Advancing wound healing with three-dimensional bioprinted hyaluronic acid-based tissue constructs: From mechanistic insights to clinical translation

Abstract

Skin functions as a primary protective barrier against mechanical injury, microbial invasion, and dehydration. Extensive trauma and chronic diseases pose significant clinical challenges to wound healing. Conventional wound dressings and skin substitutes often lack the structural and biochemical sophistication to dynamically interact with the wound. Hyaluronic acid (HA), a key glycosaminoglycan in the extracellular matrix, has emerged as a versatile biomaterial for wound repair due to its biocompatibility, hydration capacity, and intrinsic bioactivity. However, native HA suffers from limitations such as rapid degradation and poor mechanical strength, necessitating advanced engineering strategies, including chemical modification, biofunctionalization, and compositing, to enhance its versatility. Three-dimensional bioprinting has recently emerged as a transformative technology, enabling the precise deposition of HA-based biomaterials to form biomimetic constructs with spatial heterogeneity. In this review, we first elucidate the mechanism by which HA orchestrates the wound healing cascade, followed by a list of engineered approaches to enhance HA’s functionality. This review then focuses on the capabilities of mainstream bioprinting technologies for fabricating HA-based wound dressings and stratified skin substitutes. Finally, we discuss prevailing challenges and outline future perspectives, emphasizing innovations in dynamic biomaterials, hybrid bioprinting strategies, and the integration of artificial intelligence to advance the clinical translation of HA products for wound healing.

Keywords

Wound healing / Hyaluronic acid / Three-dimensional bioprinting / Wound dressing / Skin substitutes

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