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Nanomaterials for the Delivery of Therapeutic Nucleic Acids
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
Michael Riley, Wilfred Vermerris
Another class of peptide-based NPs are the elastin-like peptides (ELPs). ELPs are artificial peptides with a repeating sequences of polypeptides (Val-Pro-Gly-X-Gly)n with X designating any amino acid (Lohcharoenkal et al. 2014). Depending on the choice of amino acid, “X” ELPs can have a tunable thermal transition temperature (T t). Below their T t, ELPs are soluble, whereas above their T t, ELPs form a viscous fluid called coacervate (Urry 1997). Dash et al. (2015) designed a dual ELP injectable system composed of an ELP gel-based scaffold and ELP hollow spheres, to deliver two different therapeutic gene doses. This system allowed them to deliver plasmids encoding nitric oxide synthase and interleukin-10 to human umbilical vein cells (HUVECs) to induce angiogenesis and reduce inflammation to treat critical limb ischemia, which manifests itself as obstruction of arteries and which can ultimately lead to loss of limbs. Monfort and Koria (2017) constructed heterogeneous NPs composed of two chimeric ELP fusion proteins with low-density lipoprotein receptor repeat 3 (LDLR3) and keratinocyte growth factor (KGF), to selectively deliver a lentiviral vector encoding GFP to cells expressing high levels of KGF. This novel NP approach provides target specificity, whereas the lentivirus by itself infects both dividing and nondividing cells, creating potential off-target effects, increased immunogenicity, and toxicity.
The Extracellular Matrix as a Substrate for Stem Cell Growth and Development and Tissue Repair
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Stephen F. Badylak, Mervin C. Yoder
The characteristic of the intact ECM that distinguishes it from other substrates for cell attachment, growth and differentiation, such as purified collagens, fibronectin or laminin, is its diversity of structural and functional proteins. In addition, the associated bioactive molecules that reside within the ECM and their unique spatial distribution provides a reservoir of biologic signals. Although cytokines and growth factors are present within ECM in very small quantities, they act as potent modulators of cell behavior. The list of growth factors is extensive and includes vascular endothelial cell growth factor (VEGF), the fibroblast growth factor (FGF) family, epithelial cell growth factor (EGF), transforming growth factor beta (TGF-beta), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF) and platelet derived growth factor (PDGF), among others. These factors tend to exist in multiple isoforms, each with its specific biologic activity. Purified forms of growth factors and biologic peptides have been investigated in recent years as therapeutic means of encouraging blood vessel formation (e.g., VEGF), inhibiting blood vessel formation (angiostatin), stimulating deposition of granulation tissue (PDGF), and encouraging epithelialization of wounds (KGF). However, this therapeutic approach has struggled with determination of optimal dose, the ability to sustain and localize the release at the desired site, and the inability to turn the factor “on” and “off” as needed during the course of tissue repair.
Bioprinting of human skin
Published in Ali Khademhosseini, Gulden Camci-Unal, 3D Bioprinting in Regenerative Engineering, 2018
Tania Baltazar, Carolina Catarino, Pankaj Karande
Soluble signaling molecules such as epidermal growth factor (EGF), keratinocyte growth factor (KGF), fibroblast growth factor (FGF), transforming growth factor (TGF), and vascular endothelial growth factor (VEGF) also play an important role in maintaining proper skin homeostasis (Yildirimer et al. 2012). In vitro, these molecules, typically supplemented in media, have been shown to regulate proliferation, migration, and differentiation of skin cells (Hasskarl et al. 2006; Peplow and Chatterjee 2013; Fuchs 1990). The inclusion of these growth factors in scaffolds has also been investigated. For example, the immobilization of EGF in gelatin sheets or biodegradable microspheres has shown improved wound healing in animal models (Ulubayram et al. 2001; Tanaka et al. 2005). In another study, a 3D-bioprinted matrix containing EGF increased proliferation of sweat gland cells (Huang et al. 2010). These biomolecules and cells, combined in a relevant manner, can be used to fabricate the bioinks for printing different layers and structures of the skin, generating a skin model with increased complexity and functionality. A comprehensive effort to develop bioinks that could sufficiently mimic the complexity of human skin is lacking. As a result, 3D-bioprinting approaches typically mimic the standard protocols for manual skin reconstruction employing relatively simple combinations of biomaterials.
Disinfection of Human Amniotic Membrane Using a Hydrodynamic System with Ozonated Water
Published in Ozone: Science & Engineering, 2023
Sílvia Móbille Awoyama, Henrique Cunha Carvalho, Túlia de Souza Botelho, Sandra Irene Sprogis Dos Santos, Debora Alicia Buendia Palacios, Sebastian San Martín Henríque, Renato Amaro Zângaro, Carlos José de Lima, Adriana Barrinha Fernandes
The stromal matrix has anti-inflammatory properties due to the presence of an extracellular matrix rich in fibrous polymers consisting mainly of collagen., resulting from the entrapment of inflammatory cells, inhibition of protease activity, decreased lipid peroxidation and the presence of various types of growth factors (Epidermal Growth Factor – EGF, Basic Fibroblast Growth Factor – b-FGF, Hepatocyte Growth Factor – HFG, Keratinocyte Growth Factor – KGF and Transforming Growth Factors – TGF) and cytokines (Interleukin 6 and 8). Other biological properties of hAM include antimicrobial and anti-fibrosis effects, along with the ability to reduce scarring and pain and promote neovascularization and wound healing (European Directorate for The Quality of Medicines and. Healthcare (EDQM) 2017; Hao et al. 2000; Paggiaro et al. 2020; Talmi et al. 1991).
Genetic variants affecting chemical mediated skin immunotoxicity
Published in Journal of Toxicology and Environmental Health, Part B, 2022
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
γδ T lymphocytes are lymphoid cells responsible for secreting keratinocyte growth factor (KGF) and insulin-like growth factor-1 (IGF-1) to maintain keratinocyte populations and migrate to draining lymph nodes after sensing stressed keratinocytes (Nguyen and Soulika 2019). γδ T lymphocytes are not MHC-restricted and recognize soluble antigens, derived from damaged or stressed cells, or those complexed with non-classical MHC molecules (Nguyen and Soulika 2019). After skin exposure to contact allergens, γδ T cells produce high amounts of IL-17 and IL-22 – pro – inflammatory cytokines that promote IL-1β secretion by keratinocytes and enhance the inflammatory process. IL-17 producing cells might participate in inflammatory processes of several skin diseases, such as psoriasis, contact hypersensitivity (CHS), atopic contact dermatitis and AD (Lee et al. 2020).