How to Select an Extracellular Matrix for Wound Repair: A Comprehensive Review.

Background: An extracellular matrix (ECM) is a network of proteins and other molecules that provide support and structure to cells and tissues in the body. Since its discovery in 1930, researchers have reproduced the ECM through an array of evolving technologies, developing products that accelerate healing times, minimize scarring, and reduce pain. When selecting which ECM product to use, physicians rely on personal experience while considering wound location, type of tissue lost, exposed structures, chronicity, and even the patient's religious preferences. While comparison trials between a few different types of ECMs exist, there lacks a thorough investigation that assesses a majority of ECMs against each other. Methods: Herein, we conducted a literature review using the PubMed database and utilized 71 articles to identify the best ECM for wound healing and positive patient outcomes. The primary search terms included extracellular matrix, xenograft, porcine, bovine, allograft, bioengineered matrix, acellularized fish skin, wounds, wound healing, and wound care. We did not exclude any specific type of research, but predominantly reviewed clinical trials, case series, and other review articles. We focused on the most popular and commonly used ECMs and constructed our results into the Table. Results: We compared the indications, advantages, and disadvantages of each ECM and concisely illustrated these findings to provide a guide on how to select an ECM (Table). Allografts, whether they are glycerol or cryopreserved, suffice as a treatment choice and are superior to exposure healing. However, they do not produce healing at the same rate or quality as bioengineered matrices, porcine and bovine xenografts, or acellularized fish skin (AFS). Bioengineered matrices and porcine and bovine xenografts offer antimicrobial properties, low immunogenicity, cost effectiveness, and availability. The compromise with these ECMs is with healing times and cosmesis. Acellularized fish skin (AFS) provides diverse utility, antimicrobial activity, low immunogenicity, faster healing times, and cosmetic superiority. However, AFS yields a potential cost burden and is not plentiful or easily accessible in some parts of the world. Conclusions: Our findings assist in removing the subjectivity component of selecting an ECM and suggest further comparison or head-to-head trials would yield a more algorithmic approach to wound healing. We suggest to consider implementing the Disabilities of the Arm, Shoulder, and Hand (DASH) score as an additional objective comparison method in these future trials.

Redesigning Sentinel Lymph Node Biopsy Guidelines in Melanoma Cases.

Background: Accurately staging and prognosticating melanoma classically depends on a sentinel lymph node biopsy (SLNB). The mainstay predictors of SLNB positivity according to the American Joint Committee on Cancer (AJCC) are Breslow depth and ulceration. Nevertheless, even with these predictors, negative SLNBs, even in deep melanomas, are a common occurrence and may result in unnecessary invasive procedures for patients. This suggests that the parameters for determining SLNB candidates are a potential area for improvement in surgical dermatology (surgical oncology and plastic surgery). Methods: The authors conducted a systemic review to assess current AJCC guidelines on when a SLNB in melanoma is indicated. We also investigated how age, mitotic rate, lymphovascular invasion, satellitosis, melanoma subtype, anatomical location, and an immunocompromised state affected positivity rates in sentinel lymph node biopsies in melanoma. Results: These variables significantly impacted SLNB positivity rates and serve as evidence to support the proposal of redesigning SLNB guidelines in melanoma. Conclusions: Integrating the current AJCC guidelines with the newly examined variables will create patient-specific recommendations centered on the aim of reducing the number of invasive procedures while increasing SLNB positivity rates and prognostication.

The dangers of human papillomavirus (HPV) laser plume and best safety practices.

Human papillomavirus (HPV) remains to be one of the most common viruses that afflicts the skin and mucosa. Direct contact with cutaneous lesions facilitates a majority of viral transmission. However, the development of laser therapy as treatment for HPV brought to attention the concern of infectious laser plume and the risk it poses to those inhaling it. We conducted a literature review using English articles in PubMed to validate this risk and propose the best safety practices dermatologists can apply when using laser therapy as treatment for HPV. Our investigation identified smoke evacuators as primary modes of mitigation, and we suggest further studies will aid in the refinement of best practice recommendations.

Bacteriophages: An Alternative to Combat Antibiotic Resistance?

BACKGROUND: Antibiotic resistance has become one of the largest pitfalls of modern medicine, and this has fueled the search for a safe and effective alternative. Of these alternatives, bacteriophage (phage) therapy has emerged as a potential option since it is capable of destroying pathogenic bacteria, without disrupting commensal bacterial populations. Although numerous studies have shown its efficacy in various conditions such as dysentery, sepsis, and meningitis, very little research has focused on its prospective usage to treat dermatological conditions. This review discusses the emerging phage therapy studies surrounding infections caused by Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae). Phage therapy shows major potential for future usage in the field of dermatology, yet further research must be performed to assure safety and efficacy in humans. J Drugs Dermatol. 2022;21(12):1311-1315. doi:10.36849/JDD.6638.

Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury.

BACKGROUND: There is evidence from various models of hypoxic-ischemic injury (HII) that nitric oxide (NO) is protective. We hypothesized that either inhaled NO (iNO) or nitrite would alleviate brain injury in neonatal HII via modulation of mitochondrial function. METHODS: We tested the effects of iNO and nitrite on the Rice-Vannucci model of HII in 7-day-old rats. Brain mitochondria were isolated for flow cytometry, aconitase activity, electron paramagnetic resonance, and Seahorse assays. RESULTS: Pretreatment of pups with iNO decreased survival in the Rice-Vannucci model of HII, while iNO administered post-insult did not. MRI analysis demonstrated that pre-HII iNO at 40 ppm and post-HII iNO at 20 ppm decreased the brain lesion sizes from 6.3±1.3% to 1.0±0.4% and 1.8±0.8%, respectively. Intraperitoneal nitrite at 0.165 µg/g improved neurobehavioral performance but was harmful at higher doses and had no effect on brain infarct size. NO reacted with complex IV at the heme a3 site, decreased the oxidative stress of mitochondria challenged with anoxia and reoxygenation, and suppressed mitochondrial oxygen respiration. CONCLUSIONS: This study suggests that iNO administered following neonatal HII may be neuroprotective, possibly via its modulation of mitochondrial function.

Tuning Subunit Vaccines with Novel TLR Triagonist Adjuvants to Generate Protective Immune Responses against Coxiella burnetii.

Coxiella burnetii is an obligate intracellular bacterium and the causative agent of Q fever. C. burnetii is considered a potential bioterrorism agent because of its low infectious dose; resistance to heat, drying, and common disinfectants; and lack of prophylactic therapies. Q-Vax, a formalin-inactivated whole-bacteria vaccine, is currently the only prophylactic measure that is protective against C. burnetii infections but is not U.S. Food and Drug Administration approved. To overcome the safety concerns associated with the whole-bacteria vaccine, we sought to generate and evaluate recombinant protein subunit vaccines against C. burnetii To accomplish this, we formulated C. burnetii Ags with a novel TLR triagonist adjuvant platform, which used combinatorial chemistry to link three different TLR agonists together to form one adjuvanting complex. We evaluated the immunomodulatory activity of a panel of TLR triagonist adjuvants and found that they elicited unique Ag-specific immune responses both in vitro and in vivo. We evaluated our top candidates in a live C. burnetii aerosol challenge model in C56BL/6 mice and found that several of our novel vaccine formulations conferred varying levels of protection to the challenged animals compared with sham immunized mice, although none of our candidates were as protective as the commercial vaccine across all protection criteria that were analyzed. Our findings characterize a novel adjuvant platform and offer an alternative approach to generating protective and effective vaccines against C. burnetii.

Linked Toll-Like Receptor Triagonists Stimulate Distinct, Combination-Dependent Innate Immune Responses.

Traditional vaccination strategies have failed to generate effective vaccines for many infections like tuberculosis and HIV. New approaches are needed for each type of disease. The protective immunity and distinct responses of many successful vaccines come from activating multiple Toll-like receptors (TLRs). Vaccines with multiple TLRs as adjuvants have proven effective in preclinical studies, but current research has not explored two important elements. First, few multi-TLR systems explore spatial organization-a critical feature of whole-cell vaccines. Second, no multi-TLR systems to date provide systematic analysis of the combinatorial space of three TLR agonists. Here, we present the first examination of the combinatorial space of several spatially defined triple-TLR adjuvants, by synthesizing a series of five triple-TLR agonists and testing their innate activity both in vitro and in vivo. The combinations were evaluated by measuring activation of immune stimulatory genes (Nf-κB, ISGs), cytokine profiles (IL12-p70, TNF-α, IL-6, IL-10, CCL2, IFN-α, IFN-ß, IFN-γ), and in vivo cytokine serum levels (IL-6, TNF-α, IL12-p40, IFN-α, IFN-ß). We demonstrate that linking TLR agonists substantially alters the resulting immune response compared to their unlinked counterparts and that each combination results in a distinct immune response, particularly between linked combinations. We show that combinations containing a TLR9 agonist produce more Th1 biasing immune response profiles, and that the effect is amplified upon conjugation. However, combinations containing TLR2/6 agonist are skewed toward TH2 biasing profiles despite the presence of TLR9. These results demonstrate the profound effects that conjugation and combinatorial administration of TLR agonists can have on immune responses, a critical element of vaccine development.