Advances and Challenges in Immune-Modulatory Biomaterials for Wound Healing Applications

Wound healing progresses through three distinct stages: inflammation, proliferation, and remodeling. Immune regulation is a central component throughout, crucial for orchestrating inflammatory responses, facilitating tissue repair, and restraining scar tissue formation. Elements such as mitochondria, reactive oxygen species (ROS), macrophages, autophagy, ferroptosis, and cytokines collaboratively shape immune regulation in this healing process. Skin wound dressings, recognized for their ability to augment biomaterials' immunomodulatory characteristics via antimicrobial, antioxidative, pro- or anti-inflammatory, and tissue-regenerative capacities, have garnered heightened attention. Notwithstanding, a lack of comprehensive research addressing how these dressings attain immunomodulatory properties and the mechanisms thereof persists. Hence, this paper pioneers a systematic review of biomaterials, emphasizing immune regulation and their underlying immunological mechanisms. It begins by highlighting the importance of immune regulation in wound healing and the peculiarities and obstacles faced in skin injury recovery. This segment explores the impact of wound metabolism, infections, systemic illnesses, and local immobilization on the immune response during healing. Subsequently, the review examines a spectrum of biomaterials utilized in skin wound therapy, including hydrogels, aerogels, electrospun nanofiber membranes, collagen scaffolds, microneedles, sponges, and 3D-printed constructs. It elaborates on the immunomodulatory approaches employed by these materials, focusing on mitochondrial and ROS modulation, autophagic processes, ferroptosis, macrophage modulation, and the influence of cytokines on wound healing. Acknowledging the challenge of antibiotic resistance, the paper also summarizes promising plant-based alternatives for biomaterial integration, including curcumin. In its concluding sections, the review charts recent advancements and prospects in biomaterials that accelerate skin wound healing via immune modulation. This includes exploring mitochondrial transplantation materials, biomaterial morphology optimization, metal ion incorporation, electrostimulation-enabled immune response control, and the benefits of composite materials in immune-regulatory wound dressings. The ultimate objective is to establish a theoretical foundation and guide future investigations in the realm of skin wound healing and related materials science disciplines.