Severe traumatic bleeding is the primary cause of death in patients. The management of traumatic hemorrhage requires rapid and effective hemostasis. Prolonged bleeding and excessive blood loss can trigger hemorrhagic shock, increasing mortality rates and significantly raising the risk of secondary complications such as coagulation disorders and organ failure [1], [2]. Timely and effective hemostatic interventions, particularly strategies implemented within the "golden hour" following traumatic blood loss, are crucial for reducing mortality and improving patient outcomes [3]. However, traditional hemostatic agents currently used in clinical practice, such as gelatin sponge, oxidized regenerated cellulose, and zeolite, usually achieve hemostatic effects by physical packing or blood concentration [4]. Although these materials provide immediate results, their single-mechanism hemostatic effect is insufficient in complex bleeding situations involving coagulation dysfunction or anticoagulant therapy [5], [6]. Furthermore, they often fail to balance biocompatibility, degradation rates, and antimicrobial properties, limiting their applicability in complex minimally invasive surgical settings [7].
Research indicates that advances in hemostatic materials can effectively address diverse bleeding scenarios, improve patient survival rates, and significantly reduce the risk of traumatic coagulopathy [8]. At the same time, due to its high biological activity, wide applicability, and accurate and efficient mechanism of action, peptide medical materials have become the focus of research in hemostasis, antibacterial therapy, and wound healing [9], [10]. The core advantage of coagulation peptides lies in their ability to mimic natural hemostatic components and precisely target bleeding sites [11]. Some coagulation peptides incorporate functional motifs such as RGD (arginine-glycine-aspartic acid) [12], directly initiating or amplifying primary hemostatic signals by targeting integrin receptors on platelet surfaces, thereby mimicking the function of natural fibrinogen [13]. Another class of coagulation peptides enhances activation of the intrinsic coagulation pathway by binding to factor XIIa (FXIIa), accelerating the formation of a stable fibrin network during secondary hemostasis [14]. These molecular design strategies enable clotting peptides to bypass or accelerate the rate-limiting steps in natural clotting cascades, providing a fundamental solution to overcome the limitations of traditional materials with a single mechanism [15], [16].
By leveraging the functional module characteristics of coagulation peptides, researchers can regulate and optimize peptide functions through the introduction of targeting sequences and the integration of diverse functional units [17]. Recent breakthroughs in molecular design and biomimetic engineering enable peptide materials to precisely target and respond to diverse wound microenvironments through short functional sequences and acid-base responsive technologies [18]. For example, advances in liposome modification and peptide hydrogel composite systems have promoted the development of a new generation of synthetic hemostatic agents [19]. These composite materials leverage the self-assembly properties of nanofibers to optimize adhesion characteristics under varying shear flow conditions, successfully mimicking the natural coagulation cascade [20]. Functionalized coagulation peptides extend beyond hemostasis; their biomimetic extracellular matrix (ECM) properties enable integration of multiple functions, including angiogenesis promotion, anti-inflammation, antimicrobial activity, and targeted drug delivery [21]. This multifunctional integrated design, particularly in applications such as anti-enzymatic barriers for postoperative pancreatic fistula (POPF) and anti-adhesion isolation for abdominal surgery, is pivotal in advancing coagulation peptides from simple hemostatic tools to comprehensive trauma treatment platforms [22], [23]. With the maturation of solid-phase peptide synthesis technology, batch consistency, purity control, and structural modification of coagulation peptides have also achieved unprecedented improvements [24].
This paper systematically reviews the latest progress in the study of coagulation peptides and constructs a comprehensive framework covering peptide source acquisition, synthesis, functional design, and clinical application. This review focuses on the preparation and engineering progress of the coagulation peptide composite system and reveals the relationship between its internal structural characteristics and hemostatic performance through integrated analysis. On the one hand, we summarized the development of nanocomposite technology and functionalization strategy of hemostatic peptides, focusing on structural optimization and its molecular mechanism. On the other hand, we critically evaluate its potential in drug delivery and clinical transformation, and explore key challenges such as clinical evidence, biosafety, and long-term stability. Overall, this review provides a key theoretical basis and technical reference for the design and improvement of a new generation of hemostatic materials, which will promote the development of more efficient clinical hemostatic strategies.
As intercellular signaling mediators, naturally occurring peptides regulate various key aspects of plant and animal growth and development [25], [26]. Active peptide drugs derived from natural sources have made important contributions to meeting the challenges of human health and agricultural development [27]. In humans, several peptides are known to regulate coagulation and participate in the coagulation process. There are amyloid-related peptides in the blood, and the stimulation of platelets
The types of coagulation peptides include both natural protein degradation products, such as tilapia peptide (TP), and various synthetically designed peptide sequences [63]. Among these, self-assembling peptides (SAPs) play a central role in coagulation peptide materials due to their biological functionality and structural programmability [42]. Coagulation self-assembling peptides can form ordered nanofiber networks in diverse physiological environments, mimicking the extracellular matrix (ECM)
The hemostatic mechanism of coagulation peptides involves a complex, multi-level, and multi-target synergistic process. The core concept is to design peptide systems that mimic or amplify natural hemostatic signals at the molecular level, thereby overcoming the limitations of traditional hemostatic materials in clotting efficiency and biological safety [78].
The self-assembling peptide RADA16 is assembled into nanofibers under physiological conditions to form hydrogel materials, which can be used as mimics of extracellular matrix (ECM) [94]. However, RADA16 peptide hydrogels are still limited in mimicking the ECM due to the lack of bioactive cues that guide biological functions such as angiogenesis. Hypoxia is an important factor influencing cell recruitment, differentiation, and angiogenesis [95], [96]. Copper (Cu) can promote angiogenesis by
Gastrointestinal bleeding is a common cause of hospitalization and a major contributor to morbidity and mortality. Intraoperative or postoperative bleeding during endoscopic procedures such as endoscopic submucosal dissection (ESD) remains one of the key complications [130], [131]. Traditional endoscopic hemostasis strategies, including epinephrine injection, mechanical clips, and thermal coagulation, are technically demanding and carry risks such as tissue injury or perforation [132].
As bioactive molecules with high procoagulant activity and structural tunability, coagulation peptides exhibit substantial potential for applications such as promoting hemostasis, reducing inflammation, and supporting tissue repair. Compared with conventional hemostatic materials, they offer distinct advantages, including customizable structural design, high biocompatibility, and low cytotoxicity. Their small size and bioactive properties enable penetration into deep tissue layers, where they
Wenwen Ma contributed to the writing and revision of the manuscript; Yumei Wang, Xin Liu, Wen Li, Wenxue Zhao, and Jumeng Di contributed to the manuscript revision; Hailin Cong and Bing Yu contributed to the ideas of review.
Wenwen Ma: Writing – review & editing, Writing – original draft. Yumei Wang: Writing – review & editing. Bing Yu: Conceptualization. Hailin Cong: Conceptualization. Wenxue Zhao: Writing – review & editing. Jumeng Di: Writing – review & editing. Xin Liu: Writing – review & editing. Wen Li: Writing – review & editing.
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hailin Cong reports financial support was provided by National Natural Science Foundation of China ( 22074072 , 22274083 ). Hailin Cong reports financial support was provided by Shandong Provincial Natural Science Foundation ( ZR2022LZY022 , ZR2023LZY005 ). Hailin Cong reports financial support was provided by Science and Technology Planing Project of South District
This study was supported by the National Natural Science Foundation of China ( 22074072 , 22274083 ), the Shandong Provincial Natural Science Foundation ( ZR2022LZY022 , ZR2023LZY005 ), the Science and Technology Planing Project of South District of Qingdao City ( 2022–4–005-YY ), the Exploration project of the State Key Laboratory of BioFibers and EcoTextiles of Qingdao University ( TSKT202101 ), the National Key R&D Program of China ( 2024YFE0104100 ), and the Medical Plus Key Project of Qingdao
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