Role of Hyaluronic Acids and Potential as Regenerative Biomaterials in Wound Healing

Abstract

The skin can protect the body from external harm, sense environmental changes, and maintain physiological homeostasis. Cutaneous repair and regeneration associated with surgical wounds, acute traumas, and chronic diseases are a central concern of healthcare. Patients may experience the failure of current treatments due to the complexity of the healing process; therefore, emerging strategies are needed. Hyaluronic acids (HAs, also known as hyaluronan), a glycosaminoglycan (GAG) of the extracellular matrix (ECM), play key roles in cell differentiation, proliferation, and migration throughout tissue development and regeneration. Recently, HA derivatives have been developed as regenerative biomaterials for treating skin damage and injury. In this review, the healing process, namely, hemostasis, inflammation, proliferation, and maturation, is described and the role of HAs in the healing process is discussed. This review also provides recent examples in the development of HA derivatives for wound healing.

Bio-inspired, bio-degradable adenosine 5′-diphosphate-modified hyaluronic acid coordinated hydrophobic undecanal-modified chitosan for hemostasis and wound healing

“…Hyaluronic acid (HA) is an anionic glycosaminoglycan in the extracellular matrix, which accounts for ∼50% of the total HAs distributed in the skin [ 16 ]. Additionally, the chemical structure of HA contains an abundant carboxyl group that endows HA with the feasibility of conjugation and modification.…”

“…Additionally, the chemical structure of HA contains an abundant carboxyl group that endows HA with the feasibility of conjugation and modification. Recently, various HA derivatives have been exploited and used for tissue repair and regeneration because of the excellent cytocompatibility of HA, which can promote cell adhesion, proliferation, and migration [ 14 , 16 , 17 ]. Adenosine 5′-diphosphate (ADP), a physiologically relevant platelet agonist, is stored in the dense granules of platelets [ 18 ].…”

Local Administration of Ginkgolide B Using a Hyaluronan-Based Hydrogel Improves Wound Healing in Diabetic Mice

“…As mentioned above, the re-epithelization, angiogenesis and collagen remodeling in the proliferation and maturation stages are closely regulated by growth factors such as TGF-β and VEGF ( Yang et al, 2021b ). In this study, HA-GB was capable of significantly increasing the level of TGF-β mRNA within diabetic wounds on Day 7 and 14 ( p < 0.05) ( Figure 7A ); accordingly, the release of TGF-β protein could also be dramatically upregulated by HA-GB ( p < 0.05, Figure 7A ).…”

Wound-Healing Promotion and Anti-Inflammatory Properties of Carvacrol Prodrugs/Hyaluronic Acid Formulations

“…The high number of sugar units composing the HA polyanionic structure allows the binding to water molecules that give HA a gluey quality, like gelatin and makes it one of the most suitable building blocks for drug delivery applications [ 8 ]. Several benefits can be attributed to HA, such as preserving joint lubrication, treating articular disorders, filling soft tissue wrinkles, and aiding WH without exerting side effects [ 9 , 10 ].…”

“…WH is a complex process involving several overlapping stages that include inflammation, formation of granulation tissue, re-epithelialization, matrix formation, and remodeling [ 9 , 10 ]. Several factors are involved in stimulating and coordinating cellular events that occur during WH and the recruitment of non-immune and immune cells, such as keratinocytes, fibroblasts, macrophages, and neutrophils, which are involved in the healing process and could negatively impact the regeneration process [ 11 , 12 , 13 ].…”