WHS guidelines for the treatment of pressure ulcers-2023 update.

The major populations at risk for developing pressure ulcers are older adults who have multiple risk factors that increase their vulnerability, people who are critically ill and those with spinal cord injury/disease. The reported prevalence of pressure ulcers in the United States is 2.5 million. However, this estimate is derived from acute care facilities and does not include people who are living at home or in nursing facilities. Despite the implementation of hospital and facility-based preventive measures, the incidence of pressure ulcers has not decreased in decades. In addition to the burden of pain, infection and death, it is estimated that hospital-acquired pressure ulcers cost the health system $26.8 billion annually with over 50% of the cost attributed to treating Stage 3 and 4 pressure injuries. Thus, it is critical to examine the literature and develop guidelines that will improve the outcomes of this complex and costly condition. This guideline update is a compendium of the best available evidence for the treatment of Pressure Ulcers published since the last update in 2015 and includes a new section based on changing demographics entitled 'Palliative wound care for seriously ill patients with pressure ulcers'. The overall goal of the Wound Healing Society Guideline project is to present clear, concise and commercial free guidelines that clinicians can use to guide care, that researchers can use to develop studies that will improve treatment and that both clinicians and researchers can use to understand the gaps in our knowledge base.

A comparative study between staple line reinforcement during laparoscopic sleeve gastrectomy and no reinforcement: an Egyptian experience.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become an increasingly popular bariatric procedure. LSG still conveys some risks, including early staple line complications such as bleeding and leaks. It has been proposed that staple line complications can be reduced by staple line reinforcement (SLR). This study aimed to compare the short-term efficacy and safety of the SLR during LSG by oversewing versus no SLR in an Egyptian cohort over a period of 11 years. PATIENTS AND METHODS: This is a retrospective study that analyzed data from patients undergoing LSG by the same surgeon over a period of 11 years. The patients' early postoperative complications were compared according to performing SLR. RESULTS: The SLR group showed significantly longer surgery time (p = 0.021) and a lower rate of postoperative bleeding (p = 0.027). All leakage cases occurred in the non-SLR group (0.7% vs. 0.0%) without statistical significance (p = 0.212). The two mortality cases occurred in the non-SLR group. The LOS was comparable in the two groups (p = 0.289). CONCLUSION: This study confirms the short-term benefits of SLR by oversewing during LSG in terms of a lower incidence of 30-day morbidity, particularly bleeding, and lower rates of reoperation, with a clinically questionable longer operation time.

Perioperative Morbidity and Mortality of Laparoscopic Sleeve Gastrectomy (LSG) in a Single-Surgeon Experience on 892 Patients Over 11 Years.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been the most frequently performed bariatric procedure since 2014, with continually growing popularity. This study aimed to present our 30-day morbidity and mortality following LSG over a period of 11 years. PATIENTS AND METHODS: This is a retrospective study that was based on prospectively collected data from patients undergoing LSG by the same surgeon from July 2011 to the end of August 2022. The LSG-associated 30-day morbidity and mortality and the risk factors for 30-day morbidity were assessed. RESULTS: This study included 892 patients who underwent LSG over the course of 11 years. Early postoperative adverse events were encountered in 16 patients (1.79%). Overall, twelve patients (1.35%) required blood transfusions, and two patients (0.22%) required ICU admission. The re-operation rate was 0.9% (n = 8) and the mortality rate was 0.22% (n = 2). The patient's BMI, hypertension, and revisional surgery were marginally significant/significant predictors of early postoperative morbidity. The mean EBWL% was 63.8 ± 15.55 at the 6-month follow-up. CONCLUSION: This study confirms the previously reported LSG's short-term safety in terms of a low rate of 30-day postoperative morbidity and mortality. Preoperative BMI, hypertension, and revisional surgery are risk factors for 30-day morbidity and mortality.

Swine Model of Biofilm Infection and Invisible Wounds.

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the involvement of the host immune system. Iterative changes in the host and pathogen during the formation of such clinically relevant biofilm can only occur in vivo. The swine wound model is recognized for its advantages as a powerful pre-clinical model. There are several reported approaches for studying wound biofilms. In vitro and ex vivo systems are deficient in terms of the host immune response. Short-term in vivo studies involve acute responses and, thus, do not allow for biofilm maturation, as is known to occur clinically. The first long-term swine wound biofilm study was reported in 2014. The study recognized that biofilm-infected wounds may close as determined by planimetry, but the skin barrier function of the affected site may fail to be restored. Later, this observation was validated clinically. The concept of functional wound closure was thus born. Wounds closed but deficient in skin barrier function may be viewed as invisible wounds. In this work, we seek to report the methodological details necessary to reproduce the long-term swine model of biofilm-infected severe burn injury, which is clinically relevant and has translational value. This protocol provides detailed guidance on establishing an 8 week wound biofilm infection using P. aeruginosa (PA01). Eight full-thickness burn wounds were created symmetrically on the dorsum of domestic white pigs, which were inoculated with (PA01) at day 3 post-burn; subsequently, noninvasive assessments of the wound healing were conducted at different time points using laser speckle imaging (LSI), high-resolution ultrasound (HUSD), and transepidermal water loss (TEWL). The inoculated burn wounds were covered with a four-layer dressing. Biofilms, as established and confirmed structurally by SEM at day 7 post-inoculation, compromised the functional wound closure. Such an adverse outcome is subject to reversal in response to appropriate interventions.

Robust critical limb ischemia porcine model involving skeletal muscle necrosis.

This work sought to develop a robust and clinically relevant swine model of critical limb ischemia (CLI) involving the onset of ischemic muscle necrosis. CLI carries about 25-40% risk of major amputation with 20% annual mortality. Currently, there is no specific treatment that targets the ischemic myopathy characteristic of CLI. Current swine models of CLI, with tolerable side-effects, fail to achieve sustained ischemia followed by a necrotic myopathic endpoint. Such limitation in experimental model hinders development of effective interventions. CLI was induced unilaterally by ligation-excision of one inch of the common femoral artery (CFA) via infra-inguinal minimal incision in female Yorkshire pigs (n = 5). X-ray arteriography was done pre- and post-CFA transection to validate successful induction of severe ischemia. Weekly assessment of the sequalae of ischemia on limb perfusion, and degree of ischemic myopathy was conducted for 1 month using X-ray arteriography, laser speckle imaging, CTA angiography, femoral artery duplex, high resolution ultrasound and histopathological analysis. The non-invasive tissue analysis of the elastography images showed specific and characteristic pattern of increased muscle stiffness indicative of the fibrotic and necrotic outcome expected with associated total muscle ischemia. The prominent onset of skeletal muscle necrosis was evident upon direct inspection of the affected tissues. Ischemic myopathic changes associated with inflammatory infiltrates and deficient blood vessels were objectively validated. A translational model of severe hindlimb ischemia causing ischemic myopathy was successfully established adopting an approach that enables long-term survival studies in compliance with regulatory requirements pertaining to animal welfare.

Bacterial Pyocyanin Inducible Keratin 6A Accelerates Closure of Epithelial Defect under Conditions of Mitochondrial Dysfunction.

Repair of epithelial defect is complicated by infection and related metabolites. Pyocyanin (PYO) is one such metabolite that is secreted during Pseudomonas aeruginosa infection. Keratinocyte (KC) migration is required for the closure of skin epithelial defects. This work sought to understand PYO-KC interaction and its significance in tissue repair. Stable Isotope Labeling by Amino acids in Cell culture proteomics identified mitochondrial dysfunction as the top pathway responsive to PYO exposure in human KCs. Consistently, functional studies showed mitochondrial stress, depletion of reducing equivalents, and adenosine triphosphate. Strikingly, despite all stated earlier, PYO markedly accelerated KC migration. Investigation of underlying mechanisms revealed, to our knowledge, a previously unreported function of keratin 6A in KCs. Keratin 6A was PYO inducible and accelerated closure of epithelial defect. Acceleration of closure was associated with poor quality healing, including compromised expression of apical junction proteins. This work recognizes keratin 6A for its role in enhancing KC migration under conditions of threat posed by PYO. Qualitatively deficient junctional proteins under conditions of defensive acceleration of KC migration explain why an infected wound close with deficient skin barrier function as previously reported.

Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair.

Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.

Pseudomonas Aeruginosa Theft Biofilm Require Host Lipids of Cutaneous Wound.

OBJECTIVE: This work addressing complexities in wound infection, seeks to test the reliance of bacterial pathogen Pseudomonas aeruginosa (PA) on host skin lipids to form biofilm with pathological consequences. BACKGROUND: PA biofilm causes wound chronicity. Both CDC as well as NIH recognizes biofilm infection as a threat leading to wound chronicity. Chronic wounds on lower extremities often lead to surgical limb amputation. METHODS: An established preclinical porcine chronic wound biofilm model, infected with PA or Pseudomonas aeruginosa ceramidase mutant (PA ∆Cer ), was used. RESULTS: We observed that bacteria drew resource from host lipids to induce PA ceramidase expression by three orders of magnitude. PA utilized product of host ceramide catabolism to augment transcription of PA ceramidase. Biofilm formation was more robust in PA compared to PA ∆Cer . Downstream products of such metabolism such as sphingosine and sphingosine-1-phosphate were both directly implicated in the induction of ceramidase and inhibition of peroxisome proliferator-activated receptor (PPAR)δ, respectively. PA biofilm, in a ceram-idastin-sensitive manner, also silenced PPARδ via induction of miR-106b. Low PPARδ limited ABCA12 expression resulting in disruption of skin lipid homeostasis. Barrier function of the wound-site was thus compromised. CONCLUSIONS: This work demonstrates that microbial pathogens must co-opt host skin lipids to unleash biofilm pathogenicity. Anti-biofilm strategies must not necessarily always target the microbe and targeting host lipids at risk of infection could be productive. This work may be viewed as a first step, laying fundamental mechanistic groundwork, toward a paradigm change in biofilm management.

Driving adult tissue repair via re-engagement of a pathway required for fetal healing.

Fetal cutaneous wound closure and repair differ from that in adulthood. In this work, we identify an oxidant stress sensor protein, nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), that is abundantly expressed in normal fetal epidermis (and required for fetal wound closure), though not in adult epidermis, but is variably re-induced upon adult tissue wounding. NPGPx is a direct target of the miR-29 family. Following injury, abundance of miR-29 is lowered, permitting a prompt increase in NPGPx transcripts and protein expression in adult wound-edge tissue. NPGPx expression was required to mediate increased keratinocyte migration induced by miR-29 inhibition in vitro and in vivo. Increased NPGPx expression induced increased SOX2 expression and ß-catenin nuclear localization in keratinocytes. Augmenting physiologic NPGPx expression via experimentally induced miR-29 suppression, using cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides, proved to be sufficient to overcome the deleterious effects of diabetes on this specific pathway to enhance tissue repair.

Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss.

This work rests on our non-viral tissue nanotransfection (TNT) platform to deliver MyoD (TNTMyoD) to injured tissue in vivo. TNTMyoD was performed on skin and successfully induced expression of myogenic factors. TNTMyoD was then used as a therapy 7 days following volumetric muscle loss (VML) of rat tibialis anterior and rescued muscle function. TNTMyoD is promising as VML intervention.

Filamentous bacteriophage delays healing of Pseudomonas-infected wounds.

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

A study of red blood cell alloimmunization and autoimmunization among 200 multitransfused Egyptian ß thalassemia patients.

The development of hemolytic erythrocyte alloantibodies and autoantibodies complicates transfusion therapy in thalassemia patients. These antibodies ultimately increase the need for blood and intensify transfusion complications. There is a scanty data on the frequency of RBC alloimmunization and autoimmunization in Egyptian ß thalassemia patients as pretransfusion antibody screening is not routinely performed. We studied the frequency of alloimmunization and autoimmunization among 200 multiply transfused ß thalassemia patients and investigated the factors that possibly affect antibody formation. Of the 200 patients in our study, 94 were males and 106 females, with the age range of 2-37 years. Alloantibodies were detected in 36 (18%) of the patients, while autoantibodies were detected in 33 (16.5%). The dominant alloantibodies were directed against Kell (33%) and Rh (24.4%) groups. Alloimmunization had a significant relationship with treatment duration and the frequency of transfusion (P = 0.007, 0.001, respectively). The presence of autoantibodies was significantly related to age (P = 0.001), total number of transfused units (P = 0.000) and splenectomy (P = 0.000). The high prevalence of alloimmunization in the study population disclosed the need for providing phenotypically matched cells for selective antigens especially for Kell and Rh subgroups to reduce risk of alloimmunization and increase the efficiency of blood transfusion.

High resolution ultrasound imaging for repeated measure of wound tissue morphometry, biomechanics and hemodynamics under fetal, adult and diabetic conditions.

Non-invasive, repeated interrogation of the same wound is necessary to understand the tissue repair continuum. In this work, we sought to test the significance of non-invasive high-frequency high-resolution ultrasound technology for such interrogation. High-frequency high-resolution ultrasound imaging was employed to investigate wound healing under fetal and adult conditions. Quantitative tissue cellularity and elastic strain was obtained for visualization of unresolved inflammation using Vevo strain software. Hemodynamic properties of the blood flow in the artery supplying the wound-site were studied using color Doppler flow imaging. Non-invasive monitoring of fetal and adult wound healing provided unprecedented biomechanical and functional insight. Fetal wounds showed highly accelerated closure with transient perturbation of wound tissue cellularity. Fetal hemodynamics was unique in that sharp fall in arterial pulse pressure (APP) which was rapidly restored within 48h post-wounding. In adults, APP transiently increased post-wounding before returning to the pre-wounding levels by d10 post-wounding. The pattern of change in the elasticity of wound-edge tissue of diabetics was strikingly different. Severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of the non-diabetic group. Wound bed of adult diabetic mice (db/db) showed persistent hypercellularity compared to littermate controls (db/+) indicative of prolonged inflammation. Normal skin strain of db/+ and db/db were asynchronous. In db/db, severe strain acquired during the early inflammatory phase persisted with a slower recovery of elasticity compared to that of non-diabetics. This study showcases a versatile clinically relevant imaging platform suitable for real-time analyses of functional wound healing.

Ad hoc hybrid synaptic junctions to detect nerve stimulation and its application to detect onset of diabetic polyneuropathy.

We report a minimally invasive, synaptic transistor-based construct to monitor in vivo neuronal activity via a longitudinal study in mice and use depolarization time from measured data to predict the onset of polyneuropathy. The synaptic transistor is a three-terminal device in which ionic coupling between pre- and post-synaptic electrodes provides a framework for sensing low-power (sub µW) and high-bandwidth (0.1-0.5 kHz) ionic currents. A validated first principles-based approach is discussed to demonstrate the significance of this sensing framework and we introduce a metric, referred to as synaptic efficiency to quantify structural and functional properties of the electrodes in sensing. The application of this framework for in vivo neuronal sensing requires a post-synaptic electrode and its reference electrode and the tissue becomes the pre-synaptic signal. The ionic coupling resembles axo-axonic junction and hence we refer to this framework as an ad hoc synaptic junction. We demonstrate that this arrangement can be applied to measure excitability of sciatic nerves due to a stimulation of the footpad in cohorts of m+/db and db/db mice for detecting loss in sensitivity and onset of polyneuropathy. The signal attributes were subsequently integrated with machine learning-based framework to identify the probability of polyneuropathy and to detect the onset of diabetic polyneuropathy.

Exosome-Mediated Crosstalk between Keratinocytes and Macrophages in Cutaneous Wound Healing.

Bidirectional cell-cell communication involving exosome-borne cargo such as miRNA has emerged as a critical mechanism for wound healing. Unlike other shedding vesicles, exosomes selectively package miRNA by SUMOylation of heterogeneous nuclear ribonucleoproteinA2B1 (hnRNPA2B1). In this work, we elucidate the significance of exosome in keratinocyte-macrophage crosstalk following injury. Keratinocyte-derived exosomes were genetically labeled with GFP-reporter (Exoκ-GFP) using tissue nanotransfection (TNT), and they were isolated from dorsal murine skin and wound-edge tissue by affinity selection using magnetic beads. Surface N-glycans of Exoκ-GFP were also characterized. Unlike skin exosome, wound-edge Exoκ-GFP demonstrated characteristic N-glycan ions with abundance of low-base-pair RNA and was selectively engulfed by wound macrophages (ωmϕ) in granulation tissue. In vitro addition of wound-edge Exoκ-GFP to proinflammatory ωmϕ resulted in conversion to a proresolution phenotype. To selectively inhibit miRNA packaging within Exoκ-GFPin vivo, pH-responsive keratinocyte-targeted siRNA-hnRNPA2B1 functionalized lipid nanoparticles (TLNPκ) were designed with 94.3% encapsulation efficiency. Application of TLNPκ/si-hnRNPA2B1 to the murine dorsal wound-edge significantly inhibited expression of hnRNPA2B1 by 80% in epidermis compared to the TLNPκ/si-control group. Although no significant difference in wound closure or re-epithelialization was observed, the TLNPκ/si-hnRNPA2B1 treated group showed a significant increase in ωmϕ displaying proinflammatory markers in the granulation tissue at day 10 post-wounding compared to the TLNPκ/si-control group. Furthermore, TLNPκ/si-hnRNPA2B1 treated mice showed impaired barrier function with diminished expression of epithelial junctional proteins, lending credence to the notion that unresolved inflammation results in leaky skin. This work provides insight wherein Exoκ-GFP is recognized as a major contributor that regulates macrophage trafficking and epithelial barrier properties postinjury.

Skin Transcriptome of Middle-Aged Women Supplemented With Natural Herbo-mineral Shilajit Shows Induction of Microvascular and Extracellular Matrix Mechanisms.

Objective: Shilajit is a pale-brown to blackish-brown organic mineral substance available from Himalayan rocks. We demonstrated that in type I obese humans, shilajit supplementation significantly upregulated extracellular matrix (ECM)-related genes in the skeletal muscle. Such an effect was highly synergistic with exercise. The present study (clinicaltrials.gov NCT02762032) aimed to evaluate the effects of shilajit supplementation on skin gene expression profile and microperfusion in healthy adult females. Methods: The study design comprised six total study visits including a baseline visit (V1) and a final 14-week visit (V6) following oral shilajit supplementation (125 or 250 mg bid). A skin biopsy of the left inner upper arm of each subject was collected at visit 2 and visit 6 for gene expression profiling using Affymetrix Clariom™ D Assay. Skin perfusion was determined by MATLAB processing of dermascopic images. Transcriptome data were normalized and subjected to statistical analysis. The differentially regulated genes were subjected to Ingenuity Pathway Analysis (IPA®). The expression of the differentially regulated genes identified by IPA® were verified using real-time polymerase chain reaction (RT-PCR). Results: Supplementation with shilajit for 14 weeks was not associated with any reported adverse effect within this period. At a higher dose (250 mg bid), shilajit improved skin perfusion when compared to baseline or the placebo. Pathway analysis identified shilajit-inducible genes relevant to endothelial cell migration, growth of blood vessels, and ECM which were validated by quantitative real-time polymerase chain reaction (RT-PCR) analysis. Conclusions: This work provides maiden evidence demonstrating that oral shilajit supplementation in adult healthy women induced genes relevant to endothelial cell migration and growth of blood vessels. Shilajit supplementation improved skin microperfusion.

Incidence of Silent Thrombosis in Patients Younger Than 60 Years With Myeloproliferative Neoplasms: Single-Center Egyptian Study.

BACKGROUND: Identification of janus kinase 2 (JAK2) mutation even in absence of myeloproliferative disorders (MPNs) was found to be related to venous thromboembolism occurrence. Venous thrombosis screening is not routinely requested in patients with myeloproliferative neoplasms unless the patient is symptomatic. It has been reported that the incidence of thrombosis in elderly patients is much higher than in young patients. The aim of this work was to screen MPN patients for venous thrombosis and study its correlation with JAK2 allele burden and with MPN 10 score. PATIENTS AND METHODS: We enrolled 73 patients with JAK2-positive MPN from our Hematology Clinic in the period August 2015 to Feb 2017. All patients had been screened for thrombosis in the venous system in lower limbs (LLs), upper limbs, portal, and mesenteric systems using color Doppler ultrasound imaging. RESULTS: Fifty-three (72.6%) patients were younger than 60 years. Twenty-two (30%) had essential thrombocytosis, 35 (47.9%) had polycythemia rubra vera, and 16 (22%) had idiopathic myelofibrosis. Twenty-seven venous thrombotic attacks were reported in 22 (30.1%) patients. Five (6.8%) had thrombosis in 2 sites. Seventeen (23%) had superior mesenteric and portal vein thrombosis. Six (8%) had iliofemoral (8%) and 4 (5%) had combined LL and portal thrombosis. Eight (10.8%) had active thrombosis at screening. Only 3 patients (4%) were symptomatic with abdominal pain during screening. Pruritis (P = .02) and abdominal pain (P = .039) were significantly different between cases with and without thrombosis. There was no significant difference in MPN 10 score between cases with active or previous thrombosis. CONCLUSION: We recommend routine screening for venous thrombosis in any case of MPN when diagnosed and screening for MPNs in any patient with venous thrombosis especially of the portal vein or atypical sites. If MPN patients present with increasing pruritus or abdominal pain, they also should be screened for venous thrombosis. Further research on a large scale in MPN age groups younger than 60 years regarding pathogenesis of thrombosis is highly recommended.

Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Decellularized matrices of biologic tissue have performed well as wound care dressings. Extracellular matrix-based dressings are subject to rapid degradation by excessive protease activity at the wound environment. Stabilized, acellular, equine pericardial collagen matrix (sPCM) wound care dressing is flexible cross-linked proteolytic enzyme degradation resistant. sPCM was structurally characterized utilizing scanning electron and atomic force microscopy. In murine excisional wounds, sPCM was effective in mounting an acute inflammatory response. Postwound inflammation resolved rapidly, as indicated by elevated levels of IL-10, arginase-1, and VEGF, and lowering of IL-1ß and TNF-α. sPCM induced antimicrobial proteins S100A9 and ß-defensin-1 in keratinocytes. Adherence of Pseudomonas aeruginosa and Staphylococcus aureus on sPCM pre-exposed to host immune cells in vivo was inhibited. Excisional wounds dressed with sPCM showed complete closure at d 14, while control wounds remained open. sPCM accelerated wound re-epithelialization. sPCM not only accelerated wound closure but also improved the quality of healing by increased collagen deposition and maturation. Thus, sPCM is capable of presenting scaffold functionality during the course of wound healing. In addition to inducing endogenous antimicrobial defense systems, the dressing itself has properties that minimize biofilm formation. It mounts robust inflammation, a process that rapidly resolves, making way for wound healing to advance.-El Masry, M. S., Chaffee, S., Das Ghatak, P., Mathew-Steiner, S. S., Das, A., Higuita-Castro, N., Roy, S., Anani, R. A., Sen, C. K. Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.

Lyophilized keratinocyte-targeted nanocarriers (TLNκ) loaded with locked nucleic acid (LNA) modified anti-miR were developed for topical application to full thickness burn injury. TLNκ were designed to selectively deliver LNA-anti-miR-107 to keratinocytes using the peptide sequence ASKAIQVFLLAG. TLNκ employed DOTAP/DODAP combination pH-responsive lipid components to improve endosomal escape. To minimize interference of clearance by non-targeted cells, especially immune cells in the acute wound microenvironment, surface charge was neutralized. Lyophilization was performed to extend the shelf life of the lipid nanoparticles (LNPs). Encapsulation efficiency of anti-miR in lyophilized TLNκ was estimated to be 96.54%. Cargo stability of lyophilized TLNκ was tested. After 9 days of loading with anti-miR-210, TLNκ was effective in lowering abundance of the hypoxamiR miR-210 in keratinocytes challenged with hypoxia. Keratinocyte uptake of DiD-labeled TLNκ was selective and exceeded 90% within 4 hr. Topical application of hydrogel-dispersed lyophilized TLNκ encapsulating LNA anti-miR-107 twice a week significantly accelerated wound closure and restoration of skin barrier function. TLNκ/anti-miR-107 application depleted miR-107 and upregulated dicer expression, which accelerated differentiation of keratinocytes. Expression of junctional proteins such as claudin-1, loricrin, filaggrin, ZO-1, and ZO-2 were significantly upregulated following TLNκ/anti-miR-107 treatment. These LNPs are promising as topical therapeutic agents in the management of burn injury.

Epidermal E-Cadherin Dependent ß-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of ß-catenin and its nuclear translocation. Nuclear ß-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of ß-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/ß-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.