Decellularized fennel and dill leaves as possible 3D channel network in GelMA for the development of an in vitro adipose tissue model

The development of 3D scaffold-based models would represent a great step forward in cancer research, offering the possibility of predicting the potential in vivo response to targeted anticancer or anti-angiogenic therapies. As regards, 3D in vitro models require proper materials, which faithfully recapitulated extracellular matrix (ECM) properties, adequate cell lines, and an efficient vascular network. The aim of this work is to investigate the possible realization of an in vitro 3D scaffold-based model of adipose tissue, by incorporating decellularized 3D plant structures within the scaffold. In particular, in order to obtain an adipose matrix capable of mimicking the composition of the adipose tissue, methacrylated gelatin (GelMA), UV photo-crosslinkable, was selected. Decellularized fennel, wild fennel and, dill leaves have been incorporated into the GelMA hydrogel before crosslinking, to mimic a 3D channel network. All leaves showed a loss of pigmentation after the decellularization with channel dimensions ranging from 100 to 500 mu m up to 3 mu m, comparable with those of human microcirculation (5-10 mu m). The photo-crosslinking process was not affected by the embedded plant structures in GelMA hydrogels. In fact, the weight variation test, performed on hydrogels with or without decellularized leaves showed a weight loss in the first 96 h, followed by a stability plateau up to 5 weeks. No cytotoxic effects were detected comparing the three prepared GelMA/D-leaf structures; moreover, the ability of the samples to stimulate differentiation of 3T3-L1 preadipocytes in mature adipocytes was investigated, and cells were able to grow and proliferate in the structure, colonizing the entire microenvironment and starting to differentiate. The developed GelMA hydrogels mimicked adipose tissue together with the incorporated plant structures seem to be an adequate solution to ensure an efficient vascular system for a 3D in vitro model. The obtained results showed the potentiality of the innovative proposed approach to mimic the tumoral microenvironment in 3D scaffold-based models

Updates on polyurethane and its multifunctional applications in biomedical engineering

Polyurethanes (PUs) have properties that make them promising in biomedical applications. PU is recognized as one of the main families of blood and biocompatible materials. PU plays a vital role in the design of medical devices in various medical fields. The structure of PU contains two segments: soft and hard. Its elastomeric feature is due to its soft segment, and its excellent and high mechanical property is because of its hard segment. It is possible to achieve specific desirable and targeted properties by changing the soft and hard chemical structures and the ratio between them. The many properties of PU each draw the attention of different medical fields. This work reviews PU highlighted properties, such as biodegradability, biostability, shape memory, and improved antibacterial activity. Also, because PU has a variety of applications, this review restricts its focus to PU's prominent applications in tissue engineering, cardiovascular medicine, drug delivery, and wound healing. In addition, it contains a brief review of PU's applications in biosensors and oral administration

Engineering thermoplastics for additive manufacturing: a critical perspective with experimental evidence to support functional applications

Among additive manufacturing techniques, the filament-based technique involves what is referred to as fused deposition modeling (FDM). FDM materials are currently limited to a selected number of polymers. The present study focused on investigating the potential of using high-end engineering polymers in FDM. In addition, a critical review of the materials available on the market compared with those studied here was completed

Design of a novel bioink suitable for the 3D printing of lymphoid cells

Introduction: For decades, in vitro 2D cell culture techniques have been employed in research, but they fail to recapitulate the complexity of natural tissues. 3D bioprinting could potentially overcome this drawback due to the possibility to control the spatial disposition of living cells and the geometry of the 3D scaffold. Materials and methods: This study reports the design and characterization of a novel bioink for extrusion bioprinting, analyzing different blend formulations composed of alginate, gelatin, and methylcellulose, suitable as cell-laden bioink for lymphoid cells, in particular those isolated from patients with Chronic Lymphocytic Leukemia (CLL). The rheological properties as a function of temperature and the printability of the formulations were investigated to define the optimal printing parameters. In vitro stability of the printed scaffolds was investigated under culture conditions and compression tests were performed on printed and bioprinted scaffolds to compare their mechanical properties with those of fresh lymphoid tissue. Finally,MEC1, aCLL cell line,was bioprinted to investigate cell viability, cell density, and cell capability to be released from the scaffold over time. Results and discussion: Results showed that, for the selected blends, good shape fidelity and printing accuracy were achieved with a limitation on the number of printed layers. Scaffolds withstood culture conditions showing stability for up to 3 weeks and their mechanical properties were similar to those of lymphoid tissues already reported in the literature. High cell viability after 21 days was observed for both MEC1 and primary peripheral mononuclear cells, confirming the possibility to use the selected formulation to successfully bioprint lymphoid cells by possibly mimicking their native lymphoid microenvironment

Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes' poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na 2 SO 4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis

Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel

Autologous chondrocyte implantation for cartilage repair represents a challenge because strongly limited by chondrocytes' poor expansion capacity in vitro. Mesenchymal stem cells (MSCs) can differentiate into chondrocytes, while mechanical loading has been proposed as alternative strategy to induce chondrogenesis excluding the use of exogenous factors. Moreover, MSC supporting material selection is fundamental to allow for an active interaction with cells. Here, we tested a novel thermo-reversible hydrogel composed of 8% w/v methylcellulose (MC) in a 0.05 M Na 2 SO 4 solution. MC hydrogel was obtained by dispersion technique and its thermo-reversibility, mechanical properties, degradation and swelling were investigated, demonstrating a solution-gelation transition between 34 and 37 °C and a low bulk degradation (<20%) after 1 month. The lack of any hydrogel-derived immunoreaction was demonstrated in vivo by mice subcutaneous implantation. To induce in vitro chondrogenesis, MSCs were seeded into MC solution retained within a porous polyurethane (PU) matrix. PU-MC composites were subjected to a combination of compression and shear forces for 21 days in a custom made bioreactor. Mechanical stimulation led to a significant increase in chondrogenic gene expression, while histological analysis detected sulphated glycosaminoglycans and collagen II only in loaded specimens, confirming MC hydrogel suitability to support load induced MSCs chondrogenesis

MXene-Integrated Silk Fibroin-Based Self-Assembly-Driven 3D-Printed Theragenerative Scaffolds for Remotely Photothermal Anti-Osteosarcoma Ablation and Bone Regeneration

Aiming to address the bone regeneration and cancer therapy functionalities in one single material, in this study, we developed a dual-functional theragenerative three-dimensional (3D) aerogel-based composite scaffold from hybridization of photo-cross-linked silk fibroin (SF) biopolymer with MXene (Ti3C2) two-dimensional (2D) nanosheets. To fabricate the scaffold, we first develop a dual-cross-linked SF-based aerogel scaffold through 3D printing and photo-cross-linking of the self-assembly-driven methacrylate-modified SF (SF-MA) gel with controlled pore size, macroscopic geometry, and mechanical stability. In the next step, to endow a remotely controlled photothermal antiosteosarcoma ablation function to fabricated aerogel scaffold, MXene 2D nanosheets with strong near-infrared (NIR) photon absorption properties were integrated into the 3D-printed scaffolds. While 3D-printed MXene-modified dual-cross-linked SF composite scaffolds can mediate the in vitro growth and proliferation of preosteoblastic cell lines, they also endow a strong photothermal effect upon remote irradiation with NIR laser but also significantly stimulate bone mineral deposition on the scaffold surface. Additionally, besides the local release of the anticancer model drug, the generated heat (45-53 ?) mediated the photothermal ablation of cancer cells. The developed aerogel-based composites and chosen therapeutic techniques are thought to render a significant breakthrough in biomaterials' future clinical applications

In vitro functional models for human liver diseases and drug screening: beyond animal testing

Liver is one of the most important and complex organs in the human body, being characterized by a sophisticated microarchitecture and responsible for key physiological functions. Despite its remarkable ability to regenerate, acute liver failure and chronic liver diseases are major causes of morbidity and mortality worldwide. Therefore, understanding the molecular mechanisms underlying such liver disorders is critical for the successful development of novel therapeutics. In this frame, preclinical animal models have been portrayed as the most commonly used tool to address such issues. However, due to significant species differences in liver architecture, regenerative capacity, disease progression, inflammatory markers, metabolism rates, and drug response, animal models cannot fully recapitulate the complexity of human liver metabolism. As a result, translational research to model human liver diseases and drug screening platforms may yield limited results, leading to failure scenarios. To overcome this impasse, over the last decade, 3D human liver in vitro models have been proposed as an alternative to pre-clinical animal models. These systems have been successfully employed for the investigation of the etiology and dynamics of liver diseases, for drug screening, and - more recently - to design patient-tailored therapies, resulting in potentially higher efficacy and reduced costs compared to other methods. Here, we review the most recent advances in this rapidly evolving field with particular attention to organoid cultures, liver-on-a-chip platforms, and engineered scaffold-based approaches

Development of biodegradable magnesium alloy stents with coating

Biodegradable stents are attracting the attention of many researchers in biomedical and materials research fields since they can absolve their specific function for the expected period of time and then gradually disappear. This feature allows avoiding the risk of long-term complications such as restenosis or mechanical instability of the device when the vessel grows in size in pediatric patients. Up to now biodegradable stents made of polymers or magnesium alloys have been proposed. However, both the solutions have limitations. The polymers have low mechanical properties, which lead to devices that cannot withstand the natural contraction of the blood vessel: the restenosis appears just after the implant, and can be ascribed to the compliance of the stent. The magnesium alloys have much higher mechanical properties, but they dissolve too fast in the human body. In this work we present some results of an ongoing study aiming to the development of biodegradable stents made of a magnesium alloy that is coated with a polymer having a high corrosion resistance. The mechanical action on the blood vessel is given by the magnesium stent for the desired period, being the stent protected against fast corrosion by the coating. The coating will dissolve in a longer term, thus delaying the exposition of the magnesium stent to the corrosive environment. We dealt with the problem exploiting the potentialities of a combined approach of experimental and computational methods (both standard and ad-hoc developed) for designing magnesium alloy, coating and scaffold geometry from different points of views. Our study required the following steps: i) selection of a Mg alloy suitable for stent production, having sufficient strength and elongation capability; ii) computational optimization of the stent geometry to minimize stress and strain after stent deployment, improve scaffolding ability and corrosion resistance; iii) development of a numerical model for studying stent degradation to support the selection of the best geometry; iv) optimization of the alloy microstructure and production of Mg alloy tubes for stent manufacturing; v) set up, in terms of laser cut and surface finishing, of the procedure to manufacture magnesium stents; vi) selection of a coating able to assure enough corrosion resistance and computational evaluation of the coating adhesion. In the paper the multi-disciplinary approach used to go through the steps above is summarized. The obtained results suggest that developed methodology is effective at designing innovative biomedical devices