Search Results (17)

Introduction: Biodegradable Temporizing Matrix (BTM) is a new synthetic dermal substitute suitable for wound closure and tissue regeneration. The data in paediatric population remain limited. The study purpose is to review the indications for BTM application in paediatric patients; evaluate the short-term and long-term results, including complications and functional outcomes, as well as to share some unique observations regarding the use of BTM in paediatric population. Patients and Methods: Patients undergoing reconstructive surgery and BTM application during the last three years were included. Data collected included patient demographics, primary diagnosis, previous surgical management, post-operative complications and final outcomes. BTM was used in 32 patients. The indications varied including epidermolysis bullosa (n = 6), burns (n = 4), trauma (n = 7), infection (n = 4), ischemia or necrosis (n = 11). Results: The results were satisfying with acceptable aesthetic and functional outcomes. Complications included haematomaunderneath the BTM leading to BTM removal and re-application (n = 1), BTM infection (n = 1) and split-thickness skin graft failure on top of BTM requiring re-grafting (n = 2). Conclusions: BTM can be a good alternative to large skin grafts, locoregional flaps or even free flaps. The big advantages over other dermal substitutes or skin grafts are that BTM is less prone to infection and offers excellent scarring by preserving the normal skin architecture. Specifically in children, BTM might not require grafting, resulting in spontaneous healing with good scarring. In critically ill patients, BTM reduces the operation time and there is no donor site morbidity. BTM should be considered in the reconstructive ladder when discussing defect coverage options in children and young people. Full article

Carboxamide derivatives are a promising class of compounds in anticancer drug discovery, owing to their ability to interact with multiple oncogenic targets and their favorable pharmacological profiles. In this study, we report the design, synthesis, and biological evaluation of a series of N-substituted 1H-indole-2-carboxamides as potential anticancer agents. The synthesized compounds were assessed for antiproliferative activity using the MTT assay against MCF-7 (breast cancer), K-562 (leukemia), and HCT-116 (colon cancer) cell lines, with normal human dermal fibroblasts included as a non-cancerous control. Several compounds demonstrated notable cytotoxicity and selectivity. Compounds 12, 14, and 4 exhibited potent activity against K-562 cells, with IC₅₀ values of 0.33 µM, 0.61 µM, and 0.61 µM, respectively. Compound 10 showed the most significant activity against HCT-116 cells (IC₅₀ = 1.01 µM) with a high selectivity index (SI = 99.4). Moderate cytotoxicity was observed against MCF-7 cells. To elucidate the mechanism of action, molecular docking and induced-fit docking studies were conducted against key cancer-related targets, including topoisomerase–DNA (PDB ID: 5ZRF), PI3Kα (4L23), and EGFR (3W32), revealing favorable binding interactions. Additionally, principal component analysis of molecular descriptors indicated that the compounds possess promising drug-like and lead-like properties, particularly compound 10. Overall, this study highlights N-substituted indole-2-carboxamides as promising scaffolds for further optimization. The integration of synthetic chemistry, biological assays, and computational modeling provides a robust foundation for the continued development of these compounds as potential anticancer agents. Full article

Background and Objectives: Traditionally, full-thickness skin defects (FTSDs) are covered with split-thickness skin grafts (STSGs). This usually provides an epidermal coverage but entails a high risk of hypertrophic scarring mainly due to the absence of the dermal layer. The Novosorb^® Biodegradable Temporising Matrix (BTM) is a novel synthetic dermal substitute that has been used for the reconstruction of various complex and/or large defects in our center. The aim of this article is to evaluate the clinical performance of the BTM as a synthetic dermal substitute for complex FTSD reconstruction in a European context. Materials and methods: This case series focused on the treatment of complex FTSDs with the BTM. After wound debridement, the BTM was applied according to a defined protocol. Once adequate vascularization was observed, the sealing membrane was removed and the neo-dermis was covered with STSGs. Patient demographics, comorbidities, wound defect localization and etiology, wound bed preparations, time of BTM application and removal, time to complete wound healing after STSG, complications, and HTS formation were recorded. Results: The BTM was used to treat FTSDs in six patients with complex wounds from degloving (3), burns (1), ulcerations (1), and necrotizing fasciitis (1). Successful integration occurred in five cases (83%), with one partial integration. The BTM remained in situ for an average of 20.7 days before delamination and STSG coverage. No major complications occurred, though one case had hypergranulation with secondary STSG infection. Two patients were lost to follow-up, while the remaining four had excellent aesthetic and functional outcomes with good-quality scars. Conclusions: Within the limits of this small and heterogeneous case series, the BTM appears to be a promising option for the reconstruction of complex FTSDs of varying etiologies. Its successful integration in most cases and limited complication rate support its clinical potential. However, given this study’s retrospective design and limited sample size, further prospective studies are required to validate these findings and assess long-term outcomes. Full article

Skin and soft tissue reconstruction has long been based on the reconstructive ladder. However, a skin substitute has become popular due to its predictable outcomes, without donor-site morbidity. The biodegradable temporizing matrix (BTM; NovoSorb, PolyNovo Ltd., Port Melbourne, Australia) is a synthetic skin substitute that has recently gained its clinical application. Compared with those of other dermal templates, the clinical efficacy and performance of the BTM are not well established, especially among the Asian population. This study aims to share our experience and strategy of using BTM in various wound conditions. The data of patients who underwent skin and soft tissue reconstruction with BTM at a single institution between January 2022 and December 2023 were reviewed. The patient demographics, wound characteristics, surgical details, secondary procedures, and complications were recorded and analyzed. Postoperative 6-month photographs were collected and independently evaluated by two plastic surgeons and two wound care center nurses using the Manchester Scar Scale (MSS). This study included 37 patients, consisting of 22 males and 15 females with a mean age of 51.8 years (range, 18–86 years old). The wound etiologies included trauma (67.6%), necrotizing soft tissue infection (16.2%), burns (10.8%), toe gangrene (2.7%), and scar excision (2.7%). The average wound area covered by BTM was 50.6 ± 47.6 cm². Among the patients, eight received concomitant flap surgery and BTM implantation, 20 (54.1%) underwent subsequent split-thickness skin grafts (STSG), and 17 had small wounds (mean: 21.6 cm²) healed by secondary intention. Infection was the most common complication, affecting six patients (n = 6 [16.2%]), five of whom were treated conservatively, and only one required debridement. Thirty-three patients (89.2%) had good BTM take, and only four had BTM failure, requiring further reconstruction. At the last follow-up, 35 out of the 37 patients (94.6%) achieved successful wound closure, and the total MSS score was 10.44 ± 2.94, indicating a satisfactory scar condition. The patients who underwent BTM grafting without STSG had better scar scores than those who received STSG (8.71 ± 2.60 vs. 11.18 ± 2.84, p = 0.039). In conclusion, the BTM is effective and feasible in treating various wounds, with relatively low complication rates, and it can thus be considered as an alternative for skin and soft tissue reconstruction. When combined with adipofasical flap reconstruction, it achieves a more comprehensive anatomical restoration. Full article

Reconstructive techniques to repair severe tissue defects include the use of autologous fasciocutaneous flaps, which may be limited due to donor site availability or lead to complications such as donor site morbidity. A number of synthetic or natural dermal substitutes are in use clinically, but none have the architectural complexity needed to reconstruct deep tissue defects. The perfusion decellularization of fasciocutaneous flaps is an emerging technique that yields a scaffold with the necessary composition and vascular microarchitecture and serves as an alternative to autologous flaps. In this study, we show the perfusion decellularization of porcine fasciocutaneous flaps using sodium dodecyl sulfate (SDS) at three different concentrations, and identify that 0.2% SDS results in a decellularized flap that is efficiently cleared of its cellular material at 86%, has maintained its collagen and glycosaminoglycan content, and preserved its microvasculature architecture. We further demonstrate that the decellularized graft has the porous structure and growth factors that would facilitate repopulation with cells. Finally, we show the biocompatibility of the decellularized flap using human dermal fibroblasts, with cells migrating as deep as 150 µm into the tissue over a 7-day culture period. Overall, our results demonstrate the promise of decellularized porcine flaps as an interesting alternative for reconstructing complex soft tissue defects, circumventing the limitations of autologous skin flaps. Full article

Full-thickness skin wounds have become a serious burden to patients, medical care, and the socio-economic environment. The development of a safe and effective acellular skin substitute that can rapidly restore intact physiological skin is required. Natural bioactive materials including collagen, gelatin, and elastin possess significant advantages over synthetic biomaterials regarding biodegradability and biocompatibility. However, low mechanical strength, a faster biodegradation rate, and thermally unstable biomaterials lead to slow-healing and a high rate of post-implantation failure. To overcome these concerns, naturally occurring genipin (GNP) flavonoids were added to improve the mechanical strength, degradation rate, and thermal properties. Therefore, this study aimed to fabricate and characterize collagen–gelatin–elastin (CollaGee) biomaterials cross-linked with GNP as an acellular skin substitute potentially used in full-thickness wound healing. CollaGee at different ratios was divided into non-cross-linked and cross-linked with 0.1% GNP (w/v). The physicochemical, mechanical, and biocompatibility properties of CollaGee were further investigated. The results demonstrated that GNP-cross-linked CollaGee has better physicochemical (>50% porosity, pore size range of 100–200 µm, swelling ratio of >1000%) and mechanical properties (resilience and cross-linking degree of >60%, modulus of >1.0 GPa) compared to non-cross-linked CollaGee groups. Furthermore, both cross-linked and non-cross-linked CollaGee demonstrated pivotal cellular compatibility with no toxicity and sustained cell viability until day 7 towards human dermal fibroblasts. These findings suggest that GNP-cross-linked CollaGee could be a promising ready-to-use product for the rapid treatment of full-thickness skin loss. Full article

In organic agriculture, synthetic pesticides and treatments are substituted by natural remedies with interesting success for product yield and environmental outcomes, but the safety of these bio-based products needs to be assessed in vertebrate and human models. Therefore, in this paper we assessed the safety profile of sweet chestnut (Castanea sativa) wood distillate (WD) on the different cellular components of tissues implied in transcutaneous absorption. We investigated the viability of different cell lines mimicking the skin (HaCaT keratinocytes), mucosa (A431), connective (normal human dermal fibroblasts, NHDF) and vascular (human umbilical vein endothelial cells, HUVEC) tissues after exposure to increasing concentrations (0.04–0.5%, v/v, corresponding to 1:2800–1:200 dilutions) of WD. A short exposure to increasing doses of WD was well tolerated up to the highest concentration. Instead, following a prolonged treatment, a concentration dependent cytotoxic effect was observed. Notably, a different behavior was found with the various cell lines, with higher sensitivity to cytotoxicity by the cells with higher proliferation rate and reduced doubling time (human keratinocytes). Moreover, to exclude an inflammatory effect at the not cytotoxic WD concentrations, the expression of the main inducible markers of inflammation, cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), were assessed, and no improvement was found both after brief and prolonged exposure. In conclusion, our data exclude any inflammatory and cytotoxic effect at the lowest WD concentrations, namely 0.07% and 0.04%, mimicking some recommended dilutions of the product and the potential exposure doses for the operators in agriculture. Nevertheless, higher concentrations showed a safe profile for short time usage, but caution should be used by farmers following persistent product exposure. Full article

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)₂-quin)₂] (1), [VO(2,5-(Me)₂-quin)₂] (2) and [VO(2-Me-quin)₂] (3). Complexes 1–3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H₂O₂ in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780). Full article

Thermal injuries have been a phenomenon intertwined with the human condition since the dawn of our species. Autologous skin translocation, also known as skin grafting, has played an important role in burn wound management and has a rich history of its own. In fact, some of the oldest known medical texts describe ancient methods of skin translocation. In this article, we examine how skin grafting has evolved from its origins of necessity in the ancient world to the well-calibrated tool utilized in modern medicine. The popularity of skin grafting has ebbed and flowed multiple times throughout history, often suppressed for cultural, religious, pseudo-scientific, or anecdotal reasons. It was not until the 1800s, that skin grafting was widely accepted as a safe and effective treatment for wound management, and shortly thereafter for burn injuries. In the nineteenth and twentieth centuries skin grafting advanced considerably, accelerated by exponential medical progress and the occurrence of man-made disasters and global warfare. The introduction of surgical instruments specifically designed for skin grafting gave surgeons more control over the depth and consistency of harvested tissues, vastly improving outcomes. The invention of powered surgical instruments, such as the electric dermatome, reduced technical barriers for many surgeons, allowing the practice of skin grafting to be extended ubiquitously from a small group of technically gifted reconstructive surgeons to nearly all interested sub-specialists. The subsequent development of biologic and synthetic skin substitutes have been spurred onward by the clinical challenges unique to burn care: recurrent graft failure, microbial wound colonization, and limited donor site availability. These improvements have laid the framework for more advanced forms of tissue engineering including micrografts, cultured skin grafts, aerosolized skin cell application, and stem-cell impregnated dermal matrices. In this article, we will explore the convoluted journey that modern skin grafting has taken and potential future directions the procedure may yet go. Full article

As the largest organ in the human body, the skin has the function of maintaining balance and protecting from external factors such as bacteria, chemicals, and temperature. If the wound does not heal in time after skin damage, it may cause infection or life-threatening complications. In particular, medical treatment of large skin defects caused by burns or trauma remains challenging. Therefore, human bioengineered skin substitutes represent an alternative approach to treat such injuries. Based on the chemical composition and scaffold material, skin substitutes can be classified into acellular or cellular grafts, as well as natural-based or synthetic skin substitutes. Further, they can be categorized as epidermal, dermal, and composite grafts, based on the skin component they contain. This review presents the common commercially available skin substitutes and their clinical use. Moreover, the choice of an appropriate hydrogel type to prepare cell-laden skin substitutes is discussed. Additionally, we present recent advances in the field of bioengineered human skin substitutes using three-dimensional (3D) bioprinting techniques. Finally, we discuss different skin substitute developments to meet different criteria for optimal wound healing. Full article

Gelatin possesses biological properties that resemble native skin and can potentially be fabricated as a skin substitute for full-thickness wound treatment. The native property of gelatin, whereby it is easily melted and degraded at body temperature, could prevent its biofunctionality for various applications. This study aimed to fabricate and characterise buffalo gelatin (Infanca halal certified) crosslinked with chemical type crosslinker (genipin and genipin fortified with EDC) and physicaly crosslink using the dihydrothermal (DHT) method. A porous gelatin sponge (GS) was fabricated by a freeze-drying process followed by a complete crosslinking via chemical—natural and synthetic—or physical intervention using genipin (GNP), 1-ethyl-3-(3-dimethylaminopropyl) (EDC) and dihydrothermal (DHT) methods, respectively. The physicochemical, biomechanical, cellular biocompatibility and cell-biomaterial interaction of GS towards human epidermal keratinocytes (HEK) and dermal fibroblasts (HDF) were evaluated. Results showed that GS had a uniform porous structure with pore size ranging between 60 and 200 µm with high porosity (>78.6 ± 4.1%), high wettability (<72.2 ± 7.0°), high tensile strain (>13.65 ± 1.10%) and 14 h of degradation rate. An increase in the concentration and double-crosslinking approach demonstrated an increment in the crosslinking degree, enzymatic hydrolysis resistance, thermal stability, porosity, wettability and mechanical strength. The GS can be tuned differently from the control by approaching the GS via a different crosslinking strategy. However, a decreasing trend was observed in the pore size, water retention and water absorption ability. Crosslinking with DHT resulted in large pore sizes (85–300 µm) and low water retention (236.9 ± 18.7 g/m²·day) and a comparable swelling ratio with the control (89.6 ± 7.1%). Moreover no changes in the chemical content and amorphous phase identification were observed. The HEK and HDF revealed slight toxicity with double crosslinking. HEK and HDF attachment and proliferation remain similar to each crosslinking approach. Immunogenicity was observed to be higher in the double-crosslinking compared to the single-crosslinking intervention. The fabricated GS demonstrated a dynamic potential to be tailored according to wound types by manipulating the crosslinking intervention. Full article

Intermediate and deep second-degree skin burn injuries are an ongoing challenge for burn surgeons, with the difficult decision regarding whether to handle them with either conservative or operative methods. In this study, the outcome of similar deep second-degree skin burn injuries is shown with the example of four family members. Clinical outcomes of the four family members which were treated at our burn center in 2017 were analyzed. The areas of burned skin (IIa°-IIb°) extended from 14% to 38% of the total burned skin area. Surgical treatment was adjusted to the rate of epithelialization after the first debridement. The excellent cosmetic long-term results of this patient cohort support the importance of stage-related therapy of deep dermal burn injuries. An initial debridement followed by early coverage is the key to early reconstitution of the epidermal barrier. However, with regard to the late effects of skin substitutes, more sensory alterations, dysesthesia, hyperpigmentation and unstable skin areas are still visible after coverage with glycerol conserved skin. The best results were seen after the use of autologous STGS and synthetic skin. Full article

Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular “off the shelf” dermal template interaction in a mouse model. Full-thickness wounds in nude mice were grafted with allogenic skin, and either collagen-based or fully synthetic dermal templates. Changes in the wound bed showed significantly higher vascularisation and fibroblast infiltration in synthetic grafts when compared to collagen-based grafts (P ≤ 0.05). Greater tissue growth was associated with higher prostaglandin-endoperoxide synthase 2 (Ptgs2) RNA and cyclooxygenase-2 (COX-2) protein levels in fully synthetic grafts. Collagen-based grafts had higher levels of collagen III and matrix metallopeptidase 2. To compare the capacity to form a double layer skin substitute, both templates were seeded with human fibroblasts and keratinocytes (so-called human skin equivalent or HSE). Mice were grafted with HSEs to test permanent wound closure with no further treatment required. We found the synthetic dermal template to have a significantly greater capacity to support human epidermal cells. In conclusion, the synthetic template showed advantages over the collagen-based template in a short-term mouse model of wound repair. Full article

Hyaluronic acid (HA) is used in substitutive and aesthetic medicine with various applications. Ultrapure absorbable HA (Bioregen^®) and a mix of reticulated and free low molecular weight HA (Regenyal Idea Bioexpander^®) (both provided by Regenyal Laboratories Srl, San Benedetto del Tronto (AP), Italy) represent a reliable hydrating device and skin filler, useful for skin blemishes, lines and wrinkles, and lip widening, respectively. The commercial products are known for their safety, but data on the molecular, cellular, and tissue responses are lacking. We aimed to evaluate the bioavailability and the pro-angiogenic features of the products Bioregen^® and Bioexpander^® in vitro on cultured endothelial cells (ECs) and dermal fibroblasts in vivo when injected into experimental animals. When added to fibroblasts and ECs, Bioexpander^® induced cell migration. The two HA preparations were well tolerated, while a transient proangiogenic behavior of Bioexpander^®, when implanted subcutaneously in mice, was found. The neovascular response was evident in the first week with higher levels of VEGF and FGF-2 before undergoing regression. In conclusion, our data strengthen the safety of HA synthetic preparations both in vitro and in vivo. Even if a proangiogenic response is documented, it is modest and transient, leading to tissue recovery and absence of an inflammatory infiltrate. Full article

Skin autografts are in great demand due to injuries and disease, but there are challenges using live tissue sources, and synthetic tissue is still in its infancy. In this study, an electrocompaction method was applied to fabricate the densely packed and highly ordered collagen/sulfated xylorhamnoglycuronan (SXRGlu) scaffold which closely mimicked the major structure and components in natural skin tissue. The fabricated electrocompacted collagen/SXRGlu matrices (ECLCU) were characterized in terms of micromorphology, mechanical property, water uptake ability and degradability. The viability, proliferation and morphology of human dermal fibroblasts (HDFs) cells on the fabricated matrices were also evaluated. The results indicated that the electrocompaction process could promote HDFs proliferation and SXRGlu could improve the water uptake ability and matrices’ stability against collagenase degradation, and support fibroblast spreading on the ECLCU matrices. Therefore, all these results suggest that the electrocompacted collagen/SXRGlu scaffold is a potential candidate as a dermal substitute with enhanced biostability and biocompatibility. Full article