Load, unload and repeat: Understanding the mechanical characteristics of zirconia in dentistry.

OBJECTIVES: Zirconia-based dental restorations and implants are gaining attention due to their bioactivity, corrosion resistance and mechanical stability. Further, surface modification of zirconia implants has been performed at the macro-, micro- and nanoscale to augment bioactivity. While zirconia's physical and chemical characteristics have been documented, its relation to mechanical performance still needs to be explored. This extensive review aims to address this knowledge gap. METHODS: This review critically compares and contrasts the findings from articles published in the domain of 'mechanical stability of zirconia\ in dentistry' based on a literature survey (Web of Science, Medline/PubMed and Scopus databases) and a review of the relevant publications in international peer-reviewed journals. Reviewing the published data, the mechanical properties of zirconia, such as fracture resistance, stress/tension, flexural strength, fatigue, and wear are detailed and discussed to understand the biomechanical compatibility of zirconia with the mechanical performance of modified zirconia in dentistry also explored. RESULTS: A comprehensive insight into dental zirconia's critical fundamental mechanical characteristics and performance is presented. Further, research challenges and future directions in this domain are recommended. SIGNIFICANCE: This review extends existing knowledge of zirconia's biomechanical performance and it they can be modulated to design the next generation of zirconia dental restorations and implants to withstand long-term constant loading.

Effect of Skin Type on Efficacy of Laser Treatment for Androgenetic Alopecia: A Review of the Literature.

The use of low-light laser therapy to treat androgenetic alopecia is a promising modality to restore hair growth. However, the effect of skin color on response to laser therapy for hair growth has not been systematically explored in the literature. The objective of this study is to systematically assess through a comprehensive literature search of the MEDLINE database whether skin type data were collected in clinical trials and analyzed in each study and determine if we can estimate an effect. 10/22 studies have defined inclusion criteria as Fitzpatrick skin types I-IV. No studies mentioned effects on darker skin types, Fitzpatrick skin types V-VI. Only 5/10 studies had statistical data on efficacy depending on Fitzpatrick skin type, with four showing no effect and one showing a significant positive effect with darker skin types having faster rate of hair growth. There are not enough data to conclude whether skin type effects laser-induced hair growth in androgenic alopecia. The studies are severely lacking in sample size. One showed a potential effect. Importantly, there are no data on black or brown skin colors. Development of optimal laser irradiating wparameters through the prediction of personalized absorbance based on skin color measurement is needed.

Fit and forget: The future of dental implant therapy via nanotechnology.

Unlike orthopedic implants, dental implants require the orchestration of both osseointegration at the bone-implant interface and soft-tissue integration at the transmucosal region in a complex oral micro-environment with ubiquitous pathogenic bacteria. This represents a very challenging environment for early acceptance and long-term survival of dental implants, especially in compromised patient conditions, including aged, smoking and diabetic patients. Enabling advanced local therapy from the surface of titanium-based dental implants via novel nano-engineering strategies is emerging. This includes anodized nano-engineered implants eluting growth factors, antibiotics, therapeutic nanoparticles and biopolymers to achieve maximum localized therapeutic action. An important criterion is balancing bioactivity enhancement and therapy (like bactericidal efficacy) without causing cytotoxicity. Critical research gaps still need to be addressed to enable the clinical translation of these therapeutic dental implants. This review informs the latest developments, challenges and future directions in this domain to enable the successful fabrication of clinically-translatable therapeutic dental implants that would allow for long-term success, even in compromised patient conditions.

How to get rid of itching.

Itch is an unpleasant sensation arising from a variety of dermatologic, neuropathic, systemic, and psychogenic etiologies. Various itch pathways are implicated according to the underlying etiology. A variety of pruritogens, or itch mediators, as well as receptors have been identified and provide potential therapeutic targets. Recent research has primarily focused on targeting inflammatory cytokines and Janus kinase signaling, protease-activated receptors, substance P and neurokinin, transient receptor potential-vanilloid ion channels, Mas-related G-protein-coupled receptors (MRGPRX2 and MRGPRX4), the endogenous opioid and cannabinoid balance, and phosphodiesterase 4. Periostin, a newly identified pruritogen, should be further explored with clinical trials. Drugs targeting neural sensitization including the gabergic system and P2X3 are other potential drugs for chronic itch. There is a need for more targeted therapies to improve clinical outcomes and reduce side effects.

Innate immunity and microbial dysbiosis in hidradenitis suppurativa - vicious cycle of chronic inflammation.

Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of disease pathology. HS is characterized by aberrant activation of the innate immune system, resulting in activation of pathways that aim to protect against pathogenic microorganisms, and also contribute to failure to resolve inflammation. Imbalance in innate immunity is evident in deregulation of host antimicrobial peptides (AMPs) and the complement system associated with the microbiome dysbiosis. The pathology is further complicated by ability of pathogens associated with HS to overcome host immune response. Potential roles of major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 and complement proteins are discussed. Dysregulated expression pattern of innate immunity components in conjunction with bacterial component of the disease warrants consideration of novel treatment approaches targeting both host immunity and pathogenic microbiome in HS.

Fish Skin Grafts with Omega-3 for Treatment of Chronic Wounds: Exploring the Role of Omega-3 Fatty Acids in Wound Healing and A Review of Clinical Healing Outcomes.

Chronic, non-healing wounds, such as diabetic foot ulcers and venous leg ulcers, have a significant economic impact on healthcare and are associated with elevated patient morbidity. Among the toolset of treatment options available to clinicians, skin grafts from other species (xenografts) are often used to promote wound closure. While porcine xenografts have been the most used skin xenograft over the years, acellular fish skin grafts from Atlantic cod (Gadus morhua) have steadily gained traction in usage. Unlike other skin grafts, acellular fish skin grafts have a substantial lipid profile primarily composed of omega-3 fatty acids, notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplementation has been shown to result in faster rates of wound epithelialization, and omega 3 fatty acids provide barrier protection against bacteria and alter the inflammatory profile of wounds. EPA and DHA have been shown to have modulatory effects on the progression of wound healing. These characteristic omega-3 fatty acids and their metabolites alter skin physiology at a cellular and molecular level. Clinically, fish skin grafts continually demonstrate increased efficacy in treatment of wounds. When applied to non-responsive diabetic foot ulcers, acellular fish skin grafts have resulted in accelerated healing rates and significantly more fully healed wounds when compared to standard options. Here, we explore the role of omega-3 fatty acids in wound regeneration and repair, with particular focus on EPA and DHA. Then, we review clinical research outcomes to address notable clinical research studies and highlight the therapeutic potential of fish skin grafts with omega-3 as a treatment for chronic, non-healing wounds.

Advancing dental implants: Bioactive and therapeutic modifications of zirconia.

Zirconium-based implants have gained popularity in the dental implant field owing to their corrosion resistance and biocompatibility, attributed to the formation of a native zirconia (ZrO2) film. However, enhanced bioactivity and local therapy from such implants are desirable to enable the earlier establishment and improved long-term maintenance of implant integration, especially in compromised patient conditions. As a result, surface modification of zirconium-based implants have been performed using various physical, chemical and biological techniques at the macro-, micro-, and nano-scales. In this extensive review, we discuss and detail the development of Zr implants covering the spectrum from past and present advancements to future perspectives, arriving at the next generation of highly bioactive and therapeutic nano-engineered Zr-based implants. The review provides in-depth knowledge of the bioactive/therapeutic value of surface modification of Zr implants in dental implant applications focusing on clinical translation.

Micro + Nano: Conserving the Gold Standard Microroughness to Nanoengineer Zirconium Dental Implants.

Zirconium has achieved popularity as a biomaterial for dental and orthopedic implants; however, its bioinertness can compromise implant-tissue integration, especially in compromised patient conditions. More recently, various nanoengineering strategies have been explored to enhance the bioactivity of Ti-based implants; however, nanoengineering of Zr-based implants has not been adequately explored. In this pioneering attempt, we report on the optimized fabrication of various nanostructures on microrough Zr surfaces and explore the influence of the underlying surface topography. In-depth optimization of electrochemical anodization (EA) is performed by tuning various parameters, including substrate topography, voltage/current and time, onto microrough (micromachined) and extremely rough Zr substrates, which represent clinically relevant implant surfaces. Variations of EA factors yielded various nanotopographies, including nanotubes, nanograss and nanotemplates, offering different topographical and chemical combinations. EA optimization and precise current-voltage recording was performed to arrive at clinically translatable and reproducible nanostructures on Zr surfaces. This study will pave the way toward the fabrication of the next generation of nanoengineered Zr-based orthopedic and dental implants.

Towards Clinical Translation: Optimized Fabrication of Controlled Nanostructures on Implant-Relevant Curved Zirconium Surfaces.

Anodization enables fabrication of controlled nanotopographies on Ti implants to offer tailorable bioactivity and local therapy. However, anodization of Zr implants to fabricate ZrO2 nanostructures remains underexplored and are limited to the modification of easy-to-manage flat Zr foils, which do not represent the shape of clinically used implants. In this pioneering study, we report extensive optimization of various nanostructures on implant-relevant micro-rough Zr curved surfaces, bringing this technology closer to clinical translation. Further, we explore the use of sonication to remove the top nanoporous layer to reveal the underlying nanotubes. Nano-engineered Zr surfaces can be applied towards enhancing the bioactivity and therapeutic potential of conventional Zr-based implants.

Understanding and optimizing the antibacterial functions of anodized nano-engineered titanium implants.

Nanoscale surface modification of titanium-based orthopaedic and dental implants is routinely applied to augment bioactivity, however, as is the case with other cells, bacterial adhesion is increased on nano-rough surfaces. Electrochemically anodized Ti implants with titania nanotubes (TNTs) have been proposed as an ideal implant surface with desirable bioactivity and local drug release functions to target various conditions. However, a comprehensive state of the art overview of why and how such TNTs-Ti implants acquire antibacterial functions, and an in-depth knowledge of how topography, chemistry and local elution of potent antibiotic agents influence such functions has not been reported. This review discusses and details the application of nano-engineered Ti implants modified with TNTs for maximum local antibacterial functions, deciphering the interdependence of various characteristics and the fine-tuning of different parameters to minimize cytotoxicity. An ideal implant surface should cater simultaneously to ossoeintegration (and soft-tissue integration for dental implants), immunomodulation and antibacterial functions. We also evaluate the effectiveness and challenges associated with such synergistic functions from modified TNTs-implants. Particular focus is placed on the metallic and semi-metallic modification of TNTs towards enabling bactericidal properties, which is often dose dependent. Additionally, there are concerns over the cytotoxicity of these therapies. In that light, research challenges in this domain and expectations from the next generation of customizable antibacterial TNTs implants towards clinical translation are critically evaluated. STATEMENT OF SIGNIFICANCE: One of the major causes of titanium orthopaedic/dental implant failure is bacterial colonization and infection, which results in complete implant failure and the need for revision surgery and re-implantation. Using advanced nanotechnology, controlled nanotopographies have been fabricated on Ti implants, for instance anodized nanotubes, which can accommodate and locally elute potent antibiotic agents. In this pioneering review, we shine light on the topographical, chemical and therapeutic aspects of antibacterial nanotubes towards achieving desirable tailored antibacterial efficacy without cytotoxicity concerns. This interdisciplinary review will appeal to researchers from the wider scientific community interested in biomaterials science, structure and function, and will provide an improved understanding of controlling bacterial infection around nano-engineered implants, aimed at bridging the gap between research and clinics.