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The Role of Hyaluronan in Skin Wound Healing

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Hyaluronan

Part of the book series: Biology of Extracellular Matrix ((BEM,volume 14))

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Abstract

Skin wound healing is a complex process involving many types of cells at different specific times. HA is a linear un-sulfated glycosaminoglycan synthesized by three HA synthases (HAS) and degraded by hyaluronidases. By binding to its receptors on cell surfaces, HA regulates the function of various types of cells at different phases of wound healing. During the first phase of wounding (inflammation phase), levels of HA increase rapidly at the wound site. Platelets cleave HMW-HA into fragments and stimulate the extrinsic clotting cascade, achieving hemostasis. The local accumulation of high molecular weight HA (HMW-HA) promotes diffusion of water molecules and facilitates the migration and infiltration of inflammatory cells into the wound area. Low molecular weight HA (LMW-HA) stimulates the secretion of proinflammatory cytokines, which induces vasodilation and increases vascular permeability, leading to more inflammatory cell migration into the wound and facilitating proinflammatory cascades. During the second (proliferative) and third (remodeling) phases of wound healing, HA has crucial roles in regulating the repair of damaged tissue elements. By binding to its receptors such as CD44, ICAM-1 and RHAMM, HA influences the activities of keratinocytes (re-epithelialization) and fibroblasts (migration, proliferation, fibroblast turnover, myofibroblast differentiation) through modulation of signaling cascades such as the TGF-beta receptor pathway. In diabetes, under hyperglycemic condition, HA and other GAGs are degraded into small fragments and become more proinflammatory, leading to damage and loss of the ECM glycocalyx in small vessels, which has a detrimental effect on endothelial cells. Due to its special physical and chemical characteristics such as good biocompatibility, biodegradability, and water-absorbing properties, HA has been widely used in various types of topical dressings and demonstrates a promising therapeutic function in promoting wound healing.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    Yan Wang & Edward V. Maytin

  2. Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA

    Edward V. Maytin

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Correspondence to Edward V. Maytin .

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  1. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Alberto Passi

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Wang, Y., Maytin, E.V. (2023). The Role of Hyaluronan in Skin Wound Healing. In: Passi, A. (eds) Hyaluronan. Biology of Extracellular Matrix, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-031-30300-5_9

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