Glycosaminoglycans' Ability to Promote Wound Healing: From Native Living Macromolecules to Artificial Biomaterials

Glycosaminoglycans (GAGs) are important for the occurrence of signaling molecules and maintenance of microenvironment within the extracellular matrix (ECM) in living tissues. GAGs and GAG-based biomaterial approaches have been widely explored to promote in situ tissue regeneration and repair by regulating the wound microenvironment, accelerating re-epithelialization, and controlling ECM remodeling. However, most approaches remain unacceptable for clinical applications. To improve insights into material design and clinical translational applications, this review highlights the innate roles and bioactive mechanisms of native GAGs during in situ wound healing and presents common GAG-based biomaterials and the adaptability of application scenarios in facilitating wound healing. Furthermore, challenges before the widespread commercialization of GAG-based biomaterials are shared, to ensure that future designed and constructed GAG-based artificial biomaterials are more likely to recapitulate the unique and tissue-specific profile of native GAG expression in human tissues. This review provides a more explicit and clear selection guide for researchers designing biomimetic materials, which will resemble or exceed their natural counterparts in certain functions, thereby suiting for specific environments or therapeutic goals. The glycosaminoglycans (GAGs), presented in tissues, participate in all stages of wound healing via binding various functional proteins, assisting signal molecule transmission, supporting cell adhesion, remodeling extracellular matrix (ECM) and other physiological processes. Inspired by the special physicochemical properties and biological activities of GAGs, including GAGs in biomaterials to construct biomimetic materials is a promising approach for improving wound healing.image