Viscoelastic parameterization of human skin cells characterize material behavior at multiple timescales

Countless biophysical studies have sought distinct markers in the cellular mechanical response that could be linked to morphogenesis, homeostasis, and disease. Here, an iterative-fitting methodology visualizes the time-dependent viscoelastic behavior of human skin cells under physiologically relevant conditions. Past investigations often involved parameterizing elastic relationships and assuming purely Hertzian contact mechanics, which fails to properly account for the rich temporal information available. We demonstrate the performance superiority of the proposed iterative viscoelastic characterization method over standard open-search approaches. Our viscoelastic measurements revealed that 2D adherent metastatic melanoma cells exhibit reduced elasticity compared to their normal counterparts—melanocytes and fibroblasts, and are significantly less viscous than fibroblasts over timescales spanning three orders of magnitude. The measured loss angle indicates clear differential viscoelastic responses across multiple timescales between the measured cells. This method provides insight into the complex viscoelastic behavior of metastatic melanoma cells relevant to better understanding cancer metastasis and aggression.

Cellular Interaction of Human Skin Cells towards Natural Bioink via 3D-Bioprinting Technologies for Chronic Wound: A Comprehensive Review

Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.

Development of Innovative Gel Sunscreen Products from Momordica cochinchinensis (Lour.) Spreng. Extract

A study on the development of sunscreen gel products from Momordica cochinchinensis(Lour.) Spreng. extract aimed to study phenolic content, inhibitory effect of Elastase and Tyrosinase, product stability, toxicity, astringent effect of M. cochinchinensis extract, skin elasticity value, suitable product formula calculation for preparing sunscreen gel products from M. cochinchinensis extract, and irritation test. The process started fromthe selection of raw materials, preparation of extracts for determining the total phenolic content, development of suitable formula, test of safety and product physical characteristics, and then test of the anti-allergic effect of 10 volunteers to get efficient and safe sunscreen gel from M. cochinchinensis extract. The study result indicated that M. cochinchinensisaril extract had antioxidant activity DPPH of 1.51±0.05 mg/ml, compared to standard substance - Vitamin C, and total phenolic content of 13.18±0.18 (mg equivalent of gallic acid per 100 g - dry weight). Regarding Cytotoxicity at a concentration of 0.0001-1 mg/ml, it revealed that M. cochinchinensisaril extract was not toxic to human skin cells with the cell survival percentage at a concentration of 1 mg/ml equaled to 95.35±1.86 and 88.15±4.73%, respectively. M. cochinchinensisaril extract concentration of 1 mg/ml had astringent effect which can stimulate human skin cells to move together faster than the control group but showed effect slower than Vitamin C concentrate of 1 mg/ml. and did not have inhibitory effect on Elastase and Tyrosinaseenzymes. Regarding M. cochinchinensis seed oil extract, it did not toxic to human skin cells at the concentration of 0.0001-1 mg/ml with the survival percentage equaled to 105.67-111.46%, and had a few antioxidants activity of unsaturated fatty acids with an IPC50 more than 1000 mg/ml. This study was only the development of sunscreen gel products from M. cochinchinensis extract.

Viability of cultured human skin cells treated with 1,6-hexamethylene diisocyanate monomer and its oligomer isocyanurate in different culture media

The isocyanate monomer 1,6-hexamethylene diisocyanate (HDI) and one of its trimers, HDI isocyanurate, are airway and skin sensitizers contained in polyurethane paint. The toxic response of cultured skin cells to these compounds was measured by evaluating the isocyanate concentrations at which 50% of the cells die (i.e., lethal concentration 50%, LC50) because the relative toxicity of each form of HDI should be considered when exposure limits of HDI-based paints are set. By using a luminescent ATP-viability assay, we compared the cytotoxic effects of HDI monomer and HDI isocyanurate on cultured human skin cells (keratinocytes, fibroblasts, and melanocytes) after 4-h isocyanate exposures using culture media with varying levels of nutrients in order to also determine the effects of media composition on isocyanate toxicity. Before analysis, experimental wells were normalized to controls containing cells that were cultured with the same vehicle and media. The measured mean LC50 values ranged from 5 to 200 µM across the experimental conditions, in which HDI isocyanurate in protein-devoid media was the most toxic to cells, producing the lowest LC50 values. For HDI monomer, keratinocytes were the most resistant to its toxicity and melanocytes were the most susceptible. However, when exposed to HDI isocyanurate, the opposite was observed, with melanocytes being the most resilient and the keratinocytes and fibroblasts were more susceptible. Depending on the type of skin cells, dose–response data indicated that HDI isocyanurate was 2–6 times more toxic than HDI monomer when using protein-devoid media whereas HDI isocyanurate was 4–13 times more toxic than HDI monomer when protein-rich media was used. Therefore, if the protein-devoid saline medium alone were used for these experiments, then a significant under-estimation of their relative toxicities in protein-rich environments would have resulted. This difference is because HDI monomer toxicity was more attenuated by the presence of protein in the culture media than HDI isocyanurate toxicity. Thus, conclusions based on comparative toxicity studies and consequent inference applied to potential human toxicity can be affected by in vitro culture media conditions. The physiochemical difference in reactivity of the two forms of HDI to biological molecules most likely explains the observed toxicity differences and may have implications for skin penetration, adverse effects like skin sensitization, and systemic responses like asthma. Future studies are warranted to investigate differences in the biological availability, cellular toxicity, and immunologic sensitization mechanisms for HDI monomer and HDI isocyanurate.