Single-Center Experience with Mass Paraquat Exposure in Nine Patients

Paraquat dichloride is a widely used, highly toxic chemical herbicide and a significant cause of fatal poisonings. Toxicity is thought to be secondary to generation of reactive oxygen species. Hours after exposure, patients may experience signs and symptoms ranging from nausea to multi-system organ failure. To mitigate complications and death, immunosuppression with cyclophosphamide and corticosteroid-based therapies have shown to be an effective option in limited studies. Our objective is to report our center’s experience treating patients that had been exposed to paraquat over a two-day period. Patients were identified using our Institutional Burn Center registry, and linked to the clinical and administrative data. Demographics, length of stay, costs and mortality were evaluated. There were nine patients admitted from the exposure. All were male. All survived. Eight were undocumented migrant farmers. The average age was 36 years (25-59 years). The average length of stay was 3.3 days (2-5 days). Seventy-eight percent had cutaneous injury, but only one required debridement and placement of a skin substitute. Thirty-three percent complained of continued shortness of breath after discharge. Average total hospital cost was $28,131 ($9,500-$51,000). Paraquat is a highly toxic herbicide and exposure can be fatal if not treated promptly. Immediate decontamination and repeated pulse therapy with cyclophosphamide and methylprednisolone may be life-saving.

Skin Substitute Preparation Method Induces Immunomodulatory Changes in Co-Incubated Cells through Collagen Modification

Chronic ulcerative and hard-healing wounds are a growing global concern. Skin substitutes, including acellular dermal matrices (ADMs), have shown beneficial effects in healing processes. Presently, the vast majority of currently available ADMs are processed from xenobiotic or cadaveric skin. Here we propose a novel strategy for ADM preparation from human abdominoplasty-derived skin. Skin was processed using three different methods of decellularization involving the use of ionic detergent (sodium dodecyl sulfate; SDS, in hADM 1), non-ionic detergent (Triton X-100 in hADM 2), and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We next evaluated the immunogenicity and immunomodulatory properties of this novel hADM by using an in vitro model of peripheral blood mononuclear cell culture, flow cytometry, and cytokine assays. We found that similarly sourced but differentially processed hADMs possess distinct immunogenicity. hADM 1 showed no immunogenic effects as evidenced by low T cell proliferation and no significant change in cytokine profile. In contrast, hADMs 2 and 3 showed relatively higher immunogenicity. Moreover, our novel hADMs exerted no effect on T cell composition after three-day of coincubation. However, we observed significant changes in the composition of monocytes, indicating their maturation toward a phenotype possessing anti-inflammatory and pro-angiogenic properties. Taken together, we showed here that abdominoplasty skin is suitable for hADM manufacturing. More importantly, the use of SDS-based protocols for the purposes of dermal matrix decellularization allows for the preparation of non-immunogenic scaffolds with high therapeutic potential. Despite these encouraging results, further studies are needed to evaluate the beneficial effects of our hADM 1 on deep and hard-healing wounds.

Accelerating skin barrier repair using novel bioactive magnesium-doped nanofibers of non-mulberry silk fibroin during wound healing

Novel magnesium doped non-mulberry silk fibroin nanofibers with ability to enhance skin barrier function were successfully fabricated using electrospinning technique for wound healing applications. Magnesium nanoparticles incorporated in the electrospun nanofibers releases Mg2+ ions at the site of implementation. The effect of Mg2+ is of considerable concern in wound healing due to its skin barrier repair ability and its role in blood coagulation. The physicochemical characterization of the scaffold was investigated by determining the morphology and secondary structure confirmation. The effects of Mg2+ ions in silk fibroin microenvironment have been evaluated using SEM, XRD, and FTIR to confirm the incorporation of magnesium in the film. The aim of this study is to see the effect of doped Mg on the structural, physical, and biological properties of non-mulberry silk fibroin (NSF) film. The magnesium doped nanofibrous film exhibited enhanced mechanical property, satisfactory blood clotting ability, and good in vitro degradability. This silk fibroin-based film mimicking extracellular matrix for skin regeneration were constructed using electrospinning technique. The wound healing efficiency of prepared nanofibers were evaluated in full-thickness wound models of rat. The Mg doped silk fibroin film exhibited faster wound healing activity (14 days) among all experimental group. The study indicates the potential of magnesium-doped silk /PVA film as skin substitute film.

Assessment of the Impact of Decellularization Methods on Mechanical Properties of Biocomposites Used as Skin Substitute

This work aimed to assess the impact of acellularization and sterilization methods on the mechanical properties of biocomposites used as a skin substitute. On the basis of the statistical analysis, it was ascertained that the values of the Young modulus for the samples before the sterilization process—only in the cases of substances such as: trypsin, 15% glycerol and dispase—changed in a statistically significant way. In the case of dispase, the Young modulus value before the sterilization process amounted to 66.6 MPa, for trypsin this value equalled 33.9 MPa, whereas for 15% glycerol it was 11 MPa. In the case of samples after the completion of the sterilization process, the analysis did not show any statistically significant differences between the obtained results of Young’s modulus depending on the respective reagents applied. It was confirmed that different methods of acellularization and the process of sterilization effect the alteration of mechanical properties of allogeneic skins. In the case of the decellularization method using SDS (Sodium Dodecyl Sulfate), liquid nitrogen and 85% glycerol the highest values of strain were observed. In the authors’ opinion, it is the above-mentioned methods that should be recommended in the process of preparation of skin substitutes.

Development of a Multi-Layer Skin Substitute Using Human Hair Keratinic Extract-Based Hybrid 3D Printing

Large-sized or deep skin wounds require skin substitutes for proper healing without scar formation. Therefore, multi-layered skin substitutes that mimic the genuine skin anatomy of multiple layers have attracted attention as suitable skin substitutes. In this study, a novel skin substitute was developed by combining the multi-layer skin tissue reconstruction method with the combination of a human-derived keratinic extract-loaded nano- and micro-fiber using electrospinning and a support structure using 3D printing. A polycaprolactone PCL/keratin electrospun scaffold showed better cell adhesion and proliferation than the keratin-free PCL scaffold, and keratinocytes and fibroblasts showed better survival, adhesion, and proliferation in the PCL/keratin electrospun nanofiber scaffold and microfiber scaffold, respectively. In a co-culture of keratinocytes and fibroblasts using a multi-layered scaffold, the two cells formed the epidermis and dermal layer on the PCL/keratin scaffold without territorial invasion. In the animal study, the PCL/keratin scaffold caused a faster regeneration of new skin without scar formation compared to the PCL scaffold. Our study showed that PCL/keratin scaffolds co-cultured with keratinocytes and fibroblasts promoted the regeneration of the epidermal and dermal layers in deep skin defects. Such finding suggests a new possibility for artificial skin production using multiple cells.

Surviving an Extensive Burn Injury Using Advanced Skin Replacement Technologies

There have been significant improvements in the technology available for treating extensive burns in the past decade. This case presents two unique, skin replacement technologies that were used to treat an 86% surface area flame burn in a pediatric patient. A temporary dermal replacement, known as “Novosorb™ Biodegradable Temporizing Matrix” was first used to stabilize the burn injury and remained in place for approximately three months. Given the large burn size and lack of available donor skin for grafting, a permanent skin replacement product known as “Self-Assembled Skin Substitute (SASS)” was then utilized to cover the burns. SASS is a novel technology that was developed to replace skin as an autologous skin graft and is currently available in Canada through a clinical trial for major burns. Ultimately, the concurrent use of these two technologies allowed for the unprecedented survival of a child following an extensive and life-threatening burn injury.

Comparison of Skin Substitutes for Acute and Chronic Wound Management

Chronic and acute wounds, such as diabetic foot ulcers and burns, respectively, can be difficult to treat, especially when autologous skin transplantations are unavailable. Skin substitutes can be used as a treatment alternative by providing the structural elements and growth factors necessary for reepithelialization and revascularization from a nonautologous source. As of 2020, there are 76 commercially available skin substitute products; this article provides a review of the relevant literature related to the major categories of skin substitutes available.

Clinical and cost efficacy of advanced wound care matrices in the treatment of venous leg ulcers: a systematic review

Background: Venous leg ulcers (VLUs) are hard-to-heal, recurrent and challenging to treat. Advanced wound care matrices (AWCMs) have been developed to supplement conventional therapies. These costly AWCMs warrant careful comparison as healthcare expenditures are subjected to increasing scrutiny. Aim: This study was designed to compare AWCMs in their ability to heal VLUs and their cost efficacy through a systematic review of randomised controlled trials (RCTs). Method: An organised search of Medline, Cochrane Library, Central and CINAHL databases identified RCTs that compared AWCMs to standard compression therapy in the healing of VLUs. Bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. Eight studies analysing bilayered skin substitute (BSS) (Apligraf), dehydrated human amnion/chorion membrane (dHACM) (Epifix), human fibroblast-derived dermal substitute (HFDDS) (Dermagraft), extracellular wound matrix (ECM) (Oasis), advanced matrix (AM) (Talymed) and matrix wound dressing (MWD) (Promogran) met the inclusion criteria. Results: Four studies reported significant improvement over standard therapy: BSS, dHACM, ECM and AM. Incremental cost per additional successful treatment was determined for each trial, ranging from $2593 (MWD) to $210,800 (HFDDS). Conclusion: Our consolidated analysis of eight major RCTs of AWCMs in the treatment of VLUs revealed a great variation in clinical and cost efficacy among these products. The included trials were inconsistent in methodology, and these limitations should be noted, but, in the absence of RCTs to compare these products, our systematic review may serve as a guide for practitioners who seek to optimise wound healing while considering cost efficacy.