Recent Advances in Natural Polysaccharide-Based Hemostatic Sponges: A Review

Abstract

Bleeding is a potentially life-threatening emergency that can result in severe complications or death regardless of the cause of bleeding. The development of hemostatic materials has been a long-standing concern for emergency treatment in surgery and combat. In recent years, there have been many reviews on hemostatic materials, but there have been few specific studies about performance requirements and development in recent years on natural polysaccharide-based hemostatic sponge as a type of hemostatic excipient. Currently, natural polysaccharide hemostatic sponge has attracted wide attention due to the enhancement or interaction of various hemostatic mechanisms. These polysaccharide sponges show a high hemostatic effect. In this paper, the application history of natural polysaccharides (chitosan, hyaluronic acid, alginate, cellulose, starch, etc.) as a new generation of hemostatic sponge materials in recent years is reviewed. The design principles and new achievements in polysaccharide-based hemostatic sponge are introduced. Finally, we summarize the advantages and disadvantages of polysaccharide hemostatic sponge and prospect the development opportunities and challenges of this material.

1. Introduction

Massive hemorrhage and excessive blood loss can lead to serious complications, including hypothermia, organ failure, shock, and even death; it is responsible for 30–40% of trauma-related mortality [1]. Hemostasis is the first step in the wound healing process and is the body’s natural mechanism to stop bleeding. In response to an injury, blood vessels vasoconstrict to restrict blood flow, and the damaged endothelial cells release von Willebrand factor to trigger a complex clotting factor cascade to form a soft platelet plug, followed by a stronger fibrin clot [2]. Often, the process of hemostasis starts within seconds of an injury, and it can take up to several minutes for the fibrin clot to be formed. It is statistically estimated that about one-third of emergency deaths originate from acute blood loss and its secondary injuries [3]. Although 50% of mortalities may be avoided with efficient hemostatic techniques [4,5], and although the body possesses an effective coagulation system and existing auxiliary hemostatic means, in the face of massive bleeding, advanced hemostatic managements are still required, particularly for the prehospital care [6].

Polysaccharides are long-chain polymeric carbohydrates abundantly found in food and are an essential component of living matter. Various biomedical and tissue engineering applications utilize polysaccharides because of their structural and biochemical similarity to the extracellular matrix. They are known to be biodegradable, biocompatible, and easily tunable to achieve desired mechanical properties and tissue response [7,8]. The following section details various polysaccharides and their use as hemostatic materials. Figure 1 depicts the chemical structures of the polysaccharides discussed in this review, while a statistical summary of the number of key reports on polysaccharide-based hemostatic materials in recent years is shown in Figure 2.

At present, conventional hemostatic materials cannot achieve a hemostatic effect for complex, penetrating, and irregular wounds in the limbs, buttocks, and other parts. As a new type of hemostatic material, hemostatic sponges have attracted much attention due to their excellent absorptive capacity and considerable compressibility of detumescence [9]. To date, polysaccharide-based hemostatic materials are various, including sponges, granules, hydrogels, and so on. Among them, sponges, being porous materials with large porosity and high specific surface area, demonstrate compressibility, excellent capability to absorb fluids from the body, and increased permeability. When in contact with human blood, hemostatic sponge can immediately induce platelet adhesion, aggregation, and thrombosis, thereby blocking blood at the wound and releasing various factors related to blood coagulation, activating the endogenous and exogenous coagulation pathways, enabling the blood to form stable polymerized fibrin proteins and form blood clots, and achieving the goal of stopping wound bleeding [10]. The traditional method for constructing polysaccharide sponges involves the freeze-drying process, where the pores inside these hemostats are created by removing ice crystals [11]. Recently, shape memory sponges have garnered attention for their potential in hemostasis [12,13]. Clinical application has found that the hemostatic effect of current products is poor, the bulk of them are not biodegradable, and they are difficult for the body to absorb, so the scope of their use is limited. Therefore, the development of new, degradable, and easily absorbed hemostatic sponge has become a research hotspot.

2. Performance Requirements of New Hemostatic Sponge

The design and development of novel polysaccharide hemostatic sponges needs to meet a number of specific requirements to ensure their effectiveness and safety in clinical applications [14]. Studies in recent years have shown that the development of this material should possess the following characteristics. (1) Biocompatibility and safety: It must ensure that the sponge is nontoxic and harmless to the human body and will not cause immune reactions or allergies. At the same time, it should not contain ingredients harmful to the human body. (2) Biodegradability: The hemostatic sponge should be able to gradually degrade in the body, not require secondary surgery to remove, and reduce patient pain and medical costs. (3) Hemostatic performance: It should have the ability to stop bleeding quickly, absorb blood, and promote blood coagulation. It should be able to adapt to different bleeding conditions, including arterial, venous, and capillary bleeding. (4) Mechanical properties: Sufficient mechanical strength is required to facilitate surgical operation and placement. It should have appropriate flexibility and elasticity to adapt to different wound shapes. (5) Water absorption and expansion: It should have efficient water absorption ability to quickly absorb blood and other liquids. Suitable expansion would quickly stop bleeding without excessive expansion causing tissue damage. (6) Convenience of operation: It should be easy to use and be quickly deployed in an emergency. Packaging design should consider sterility and portability. (7) Antibacterial properties: Some hemostatic sponges need to have certain antibacterial properties to reduce the risk of infection. (8) Cost effectiveness: The production cost should reasonable, the price should be moderate, and the application should be promoted on a large scale. In the long run, it should be able to reduce medical costs and improve economic efficiency. (9) Regulatory compliance: It must comply with relevant national and international regulations and standards, undergoing a rigorous clinical trial and registration approval process. (10) Environmental protection: The production and use process should minimize the impact on the environment, such as reducing waste and pollution. (11) Patient satisfaction: The use of the new hemostatic sponge should reduce the pain of patients, shorten the postoperative recovery time, and improve the quality of life of patients. Product performance should be continuously improved through patient feedback. These requirements not only help ensure the safety and effectiveness of the new hemostatic sponge but improve its application value in clinical practice. In summary, the most important requirements should be followed in the design process of natural polysaccharide hemostatic sponge: safety, high efficiency, and antibacterial properties.

Traditional hemostatic products, such as inorganic clay [15,16,17], tend to contain some substances with uncontrollable leakage (such as small molecules and inorganic nanosheets), which cause potential risks to the human body, such as infection and thrombosis [18]. These hemostatic products or technologies often achieve the purpose of wound hemostasis by mobilizing coagulation factors in the body. However, uncontrolled, excessive hemostasis often leads to the formation of thrombosis without blood vessel rupture. Studies have shown that plasma fibronectin is particularly important for anticoagulant induction of fibrous hemostasis at defect sites, and it also prevents bleeding, excessive thrombosis, and vascular obstruction. In addition, cell connexin also has prothrombin activity, which can lead to thrombosis complications in various diseases [19]. The two are antagonistic. Therefore, in the design process of polysaccharide-based hemostatic sponges, it is necessary to adjust the content of various components in the blood to stop bleeding in the shortest possible time but prevent the formation of thrombosis and other complications so as to ensure the safety of the hemostatic material.

Hemostatic efficiency is always the first priority in designing new hemostatic products. Bleeding can occur in any part of the body, so hemostatic materials that can be applied to more body tissues are more sought after by clinical needs. An engineered hemostatic polymer (PolySTAT) has been used to develop a rapid hemostatic device made from natural polysaccharides (lignocellulosic and chitosan). Its hemostatic principle is as follows: When a blood clot is encountered at the site of vascular injury, PolySTAT cross-links the newly formed fibrin matrix, just like glutamine transaminase factor XIII, which strengthens the blood clot and enhances its resistance to the overactive degrading enzymes in the trauma, thus forming a hemostatic barrier with a survival rate of 100% [20]. Irregular wound bleeding or uncontrolled bleeding is the leading cause of traumatic death in war or accidents [21]. A greater variety of new hemostatic materials are required to achieve instantaneous absorption in order to accelerate the coagulation of coagulation factors in the wound and reduce the rate of blood loss. If the material is made into a porous/multichannel sponge structure, then the sealing effect of its expansion on the wound can achieve twice the purpose of half the effort. Therefore, in the design of hemostatic materials, the selection of raw materials and structural design are critical.

After the wound stops bleeding, it enters the inflammatory healing period, when it is easy for it to be infected with exogenous pathogenic microorganisms, resulting in delayed wound healing. The common clinical treatment is to take or inject a large number of anti-inflammatory and analgesic drugs. Most of the drugs travel through the blood to other parts of the body, which causes some damage to normal tissues and organs. Since antibiotics began to be widely used in the field of wound anti-infection, the ensuing drug resistance has become a major problem plaguing mankind. Therefore, anti-infection is an important problem that cannot be ignored in the preparation of hemostatic materials. From the perspective of treatment, it is of great academic value and significance to people’s lives to develop multifunctional hemostatic materials that integrate hemostasis, anti-inflammation, and wound healing. Among the natural polysaccharides, chitosan water-soluble cationic quaternary ammonium salts have good antibacterial, cation adsorption, film-forming, and antistatic properties. More importantly, it has the characteristic of promoting wound healing [22]. In addition, because of the limitations of antibiotics, silver (Ag), with its excellent antibacterial properties, has been widely used in hemostatic sponges [23,24,25]. Although Ag itself is nontoxic, its compounds can have toxic effects on humans. Ag⁺ can bind to proteins to form insoluble protein salts, high concentrations of which can lead to cell damage and dysfunction. Therefore, the preparation of new hemostatic products by combining such natural polysaccharides with natural bacteriostatic agents is the focus of current research.

3. Hemostatic Mechanism of Hemostatic Sponge

The hemostatic effect is achieved through three kinds of mechanisms: (1) activating or participating in the coagulation system; (2) promoting the aggregation of blood components in the wound site through absorbing water from the blood and concentrating blood components; (3) forming a physical barrier to stop bleeding through strong adhesion (Figure 3) [14,26,27].

In the hemostatic sponge, all of these mechanisms may interact to form blood clots to stop bleeding. The porous hemostatic sponge has the characteristics of rapid adsorption from blood of the wound surface; thus, the red blood cells and platelets can be effectively concentrated and activated to achieve rapid hemostasis [28]. This type of hemostatic material is often used in stomatology, obstetrics, gynecology, and other wound hemostasis or postoperative healing. Meanwhile, the commercial absorbable hemostatic sponge (known as high expansion sponge) has high expansion characteristics. When in contact with blood, the high-expansion hemostatic sponge can rapidly compress the deep, narrow, or irregular wound bleeding sites caused by veins, capillaries, or even small arteries and treat bleeding. This is more effective than traditional hemostatic methods (such as compression, ligation, or electrocoagulation) [29].

It is an effective strategy to absorb water from the blood so as to concentrate blood components, which is in line with the design philosophy of most hemostatic sponges today. However, swelling of the sponges due to water absorption often leads to decreased adhesion and may trigger increased blood loss due to overabsorption [30]. With the development of the field of medical materials, different components, design ideas, and preparation methods have been used to improve the combined properties of hemostatic sponges. The raw material of hemostatic sponges is usually composed of one or more ingredients, such as cellulose, chitosan, starch, alginate, polyvinyl alcohol, gelatin, etc. [31]. In order to further improve the overall performance of sponges, numerous polysaccharide-related materials covered in the current research review have been reported to design sponges with hemostatic, antibacterial, and agglutinating properties.

The polysaccharides usually contain hydroxyl, amino, carboxyl, and other functional groups, which impart to them hydrophilicity, biodegradability, and biocompatibility [32]. Among these, the hydroxyl group is the most important functional group in the basic structural unit of polysaccharides. Therefore, polysaccharides can be effectively cross-linked or surface grafted by physical/chemical means. In this way, polysaccharide-based hemostatic sponges are endowed with active and/or passive hemostatic properties, which greatly improves their application in the field.

4. Research Progress of the New Polysaccharide-Based Hemostatic Sponge

Hemostatic sponges with natural polysaccharides are a kind of biomaterial used for rapid hemostasis in medical surgery or first aid. Such sponges are usually composed of a variety of components, of which polysaccharides are among the key components. Polysaccharides can play the following important roles in such hemostatic materials: (1) water absorption and expansibility; (2) biocompatibility; (3) biodegradability; (4) procoagulant activity; (5) cell adhesion and tissue repair; (6) antibacterial properties; and so on [2,7,9,10,11,14]. In summary, polysaccharides play an integral role in polysaccharide-based hemostatic sponges, not only providing basic physical properties but facilitating hemostasis and wound healing processes through their own biological activity. Based on the development of hemostatic sponges prepared with polysaccharides as the main component, the progress of research on new hemostatic sponges prepared with polysaccharides and other components in recent years is summarized below. We hope to provide reference for the subsequent development of hemostatic materials containing natural polysaccharides.

4.1. Chitosan Hemostatic Sponges

As the only known natural cationic polysaccharide in nature, chitosan has a special free amino molecule and carries a positive charge [33]. As a medical dressing, it can act rapidly with red blood cells that carry negative charges and promote the aggregation of red blood cells during the application of wound hemostasis. Similarly, platelets can be activated and stop bleeding quickly. Furthermore, chitosan is a kind of natural antibacterial material. The mechanism of bacteriostasis is that bacteria attach to the surface of chitosan by the free amine group, and their cell walls are destroyed, which eventually leads to bacterial cell lysis [10,34]. In addition, chitosan chains are rich in active groups, such as amino and hydroxyl groups. To improve chemical modification, they can be well adjusted for solubility, antibacterial ability, and mechanical and other physical and chemical properties for satisfactory hemostatic effects [9]. Hence, chitosan and its derivatives has been widely used in hemostasis, regenerative medicine, drug delivery, and other fields [35].

In recent years, there have been many reports that chitosan as base material was used to prepare hemostatic sponge. Yan et al. [36] and Deng et al. [37] severally prepared chitosan–calcium pyrophosphate (CaP) microflowers, metronidazole-loaded calcium alginate sponges (CA@CM/MD), and quaternary ammonium chitosan/carboxymethyl starch/alginate sponges (ACQ). They demonstrated that these have enhanced antibacterial, hemostatic, and osteogenic properties to prevent dry socket after tooth extraction via Ca²⁺ cross-linking, lyophilization, and electrostatic interactions. This material is used for massive bleeding after tooth extraction, postoperative infection, and bone resorption, resulting in alveolar dryness. Quan et al. [38] created biomultifunctional sponges by coupling alginate and chitosan with polysaccharides from Sargassum pallidum (Turn.) C. Ag through electrostatic interactions, calcium ion (Ca²⁺) cross-linking, and lyophilization. The results showed that alginate/chitosan sponges (ACS) with concentrations of Sargassum pallidum polysaccharides of 1% and 2.5% (ACS-1% and ACS-2.5%) exhibited high water vapor transmission rates and water absorption, as well as good hemostatic and antibacterial abilities. In particular, the latter sponge facilitated wound closure, angiogenesis, and re-epithelialization in the dermis. There have been many such reports, such as a biodegradable wound dressing composed of carboxymethyl chitosan/sodium alginate/tea polyphenols with a two-layer porous structure [39]. Chitosan can not only be combined with a variety of organic materials to form multifunctional hemostatic sponges but be organically combined with inorganic materials. It is undeniable that chitosan has the disadvantages of insufficient flexibility and bioreactivity. Clay mineral halloysite nanotubes (HNTs) are hollow, tubular structures with excellent hemostatic properties, which can effectively improve the mechanical properties of biomaterials [40,41,42]. A chitosan–HNT composite sponge was prepared by Liu et al., and the results showed the addition of HNTs improved the compressive strength and toughness of the chitosan sponge, increased the coagulation rate of this material, and greatly promoted the speed of wound healing [43].

4.2. Starch Hemostatic Sponges

Starch is a naturally occurring biodegradable material with good biocompatibility [44]. Porous starch acts as a molecular sieve, creating a mechanical barrier to dehydrate and clot blood, thereby promoting hemostasis [45]. Therefore, in clinical application, porous sponges prepared with starch are considered to be the ideal hemostatic drugs [46].

In the process of hemostasis, it is very important to avoid wound infection [47]. Single-starch-based hemostatic sponges are weak in inhibiting bacterial infection. If appropriate antibacterial substances are added, the value of this hemostatic adjuvant is greatly enhanced. Chen et al. [48] used trimethylphosphate sodium (STMP) to cross-link CS with composite porous starch (PS) to prepare an STMP/PS/CS (SPC) sponge for synergistic hemostasis. KR12 (Krivkrikkwlr), as a widely used antimicrobial peptide, has broad-spectrum antibacterial activity and can be used safely for a long time [49]. In order to prolong antibacterial activity and reduce cytotoxicity, Binu et al. [50] used sulfhydryl bonding reaction to covalentially immobilize KR12 on the surface of starch-based macroporous sponges (KRs-Sps). KRs-Sps is considered to be a good hemostatic and antibacterial product for intraoperative wound management [51]. Starch has a high swelling capacity, but its powder formulation is limited when incompressible bleeding occurs. Lee et al. [52] mixed starch with filamentin and cross-linked it using glycerol to improve structural integrity. The silk/starch solution was freeze-dried to form an interporous sponge, which absorbed plasma by increasing swelling rate and underwater retention, facilitating blood clotting. In addition, inspired by the traditional Chinese bread steaming process, Chen et al. [53] designed a hemostatic sponge composed of acellular dermal matrix gel, hydroxyethyl starch, and rice-hydrolyzed protein. This material integration improved the mechanical and hemostatic properties of the sponge and enhanced its porosity. This enhancement promoted rapid blood absorption, accelerated clot formation, and stimulated the clotting cascade.

4.3. Hyaluronic Acid Hemostatic Sponges

Hyaluronic acid (HA) is a natural nonsulfate dextran macromolecule. It has the ability to maintain favorable hemostatic and wound healing conditions and thus has a wide range of applications in the field of biomedical materials [34]. However, the poor mechanical properties of natural HA limit its development. It is often cross-linked with other materials to improve its mechanical properties. Their modified form has the characteristics of good biocompatibility, fast water absorption, and strong adhesion; thus, HA can be made into a hemostatic sponge. It can not only absorb wound exudates and increase the concentration of coagulation factors in the blood but compress the wound through physical channels to stop bleeding, thereby reducing blood loss and shortening coagulation time [54].

In order to avoid alveolar bone injury, Catanzano et al. [55] prepared a alginate/hyaluronic acid composite sponge with tranexamic acid controlled release function. The results exhibited that the content of HA could affect the microstructure of the sponge, reduce the porosity, change its water absorption kinetics, and improve its compressive performance. Liu et al. [56] prepared a polysaccharide-based polyporous hemostatic sponge composed of HA and cationic dextran (Dex-PDM) using a convenient spontaneous bubble method. The mixture of HA and Dex-PDM can produce a self-bubbling solution when strongly stirred under green conditions. The foam solution can also simply be cross-linked with sodium trymethylphosphate (STMP) to prepare an STMP/HA/Dex-PDM sponge (SHDP). In addition, the Dex-PDM side chain was partially quaternized to obtain an STMP/HA/Dex-QPDM sponge (SHDQ). The results showed that both the SHDP and SHDQ had good biocompatibility (the hemolysis rate was less than 5%). The hemostatic experiment displayed that the hemostatic performance of the SHDQ was better than SHDP. The experiment proved that HA/Dex-PDM sponges prepared spontaneously under green conditions are expected to be a new high-efficiency hemostatic material.

4.4. Alginate Hemostatic Sponges

Alginate is a kind of natural anionic polymer, and the abundant -COOH in its macromolecular chain can react with NaCl in the blood to generate sodium alginate, break the ionization balance of the blood, and activate coagulation factors [57]. Alginate sponges can absorb a large amount of wound exudate, provide a moist physiological microenvironment, and promote wound healing. At the same time, the viscosity formed after sodium alginate dissolution blocks the ends of capillaries, and platelets can adhere rapidly; thus, alginate sponges can play a hemostatic role [58].

Single alginate (ALG) sponges have poor chemical stability and mechanical strength, which is the bottleneck restricting their further application. The mechanical properties of ALG or the drug loading properties of hydrogel can be improved by cross-linking -OH on the polyhydroxyl polymer with -COOH on ALG. Catanzano et al. [55] cross-linked alginate/hyaluronic acid with glucose lactone, loaded trantranic acid (TA) on ALG/hyaluronic acid cross-linking, and then freeze-dried to prepare a macroporous ALG/hyaluronic acid /TA sponge. Whole blood clotting time results showed that the sponge not only facilitated the loading and release of drugs but significantly accelerated the clotting process. Through a simple chemical gas-foaming method, Salmanipour et al. cross-linked long-chain polyphosphates with nano-kaolin and Ca²⁺ in alginate structure to synergistically activate the coagulation pathway and create an ultraporous and highly absorbable hemostatic sponge [59]. The obtained ultralight sponges (>90% porosity) exhibited ultrarapid water/blood absorption capacity (4000%), which effectively concentrated coagulation factors. Moreover, the application of these new sponges resulted in a complete hemostasis time of 60 s by significant reductions in hemostasis time (6.7–8.3 fold) and blood loss (2–2.8 fold) compared with commercially available hemostatic agents (p < 0.001).

4.5. Others

Hemostatic sponges prepared from cellulose and its derivatives have also been frequently reported. Han et al. [60] cross-linked konjac glucomannan and chitosan once to form a dynamic covalent bond network, uniformly dispersed encapsulated nanocellulose, and constructed a basic three-dimensional fiber porous network framework. This sponge scaffold, with a self-expanding, interpenetrating, macroporous structure, was designed by a two-step cross-linking method and had hemostasis and photothermal antibacterial activity. The composite sponge had strong blood cell adhesion and platelet activation ability. In tests of rat liver injury model, the hemostatic time of the composite sponge was short (12 ± 2.17 s), the blood loss was low (0.1 ± 0.052 g), and the sponge had an adhesion effect. Cao et al. [61] prepared a novel hemostatic nanocomposite (oxidized bacterial cellulose–dopamine/dopamine–montmorillonite/Ag nanoparticle: OBC-PDA/PDA-MMT/Ag NP) sponge by adding hydrochloric-acid-modified MMT coated with PDA as functional hemostatic particles into oxidized bacterial cellulose. The hemostatic sponge had suitable mechanical strength, broad-spectrum antibacterial performance, and good biodegradability. The hemostatic sponge with PDA-MMT and AgNPs is expected to provide rapid hemostasis, antibacterial, and wound healing functions.

Because of its loose porous structure, gelatin (a denaturated protein) sponges can absorb a large amount of water in the blood and make the blood become viscous; they also have excellent hemostatic performance [14]. At the same time, the negative charge of gelatin can activate some clotting factors and accelerate the formation of fibrin and platelet aggregation. Gelatin sponges act on wounds by first absorbing water and then expanding, which can mechanically compress or fill the wound and play a bonding role on the bleeding wound, not only accelerating blood coagulation but promoting wound healing [62]. The disadvantages of gelatin are that it may increase wound infection, has poor adhesion, and can easily fall off. In addition, the hemostatic effect of gelatin sponges is not ideal for people with impaired coagulation mechanisms.

The active polysaccharide component obtained from natural products is also a good raw material for hemostatic sponges, as efficient or better than gelatin. Li et al. [63] proposed a sponge with a layered porous structure (BC-S) for the treatment of bleeding. BC-S was prepared by a simple self-assembly method from Bletilla striata polysaccharide and Bletilla Striata and Coptidis Rhizoma alkaloids. BC-S has good structural design and an effective hemostatic mechanism. Compared with typical gelatin hemostatic sponge, BC-S had better hemostatic performance in different models in vivo and in vitro. This work provides reference for promoting the development of new hemostatic agents. This part summarizes the preparation (Figure 4) and hemostatic effect (

Table 1. Summary of the hemostatic effects of polysaccharide-based sponges from chitosan, starch, hyaluronic acid, alginate, and so on in the past five years.

Resources	Coagulation Effect	Hemostasis Time (HT), Blood Loss (BL)	Model	Ref.
Chitosan-CaP microflowers and metronidazole-loaded calcium alginate sponges	OD value: 0.015–0.065	_	Coagulation test in vitro	[36]
Alginate/chitosan/ sargassum sponges	OD value: 0.03–0.065	_	Blood-clotting study in vitro	[38]
Microporous sponges based on silk fibroin and starch	BCI: 40–80%	Clotting time: 2.5–3.5 min	Blood-clotting assays in vitro	[52]
Polysaccharide on the invisible hemostasis of acellular dermal matrix sponges	_	HT in rat tail/liver: ≈ 80 s; BL in rat tail/liver: ≈ 0.15 g	An SD rat liver injury model	[53]
Alginate/hyaluronic acid composite sponges	BCI: 60–90%	_	Dynamic whole blood clotting studies in vitro	[55]
HA/Dex-PDM (SHDP), HA/Dex-QPDM (SHDQ) sponges	_	BL: SHDQ: 23.2 mg SHDP-2: 50.1 mg	Hemorrhaging liver models of SD rats	[56]
Polyphosphate/nanokaolin-modified alginate sponges	BCI: 10–60%	Blood coagulation time: 20–50 s HT: 20–200 s; BL: 3–5 g	Whole blood clotting measurement in vitro	[59]
Multifunctional hemostatic polysaccharide-based sponges enhanced by tunicate cellulose	_	HT: 12.0 s; BL: 0.1 g	Tests of rat liver injury model	[60]
Chinese polysaccharide sponges with hierarchical porous structure	_	HT: 221.67 s; BL: 1450.67 mg	Liver injury experiment	[63]
Antibacterial and hemostatic chitin sponges	BCI: 23.6–42.7%	HT: 12 s (AQTS) BL: 101 mg (AQTS)	Rat liver injury model	[64]
Asymmetric dual-layer polysaccharide-based porous structures (asymmetric dual-layer CC/SA/TA porous structures)	BCI: 10–40%	_	_	[65]
Epoxy Bletilla striata polysaccharide collagen sponges	BCI: 38–50	HT: 26.75 s (EC-12) BL: 88 mg (EC-12)	Full-layer skin defect model	[66]

) of some polysaccharide based hemostatic sponges from the cases provided herein.

4.6. Comparison Between Typical Hemostatic Materials and Polysaccharide-Based Sponges

Hemostatic materials are an important tool for bleeding control in medical treatment and first aid. Traditionally, hemostatic gauze, gelatin sponge, oxidized cellulose, and other materials have been widely used, but in recent years, polysaccharide hemostatic sponges have gradually attracted attention because of their superior performance. The differences between these typical hemostatic agents and the new polysaccharide hemostatic materials are reflected in (1) hemostatic efficiency: polysaccharide hemostatic sponges are usually more efficient than traditional materials, especially in the treatment of large or deep tissue bleeding; (2) biosafety: polysaccharide materials tend to have better biocompatibility and lower risk of immune response, reducing the possibility of postoperative complications; (3) degradability and absorbability: polysaccharide sponges are usually fully absorbable, meaning that they can break down in the body on their own without the need for a second surgery to remove them, while some traditional materials may need to be removed; (4) additional functions: for example, chitosan sponge not only has excellent hemostatic properties but has additional benefits such as anti-inflammatory effects and healing promotion; (5) scope of application: although both types of materials can be used in a variety of surgical scenarios, polysaccharide sponges may be more suitable in some specific applications (such as neurosurgery, plastic surgery) because of their unique properties. To sum up, although typical hemostatic materials still occupy an important position, with the progress of research and technology, polysaccharide hemostatic sponges are becoming an increasingly popular choice in modern medicine with their unique advantages.

5. Future Perspectives

The future development trend of polysaccharide hemostatic sponges can be analyzed from the following points:

5.1. Technological Innovation Trend

Development of new materials: with the in-depth understanding of the chemical properties of polysaccharides, more new natural polysaccharide materials from different sources may be developed in the future. These materials will have better biocompatibility, stronger hemostatic ability, and better biodegradability. Development of composite materials: combining the advantages of polysaccharides and other biological materials (such as gelatin, etc.), the composite hemostatic sponge was developed to realize the multifunction integration of antibacterial effects, wound healing, etc.

5.2. Expansion of Application Fields

Deepening of application in the medical field: in addition to traditional surgical hemostasis, polysaccharide hemostatic sponges may also be more widely used in trauma first aid, dentistry, ophthalmology, and other medical fields. Nonmedical field exploration: in view of the unique properties of polysaccharide hemostatic sponges, in the future, the possibilities may be explored of their application in nonmedical fields, such as environmental protection, industrial production, and so on.

5.3. Improved Safety and Biocompatibility

Reducing immune response: by improving the preparation process or selecting a specific type of polysaccharide, the immune response caused by the material can be further reduced, improving the safety of long-term use. Environmental friendliness: this requirement is to ensure the complete biodegradability of the material, reduce the impact on the environment, and meet the requirements of sustainable development.

5.4. Cost-Effectiveness Optimization

Production process optimization: through technological innovation to reduce costs and enhance production efficiency, the polysaccharide hemostatic sponge will become more economical and conducive to widespread application. Maximize resource utilization: new sources of polysaccharides will be developed, especially those with lower costs and abundant resources, to achieve efficient use of resources.

5.5. Development of Personalized Medicine

Customized products: with the development of the concept of precision medicine, polysaccharide hemostatic sponges customized for different patient needs may appear in the future to better meet the needs of individual treatment. Intelligent response materials: the study of polysaccharide hemostatic sponges with intelligent response characteristics, such as pH sensitivity, temperature sensitivity, etc., could permit automatically activating or changing performance under specific conditions to improve the treatment effect.

5.6. Construction of Regulations and Standards

Strengthen supervision: with the continuous emergence of new polysaccharide hemostatic sponges, it is crucial to establish and improve the evaluation system of the safety and effectiveness of related products to ensure product quality. International standard development: in the future, efforts should be made to strengthen international technical exchanges and cooperation, jointly develop unified industry standards, and promote the research and application of polysaccharide hemostatic sponges worldwide.

6. Conclusions

Natural polysaccharides are widely used in biomedicine because of their good biocompatibility, biodegradability, nonimmunogenicity, and antibacterial, antibleeding, and wound healing properties. As a newly developed form of polysaccharide-based materials, hemostatic sponges have high-efficiency liquid absorption and shape memory ability, and they can achieve a rapid hemostatic effect by wrapping or filling wounds. However, polysaccharide-based hemostatic sponges still have some potential drawbacks. For example, the role of the amino group in chitosan hemostatic sponge may be significantly reduced in neutral environments, and some modified chitosan can improve the water solubility of chitosan but affect its antibacterial performance. In addition, most polysaccharide sponges tend to have limited mechanical strength and function. Therefore, polysaccharide-based hemostatic sponges are still in the initial stage, and the development of a new generation of hemostatic materials with ideal properties has attracted more and more attention.

In order to improve the solubility and the mechanical and antibacterial properties of polysaccharides, various functional modifications of polysaccharide groups (hydroxyalkyl, carboxyl, alkyl, etc.) are often carried out. In addition, many functional materials have been used as fillers of polysaccharide sponges to improve the hemostasis, anti-inflammatory effect, cell proliferation, and remodeling of sponges. Fillings can be inorganic materials, including carbon nanotubes/fibers, hydroxyapatite, calcium pyrophosphate, etc. Moreover, natural polymers including starch, cellulose, gelatin, and some synthetic polymers (such as PEG, PVA, PVP, etc.) can be easily mixed to improve the mechanical properties and swelling properties of polysaccharide sponges. In fact, the requirement to combine these organic and inorganic functional materials in a suitable physical/chemical manner to achieve a versatile and high-performance hemostatic sponge for hemostasis and wound healing has attracted great attention. At present, the new generation of hemostatic material commercial products, such as XStat equipment, HemCon, Celox, etc., has been widely used. However, the existing natural polysaccharide hemostatic sponge products are still far from meeting the demand.

In summary, the research and development of polysaccharide hemostatic sponges are in a stage of rapid progress. In the future, significant breakthroughs are expected not only in material properties and scope of application but to face many challenges, such as how to balance cost and performance and ensure material safety. Therefore, continuous technological innovation and interdisciplinary collaboration will be important driving forces for the advancement of this field.