Preoperative Skin Conditioning: Extracellular Matrix Clearance and Skin Bed Preparation, A New Paradigm.

This paper introduces the concept of "skin bed preparation" prior to surgical procedures. Following the theory of chronic wound bed preparation and adapting the skin model to one of chronic wound changes related to extrinsic and intrinsic factors, a topical formulation aimed at recycling the extracellular matrix (ECM) from accumulated waste products is evaluated and discussed. The clearance of these products and stimulation of new replacements has the potential to change the regenerative milieu of the skin so that when procedures are carried out, cellular signaling and cross-talk at the dermal level are improved and healing is optimized. By introducing a combination of peptides and other synergistic active agents, a sequence of clearance, regeneration, and remodeling is initiated. This is confirmed and validated by a series of biopsies and clinical studies that demonstrate changes in the ECM as early as 2 to 3 weeks after application. Clinical studies related to resurfacing procedures show accelerated healing and improved symptomatic relief compared with standard of care by preconditioning the skin 2 weeks prior to the procedure. A similar approach is suggested as a potential advantage for invasive surgical procedures based on similar scientific principles elucidated on in the text

Endothelial progenitor cells and burn injury - exploring the relationship.

Burn wounds result in varying degrees of soft tissue damage that are typically graded clinically. Recently a key participant in neovascularization, the endothelial progenitor cell, has been the subject of intense cardiovascular research to explore whether it can serve as a biomarker for vascular injury. In this review, we examine the identity of the endothelial progenitor cell as well as the evidence that support its role as a key responder after burn insult. While there is conflicting evidence with regards to the delta of endothelial progenitor cell mobilization and burn severity, it is clear that they play an important role in wound healing. Systematic and controlled studies are needed to clarify this relationship, and whether this population can serve as a biomarker for burn severity

Topical Negative Pressure on Burns: An Innovative Method for Wound Exudate Collection.

Burn wound exudate is an important source of information on the wound-healing process and systemic improvement of burn patients. Identification of biomarkers for the prediagnosis of local or systemic complications in patients will have a great impact on adapting personalized procedures in burn treatment. No efficient exudate collection method exists that offers a direct and continuous collection over time. We developed an innovative system based on the negative pressure wound therapy technique to directly collect exudate from burn wounds over several days after burn. This method did not cause any complication or pain for patients, and positive influence on wound healing was seen. Exudate samples were further used in different projects for studying biochemical profile, trace element content, kinetics of bacterial growth, and cell cytotoxicity

Adipose Tissue, Regeneration, and Skin Health: The Next Regenerative Frontier.

Adipose tissue, or fat compartments, has long been considered a storage depot and an energy source. However, a large part of new research, starting with the discovery of adipose-derived stem cells, has redirected this thinking toward the tremendous regenerative capacity that adipose tissue possesses when it is healthy. This has resulted in multiple technologies being explored with fat as a basis or with fat as a target aiming at the stimulation of new small hyperplastic adipose cells exuding adipokines and encouraging the proliferation of a whole host of progenitor cells that can have positive effects on many organ systems. One of these organ systems is skin, and there is a direct correlation with various fat compartments and skin health. Dermal fat tissue, also known as dermal white adipose tissue, is one such compartment that originates from dermal preadipocytes transdifferentiating into adipocytes and progenitor adipose cells under the right cues. The author of this paper discusses these potential cues, including injectable fillers, fat grafts, and topical formulations, and their capacity to impact skin health through the generation of healthy fat tissue. In addition, small molecules such as glucagon-like peptide-1 peptides and their impact on fat tissue are discussed. Adipose tissue is being recognized as the next regenerative frontier with exciting prospects ahead

TriHex 2.0-Advancing Skin Health Science and the TriHex Technology.

BACKGROUND: The original TriHex combination-Tripeptide-1 and Hexapeptide-12 (TriHex) encompasses a peptide combination selected for its ability to modulate the extracellular matrix (ECM) by progressively eliminating clumped collagen and elastin fragments and then stimulating replacement with new collagen and elastin. Incorporation of a proprietary, patent-pending Octapeptide-45 (Octa) to the TriHex original provides potential for added benefit based on the peptides capacity to stimulate hyaluronic acid (HA) and its anticipated added benefit in wound healing. This is named TriHex 2.0 in the paper. MATERIALS AND METHODS: A full-scale validation process was structured to assess Octa synergy with TriHex using an ex vivo model, assessing ECM changes histologically in relation to elastin, HA and basement membrane components. In addition, gene expression studies were undertaken, including bulk and single cell sequencing analysis to assess the particular changes that occurred by adding Octa to the TriHex. Following the gene expression analysis, a further round of ex vivo studies was conducted to assess protein expression of the defined differentially expressed genes using histological staining. RESULTS: Octa synergized with TriHex as demonstrated by significantly upregulated genes (p < 0.05) affecting the ECM and basement membrane. A histological assessment using the ex vivo model demonstrated tropoelastin intensity significantly increasing with TriHex (43%) and 2.0 (42%) (p < 0.05 for both) compared to untreated explants. HA levels (CD44 intensity) significantly increased with TriHex (69%; p < 0.01), while TriHex 2.0 demonstrated HA levels 160% greater (p < 0.001) than the untreated tissue. Single cell sequencing identified a gene expression profile upregulation relating to ECM modulation and wound healing in both TriHex and 2.0, but TriHex 2.0 showed additional activities in basement membrane physiology, stem cell recruitment, and protection of fibroblasts against cellular senescence. CONCLUSION: The addition of Octapeptide-45 to TriHex technology in the form of TriHex 2.0 is a significant advance to TriHex technology science. Both forms demonstrate ECM remodeling and positive wound healing, but supplementary benefits are evident including increased elastin and hyaluronic acid stimulation, added effects on the basement membrane, additional wound healing capacity in basal keratinocytes and anti-senescent effects in fibroblasts. This is helpful for pre-conditioning of the skin prior to procedures and post procedure related to additional ECM remodeling, wound healing advantages, senescent cell targeting and DEJ strengthening. Clinical studies to follow

Molecularly Engineered Self-Assembling Membranes for Cell-Mediated Degradation

The use of peptide engineering to develop self-assembling membranes that are responsive to cellular enzyme activities is reported. The membranes are obtained by combining hyaluronan (HA) and a rationally designed peptide amphiphile (PA) containing a proteolytic domain (GPQGIWGQ octapeptide) sensitive to matrix metalloproteinase-1 (MMP-1). Insertion of an octapeptide in a typical PA structure does not disturb its self-assembly into fibrillar nanostructures neither the ability to form membranes with HA. In vitro enzymatic degradation with hyaluronidase and MMP-1 shows that membranes containing the MMP-1 substrate exhibit enhanced enzymatic degradation, compared with control membranes (absence of MMP-1 cleavable peptide or containing a MMP-1 insensitive sequence), being completely degraded after 7 days. Cell viability and proliferation is minimally affected by the enzymatically cleavable functionality of the membrane, but the presence of MMP-1 cleavable sequence does stimulate the secretion of MMP-1 by fibroblasts and interfere with matrix deposition, particularly the deposition of collagen. By showing cell-responsiveness to biochemical signals presented on self-assembling membranes, this study highlights the ability of modulating certain cellular activities through matrix engineering. This concept can be further explored to understand the cellular remodeling process and as a strategy to develop artificial matrices with more biomimetic degradation for tissue engineering applications.This work was funded by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme "COMPETE" (FCOMP-01-0124-FEDER-014758) and national funds through the Portuguese Foundation for Science and Technology (FCT) under the project PTDC/EBB-BIO/114523/2009. The authors also thank a start-up grant provided by the School of Engineering and Materials Science at QMUL. D.S.F. gratefully acknowledges FCT for the PhD scholarship (SFRH/BD/44977/2008)

Degloving injuries and flap viability assessment

Degloving injuries are associated with major morbidity. The management of these injuries is still not resolved. The method of management used by the authors involves the harvesting of split skin from the surface of the flap and assessment of flap viability based on surface dennal capillary bleeding. The skin grafts are then used to cover denuded areas. This technique has proved to be effective, time-saving and morbidity-reducing in the cases reviewed here and in recent publications.The issue addressed in this trial was the effect of partial de-epithelialisation on the survival length of a flap. Two groups of dorsal rat flaps were compared. In one group, the flaps were raised and restitched after a period of time and in the second group, the surfaces of identical flaps were partially de-epithelialised and then restitched. The survival length of these flaps was compared, as well as the metabolic responses to surgery in the two groups. No statistically significant differences were found in these 2 groups. It was concluded that partial de-epithelialisation did not have a detrimental effect on duration of flap length survival, thus encouraging the continued use of the clinical technique described above in the handling of degloving injuries

Adipogenic Effect of Magnolol in Primary Human Pre-Adipocytes With Potential Skin Health and Volumizing Effect.

BACKGROUND: Aging is associated with fat atrophy and fibrosis with loss of adipocyte differentiation from preadipocytes. New approaches to this loss involve agents that can renew the proliferative and differentiative capacities of preadipocytes with the aim of creating new healthy adipose tissue that secrete adipokines that positively impact on skin health. MATERIAL & METHODS: We investigated the effect of Magnolol (ML), a naturally derived compound, on human primary pre-adipocyte viability and proliferation as well as adipogenic gene expression and increase in lipid production. Cell proliferation was assessed using fluorescent signaling, and adipocyte differentiation was monitored by following morphological and microscopic changes. RNA purification and real-time PCR were undertaken to examine gene expression changes, and Oil red O staining was used to confirm adipose cell transformation. Adipokine expression, in particular adiponectin quantification, was also undertaken. RESULTS: Magnolol, at a relatively low concentration, demonstrated clear adipogenic activity: with a significant increase in preadipocyte proliferation after 48 h and a significant accumulation of adipocytes as demonstrated by oil red staining. Increased gene expression of PLN1 and FABP4 and a significant increase in adiponectin protein expression was demonstrated. CONCLUSION: Magnolol stimulates preadipocyte proliferation and conversion to adipokine-producing adipocytes. This has the potential for a positive skin health and volumizing effect if used in a topical formulation

A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ(2) 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison

Antioxidants with proven efficacy and elastin‐conserving vitamin C—A new approach to free radical defense

BackgroundThis paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen radicals. Secondly, the investigation into whether a vitamin C derivative sodium salt was elastin conserving in contrast to current vitamin C/l-ascorbic acid variations that have been reported to negatively affect elastin constitution and regeneration.Materials and methodsA leading l-ascorbic acid antioxidant available on the market was compared with the experimental new product in two studies. In the first experiment, the products were compared to assess their antioxidant properties. The evaluated products TOPICAL ANTIOXIDANT 1 and TOPICAL ANTIOXIDANT 2 were applied to human skin cultures (25-30 mg/cm2 ) for a total of 72 h of treatment and exposed to oxidative stress. The generation of free radicals was semi-quantitatively assessed by measuring the fluorescence intensity of the deacetylation and oxidation of the probe dichlorofluorescein diacetate (DCFH-DA). In the second experiment, an ex vivo skin model (derived from patients undergoing facelift procedures) was used to assess elastin preservation. Three skin explants were topically subjected to the two formulations daily for 7 days. The skin was then prepared and fixed for immunofluorescent assessment after staining with CD44 and tropoelastin antibodies. Images were then analyzed using ImageJ.ResultsA full description of the different components selected for the new formulation is presented. In the first study, the experimental formulation performed with absolute equivalence to the comparator in its radical quenching capacity; both showed extremely effective antioxidant function. In the second study, the comparator negatively affected the existing elastin with areas of breakdown and diminished staining. In contrast, the new formulation showed good conservation of healthy elastin in all sections demonstrating elastin preservation.ConclusionA new antioxidant formulation was carefully designed with multiple actives that show an equivalent antioxidant capacity to a leading product on the market. More importantly, the vitamin C component shows direct elastin conservation and improvement as opposed to the comparator, which had negative effects on elastin preservation. This is in keeping with little-known literature reports on vitamin C and its negative effects on elastin and validates the use of a sodium salt derivative, which appears to have protective effects on elastin. These findings support the overall regenerative extracellular matrix changes seen with TriHex® technology in other products