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Controlled Therapeutic Delivery in Wound Healing
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
Adam Jorgensen, Zishuai Chou, Sean Murphy
The cell source employed in cellularized wound healing therapies is an important component that has direct implications on cost, speed, and effectiveness of patient therapies. The widespread application of skin grafts have led researchers to explore delivering the cellular components of the grafts over a wider wound area, facilitating reduced donor site requirements through increased efficiency. Specifically, the harvesting of keratinocytes, fibroblasts, and other primary skin cell types and the distribution over the wound site through spraying or bioprinting has produced promising results in preclinical and clinical trials [143,144]. Human skin keratinocytes are one of the most obvious cell types used for wound healing, as one of the main goals of a given therapy is to regenerate the keratinocyte-based epithelial skin layer. Next, dermal fibroblasts are essential to a healing wound for producing a normal collagen ECM. As described above, the hair follicle bulb also contains a valuable stem cell niche which could be used for further enhancement of wound healing. One well-established method of using primary skin cells for grafting is the cultured epithelial autograft. Still other, more complex attempts to produce full-thickness skin through bioprinting and molding have also been performed.
Therapeutic Nanostructures for Improved Wound Healing
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Lalduhsanga Pachuau, Pranab Jyoti Das, Bhaskar Mazumder
Epithelial cells and fibroblasts, which are the key cells involved in the formation of the extracellular matrix, migrate to the injured site, replacing the damaged and lost tissue. Keratinocytes also migrate across the wound bed. This migration takes place from the margin and lasts for 2–3 days. Migration coupled with wound contraction results in re-epithelialization and wound closure.
The Challenge of Human Skin
Published in George K. Knopf, Amarjeet S. Bassi, Smart Biosensor Technology, 2018
Puneet Khanna, Steven Hoath, Rod Smallwood, Shekhar Bhansali
The protection provided by the epidermis forms the first barrier against harmful foreign substances. Most of the cells (∼90%) in the epidermis are keratinocytes. They produce a tough, fibrous, and intracellular protein called keratin; hence the name. The keratinocytes are stacked in layers. The youngest cells occupy the lower layers, while older cells are present in the upper ones. The lower layer cells multiply continually, while the older upper layer keratinocytes constantly slough off. By the time the cells move up to the uppermost layer of the epidermis, they are dead and completely filled with the keratin. From bottom to top, the layers are named stratum basale, stratum spinosum, stratum granulosum, and SC [9].
Polymeric biomaterials for wound healing applications: a comprehensive review
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Ahmed Olanrewaju Ijaola, Damilola O. Akamo, Fouad Damiri, Cletus John Akisin, Emmanuel Anuoluwa Bamidele, Emmanuel Gboyega Ajiboye, Mohammed Berrada, Victor Onyebuchukwu Onyenokwe, Shang-You Yang, Eylem Asmatulu
The proliferation stage of the wound-healing process is the third phase when the wound is “rebuilt” through the proliferation of fibroblasts and collagen deposition to replace the tentative fibrin matrix. This stage commences about two to three days following the trauma and proceeds until the wound is closed [22]. This phase entails angiogenesis, re-epithelialization, tissue granulation, and wound contraction. Angiogenesis, a process where endothelial cells form new capillaries, takes place during the proliferation stage and is induced by some growth factors such as vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF), TGF- and PDGF [42]. The newly generated capillaries convey oxygen and nutrients to the wound site and remove waste products. Angiogenesis is important for tissue granulation to occur during the proliferation stage, and these granulation tissues help starts the re-epithelialization. The formation of granulation tissue is triggered by inflammatory cytokines, which trigger fibroblasts to make growth factors which consequently cause keratinocytes to move to the wound bed [43]. Basal keratinocytes move from the wound edges and skin appendages to the injured site where they proliferate, differentiate, and immediately form a cover over the wound. On the other hand, fibroblasts could also move from bone marrow to the wound to activate and synthesize the extracellular matrix by releasing several extracellular matrix proteins such as fibronectin, hyaluronan or hyaluronic acid (HA), and collagens, as illustrated in Figure 4. Subsequently, wound contraction occurs, whereby the fibroblast, which is already in the wound bed, differentiates into myofibroblasts that close the wound area by pulling in the wound edges.
Keratinocytes-hair follicle bulge stem cells-fibroblasts co-cultures on a tri-layer skin equivalent derived from gelatin/PEG methacrylate nanofibers
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Babitha Sumathy, Prabha D Nair
Skin is the largest organ of the vertebrate body and because it interfaces with the environment, skin is the first line of defence against a host of environmental aggressors. The skin has two principle layers-the epidermis, which is the epithelial tissue layer of the skin and the dermis, the connective tissue layer of the skin. Embedded within the dermis are the adnexal structures including hair follicles and sweat glands as well as blood vessels and sensory nerve endings. Hair follicles, sebaceous glands, and sweat glands are epithelial invaginations from the epidermis. A third layer, the hypodermis is composed mainly of fat and a layer of loose connective tissue. These three layers play a vital role in protecting the body from any mechanical damage such as wounding. Skin with its adnexa maintains internal homeostasis by preventing excessive water and heat loss. When normal anatomic structure and function of the skin is disrupted by means of a wound or burn, the normal homeostatic functions of the skin are lost. Normally, tissue loss or damage initiates the wound healing process that involves orchestrated interaction of multiple growth factors, cytokines, chemokines, and different cell types [1]. Wound heals by epithelialization from the margins of the wound, where the basal keratinocytes change into a proliferating migratory cell type and cover the damaged area. Any dysregulation of the wound healing process could result in chronic or “hard- to- heal” wounds. Current treatment methods include wound dressings [2], autologous skin grafts [3], allogeneic skin grafts [4] and tissue-engineered skin repair [5]. The downsides of wound dressings are the low adhesion to the lesion, ineffective in achieving skin regeneration and sufficient recovery of skin appendages – hair follicles, sweat and sebaceous glands – that are critical for skin to exert its biological functions [6]. Being non-immunogenic, autologous skin grafts are considered as the gold standard for skin regeneration. However, the limited availability of autologous skin, especially in case of large wound area; scarring, infection and pain at the donor site are some of the significant drawbacks of autologous skin grafts [7]. Allogeneic skin grafts from non-genetically identical individuals or cadaver skin and xenogeneic skin grafts from different species can evoke strong immune responses that lead to acute rejection of the graft tissues [8].
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
The epidermis is mainly composed of keratinocytes (>90%) but also contains melanocytes and Langerhans cells (LC) (Abdo, Sopko, and Milner 2020), which are antigen-presenting cells (APCs) and take part in the skin immune system. Besides the essential role played by keratinocytes in maintaining the mechanical (Agache and Varchon 2017) and barrier functions of the epidermis, these cells also present sensor receptors able to trigger inflammatory responses, such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (Baker et al. 2003; Burian and Yazdi 2018). Upon binding to metabolites of stressed cells or exogenous substances (Lai and Gallo 2008; Patel 2018), these receptors engage in signal transduction pathways that activate several proinflammatory genes (Tabas and Glass 2013). Consequently, keratinocytes express proinflammatory cytokines – small hormone-like peptides involved in autocrine, paracrine, and endocrine signaling to act as immunomodulating agents and activate other cells, inducing an immune response (Zhang and An 2007). Proinflammatory cytokines produced by activated keratinocytes, such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1), induce the expression of the intercellular adhesion molecule-1 (ICAM-1), facilitating blood cell endothelial infiltration. The interferon – γ (IFN-γ) released by T cells might mediate the upregulation of MHC class II (MHC-II) on keratinocytes surface and enable them to promote antigen presentation to CD4+ T cells, as professional APCs (Black et al. 2007; Fan et al. 2003; Kim et al. 2009). In the context of tissue inflammation, keratinocytes directly activate autoreactive CD4+ T cells and participate in autoimmune skin diseases, such as psoriasis (Albanesi et al. 2005; Fan et al. 2003). Keratinocytes also present antigens to CD8+ T effector/memory cells (via MHC class I) in an antigen-specific manner (Black et al. 2007; Kim et al. 2009). Increased ICAM-1 and MHC-II expression on keratinocytes are also associated with many cutaneous diseases including psoriasis, AD, and delayed hypersensitivity reactions (Albanesi et al. 2005; Fan et al. 2003). In addition, keratinocytes might also express CD80 costimulatory molecule when exposed to specific allergens such as nickel chloride, oxazolone and Balsam of Peru and irritants such as treatment with IFN-γ plus 12-O-tetradecanoyl phorbol 13-acetate ester, sodium lauryl sulfate, dimethyl sulfoxide and phenol) (Wakem et al. 2000). CD80 can participate in the breaking of immunologic tolerance of the skin in AD and irritant contact dermatitis (Wakem et al. 2000). Similarly, in addition to playing a role in melanin production, melanocytes also express TLRs, MHC-II and immunoregulatory cytokines (Hong et al. 2015), indicating their function in immune system as nonprofessional APCs.