Dermal Fibrosis and the Current Scope of Hydrogel Strategies for Scarless Wound Healing

ABSTRACT: Dermal fibrosis poses a significant challenge in wound healing, affecting both the appearance and functionality of the scarred skin tissue. Beyond aesthetic implications, fibrosis can lead to pruritus, chronic pain, loss of mechanical flexibility, and impeded restoration of skin appendages, blood vessels, and nerves. Therefore, scar prevention remains a priority in wound management, and hydrogels, with their hydrophilic three-dimensional network and extracellular matrix-mimicking properties, have emerged as promising biomaterials for achieving scarless wound regeneration. In this review, we explore advancements in various hydrogel strategies designed to regulate myofibroblast differentiation, control the wound microenvironment, and mitigate dermal fibrosis. We provide an overview of dermal fibrosis, the scar-forming cells involved, and the various types of dermal scars. We then summarise advancements made in antifibrotic hydrogel formulations, emphasizing their practical applications in scarless skin wound healing. By reviewing the current research landscape and highlighting key hydrogel-based biomaterial strategies employed in this field, we aim to offer insights into design principles and underlying mechanisms of action. We intend for this review to serve as a valuable resource for researchers and clinicians interested in entering this field or exploring the potential of hydrogels to promote scarless wound healing.