Dermal Pericytes Exhibit Declined Ability to Promote Human Skin Regeneration with Ageing in 3D Organotypic Culture Models.

The well documented decline in the regenerative ability of ageing human skin has been attributed to many factors including genomic instability, telomere shortening, poor nutrient sensing, cellular senescence, and stem cell exhaustion. However, a role for the dermal cellular and molecular microenvironment in skin ageing is just emerging. We previously showed that dermal pericytes co-operate with fibroblasts to improve human skin regeneration in an organotypic skin culture model, and even do so in the absence of fibroblasts. Here, we report that the number of dermal cells, particularly pericytes, declines significantly in human skin of donors aged > 50 years. Notably, aged pericytes promoted epidermal regeneration of neonatal keratinocytes in organotypic cultures and the resulting epithelium exhibited a Ki67+/ΔNp63+ basal layer and terminal differentiation. However, the epithelium lacked several features of homeostasis displaying lower levels of ΔNp63 expression, decreased LAMA5 deposition at the dermo-epidermal junction, and the absence of basement membrane and hemi-desmosome assembly. We conclude that a decline in pericyte incidence and function contribute to an impaired epidermal microenvironment and poor skin regeneration with ageing in the human skin

Plasma Polymer Coatings To Direct the Differentiation of Mouse Kidney-Derived Stem Cells into Podocyte and Proximal Tubule-like Cells

Kidney disease is now recognised as a global health problem and is associated with increased morbidity and mortality, along with high economic costs. To develop new treatments for ameliorating kidney injury and preventing disease progression, there is a need for appropriate renal culture systems for screening novel drugs and investigating the cellular mechanisms underlying renal pathogenesis. There is a need for in vitro culture systems that promote the growth and differentiation of specialised renal cell types. In this work, we have used plasma polymerisation technology to generate gradients of chemical functional groups to explore whether specific concentrations of these functional groups can direct the differentiation of mouse kidney-derived stem cells into specialised renal cell types. We found that amine-rich (-NH2) allylamine-based plasma polymerised coatings could promote differentiation into podocyte-like cells, whereas methyl-rich (CH3) 1,7-octadiene-based coatings promoted differentiation into proximal tubule-like cell (PTC). Importantly, the PT-like cells generated on the substrates expressed the marker megalin and were able to endocytose albumin, indicating that the cells were functional

Bio-Inspired Nanostructured Ti-6Al-4V Alloy: The Role of Two Alkaline Etchants and the Hydrothermal Processing Duration on Antibacterial Activity

Inspired by observations that the natural topography observed on cicada and dragonfly wings may be lethal to bacteria, researchers have sought to reproduce these nanostructures on biomaterials with the goal of reducing implant-associated infections. Titanium and its alloys are widely employed biomaterials with excellent properties but are susceptible to bacterial colonisation. Hydrothermal etching is a simple, cost-effective procedure which fabricates nanoscale protrusions of various dimensions upon titanium, depending on the etching parameters used. We investigated the role of etching time and the choice of cation (sodium and potassium) in the alkaline heat treatment on the topographical, physical, and bactericidal properties of the resulting modified titanium surfaces. Optimal etching times were 4 h for sodium hydroxide (NaOH) and 5 h for potassium hydroxide (KOH). NaOH etching for 4 h produced dense, but somewhat ordered, surface nanofeatures with 75 nanospikes per µm2. In comparison, KOH etching for 5 h resulted sparser but nonetheless disordered surface morphology with only 8 spikes per µm2. The NaOH surface was more effective at eliminating Gram-negative pathogens, while the KOH surface was more effective against the Gram-positive strains. These findings may guide further research and development of bactericidal titanium surfaces which are optimised for the predominant pathogens associated with the intended application

Nanoparticles Surface Chemistry Influence on Protein Corona Composition and Inflammatory Responses

Nanoparticles are widely used for biomedical applications such as vaccine, drug delivery, diagnostics, and therapeutics. This study aims to reveal the influence of nanoparticle surface functionalization on protein corona formation from blood serum and plasma and the subsequent effects on the innate immune cellular responses. To achieve this goal, the surface chemistry of silica nanoparticles of 20 nm diameter was tailored via plasma polymerization with amine, carboxylic acid, oxazolines, and alkane functionalities. The results of this study show significant surface chemistry-induced differences in protein corona composition, which reflect in the subsequent inflammatory consequences. Nanoparticles rich with carboxylic acid surface functionalities increased the production of pro-inflammatory cytokines in response to higher level of complement proteins and decreased the number of lipoproteins found in their protein coronas. On another hand, amine rich coatings led to increased expressions of anti-inflammatory markers such as arginase. The findings demonstrate the potential to direct physiological responses to nanomaterials via tailoring their surface chemical composition

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions

Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics

Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications

Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a “nanoengineered surface” for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties

Plasma deposited poly-oxazoline nanotextured surfaces dictate osteoimmunomodulation towards ameliorative osteogenesis

Developing “osteoimmune-smart” bone substitute materials have become the forefront of research in bone regeneration. Biocompatible polymer coatings are applied widely to improve the bioactivity of bone substitute materials. In this context, polyoxazolines (Pox) have attracted substantial attention recently due to properties such as biocompatibility, stability, and low biofouling. In view of these useful properties, it is interesting to explore the capacity of Pox as an osteoimmunomodulatory agent to generate a favorable osteoimmune environment for osteogenesis. We applied a technique called plasma polymerization and succeeded in preparing Pox-like coatings (Ppox) and engineered their nanotopography at the nanoscale. We found that Ppox switched macrophages towards M2 extreme, thus inhibiting the release of inflammatory cytokines. The underlying mechanism may be related to the suppression of TLR pathway. The generated osteoimmune environment improved osteogenesis while inhibited osteoclastogenesis. This may be related to the release of osteogenic factors, especially Wnt10b from macrophages. The addition of nanotopography (16 nm, 38 nm, 68 nm) can tune the Ppox-mediated inhibition on inflammation and osteoclastic activities, while no significant effects were observed within the tested nano sizes on the Ppox-mediated osteogenesis. These results collectively suggest that Ppox can be useful as an effective osteoiumunomodulatory agent to endow bone substitute materials with favourable osteoimmunomodulatory property. Statement of Significance: In this study, we succeeded in preparing plasma deposited Pox-like nano-coatings (Ppox) via plasma polymerization and found that Ppox nanotopographies are useful osteoimmunomodulatory tools. Their osteoimmunodolatory effects and underlying mechanisms are unveiled. It is the first investigation into the feasibility of applying poly-oxazoline as an osteoimmunomodulatory agent. This expand the application of poly-oxazoline into the forefront in bone regeneration area for the development of advanced “osteoimmune-smart” bone substitute materials.</p

Correction to "Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications"

After online publication of this Article, the authors noticed an error in the Supplementary Figure 3 lower magnification of 38AApp SEM image. The correct Supplementary Figure 3 of this Article should have appeared as below. The authors apologize for any inconvenience caused. (Figure Presented).</p

Protein Interactions with Nanoengineered Polyoxazoline Surfaces Generated via Plasma Deposition

Protein adsorption to biomaterials is critical in determining their suitability for specific applications, such as implants or biosensors. Here, we show that surface nanoroughness can be tailored to control the covalent binding of proteins to plasma-deposited polyoxazoline (PPOx). Nanoengineered surfaces were created by immobilizing gold nanoparticles varying in size and surface density on PPOx films. To keep the surface chemistry consistent while preserving the nanotopography, all substrates were overcoated with a nanothin PPOx film. Bovine serum albumin was chosen to study protein interactions with the nanoengineered surfaces. The results demonstrate that the amount of protein bound to the surface is not directly correlated with the increase in surface area. Instead, it is determined by nanotopography-induced geometric effects and surface wettability. A densely packed array of 16 and 38 nm nanoparticles hinders protein adsorption compared to smooth PPOx substrates, while it increases for 68 nm nanoparticles. These adaptable surfaces could be used for designing biomaterials where proteins adsorption is or is not desirable

The introduction of nanotopography suppresses bacterial adhesion and enhances osteoinductive capacity of plasma deposited polyoxazoline surface

The plasma deposited polyoxazoline (PPOx) has been emerging in biomedical applications, especially for the surface modification of bone tissue engineering scaffold and/or bone implants. Herein, PPOx surfaces were generated by plasma polymerization with the introduction of surface nanotopography gradient, achieved by immobilization of different density of 16 nm gold nanoparticles. The introduction of surface nanotopography suppressed the adhesion of S. aureus on PPOx surface. Moreover, the introduction of surface nanotopography enhanced the initial attachment and spreading of hMSCs, as well as promoted the osteogenic differentiation of hMSCs. RhoA/ROCK signaling pathway may be involved in the enhancement of osteoinductive capacity of PPOx surface by nanotopography