Key Takeaways & Executive Findings
- •• An all-in-one cryogel integrates hemostasis and wound healing for coagulopathic and diabetic patients. • The cryogel exhibits rapid liquid-triggered volume expansion and synergistic physicochemical hemostatic properties. • It provides photothermal antibacterial activity, ROS scavenging, oxygen release, and promotes angiogenesis. • In vivo studies demonstrate superior performance in coagulopathic bleeding and infected diabetic wound healing compared to commercial dressings.
Abstract
Traditional hemostatic materials are difficult to meet the needs of non-compressible bleeding and for coagulopathic patients. In addition, open wounds are susceptible to infection, and then develop into chronic wounds. However, the development of integrated dressings that do not depend on coagulation pathway and improve the microenvironment of chronic wounds remains a challenge. Inspired by the porous structure and composition of the natural extracellular matrix, adipic dihydrazide modified gelatin (GA), dodecylamine-grafted hyaluronic acid (HD), and MnO2 nanozyme (manganese dioxide)@DFO (deferoxamine)@PDA (polydopamine) (MDP) nanoparticles were combined to prepare GA/HD/MDP cryogels through amidation reaction and hydrogen bonding. These cryogels exhibited good fatigue resistance, photothermal antibacterial (about 98% killing ratios of both Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) after 3 min near-infrared irradiation), reactive oxygen species scavenging, oxygen release, and angiogenesis properties. Furthermore, in the liver defect model of rats with coagulopathy, the cryogel displayed less bleeding and shorter hemostasis time than commercial gelatin sponge. In MRSA-infected diabetic wounds, the cryogel could decrease wound inflammation and oxidative stress, alleviate the hypoxic environment, promote collagen deposition, and induce vascular regeneration, showing a better repair effect compared with the Tegaderm™ film. These results indicated that GA/HD/MDP cryogels have great potential in non-compressible hemorrhage for coagulopathic patients and in healing infected wounds for diabetic patients.
1. Introduction
Wound hemostasis and wound healing are always the major public health issues with global concern. More than 5.8 million people die globally each year caused by severe trauma such as wars and accidents [1]. The main cause of death is because of bleeding from non-compressible blooding [2]. In addition, one-quarter of severely traumatized patients have coagulation disorders in the early stages, resulting in excessive blood loss owing to platelet insufficiency as well as coagulation factor deficiencies, which threaten the patient’s life [3]. Furthermore, open wounds are susceptible to developing into chronic wounds because of local and systemic factors. The diabetic wound is a common and serious chronic wound with bacterial infection, excessive inflammation, oxidative imbalance, hypoxia, and vascular network destruction [4]. These factors lead to prolonged healing times, imposing a significant economic burden and decreasing the quality of patients’ lives [5]. In summary, the development of multifunctional materials is crucial to address the challenges of hemostasis in non-compressible bleeding among coagulation-disordered patients and to promote healing in chronic wounds among diabetic patients.
Different forms of materials have been developed to address the above challenges. Cryogel, with its interconnected porous structure, can effectively concentrate blood during hemostasis and provide a moist and breathable environment during healing, which makes it an ideal dressing form [6, 7]. However, for coagulation-disordered patients, simple physical sealing is not effective in hemostasis, and it is difficult to rely on biological and chemical strategies to activate the coagulation pathway resulting in synergistic hemostasis [8]. Therefore, researchers have proposed that aggregating and activating red blood cells and platelets can promote blood clot formation independent of coagulation cascades reaction, which in turn accelerates coagulation [9]. Among the various components that interact with blood cells, the dodecyl hydrophobic chain can insert and anchor to the lipid bilayer of cell membrane, inducing the aggregation of red blood cells and platelets through hydrophobic interactions [10, 11]. Furthermore, the catechol group of polydopamine (PDA) can interact covalently and non-covalently with the reactive groups of proteins or polysaccharides in blood cells [8]. It effectively adheres and activates red blood cells and platelets, which in turn accelerates coagulation.
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Jiaxin Wang, Yutong Yang, Huiru Xu, Shengfei Huang, Baolin Guo, Juan Hu (2025). All-in-One: A Multifunctional Composite Biomimetic Cryogel for Coagulation Disorder Hemostasis and Infected Diabetic Wound Healing. Nano-Micro Letters. https://doi.org/10.1007/s40820-024-01603-1
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Frequently Asked Questions
What is the main innovation of this cryogel?
The cryogel integrates multiple functions: it provides hemostasis independent of the coagulation cascade, making it effective for coagulopathic patients, and it also promotes infected diabetic wound healing through antibacterial, ROS scavenging, oxygen release, and angiogenesis properties.
How does the cryogel achieve hemostasis in coagulopathic conditions?
The cryogel contains dodecyl hydrophobic chains and polydopamine catechol groups that interact with red blood cells and platelets, inducing aggregation and activation independent of the coagulation cascade, thus promoting clot formation even in coagulopathic patients.
What are the key components of the cryogel?
The cryogel is composed of adipic dihydrazide modified gelatin (GA), dodecylamine-grafted hyaluronic acid (HD), and MnO2 nanozyme@deferoxamine@polydopamine (MDP) nanoparticles, crosslinked via amidation and hydrogen bonding.
How does the cryogel aid in diabetic wound healing?
The cryogel releases oxygen and deferoxamine, which help alleviate hypoxia, reduce oxidative stress, decrease inflammation, promote collagen deposition, and induce vascular regeneration, thereby accelerating healing of infected diabetic wounds.
What are the advantages of the cryogel over commercial dressings?
In vivo studies show that the cryogel achieves less bleeding and shorter hemostasis time than commercial gelatin sponge in coagulopathic liver defects, and better wound repair than Tegaderm™ film in MRSA-infected diabetic wounds.
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