FTMs. The hC-FTMs contain a dermal equivalent that mimics the native stromal tissue to a higher extent. Therefore these in vitro skin models can be used as promising tool for research purposes that contribute to animal-free experimentation.

Comparison of two decellularized dermal equivalents

Immunologically inert allogeneic acellular dermal scaffolds provide a matrix with molecular architecture close to native tissues, which synthetic scaffolds cannot. Not all nature-derived scaffolds possess the same biological and physical properties. The different properties of scaffolds supporting cellular growth used for manufacturing tissue engineered grafts could lead to different implantation results. The scaffold properties should be carefully considered in order to meet the expected outcomes of tissue engineered grafts. In this report, we evaluated the cellular growth on AlloDerm® and Allopatch, 2 acellular scaffolds derived from human cadaver skin, using a fabricated 3D organotypic culture with primary human oral keratinocytes to produce an ex vivo produced oral mucosa equivalent (EVPOME). A well stratified epithelium could be constructed on both scaffolds. AlloDerm® and Allopatch EVPOMEs were also implanted into severe combined immunodeficiency mice to compare the ingrowth of blood vessels into the dermal component of the two EVPOMEs. Blood vessel counts were 3.3 times higher (p=.01) within Allopatch EVPOMEs than within AlloDerm® EVPOMEs. An oral and skin keratinocyte co-culture, separated by a physical barrier to create a cell-free zone, was used to evaluate cell migration on AlloDerm® and Allopatch. Slower cell migration was observed on Allopatch than on AlloDerm®.

Avian Collagen Is Useful for the Construction of Skin Equivalents

As a result of restrictions on animal experimentation, improved skin equivalents (SEs) are needed as alternative test models. This work investigated the effects of avian collagen on the construction of SEs, and to the best of our knowledge is the first study to do so. Hematoxylin and eosin and immunohistochemical staining were used to analyze the SEs. In models containing avian collagen as a dermal equivalent (DE) ingredient, fibroblast proliferation increased by about 60% relative to the control model. Immunohistochemical staining showed that the expression of proliferating cell nuclear antigen (PCNA) and p63 increased in the avian collagen models, while the expression of involucrin, integrin α₆, and integrin β₁ remained unchanged. Next, DEs were cryopreserved to allow the easier creation of SEs. Keratinocytes were seeded on thawed DEs, and SEs were constructed. Avian collagen increased the viability of DEs relative to the control. Furthermore, avian collagen increased the expression of PCNA and p63 in keratinocytes on thawed DEs. The results indicate that DEs containing avian collagen can be thawed as needed after cryopreservation. Avian collagen can improve the construction of SEs and be used as part of a dermal kit for SE construction.

Growth factor-functionalized silk membranes support wound healing in vitro

Chronic wounds represent a serious problem in daily medical routine requiring improved wound care. Silk of the domesticated silkworm (Bombyx mori) has been used to form a variety of biomaterials for medical applications. We genetically engineered B. mori to produce silk functionalized with growth factors to promote wound healing in vitro. In this study FGF-, EGF-, KGF-, PDGF- or VEGF-functionalized silk membranes were compared to native B. mori silk membranes without growth factors for their ability to support wound healing in vitro. All silk membranes were cytocompatible and supported macrophage secretion of neutrophil recruiting factor CXCL1 and monocyte chemoattractant protein 1 (MCP-1). VEGF-functionalized silk significantly outperformed other growth factor-functionalized silk membranes, but not native silk in angiogenesis assays. In addition, EGF- and VEGF-functionalized silk membranes slightly enhanced macrophage adhesion compared to silk without growth factors. In wound healing assays in vitro (reduction of wound lesion), dermal equivalents showed a higher wound healing capacity when covered with EGF-, FGF- or VEGF-functionalized silk membranes compared to native, KGF- or PDGF-functionalized silk membranes. Keratinocyte migration and growth is overstimulated by KGF- and VEGF-functionalized silk membranes. In conclusion, growth factor-functionalized silk membranes prepared from genetically engineered silk worm glands are promising wound dressings for future wound healing therapies.

561 Utilizing 3D dermal equivalents to evaluate effects of carob seed extract on dermal maturation

561 Utilizing 3D dermal equivalents to evaluate effects of carob seed extract on dermal maturation

In vitro skin models to study epithelial regeneration from the hair follicle.

The development of dermal equivalents (DEs) for the treatment of burns has contributed toward efficient wound closure. A collagen-glycosaminoglycan DE (C-GAG) grafted with hair follicles converted a full-thickness wound to partial-thickness resulting in complete wound closure and restored hair. In this study we compared the ability of both intact pilosebaceous units (PSU) or truncated hair follicles (THF) to regenerate a multilayered epidermis in vitro when implanted into de-epidermalized dermis (DED) or C-GAG with the epidermis generated in vivo using C-CAG. Keratinocytes explanted from the outer root sheath of PSU and THF in both DED and C-GAG but only formed a multilayered epidermis with PSU in DED. PSU were more effective at forming multilayered epidermis in DED than THF. Both DED and C-GAG skin expressed proliferation (PCNA), differentiation (K1, K10), hyperproliferation (K6, K16), basal (K14), putative stem cell (p63), extracellular matrix protein (Collagen IV), mesenchymal (vimentin) and adherens junction (β-catenin) markers. These data suggest DEs supported initial maintenance of the implanted hair follicles, in particular PSU, and provide an excellent model with which to investigate the regulation of hair follicle progenitor epithelial cells during epidermal regeneration. Although neither PSU nor THF formed multilayered epidermis in C-CAG in vitro, hair follicles implanted into engrafted C-GAG on a burns patient resulted in epithelial regeneration and expression of proliferation and differentiation markers in a similar manner to that seen in vitro. However, the failure of C-GAG to support epidermal regeneration in vitro suggests in vivo factors are essential for full epidermal regeneration using C-GAG.

Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices.

Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies.

Long-term homeostasis and wound healing in an in vitro epithelial stem cell niche model

Cultures of epithelial cells are limited by the proliferative capacity of primary cells and cell senescence. Herein we show that primary human epithelial cell sheets cultured without dermal equivalents maintained homeostasis in vitro for at least 1 year. Transparency of these sheets enabled live observation of pigmented melanocytes and Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) labeled epithelial cells during wound healing. Cell turn over and KRT15 expression pattern stabilized within 3 months, when KRT15 bright clusters often associated with niche-like melanocytes became apparent. EdU labels were retained in a subset of epithelial cells and melanocytes after 6 months chasing, suggesting their slow cell cycling property. FUCCI-labeling demonstrated robust cell migration and proliferation following wounding. Transparency and long-term (1 year) homeostasis of this model will be a powerful tool for the study of wound healing and cell linage tracing.

Engulfment of ceramic particles by fibroblasts does not alter cell behavior

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium–zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 μg ml−1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium–zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium–zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium–zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.

Human Umbilical Cord Wharton Jelly-Derived Adult Mesenchymal Stem Cells, in Biohybrid Scaffolds, for Experimental Skin Regeneration.

The ultimate goal for skin tissue engineering is to regenerate skin lesions to allow the full restoration of morphological and functional properties as what they were before injury. To this end, we have assembled a new prototype of a biomimetic human umbilical cord adult mesenchymal stem cell (hUCMS)/fibrin-based scaffold. We have fully characterized the proposed dermal equivalent (DE) in vitro, to assess morphological, functional, and biological properties of the encased cells. We transplanted DE subcutaneously into immunocompetent rodents, to verify its full biocompatibility. Finally, we studied DE graft effects on full-thickness wounds, in immunocompetent mice to demonstrate its capability to drive the healing process in the absence of significant scarring tissue. The excellent outcome of these in vivo studies fuels hope that this new approach, based on a biohybrid DE, may be applied to the operative treatment of skin lesions (i.e., diabetic foot ulcers and burns) in man.

MAST CELLS CONTENT IN THE STRUCTURES OF THE ISCHEMIC MODEL WOUND ON THE 12TH DAY OF REGENERATIVE POTENTIAL STIMULATION BY AUTO- AND HETEROFIBROBLASTS AND DERMAL EQUIVALENT

Mast cell is a traditional cell for wound healing, but their content in the wound after transplantation of autoand heterofibroblasts and dermal equivalent on the basis of these cells remains poorly studied. Aim. To study the morphological structure, collagen formation, angiogenesis and content of mast cells in biopsy materials of the newly formed epidermis and dermis on the 12th day of their recovery in a model ischemic wound after administration of auto- and heterofibroblasts and after transplantation of dermal equivalent with heterofibroblasts. Materials and methods . The study was performed on 28 white mature mice of the C57 / B1 line aged up to 1 year. 0.4 ml of suspension with 1.33 million fibroblasts in growth medium DMEM F12 (Lonza) and in dermal equivalent were administered around and into the bottom of skin surgical model wound in the scapular region. The scar was embedded in paraffin and stained with hematoxylin and eosin, according to Weigert-Van Gieson, and kit for mast cells staining (Biovitrum). Results . On the 12th day epidermis is thicker after introduction of autofibroblasts, but it is more differentiated after transplantation of dermal equivalent with heterofibroblasts. Angiogenesis is also most active after the administration of autofibroblasts. Fibroblasts production of collagen fibers in granulation tissue, angiogenesis and the content of functionally active mast cells indicates the most favorable influence of autofibroblasts transplantation on the wound healing. Conclusion. The effect of dermal equivalent with heterofibroblasts differs from exposure autofibroblasts by several percent: the area of collagen fibers – by 2%, the area of blood vessels − by 5%, the index of degranulation of mast cells – by 4%.

A Dermal Equivalent Engineered with TGF-β3 Expressing Bone Marrow Stromal Cells and Amniotic Membrane: Cosmetic Healing of Full-Thickness Skin Wounds in Rats.

Transforming growth factor beta-3 (TGF-β3) has been shown to decrease scar formation after scheduled topical applications to the cutaneous wounds. This study aimed to continuously deliver TGF-β3, during the early phase of wound healing, by engineering a dermal equivalent (DE) using TGF-β3 expressing bone marrow stromal cells (BM-SCs) and human dehydrated amniotic membrane (hDAM). To engineer a DE, rat BM-SCs were seeded on the hDAM and TGF-β3 was transiently transfected into the BM-SCs using a plasmid vector. Pieces of the dermal equivalent were transplanted onto the full-thickness excisional skin wounds in rats. The process of wound healing was assessed by image analysis, Manchester Scar Scale (MSS), and histopathological studies 7, 14, 21, and 85 days after the excision. The results confirmed accurate construction of recombinant pcDNA3.1-TGF-β3 expression system and showed that the transfected BM-SCs seeded on hDAM expressed TGF-β3 mRNA and protein from day 3 through day 7 after transfection. After implantation of the DE, contraction of the wounds was measured from day 7 through 21 and analyzed by linear regression, which revealed that the rate of wound contraction in all experimental groups was similar. Histologic evaluation demonstrated that transfected BM-SCs decreased retention and recruitment of the cells during the early stage of wound healing, decreased the formation of vascular structures and led to formation of uniformly parallel collagen bundles. MSS scores showed that TGF-β3 secreting cells significantly improved the cosmetic appearance of the healed skin and decreased the scar formation. From these results, it could be concluded that transient secretion of TGF-β3, during the early phase of healing, by BM-SCs seeded on hDAM can improve the cosmetic appearance of the scar in cutaneous wounds without negatively affecting the process of wound repair.

Comparative evaluation of dermal equivalent effectiveness in neuropathic/and neuroischemic form of diabetic foot syndrome

<p><strong>Aim.</strong> It was to evaluate the effectiveness of dermal equivalent application when treating ulcers in patients with neuropathic and neuroischemic forms of diabetic foot syndrome (DFS), as well as to compare it with conventional treatment. <br /><strong>Methods.</strong> The study included 60 patients with DFS neuropathic and neuroischemic forms who were treated at Purulent Surgery Departments of War Veterans Hospital and City Hospital No. 14 (Saint Petersburg, Russia) in 2013–2016 years. The patients were divided in two subgroups comparable in age and sex: subgroup A included patients with DFS neuropatic form, subgroup B – those with DFS neuroischemic form. Thus, the study group of patients was formed, who, in addition to conventional treatment of diabetic ulcers, received dermal equivalent application. To assess the effectiveness of dermal equivalent use, two control groups: 10 patients with a neuropathic form and 10 patients with a neuroischemic form of DFS were formed and routinely managed. <br /><strong>Results.</strong> 33 patients (82.5%) (18 patients from subgroup A and 15 patients from subgroup B) out of 40 patients of the study group demonstrated a significantly higher rate of epithelization (p<0.05) as compared to the corresponding subgroup in the control group. <br /><strong>Conclusion.</strong> The efficacy of dermal equivalent is higher when treating a neuropathic form of DFS. The speed of epithelization after the use of dermal equivalent in patients with a neuropathic form of DFS is higher in comparison with a neuroischemic form of DFS.</p><p>Received 5 August 2016. Accepted 23 September 2016.</p><p><strong>Funding:</strong> The study has not been sponsored or awarded a grant.<br /><strong>Conflict of interest:</strong> The authors declare no conflict interests.</p>