Prevascularized spongy-like hydrogels maintain their angiogenic potential after prolonged hypothermic storage.

The chronic shortage of organs and tissues for transplantation represents a dramatic burden on healthcare systems worldwide. Tissue engineering offers a potential solution to address these shortages, but several challenges remain, with prevascularization being a critical factor for in vivo survival and integration of tissue engineering products. Concurrently, a different challenge hindering the clinical implementation of such products, regards their efficient preservation from the fabrication site to the bedside.

Generation of 3D melanoma models using an assembloid-based approach.

While 3D tumor models have greatly evolved over the past years, there is still a strong requirement for more biosimilar models which are capable of recapitulating cellular crosstalk within the tumor microenvironment while equally displaying representative levels of tumor aggressiveness and invasion. Herein, we disclose an assembloid melanoma model based on the fusion of individual stromal multicellular spheroids (MCSs). In contrast to more traditional tumor models, we show that it is possible to develop self-organizing, heterotypic melanoma models where tumor cells present stem-cell like features like up-regulated pluripotency master regulators SOX2, POU5F1 and NANOG.

Effect of photobiomodulation on the behaviour of mesenchymal stem cells in three-dimensional cultures.

Photobiomodulation (PBM) has been proposed as a strategy to improve the regenerative capacity of human adipose-derived stem cells (hASCs). Yet, this effect has been proved in 2D culture conditions. To analyze the effect of different doses of laser irradiation (660 nm) with different levels of energy (1 J, 2 J and 6 J) on hASCs cultured at 2D and 3D conditions.

Gellan gum spongy-like hydrogel-based dual antibiotic therapy for infected diabetic wounds.

Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions.

Gellan gum-based hydrogels support the recreation of the dermal papilla microenvironment.

The dermal papilla (DP), a specialized compartment within the hair follicle, regulates hair growth. However, human DP cells rapidly lose their inductivity in 2D-culture given the loss of positional and microenvironmental cues. Spheroids have been capable of recreating the 3D intercellular organization of DP cells, however, DP cell-matrix interactions are poorly represented.

Spongy-like hydrogels prevascularization with the adipose tissue vascular fraction delays cutaneous wound healing by sustaining inflammatory cell influx.

In vitro prevascularization is one of the most explored approaches to foster engineered tissue vascularization. We previously demonstrated a benefit in tissue neovascularization by using integrin-specific biomaterials prevascularized by stromal vascular fraction (SVF) cells, which triggered vasculogenesis in the absence of extrinsic growth factors. SVF cells are also associated to biological processes important in cutaneous wound healing.

Highly tailorable gellan gum nanoparticles as a platform for the development of T cell activator systems.

Background: T cell priming has been shown to be a powerful immunotherapeutic approach for cancer treatment in terms of efficacy and relatively weak side effects. Systems that optimize the stimulation of T cells to improve therapeutic efficacy are therefore in constant demand. A way to achieve this is through artificial antigen presenting cells that are complexes between vehicles and key molecules that target relevant T cell subpopulations, eliciting antigen-specific T cell priming.

Integrin-specific hydrogels for growth factor-free vasculogenesis.

Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1 cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors.

An optimized mouse model of Staphylococcus aureus infected diabetic ulcers.

Objective: Diabetic foot infection (DFI) represents a major healthcare burden, for which treatment is challenging owing to the pathophysiological alterations intrinsic to diabetes and the alarming increase of antimicrobial resistance. Novel therapies targeting DFI are therefore a pressing research need for which proper models of disease are required.

Results: Here, we present an optimized diabetic mouse model of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, that resemble key features of DFI, such as pathogen invasion through wound bed and surrounding tissue, necrosis, persistent inflammation and impaired wound healing.

Mechanomodulatory biomaterials prospects in scar prevention and treatment.

Scarring is a major clinical issue that affects a considerable number of patients. The associated problems go beyond the loss of skin functionality, as scars bring aesthetic, psychological, and social difficulties. Therefore, new strategies are required to improve the process of healing and minimize scar formation.

Development of an antibiotics delivery system for topical treatment of the neglected tropical disease Buruli ulcer.

Skin infection by Mycobacterium ulcerans causes Buruli ulcer (BU) disease, a serious condition that significantly impact patient' health and quality of life and can be very difficult to treat. Treatment of BU is based on daily systemic administration of antibiotics for at least 8 weeks and presents drawbacks associated with the mode and duration of drug administration and potential side effects. Thus, new therapeutic strategies are needed to improve the efficacy and modality of BU therapeutics, resulting in a more convenient and safer antibiotic regimen.

Pushing the Natural Frontier: Progress on the Integration of Biomaterial Cues toward Combinatorial Biofabrication and Tissue Engineering.

The engineering of fully functional, biological-like tissues requires biomaterials to direct cellular events to a near-native, 3D niche extent. Natural biomaterials are generally seen as a safe option for cell support, but their biocompatibility and biodegradability can be just as limited as their bioactive/biomimetic performance. Furthermore, integrating different biomaterial cues and their final impact on cellular behavior is a complex equation where the outcome might be very different from the sum of individual parts.

Bioinks Enriched with ECM Components Obtained by Supercritical Extraction.

Extracellular matrix (ECM)-based bioinks have been steadily gaining interest in the field of bioprinting to develop biologically relevant and functional tissue constructs. Herein, we propose the use of supercritical carbon dioxide (scCO) technology to extract the ECM components of cell-sheets that have shown promising results in creating accurate 3D microenvironments replicating the cell's own ECM, to be used in the preparation of bioinks. The ECM extraction protocol best fitted for cell sheets was defined by considering efficient DNA removal with a minor effect on the ECM.

Numerical and experimental simulation of a dynamic-rotational 3D cell culture for stratified living tissue models.

Human tissues and organs are inherently heterogeneous, and their functionality is determined by the interplay between different cell types, their secondary architecture, and gradients of signalling molecules and metabolites. To mimic the dynamics of native tissues, perfusion bioreactors and microfluidic devices are widely used in tissue engineering (TE) applications for enhancing cell culture viability in the core of 3D constructs. Still, mostscreening methods for compound efficacy and toxicity assessment include cell or tissue exposure to constant and homogeneous compound concentrations over a defined testing period.

Recreation of a hair follicle regenerative microenvironment: Successes and pitfalls.

The hair follicle (HF) is an exquisite skin appendage endowed with cyclical regenerative capacity; however, de novo follicle formation does not naturally occur. Consequently, patients suffering from extensive skin damage or hair loss are deprived of the HF critical physiological and/or aesthetic functions, severally compromising skin function and the individual's psychosocial well-being. Translation of regenerative strategies has been prevented by the loss of trichogenic capacity that relevant cell populations undergo in culture and by the lack of suitable human-based in vitro testing platforms.

Correction: Strategies for the hypothermic preservation of cell sheets of human adipose stem cells.

[This corrects the article DOI: 10.1371/journal.pone.

Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers.

Solid-state optics has been the pillar of modern digital age. Integrating soft hydrogel materials with micro/nanooptics could expand the horizons of photonics for bioengineering. Here, wet-spun multilayer hydrogel fibers are engineered through ionic-crosslinked natural polysaccharides that serve as multifunctional platforms.

Vascularization in skin wound healing: where do we stand and where do we go?

Cutaneous healing is a highly complex process that, if altered due to, for example, impaired vascularization, results in chronic wounds or repaired neotissue of poor quality. Significant progress has been achieved in promoting neotissue vascularization during tissue repair/regeneration. In this review, we discuss the strategies that have been explored and how each one of them contributes to regulate vascularization in the context of cutaneous wound healing from two different perspectives - biomaterial-based and a cell-based approaches.

3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network.

Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features.

3D-Printed Gelatin Methacrylate Scaffolds with Controlled Architecture and Stiffness Modulate the Fibroblast Phenotype towards Dermal Regeneration.

Impaired skin wound healing due to severe injury often leads to dysfunctional scar tissue formation as a result of excessive and persistent myofibroblast activation, characterised by the increased expression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) proteins. Yet, despite extensive research on impaired wound healing and the advancement in tissue-engineered skin substitutes, scar formation remains a significant clinical challenge. This study aimed to first investigate the effect of methacrylate gelatin (GelMA) biomaterial stiffness on human dermal fibroblast behaviour in order to then design a range of 3D-printed GelMA scaffolds with tuneable structural and mechanical properties and understand whether the introduction of pores and porosity would support fibroblast activity, while inhibiting myofibroblast-related gene and protein expression.