Search Results (99)

Dermal drug delivery is a promising alternate route of drug administration, offering localized therapeutic effects, reduced systemic effects, and improved patient compliance. However, the skin’s intricate configuration, especially the stratum corneum (SC), presents formidable barriers, restricting drug permeation. This review summarizes biological, synthetic, and methodological models employed to study dermal absorption and permeability. Ex vivo human skin is a reference point, but limited availability and ethical constraints necessitate reliance on animal models, including porcine, rodent, rabbit, monkey, and even snake skin, each with unique advantages and drawbacks. Synthetic substitutes, e.g., reconstructed human epidermis and Strat-M^® membranes, provide reproducibility and economic practicality, though none fully mimic the barrier functions of human skin. Innovative analytical methods, including diffusion cells, skin-PAMPA, tape stripping, and advanced imaging techniques, enable quantitative, semi-quantitative, and qualitative insights into drug transport. Collectively, these tools support formulation optimization and aid regulatory bioequivalence assessments. However, challenges remain in correlating in vitro, ex vivo, and in vivo outcomes and in replicating the skin’s dynamic physiology. This review highlights current opportunities and limitations, emphasizing the need for more physiologically relevant models to advance safe, effective, and innovative dermal drug delivery systems. Full article

The exposure of endothelial cells to high glucose concentrations promotes angiogenesis. The present study investigated whether this pro-angiogenic effect of glucose is suitable to improve the capability of nanofat to vascularize implanted dermal substitutes. Nanofat was processed from white adipose tissue originating from green fluorescent protein (GFP)⁺ C57BL/6J donor mice and incubated for 1 h in Hank’s Balanced Salt Solution with or without (control) a high level of glucose (30 mM). The pretreated nanofat was seeded onto dermal substitutes, which were analyzed by intravital fluorescence microscopy, histology and immunohistochemistry in dorsal skinfold chambers of GFP⁻ C57BL/6J mice to assess their vivo performance over a period of 14 days. A high level of glucose-pretreated nanofat did not induce a stronger immune response when compared to the control. However, it improved the vascularization of the implants, as shown by a significantly higher density of blood-perfused microvessels in the border zones (~3.6-fold increase) and more CD31⁺/GFP⁺ microvessels (~3-fold increase) inside the implants. Accordingly, high glucose-pretreated nanofat levels also enhanced the tissue integration of the dermal substitutes, as indicated by the deposition of more type I collagen (~2.9-fold increase). These findings suggest that the short-term exposure of nanofat to a high level of glucose represents a promising and clinically feasible strategy to enhance its regenerative properties when seeded onto dermal substitutes. Full article

Burn injuries remain a complex clinical challenge, particularly in reconstructive settings where donor sites are limited. Integra^® Dermal Regeneration Template (IDRT), a bilayer dermal substitute, facilitates neodermis formation and supports functional and aesthetic recovery following burn trauma. This narrative review and expert opinion synthesizes current literature and clinical experience on the application of IDRT in post-burn reconstruction. It discusses the biological mechanism of dermal regeneration, surgical protocols including wound bed preparation and grafting, and considerations for anatomical regions such as the face, torso, and limbs. The review emphasizes key factors influencing successful outcomes, including patient selection, timing, and multidisciplinary coordination. Potential complications, such as infection, hematoma, and poor graft adherence, are addressed along with prevention and management strategies. Special considerations for pediatric and elderly populations are also highlighted. Through evidence-based insights and illustrative case examples, this review aims to inform surgical decision-making and promote best practices in reconstructive burn care using IDRT. Full article

Background: The treatment of burns is a socio-economic challenge for both patients and the National Health Service. Early debridement and skin graft reduces the risk of local and systemic complications. However, when skin autografting is unfeasible or contraindicated, alternative options are required. Recent research has introduced new potential tools: fish skin grafts (FSGs). This systematic review focuses on FSGs with the aim of improving the management of burn patients. Methods: A systematic search on articles concerning FSG for the treatment of burns was performed by searching PubMed, Web of Science and Embase according to the PRISMA statement. Clinical trials, retrospective studies, case series and case reports were included. Results: A total of 36 studies were identified through the search strategy and imported for screening. After duplicate removal, 26 studies were considered. Based on predetermined criteria, 20 full texts were assessed for eligibility, leaving 18 articles to be included in the systematic review. Conclusions: By virtue of the safety and effectiveness of FSGs, including low risk of zoonosis transmission and valuable outcomes even in austere environments, FSGs could represent a new alternative for the treatment of burns. Full article

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 haematoma underneath 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

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Soft tissue reconstruction in patients with upper extremity necrotizing soft tissue infections (NSTIs) can be challenging; these defects can be large with exposed critical structures. Following appropriate source control and debridement, soft tissue reconstruction is based on size, exposed structures, medical co-morbidities and the physiologic status of the patient. There are multiple options for soft tissue coverage from local wound care to free tissue transfer. Dermal substitutes can help prepare a healthy wound bed that can later accept a skin graft. Local rotational flaps, distant pedicled flaps and free flaps are also options depending on the patient and the defect. Patients can have good functional outcomes after soft tissue reconstruction after upper extremity NSTI. Full article

Considered one of the most severe types of trauma with a high impact upon patient survival, burns are the leading cause of disability-adjusted life-years (DALYs), and are responsible for high morbidity, prolonged hospitalization, disfigurement and social stigma. Of particular interest are injuries that affect the functional areas: face, neck, hand and fingers, joints, feet and soles and perineum. Burns to these regions highly influence the day-to-day activities of patients due to the formation of vicious scars and contractures, which may affect both quality of life and functional capacity. One of the primary challenges in the management of burn patients is the effective coverage of tissue defects resulting from such injuries. Cases that have a large area of burned surface also have a limited amount of total available skin. As such, the importance of skin substitutes increases, particularly in the treatment of these areas. Skin substitutes are widely utilized in plastic surgery due to their ability to promote wound healing by providing an extracellular matrix. Consequently, ongoing research has focused on developing skin substitutes that can serve as alternatives to autografts, addressing the challenges associated with large-scale tissue loss. This article aims to present and compare the most used skin substitutes, highlighting their respective advantages and limitations. This topic continues to be a subject of significant debate, as an ideal substitute has yet to be created. The cost–efficiency ratio is a practical consideration that must be tailored to each specific medical system. The available data in the literature usually present general guidelines, not rules, and as such, they need to be adapted to each patient’s necessities. 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

Background: Organ transplant recipients are at a significantly higher risk of developing skin cancer compared to the general population, particularly cutaneous squamous cell carcinoma. Approximately 3–8% of these carcinomas are located on the scalp. Scalp reconstruction is particularly challenging, especially for large excisions, due to the thickness of the scalp, the inelastic aponeurosis of the galea, and the integrity of the hair-bearing scalp. Additionally, in organ transplant recipients, the presence of numerous comorbidities and the increased risk of infection due to immunosuppressive therapy make management more complex. Based on our experience and the existing literature, we aim to describe possible reconstruction methods and discuss the combined management of medical and immunosuppressive therapy. Method: We present our experience with seven kidney transplant patients who underwent excision of cutaneous squamous cell carcinoma with a diameter larger than 3 cm. The crane technique involves three key steps. First, the tumor is excised with wide margins of disease-free tissue. Next, a pericranial flap is rotated and positioned to cover the exposed cranial bone. Finally, a bilayer dermal substitute is applied to create a microenvironment that supports skin graft implantation. Results: The crane technique was used for six patients. In one case, an O-Z rotation flap was used. All patients modified their immunosuppressive therapy, with those receiving antiproliferative therapy switching everolimus after surgery. Conclusions: When combined with a post-operative modification of the immunosuppressive regimen, the crane technique could be considered a feasible, safe, and effective approach to managing large cSCC of the scalp in fragile patients. Full article

Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: DNP63A, GRHL2, TFAP2A, and MYC) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac^® dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac^® dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications. Full article

Wound infection is the leading cause of delayed wound healing. Despite ongoing research, the ideal treatment for full-thickness skin wounds is yet to be achieved. Skin tissue engineering provides an alternative treatment, with the potential for skin regeneration. Background/Objectives: Previously, we characterized a collagen–gelatin–elastin (CollaGee) acellular skin substitute and evaluated its cytocompatibility. The assessments revealed good physicochemical properties and cytocompatibility with human dermal fibroblasts (HDF). This study aimed to incorporate thymoquinone (TQ) as the antibacterial agent into CollaGee biomatrices and evaluate their cytocompatibility in vitro. Methods: Briefly, dose–response and antibacterial studies were conducted to confirm the antimicrobial activity and identify the suitable concentration for incorporation; 0.05 and 0.1 mg/mL concentrations were selected. Then, the cytocompatibility was evaluated quantitatively and qualitatively. Results: Cytocompatibility analysis revealed no toxicity towards HDFs, with 81.5 + 0.7% cell attachment and 99.27 + 1.6% cell viability. Specifically, the 0.05 mg/mL TQ concentration presented better viability, but the differences were not significant. Immunocytochemistry staining revealed the presence of collagen I, vinculin, and alpha smooth muscle actin within the three-dimensional biomatrices. Conclusions: These results suggest that TQ-incorporated CollaGee biomatrices are a promising candidate for enhancing the main key player, HDF, to efficiently regenerate the dermal layer in full-thickness skin wound healing. Further investigations are needed for future efficiency studies in animal models. Full article

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)⁺ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra^®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP⁺ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility. Full article

Background: Radiation therapy is a crucial component of breast cancer treatment. However, it is well known to increase the risk of unsatisfactory cosmetic outcomes and higher complication rates. The aim of this study is to provide further insight into the use of acellular dermal matrices (ADMs) for the prevention of capsular contracture. Materials and Methods: This single-center, retrospective study analyzed irradiated patients who underwent post-mastectomy, ADM-assisted implant reconstructions. Of the 60 patients included, 26 underwent expander-to-implant substitution after radiotherapy (Group A), while 34 required implant replacement due to capsular contracture following radiotherapy (Group B). The primary objective was to evaluate the effectiveness of ADMs in reducing reconstructive failures, complications, and capsular contracture after breast irradiation. Results: We recorded a total of 15 complications and four implant losses. Reconstructive failures were attributed to implant exposure in two cases, full-thickness skin necrosis in one case, and severe Baker grade IV contracture in one case. Both Group A and Group B showed a significant decrease in postoperative Baker grades. US follow-up was used to demonstrate ADM integration with host tissues over time. Conclusions: Based on our findings, the use of ADM in selected cases appears to be a viable option for treating and preventing capsular contracture in irradiated breasts. This approach is associated with relatively low complication rates, a low rate of reconstructive failure, and satisfactory cosmetic outcomes and can be applied both in breast reconstructed with implants and with expanders. Full article

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties. Full article