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

PurposeOur 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

CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8

Characterization of pulp derived nanocellulose hydrogels using AVAP® technology

Bioinspiration from hierarchical structures found in natural environments has heralded a new age of advanced functional materials. Nanocellulose has received significant attention due to the demand for high-performance materials with tailored mechanical, physical and biological properties. In this study, nanocellulose fibrils, nanocrystals and a novel mixture of fibrils and nanocrystals (blend) were prepared from softwood biomass using the AVAP® biorefinery technology. These materials were characterized using transmission and scanning electron microscopy, and atomic force microscopy. This analysis revealed a nano- and microarchitecture with extensive porosity. Notable differences included the nanocrystals exhibiting a compact packing of nanorods with reduced porosity. The NC blend exhibited porous fibrillar networks with interconnecting compact nanorods. Fourier transform infrared spectroscopy and X-ray diffraction confirmed a pure cellulose I structure. Thermal studies highlighted the excellent stability of all three NC materials with the nanocrystals having the highest decomposition temperature. Surface charge analysis revealed stable colloid suspensions. Rheological studies highlighted a dominance of elasticity in all variants, with the NC blend being more rigid than the NC fibrils and nanocrystals, indicating a double network hydrogel structure. Given these properties, it is thought that these materials show great potential in (bio)nanomaterial applications where careful control of microarchitecture, surface topography and porosity are required

Transforming healthcare through regenerative medicine

Regenerative medicine therapies, underpinned by the core principles of rejuvenation, regeneration and replacement, are shifting the paradigm in healthcare from symptomatic treatment in the 20th century to curative treatment in the 21st century. By addressing the reasons behind the rapid expansion of regenerative medicine research and presenting an overview of current clinical trials, we explore the potential of regenerative medicine to reshape modern healthcare

Homozygous Factor V Leiden Thrombophilia in a Patient With Histologically Confirmed Thromboangiitis Obliterans

Thromboangiitis obliterans (TAO) is a vasculitis characterised by segmental occlusions of small to medium-sized arteries and superficial veins, and a curious predilection for young male smokers. The exact aetiology remains unknown. Current theories postulate it is an autoimmune endarteritis, triggered by some constituent of tobacco and occurring in genetically susceptible individuals. The disease can pose a diagnostic challenge, requiring a high degree of clinical suspicion, particularly in male smokers aged between 20-45 presenting with peripheral ischaemia. The fundamental principle of management is absolute tobacco abstinence. In this article, we report the case of a 27-year-old man who presented with infected, chronic wounds of his upper and lower extremities. He was initially treated with antibiotics and surgical debridement. Unfortunately he went on to develop a protracted course of complications due to poor wound healing ultimately leading to amputation of several digits. A diagnosis of TAO was suspected, and this was later confirmed histologically. Incidentally and of note, the patient was also found to be homo zygous for factor V Leiden. An association between TAO and hypercoagulable states, specifically hetero zygous factor V Leiden mutation, has been previously described. It is unclear if a synergistic effect between TAO and homozygosity for factor V Leiden may have contributed to the severity and unremitting nature of our patient’s symptoms. We present this case in order to highlight the importance of early recognition of the condition and the need to offer comprehensive smoking cessation support in order to prevent amputation and other complications of poor wound healing

Late Presentation of Infected Silicone Granulomas in the Lower Limb

Introduction: Dermal fillers are used for multiple cosmetic indications including gluteal and thigh augmentation. Complications, although infrequent, are increasing due to the dramatic growth of dermal filler use. Our aim was to describe how the complication of infected silicone granulomas can present following lower limb augmentation. Methods: Two cases presented with pain, oedema, and erythema at the site of previous silicone filler injection, following a considerable delay after the last injection (range 4-7 years). We collected data on their biochemistry, haematology, histology, microbiology, and imaging at the time of presentation. Results: Complications included prolonged cellulitis with recurrent abscesses at sites of previous silicone dermal filler injection. Histology revealed infiltration of chronic inflammatory cells suggestive of silicone granuloma in both cases. Patients were reluctant to divulge use of cosmetic fillers or failed to recognise their significance given the time delay making diagnosis difficult. Delayed or recurring infections can suggest the presence of atypical organisms and we present the first reported case of silicone granuloma infection with Propionibacterium acnes . Conclusions: Microorganisms can induce immune-mediated hypersensitivity and are believed to be the trigger for delayed activation of a quiescent foreign body to a granulomatous reaction. The substantial time delay between injection and reaction must be recognised and may be attributable to atypical microorganisms or biofilm formation. Previous antibiotic use can affect expedient microbiological diagnosis and treatment requires close collaboration with microbiologists. It is important that clinicians are aware of these important complications which are becoming more common with increased use of filler augmentation