Design strategies for hydrogels with paracrine effects and their ability to promote wound healing: status and...

Wound healing is a complex process involving various stages such as hemostasis, inflammation, cell proliferation, and tissue remodeling. If a wound fails to heal promptly, it can lead to ulcers, necrosis, and even limb amputation, resulting in significant losses. Over the years, many clinical studies have explored the role of dressings in wound healing. Although numerous dressings have been introduced to the market, traditional ones typically influence only external factors such as temperature, humidity, and pH, often causing issues like excessive moisture or dryness, allergic reactions, secondary injuries, and limited applicability across different wound types. In response, paracrine effect hydrogels, a novel class of biomaterials, have shown great promise in overcoming these limitations. Unlike traditional dressings or simple bioactive delivery systems, paracrine-oriented hydrogels function as microenvironmental regulators that influence intercellular communication, immune responses, and tissue regeneration. These dressings target the internal wound microenvironment, enhancing functions like exudate absorption, anti-inflammatory effects, and antibacterial activity. Although research on paracrine effect-type hydrogels is still developing, they are expected to become a emerging strategy in wound healing. This paper reviews the design principles, classification, mechanisms, and clinical applications of hydrogel dressings that leverage paracrine effects. It also highlights the historical development of hydrogel dressings, recent advancements, and the role of paracrine signaling in tissue repair. Finally, the paper discusses the current challenges and future directions in this field, offering valuable insights for the design of innovative hydrogel-based wound care products.