Thermophysical and mechanical properties of biological tissues as a function of temperature: a systematic literature review.

BACKGROUND: Detailed information on the temperature dependence of tissue thermophysical and mechanical properties is pivotal for the optimal implementation of mathematical models and simulation-based tools for the pre-planning of thermal ablation therapies. These models require in-depth knowledge of the temperature sensitivity of these properties and other influential terms (e.g., blood perfusion and metabolic heat) to maximize the treatment prediction outcome. METHODOLOGY: A systematic literature review of experimental trials investigating thermophysical and mechanical properties of biological media, as well as blood perfusion and metabolic heat, as a function of temperature in hyperthermic and ablative thermal range, was conducted up to June 2021. RESULTS: A total of 61 articles was selected, thus enabling a comprehensive overview of the temperature dependence of thermophysical properties (i.e. thermal conductivity, specific heat, volumetric heat capacity, density, thermal diffusivity), and mechanical properties (shear, elastic, storage, loss and complex moduli, loss factor, stiffness) along with the principal measurement techniques. The reviewed studies considered different tissues, e.g., liver, fat, cartilage, brain, myocardium, muscle, bone, skin, pancreas tissues, and also some tumorous tissues. CONCLUSIONS: The thermophysical properties of soft tissues appear rather constant until 90 °C, with slight differences ascribable to tissues characteristics and measurement methods. Conversely, the information on mechanical properties is heterogeneous because most of the articles investigated different types of properties in different biological tissues. Furthermore, most of the experiments were conducted ex vivo; only a small percentage concerned in vivo studies. Limited recent information about the temperature dependence of metabolic heat and blood perfusion was observed.

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells.

Functionalized graphene oxide (GO) nanoparticles are being increasingly employed for designing modern drug delivery systems because of their high degree of functionalization, high surface area with exceptional loading capacity, and tunable dimensions. With intelligent controlled release and gene silencing capability, GO is an effective nanocarrier that permits the targeted delivery of small drug molecules, antibodies, nucleic acids, and peptides to the liquid or solid tumor sites. However, the toxicity and biocompatibility of GO-based formulations should be evaluated, as these nanomaterials may introduce aggregations or may accumulate in normal tissues while targeting tumors or malignant cells. These side effects may potentially be impacted by the dosage, exposure time, flake size, shape, functional groups, and surface charges. In this review, the strategies to deliver the nucleic acid via the functionalization of GO flakes are summarized to describe the specific targeting of liquid and solid breast tumors. In addition, we describe the current approaches aimed at optimizing the controlled release towards a reduction in GO accumulation in non-specific tissues in terms of the cytotoxicity while maximizing the drug efficacy. Finally, the challenges and future research perspectives are briefly discussed.

Harnessing graphene oxide nanocarriers for siRNA delivery in a 3D spheroid model of lung cancer.

Gene therapy has been recently proposed as an effective strategy for cancer treatment. A significant body of literature proved the effectiveness of nanocarriers to deliver therapeutic agents to 2D tumour models, which are simple but not always representative of the in vivo reality. In this study, we analyze the efficiency of 3D spheroids combined with a minimally modified graphene oxide (GO)-based nanocarrier for siRNA delivery as a new system for cell transfection. Small interfering RNA (siRNA) targeting cluster of differentiation 47 (CD47; CD47_siRNA) was used as an anti-tumour therapeutic agent to silence the genes expressing CD47. This is a surface marker able to send a "don't eat me" signal to macrophages to prevent their phagocytosis. Also, we report the analysis of different GO formulations, in terms of size (small: about 100 nm; large: >650 nm) and functionalization (unmodified or modified with polyethylene glycol (PEG) and the dendrimer PAMAM), aiming to establish the efficiency of unmodified GO as a nanocarrier for the transfection of A549 lung cancer spheroids. Small modified GO (smGO) showed the highest transfection efficiency values (>90%) in 3D models. Interestingly, small unmodified GO (sGO) was found to be promising for transfection, with efficiency values >80% using a higher siRNA ratio (i.e., 3 : 1). These results demonstrated the higher efficiency of spheroids compared to 2D models for transfection, and the high potential of unmodified GO to carry siRNA, providing a promising new in vitro model system for the analysis of anticancer gene therapies.

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 µm up to 3 µm, comparable with those of human microcirculation (5-10 µm). 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.