From crosslinking to clotting: Mechanistic insights into calcium chloride-crosslinked hydrogels for wound hemostasis.

Abstract

Effective wound management requires rapid hemostasis and efficient healing. Calcium chloride (CaCl₂)-crosslinked hydrogels are emerging as promising biomaterials that combine structural stability with bioactivity. This review aims to elucidate the hemostatic mechanisms, cellular interactions, and clinical potential of CaCl₂-crosslinked hydrogels, while addressing the challenges and future directions for their application in wound care. A narrative synthesis of recent studies was conducted, focusing on the composition, crosslinking mechanisms, and biological functions of these hydrogels. Comparative analyses with alternative materials and innovations to overcome current limitations are also included. CaCl₂-crosslinked hydrogels demonstrate superior hemostatic performance, defined as the ability to accelerate clot initiation, enhance platelet adhesion and aggregation, lower the blood clotting index, and reduce blood loss. This is achieved by stabilizing fibrin networks, activating clotting factors (II, VII, IX, X), and promoting platelet aggregation. Calcium ions regulate keratinocyte proliferation, fibroblast differentiation, and angiogenesis, thereby accelerating tissue repair. Notable challenges such as rapid gelation and uncontrolled calcium release are being addressed through advanced engineering strategies like multi-modal crosslinking and controlled ion-release systems. CaCl₂-crosslinked hydrogels offer a dual benefit of rapid hemostasis and enhanced wound healing, positioning them as valuable tools in wound care. Addressing current challenges through interdisciplinary research and clinical validation will maximize their therapeutic potential and that may contribute to improved standards in regenerative medicine.