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In Vitro Alternative Methods for the Assessment of Dermal Irritation and Inflammation
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
David W. Hobson, James A. Blank
Serum-free culture of human epidermal keratinocytes has recently become possible. Efforts have recently been focused on the development of assays using these cultures which measure cellular viability and metabolism to predict the irritative potential of chemicals within a given chemical class. It may be of benefit to direct future efforts toward the development of endpoints to measure the release of inflammatory mediators such as platelet activating factor, complement products (e.g., C5a), arachidonic acid oxidation metabolites, interleukins, or other agents acting as chemoattractants and activators of leukocytes. This may potentially increase the ability of in vitro systems to predict inflammation. Although cultured human keratinocytes may not be able to serve as a complete replacement for in vivo dermal testing, the model appears to be viable as a screen prior to in vivo testing. In order to examine the potential hypersensitivity of chemicals or chemical interactions with other skin components, it will be necessary to develop more sophisticated cell culture systems such as keratinocyte co-culture models or even to use dermal equivalent systems that contain several different cell types.
Gingiva and Periodontal Tissue Regeneration
Published in Vincenzo Guarino, Marco Antonio Alvarez-Pérez, Current Advances in Oral and Craniofacial Tissue Engineering, 2020
Avita Rath, Preena Sidhu, Priyadarshini Hesarghatta Ramamurthy, Bennete Aloysius Fernandesv, Swapnil Shankargouda, Sultan Orner Sheriff
When culturing fibroblasts on a lactate-glycolate copolymer scaffold to form a dermal-equivalent tissue, they observed that the cellular content of Vascular Endothelial Growth Factor (VEGF) messenger ribonucleic acid in these 3D cultures was 22 times greater than that in the same fibroblasts grown as monolayers. In addition, the pore size of the scaffolds has been shown to be a critical determinant of blood vessel in growth, which is significantly faster in pores with a size greater than 250 mm than in those less than 250 mm Finally, molecular deteriorations that are induced during the incorporation process of the implant might influence the in growth of blood vessels into scaffolds. This may explain why currently used biomaterials partly fail to vascularize, independent of their material properties. Fibronectin, for example, is the only mammalian adhesion protein that binds and activates a 5b1-integrins, which are known to exert proangiogenic actions, although Vogel and Baneyx, who investigated the role of this adhesion protein in scaffold vascularization, could not demonstrate an acceleration or improvement of implant vascularization but documented an inhibitory action on the process of new vessel formation.
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
In other tissue and organ systems, RA is similarly involved in differentiation and maturation of cells, such as retinal cells of the eye (41), blood cells (42,43), sperm (44,45), and so on. RA has long been known to modulate cell growth and differentiation in many epithelial tissues, including the epidermis. When human keratinocytes are grown on fabricated collagen lattices as dermal equivalent, physiologic concentrations (1–10 nm) of RA induce keratinocyte differentiation and formation of epithelium, similar to that in normally keratinized epidermis. Higher concentration (>0.1 μm) of RA reduces epidermal maturation and produces parakeratosis, while deficiency of RA leads to hyperkeratosis (46). Excess of vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium, and this process is mediated via Gbx1 homeobox genes which is a direct target of RA (47).
Cell-Biomaterial constructs for wound healing and skin regeneration
Published in Drug Metabolism Reviews, 2022
Ingrid Safina, Luke T. Childress, Srinivas R. Myneni, Kieng Bao Vang, Alexandru S. Biris
The 3 D bioprinted skin constructs were compared side by side to conventional skin constructs created using the manual deposition method, which consisted of manually depositing both the matrix and cell suspension (Gangatirkar et al. 2007) in specific concentrations calculated from the printing parameters used to create the bioprinted constructs. Lee et al. created the conventional skin construct in two steps: first, the dermal equivalent was made by mixing collagen matrix (final concentration: 2.66 mg/mL) and fibroblast suspension (final cell density: 2.3 × 105/mL). Second, keratinocytes were seeded on top of the dermal equivalent at a surface cell density of 1.4 × 105/cm2 then incubated for 1 week in submerged cell culture conditions.