Candidate Bioinks for Extrusion 3D Bioprinting-A Systematic Review of the Literature.

Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks. Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication. Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells. Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.

Facial Reconstruction: A Systematic Review of Current Image Acquisition and Processing Techniques.

Introduction: Plastic and reconstructive surgery is based on a culmination of technological advances, diverse techniques, creative adaptations and strategic planning. 3D imaging is a modality that encompasses several of these criteria while encouraging the others. Imaging techniques used in facial imaging come in many different modalities and sub-modalities which is imperative for such a complex area of the body; there is a clear clinical need for hyper-specialized practice. However, with this complexity comes variability and thus there will always be an element of bias in the choices made for imaging techniques. Aims and Objectives: The aim of this review is to systematically analyse the imaging techniques used in facial reconstruction and produce a comprehensive summary and comparison of imaging techniques currently available, including both traditional and novel methods. Methods: The systematic search was performed on EMBASE, PubMed, Scopus, Web of Science and Cochrane reviews using keywords such as "image technique/acquisition/processing," "3-Dimensional," "Facial," and "Reconstruction." The PRISMA guidelines were used to carry out the systematic review. Studies were then subsequently collected and collated; followed by a screening and exclusion process with a final full-text review for further clarification in regard to the selection criteria. A risk of bias assessment was also carried out on each study systematically using the respective tool in relation to the study in question. Results: From the initial 6,147 studies, 75 were deemed to fulfill all selection criteria and selected for meta-analysis. The majority of papers involved the use of computer tomography, though the use of magnetic resonance and handheld scanners using sonography have become more common in the field. The studies ranged in patient population, clinical indication. Seminal papers were highlighted within the group of papers for further analysis. Conclusions: There are clearly many factors that affect the choice of image acquisition techniques and their potential at being ideal for a given role. Ultimately the surgical team's choice will guide much of the decision, but it is crucial to be aware of not just the diagnostic ability of such modalities, but their treatment possibilities as well.

Could Vitamins Help in the Fight Against COVID-19?

There are limited proven therapeutic options for the prevention and treatment of COVID-19. The role of vitamin and mineral supplementation or "immunonutrition" has previously been explored in a number of clinical trials in intensive care settings, and there are several hypotheses to support their routine use. The aim of this narrative review was to investigate whether vitamin supplementation is beneficial in COVID-19. A systematic search strategy with a narrative literature summary was designed, using the Medline, EMBASE, Cochrane Trials Register, WHO International Clinical Trial Registry, and Nexis media databases. The immune-mediating, antioxidant and antimicrobial roles of vitamins A to E were explored and their potential role in the fight against COVID-19 was evaluated. The major topics extracted for narrative synthesis were physiological and immunological roles of each vitamin, their role in respiratory infections, acute respiratory distress syndrome (ARDS), and COVID-19. Vitamins A to E highlighted potentially beneficial roles in the fight against COVID-19 via antioxidant effects, immunomodulation, enhancing natural barriers, and local paracrine signaling. Level 1 and 2 evidence supports the use of thiamine, vitamin C, and vitamin D in COVID-like respiratory diseases, ARDS, and sepsis. Although there are currently no published clinical trials due to the novelty of SARS-CoV-2 infection, there is pathophysiologic rationale for exploring the use of vitamins in this global pandemic, supported by early anecdotal reports from international groups. The final outcomes of ongoing trials of vitamin supplementation are awaited with interest.

Artificial intelligence, regenerative surgery, robotics? What is realistic for the future of surgery?

The potential of surgery lies in the technological advances that would complement it. The landscape of the field will differ depending on the time period being looked at and would no doubt include conjecture. Initial breakthroughs will need to pave the way for future medical technology and apply to the surgical sciences. Within the next 10 years we would expect to see the emergence of big data analysis, cuttingedge image processing techniques for surgical planning and better implementation of virtual and augmented reality in operating theatres for both patient care and teaching purposes. Over the next 50 to 100 years, the use of quantum computing should lead to increased automation in our healthcare systems. The inception of novel biomaterial invention and advanced genetic engineering will usher in the new age of regenerative medicine in the clinical setting. The future of surgery includes many predictions and promises, but it is apparent that the development will lead to bettering outcome and focus on patient care.

Skin tissue engineering using 3D bioprinting: An evolving research field.

BACKGROUND: Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin. METHODS: We conducted a literature review using PubMed, EMBASE and Web of Science for studies on skin 3D bioprinting between 2009 and 2016, evaluating the bioprinting technique, cell source, scaffold type and in vitro and in vivo outcomes. RESULTS: We outline the evolution of biological skin replacements, principles of bioprinting and how they apply to the skin tissue engineering field, potential clinical applications as well the current limitations and future avenues for research. Of the studies analysed, the most common types of bioinks consisted of keratinocytes and fibroblasts combined with collagen, although stem cells are gaining increasing recognition. Laser assisted deposition was the most common printing modality, although ink-jet and pneumatic extrusion have also been tested. Bioprinted skin promoted accelerated wound healing, was able to mimic stratified epidermis but not the thick, elastic, vascular dermis. CONCLUSIONS: Although 3D bioprinting shows promise in engineering skin, evidenced by large collective investments from the cosmetic industry, the research is still in its infancy. The resolution, vascularity, optimal cell and scaffold combinations and cost of bioprinted skin are hurdles that need to be overcome before the clinical applicability can be realised. Small scale 3D skin tissue models for cosmetics, drug and toxicity testing as well as tumour modelling are likely to be translated first before we see this technology used in reconstructive surgery patients.

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy.

Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.