Cryogels, an advanced subclass of hydrogels, are widely used in biomedical applications such as tissue engineering, drug delivery, and immunotherapy. Biopolymers, like hyaluronic acid (HA), are key building blocks for cryogel fabrication due to their intrinsic biological properties, biocompatibility, and biodegradability. HA undergoes biodegradation through hydrolysis, enzymatic degradation, and oxidation, but becomes less susceptible to degradation once chemically modified. This modification is necessary for producing HA-based cryogels with unique properties, including an open macroporous network, mechanical resilience, shape memory, and syringe injectability. Endowing cryogels with resorbable features is essential for meeting regulatory requirements and improving treatment outcomes. To this end, HA was oxidized with sodium periodate (HAox) and chemically modified with glycidyl methacrylate (HAoxGM) to create HAoxGM cryogels with controlled degradation. Oxidation of HA increased the susceptibility of the polymer backbone to breakdown through various mechanisms, including oxidative cleavage and alkaline hydrolysis. Compared to their poorly degradable counterparts, HAoxGM cryogels retained their advantageous properties despite reduced compressive strength. HAoxGM cryogels were highly cytocompatible, biocompatible, and tunable in degradation. When injected subcutaneously into mice, the HAoxGM cryogels were biocompatible and resorbed within two weeks. To validate the beneficial effect of controlled biodegradation in a relevant in vivo setting, we demonstrated that the degradation of HAoxGM cryogels accelerates ovalbumin release and enhances its uptake and response by immune cells in mice. This versatile oxidation strategy can be applied to a wide range of polymers, allowing better control over cryogel degradation, and advancing their potential for biomedical applications and clinical translation.

This study presents a novel approach for the controlled synthesis and real-time characterization of crosslinked hyaluronic acid (HA) hydrogels utilizing a microfluidic platform coupled with hyphenated electrospray-differential mobility analysis (ES-DMA). By precisely controlling key synthesis parameters within the microfluidic environment, including pH, temperature, reaction time, and the molar ratio of HA to crosslinker (1,4-butanediol diglycidyl ether, BDDE), we successfully synthesized HA hydrogels with tailored size and properties. The integrated ES-DMA system provides rapid, in-line analysis of hydrogel particle size and distribution, enabling real-time monitoring and optimization of the synthesis process. Furthermore, small-angle x-ray scattering (SAXS) was employed to complement ES-DMA analysis, providing valuable insights into the internal structure and extent of crosslinking within the synthesized hydrogels. The evolution of the number-based particle size distribution revealed a strong correlation with the synthesis conditions, demonstrating the high degree of controllability achieved by this integrated approach. This novel methodology offers a promising platform for the high-throughput synthesis of uniform and well-defined hydrogel nanoparticles with enhanced traceability, paving the way for advancements in various applications including drug delivery, tissue engineering, and biomaterials.

Uncontrolled hemorrhage remains the leading cause of death in clinical and emergency care, posing a major threat to human life. To achieve effective bleeding control, many hemostatic materials have emerged. Among them, nature-derived biopolymers occupy an important position due to the excellent inherent biocompatibility, biodegradability and bioactivity. Additionally, sponges have been widely used in clinical and daily life because of their rapid blood absorption. Therefore, we provide the overview focusing on the latest advances and smart designs of biopolymer-based hemostatic sponge. Starting from the component, the applications of polysaccharide and polypeptide in hemostasis are systematically introduced, and the unique bioactivities such as antibacterial, antioxidant and immunomodulation are also concerned. From the perspective of sponge structure, different preparation processes can obtain unique physical properties and structures, which will affect the material properties such as hemostasis, antibacterial and tissue repair. Notably, as development frontier, the multi-functions of hemostatic materials is summarized, mainly including enhanced coagulation, antibacterial, avoiding tumor recurrence, promoting tissue repair, and hemorrhage monitoring. Finally, the challenges facing the development of biopolymer-based hemostatic sponges are emphasized, and future directions for in vivo biosafety, emerging materials, multiple application scenarios and translational research are proposed.

Hemorrhage continues to pose a significant challenge in various medical contexts, underscoring the need for advanced hemostatic materials. Hemostatic hydrogels have gained recognition as innovative tools for addressing uncontrollable bleeding, attributed to their distinctive features including biological compatibility, tunable mechanical properties, and exceptional hemostatic performance. This review provides a comprehensive overview of hemostatic hydrogels that offer rapid and effective bleeding control. Particularly, this review focuses on hemostatic hydrogel design and associated hemostatic mechanisms. Additionally, recent advancements in the application of these materials are discussed in detail, especially in clinical trials. Finally, the challenges and potential advancements of hemostatic hydrogels are analyzed and assessed. This review seeks to emphasize the role of hydrogels in biomedical applications for hemorrhage control and provide perspectives on the innovation of clinically applicable hemostatic materials.

Diabetic wounds remain a critical clinical challenge due to their harsh microenvironment, which impairs cellular function, hinders re-epithelialization and tissue remodeling, and slows healing. Injectable nanocomposite hydrogel dressings offer a promising strategy for diabetic wound repair. In this study, we developed an injectable nanocomposite hydrogel dressing (HDL@W379) using LAP@W379 nanoparticles and an injectable hyaluronic acid-based hydrogel (HA-ADH-ODEX). This dressing provided a sustained, pH-responsive release of W379 antimicrobial peptides, effectively regulating the wound microenvironment to enhance healing. The HDL@W379 hydrogel featured multifunctional properties, including mechanical stability, injectability, self-healing, biocompatibility, and tissue adhesion. In vitro, the HDL@W379 hydrogel achieved synergistic biofilm elimination and subsequent activation of basal cell migration and endothelial cell tube formation. Pathway analysis indicated that the HDL@W379 hydrogel enhances basal cell migration through MEK/ERK pathway activation. In methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds, the HDL@W379 hydrogel accelerated wound healing by inhibiting bacterial proliferation and promoting re-epithelialization, regenerating the granulation tissue, enhancing collagen deposition, and facilitating angiogenesis. Overall, this strategy of biofilm elimination and basal cell activation to continuously regulate the diabetic wound microenvironment offers an innovative approach to treating chronic wounds.

The development of new wound dressings with fast hemostatic and bactericidal properties for prehospital care is critical. Antibacterial photodynamic therapy (aPDT) has attracted attention due to its broad-spectrum antibacterial activity and minimal bacterial resistance. However, photosensitizers used in aPDT often face issues such as poor water solubility, short-lived singlet oxygen (1O2), and limited 1O2 diffusion range. In this study, sodium alginate was covalently modified with the photosensitizer toluidine blue O (TBO) and phenylboronic acid (PBA). The modified alginate was then cross-linked with Ca(II) ions and lyophilized to form a cryogel, named SA@Ca(II)@TBO@PBA (SCTP). This cryogel functions as an antibacterial photodynamic wound dressing. The chemical immobilization of TBO and PBA enhanced the cryogel's targeting ability. PBA formed reversible covalent bonds with diol groups on bacterial cell surfaces, allowing the cryogel to capture bacteria effectively and enhance aPDT. The bactericidal efficiency of the cryogel was tested through in vitro antibacterial assays, and its hemostatic properties were confirmed in vivo. The results indicate that this cryogel has excellent hemostatic and antibacterial capabilities, showing great promise as a wound dressing for clinical applications.

This study aims to develop a medical patch surface material featuring a microporous polyurethane (PU) membrane and to assess the material's properties and biological performance. The goal is to enhance the clinical applicability of pelvic floor repair patch materials.

PU films with a microporous surface were prepared using PU prepolymer foaming technology. The films were produced by optimizing the PU prepolymer isocyanate index (R value) and the relative humidity (RH) of the foaming environment. The surface morphology of the PU microporous films was observed by scanning electron microscopy, and the chemical properties of the PU microporous films, including hydrophilicity, were analyzed using infrared spectroscopy, Raman spectroscopy, and water contact angle measurements. In vitro evaluations included testing the effects of PU microporous film extracts on the proliferation of L929 mouse fibroblasts and observing the adhesion and morphology of these fibroblasts. Additionally, the effect of the PU microporous films on RAW264.7 mouse macrophages was studied. Immune response and tissue regeneration were assessed in vivo using Sprague Dawley (SD) rats.

The PU films exhibited a well-defined and uniform microporous structure when the R value of PU prepolymer=1.5 and the foaming environment RH=70%. The chemical structure of the PU microporous films was not significantly altered compared to the PU films, with a significantly lower water contact angle ([55.7±1.5]° ) compared to PU films ([69.5±1.7]° ) and polypropylene (PP) ([ 104.3±2.5]°), indicating superior hydrophilicity. The extracts from PU microporous films demonstrated good in vitro biocompatibility, promoting the proliferation of L929 mouse fibroblasts. The surface morphology of the PU microporous films facilitated fibroblast adhesion and spreading. The films also inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β by RAW264.7 macrophages while enhancing IL-10 and IL-4 secretion. Compared to 24 hours, after 72 hours of culture, the expression levels of TNF-α and IL-1β were reduced in both the PU film and PU microporous film groups and were significantly lower than those in the PP film group (P<0.05), with the most notable decreases observed in the PU microporous film group. IL-10 and IL-4 levels increased significantly in the PU microporous film group, surpassing those in the PP film group (P<0.01), with the most pronounced increase in IL-4. The PU microporous film induced mild inflammation with no significant fibrous capsule formation in vivo. After 60 days of implantation, the film partially degraded, showing extensive collagen fiber growth and muscle formation in its central region.

The PU microporous film exhibits good hydrophilicity and biocompatibility. Its surface morphology enhances cell adhesion, regulates the function of RAW264.7 macrophages, and promotes tissue repair, offering new insights for the design of pelvic floor repair and reconstruction patch materials.

Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.

Skin injuries can have unexpected surfaces, leading to uneven wound surfaces and inadequate dressing contact with these irregular surfaces. This can decrease the dressing's haemostatic action and increase the healing period. This study recommends the use of sticky and flexible cryogel coverings to promote faster haemostasis and efficiently handle uneven skin wounds. Alginate cryogels have a fast haemostatic effect and shape flexibility due to their macroporous structure. The material demonstrates potent antibacterial characteristics and enhances skin adherence by adding grafted chitosan with gallic acid. In irregular defect wound models, cryogels can cling closely to uneven damage surfaces due to their amorphous nature. Furthermore, their macroporous structure allows for quick haemostasis by quickly absorbing blood and wound exudate. After giving the dressing a thorough rinse, its adhesive strength reduces and it is simple to remove without causing any damage to the wound. Cryogel demonstrated faster haemostasis than gauze in a wound model on a rat tail, indicating that it has considerable potential for use as a wound dressing in the biomedical area.

Massive bleeding resulting from civil and martial accidents can often lead to shock or even death, highlighting the critical need for the development of rapid and efficient hemostatic materials. While various types of hemostatic materials are currently utilized in clinical practice, they often come with limitations such as poor biocompatibility, toxicity, and biodegradability. Polysaccharides, such as alginate (AG), chitosan (CS), cellulose, starch, hyaluronic acid (HA), and dextran, have exhibit excellent biocompatibility and in vivo biodegradability. Their degradation products are non-toxic to surrounding tissues and can be absorbed by the body. As a result, polysaccharides have been extensively utilized in the development of hemostatic materials and have gained significant attention in the field of in vivo hemostasis. This review offers an overview of the different forms, hemostatic mechanisms, and specific applications of polysaccharides. Additionally, it discusses the future opportunities and challenges associated with polysaccharide-based hemostats.

Hydrogels containing catechol group have received attention in the biomedical field due to their robust adhesive/cohesive capabilities, biocompatibility, and hemostatic abilities. Catechol-functionalized chitosan holds promise for preparing self-assembly hydrogels. However, issues of inefficient gelation and instability still persist in these hydrogels. In the current study, we synthesized chitosan catechol (CC) of high catechol substitution (∼28 %) and combined CC with tannic acid (TA, which also contains catechol) to form self-healing CC-TA hydrogels. The catechol-enriched CC-TA composite hydrogels showed rapid gelation and mechanical reinforcement (shear modulus ∼110 Pa). In situ coherent small-angle X-ray scattering (SAXS) coupled with rheometry revealed a morphological feature of mesoscale clusters (∼20 nm) within CC-TA hydrogel. The clusters underwent dynamic destruction under large-amplitude oscillatory shear, corresponding with the strain-dependent and self-healing behavior of the CC-TA hydrogel. The composite hydrogel had osmotic-responsive and notable adhesive properties. Meanwhile, CC-TA composite cryogel prepared simply through freeze-thawing procedures exhibited distinctive macroporous structure (∼200 μm), high water swelling ratio (∼7000 %), and favorable compressive modulus (∼8 kPa). The sponge-like cryogel was fabricated into swabs, demonstrating hemostatic capacity. The CC-TA composites, in both hydrogel and cryogel forms, possessed ROS scavenging ability, antimicrobial activity, and cell compatibility with potentials in biological applications.

Hemorrhage remains a critical challenge in various medical settings, necessitating the development of advanced hemostatic materials. Hemostatic hydrogels have emerged as promising solutions to address uncontrolled bleeding due to their unique properties, including biocompatibility, tunable physical characteristics, and exceptional hemostatic capabilities. In this review, a comprehensive overview of the preparation and biomedical applications of hemostatic hydrogels is provided. Particularly, hemostatic hydrogels with various materials and forms are introduced. Additionally, the applications of hemostatic hydrogels in trauma management, surgical procedures, wound care, etc. are summarized. Finally, the limitations and future prospects of hemostatic hydrogels are discussed and evaluated. This review aims to highlight the biomedical applications of hydrogels in hemorrhage management and offer insights into the development of clinically relevant hemostatic materials.

Intraoperative bleeding and delayed postsurgical wound healing caused by persistent inflammation can increase the risk of tumor recurrence after surgical resection. To address these issues, Enteromorpha prolifera polysaccharide (PEP) with intrinsic potentials for hemostasis and wound healing, is chemically modified into aldehyde-PEP and hydrazine-PEP. Thereby, an injectable double-network hydrogel (OPAB) is developed via forming dual dynamic bonding of acylhydrazone bonds between the decorated aldehyde and hydrazine groups and hydrogen bonds between hydroxyl groups between boric acid and PEP skeletons. The OPAB exhibits controllable shape-adaptive gelation (35.0 s), suitable mechanical properties, nonstimulating self-healing (60 s), good wet tissue adhesion (30.9 kPa), and pH-responsive biodegradability. For in vivo models, owing to these properties, OPAB can achieve rapid hemostasis within 30 s for the liver hemorrhage, and readily loading of curcumin nanoparticles to remarkably accelerate surgical wound closure by alleviating inflammation, re-epithelialization, granulation tissue formation, and collagen deposition. Overall, this multifunctional injectable hydrogel is a promising material that facilitates simultaneous intraoperative hemorrhage and postsurgical wound repair, holding significant potential in the clinical managements of bleeding and surgical wounds for tumor resection.

Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.

Hemorrhage is a potentially life-threatening emergency that can occur at any time or place. Whether traumatic, congenital, surgical, disease-related, or drug-induced, bleeding can lead to severe complications or death. Therefore, the development of efficient hemostatic materials is critical. However, the results and prognosis demonstrated by clinical means of hemostasis do not reach expectations. With the development of technology, novel hemostatic materials have been developed from polysaccharides (chitosan, hyaluronic acid, alginate, cellulose, cyclodextrins, starch, dextran, and carrageenan), peptides (self-assembling peptides), and proteins (silk fibroin, collagen, gelatin, keratin, and thrombin). These new materials exhibit high hemostatic efficacy due to the enhancement or interaction of various hemostatic mechanisms. The main forms include adhesives, sealants, bandages, hemostatic powders, and hemostatic sponges. This article introduces the clotting process and principles of hemostatic methods and reviews the research on polysaccharide-, peptide-, and protein-based hemostatic materials in the last five years. The design ideas and hemostatic principles of polysaccharide-, peptide-, and protein-based hemostatic materials are mainly introduced. Finally, we summarize material designs, advantages, disadvantages, and challenges regarding hemostatic materials.

Uncontrolled hemorrhage results in various complications and is currently the leading cause of death in the general population. Traditional hemostatic methods have drawbacks that may lead to ineffective hemostasis and even the risk of secondary injury. Therefore, there is an urgent need for more effective hemostatic techniques. Polymeric hemostatic materials, particularly hydrogels, are ideal due to their biocompatibility, flexibility, absorption, and versatility. Functional hemostatic hydrogels can enhance hemostasis by creating physical circumstances conducive to hemostasis or by directly interfering with the physiological processes of hemostasis. The procoagulant principles include increasing the concentration of localized hemostatic substances or establishing a physical barrier at the physical level and intervention in blood cells or the coagulation cascade at the physiological level. Moreover, synergistic hemostasis can combine these functions. However, some hydrogels are ineffective in promoting hemostasis or have a limited application scope. These defects have impeded the advancement of hemostatic hydrogels. To provide inspiration and resources for new designs, this review provides an overview of the procoagulant principles of hemostatic hydrogels. We also discuss the challenges in developing effective hemostatic hydrogels and provide viewpoints.

The integration of hydrogels with bio-friendly functional components through simple and efficient strategies to construct wound dressings with broad-spectrum antibacterial and immunomodulatory properties to promote the healing of infected diabetic wounds is highly desirable but remains a major challenge. Here, wormwood essential oil (WEO) is effectively encapsulated in the hydrogel via an O/W-Pickering emulsion during the polymerization of methacrylic anhydride gelatin (GelMA), acrylamide (AM), and acrylic acid N-hydroxysuccinimide ester (AAc-NHS) to form a multifunctional hydrogel dressing (HD-WEO). Compared with conventional emulsions, Pickering emulsions not only improve the encapsulation stability of the WEO, but also enhance the tensile and swelling properties of hydrogel. The synergistic interaction of WEO's diverse bioactive components provides a broad-spectrum antibacterial activity against S. aureus, E. coli, and MRSA. In addition, the HD-WEO can induce the polarization of macrophages from M1 to M2 phenotype. With these advantages, the broad-spectrum antibacterial and immunomodulatory HD-WEO effectively promotes the collagen deposition and neovascularization, thereby accelerating the healing of MRSA-infected diabetic wounds.

The healing of wounds in diabetic patients is a huge challenge issue in clinical medicine due to the disordered immune. Recruiting endogenous cells to play a role in the early stage and timely reducing inflammation to promote healing in the middle or late of injuring are both prerequisites for effective treatment. Here, inspired by natural extracellular matrix, three-dimensional porous polyurethane-hyaluronic acid hybrid hydrogel scaffolds (PUHA) were prepared to repair diabetic wound through activate cell immunity by moderate foreign body reaction, provide cell adhesion growth extracellular matrix of hyaluronic acid (HA) and exhibit anti-inflammatory effect of polyurethane (PU). The interaction between PU and HA alters the compact PU hydrogel into macroporous PUHA hydrogel scaffolds with super-swelling, elastic mechanical properties, and controllable degradation, which are suitable for endogenous cells infiltration, growth and immune activation. Additionally, incorporating with RGD, PUHA hydrogel scaffolds with bioactive physicochemical features can evidently reduce the inflammation and modulate the polarization of macrophage apparently both in vitro and in vivo, mainly through downregulation of cytokine-cytokine receptor interaction genes, leading to reprogramming immune-microenvironment and rapid diabetic wound healing. This method of gathering cells initially and intervening immune-microenvironment in time provides an expected way to design biomaterials for chronic wound healing.

The inability of wounds to heal effectively through normal repair has become a burden that seriously affects socio-economic development and human health. The therapy of acute and chronic skin wounds still poses great clinical difficulty due to the lack of suitable functional wound dressings. It has been found that dressings made of polyurethane exhibit excellent and diverse biological properties, but lack the functionality of clinical needs, and most dressings are unable to dynamically adapt to microenvironmental changes during the healing process at different stages of chronic wounds. Therefore, the development of multifunctional polyurethane composite materials has become a hot topic of research. This review describes the changes in physicochemical and biological properties caused by the incorporation of different polymers and fillers into polyurethane dressings and describes their applications in wound repair and regeneration. We listed several polymers, mainly including natural-based polymers (e.g., collagen, chitosan, and hyaluronic acid), synthetic-based polymers (e.g., polyethylene glycol, polyvinyl alcohol, and polyacrylamide), and some other active ingredients (e.g., LL37 peptide, platelet lysate, and exosomes). In addition to an introduction to the design and application of polyurethane-related dressings, we discuss the conversion and use of advanced functional dressings for applications, as well as future directions for development, providing reference for the development and new applications of novel polyurethane dressings.

The dura mater is the final barrier against cerebrospinal fluid leakage and plays a crucial role in protecting and supporting the brain and spinal cord. Head trauma, tumor resection and other traumas damage it, requiring artificial dura mater for repair.  However, surgical tears are often unavoidable. To address these issues, the ideal artificial dura mater should have biocompatibility, anti-leakage, and self-healing properties. Herein, this work has used biocompatible polycaprolactone diol as the soft segment and introduced dynamic disulfide bonds into the hard segment, achieving a multifunctional polyurethane (LSPU-2), which integrated the above mentioned properties required in surgery. In particular, LSPU-2 matches the mechanical properties of the dura mater and the biocompatibility tests with neuronal cells demonstrate extremely low cytotoxicity and do not cause any negative skin lesions. In addition, the anti-leakage properties of the LSPU-2 are confirmed by the water permeability tester and the 900 mm H2 O static pressure test with artificial cerebrospinal fluid. Due to the disulfide bond exchange and molecular chain mobility, LSPU-2 could be completely self-healed within 115 min at human body temperature. Thus, LSPU-2 comprises one of the most promising potential artificial dura materials, which is essential for the advancement of artificial dura mater and brain surgery.

Articular cartilage injuries are very frequent lesions that if left untreated may degenerate into osteoarthritis. Gene transfer to mesenchymal stem cells (MSCs) provides a powerful approach to treat these lesions by promoting their chondrogenic differentiation into the appropriate cartilage phenotype. Non-viral vectors constitute the safest gene transfer tools, as they avoid important concerns of viral systems including immunogenicity and insertional mutagenesis. However, non-viral gene transfer usually led to lower transfection efficiencies when compared with their viral counterparts. Biomaterial-guided gene delivery has emerged as a promising alternative to increase non-viral gene transfer efficiency by achieving sustained delivery of the candidate gene into cellular microenvironment. In the present study, we designed hyaluronic acid-based gene-activated cryogels (HACGs) encapsulating a novel formulation of non-viral vectors based on niosomes (P80PX) to promote MSCs in situ transfection. The developed HACG P80PX systems showed suitable physicochemical properties to promote MSCs in situ transfection with very low cytotoxicity. Incorporation of a plasmid encoding for the transcription factor SOX9 (psox9) into HACG P80PX systems led to an effective MSCs chondrogenic differentiation with reduced expression of fibrocartilage and hypertrophic markers. The capacity of the developed systems to restore cartilage extracellular matrix was further confirmed in an ex vivo model of chondral defect.

The symptomatic management of hemorrhagic shock complicated by open fractures is a great challenge, because it is also complicated by complex wound bleeding, bacterial infection, and bone defects. Inspired by the water absorption and cross-sectional microstructure of sea cucumbers, in this study, a new sea cucumber-like aerogel (GCG) is proposed. Its aligned porous structure and composition can stop bleeding rapidly and effectively with a blood clotting index of 3.73 ± 1.8%. More importantly, the data of in vivo hemostasis test in an amputating rat tail hemostatic model (15.69 ± 2.45 s, 26.95 ± 8.43 mg) and liver puncture bleeding model (23.77 ± 2.68 s, 36.22 ± 16.92 mg) also indicate the excellent hemostatic performance of GCG. In addition, GCG also shows a significant inhibitory effect on S. aureus and E. coli, which can prevent the occurrence of postoperative osteomyelitis. Not only that, after filling in the bone defect, it is shown that this GCG aerogel completely degrades eight weeks after surgery and induces new bone ingrowth, achieving functional regeneration after hemostasis of an open fracture defect. Generally, because of its combination of hemostatic, antibacterial, and osteogenic activities, this new aerogel is a promising option for open fractures treatment.

Development of an inflammation modulating polypropylene (PP) mesh in pelvic floor repair is an urgent clinical need. This is because PP mesh for pelvic floor repair can cause a series of complications related to foreign body reactions (FBR) in postoperative period. Therefore, we successfully prepared PP composite mesh that can scavenge reactive oxygen species (ROS) and inhibit inflammation to moderate FBR by a simple method. First, a pregel layer was formed on PP mesh by dip coating. Among them, polyurethane with polythioketal (PTK) is an excellent ROS scavenger, and dopamine methacrylamide (DMA) improves the stability of the coating and synergistically scavenges ROS. Then, a composite mesh (optimal PU50-PP) was obtained by photopolymerization. The results showed that the polyurethane gel layer was able to scavenge more than 90% of free radicals and about 75% of intracellular ROS. In vitro, PU50-PP mesh significantly scavenged ROS and resisted macrophage adhesion. After implantation in the posterior vaginal wall of rats, PU50-PP eliminated 53% of ROS, inhibited inflammation (decreased IL-6, increased IL-10), and dramatically reduced collagen deposition by about 64%, compared to PP mesh. Thus, the composite PP mesh with ROS scavenging and anti-inflammatory properties provides a promising approach for mitigating FBR.

Hydrogels have been extensively used in the field of biomedical engineering. In order to achieve non-invasive and real-time visualization of the in vivo status of hydrogels, we designed a fluorescent polyurethane-oxidized dextran (PU-OD) hydrogel with good injectability and self-healing properties, which was cross-linked from a tetraphenyl ethylene (TPE)-containing fluorescent polyurethane emulsion with oxidized dextran by dynamic acylhydrazone bonds. The hydrogel can be used as a visual platform for drug delivery as well as monitoring its own degradation. The network structure of the hydrogel gave it drug-loading capability, and the acylhydrazone bond enabled its pH-responsive drug release. Meanwhile, the PU-OD hydrogel could undergo fluorescence resonance transfer with doxorubicin hydrochloride, showing its potential application in monitoring drug release. In addition, fluorometric and weighing methods were performed to monitor the degradation behavior of the hydrogels in vivo and in vitro, respectively, showing that the non-invasive fluorometric method can be consistent with the invasive weighing method. This work highlights that the introduction of aggregation-induced emission molecules into polyurethanes provides a visual platform that allows for non-invasive monitoring of the material without affecting its own function, which is convenient and less damaging to the body or animals. Consequently, it possesses excellent and promising potential in biomedical materials technologies.

Lipid-based nanocarriers have been extensively investigated for their application in drug delivery. Particularly, liposomes are now clinically established for treating various diseases such as fungal infections. In contrast, extracellular vesicles (EVs) - small cell-derived nanoparticles involved in cellular communication - have just recently sparked interest as drug carriers but their development is still at the preclinical level. To drive this development further, the methods and technologies exploited in the context of liposome research should be applied in the domain of EVs to facilitate and accelerate their clinical translation. One of the crucial steps for EV-based therapeutics is designing them as proper dosage forms for specific applications. This review offers a comprehensive overview of state-of-the-art polysaccharide-based hydrogel platforms designed for artificial and natural vesicles with application in drug delivery to the skin. We discuss their various physicochemical and biological properties and try to create a sound basis for the optimization of EV-embedded hydrogels as versatile therapeutic avenues.

The treatment of skin wounds caused by trauma and pathophysiological disorders has been a growing healthcare challenge, posing a great economic burden worldwide. The use of appropriate wound dressings can help to facilitate the repair and healing rate of defective skin. Natural polymer biomaterials such as collagen and hyaluronic acid with excellent biocompatibility have been shown to promote wound healing and the restoration of skin. However, the low mechanical properties and fast degradation rate have limited their applications. Skin wound dressings based on biodegradable and biocompatible synthetic polymers can not only overcome the shortcomings of natural polymer biomaterials but also possess favorable properties for applications in the treatment of skin wounds. Herein, we listed several biodegradable and biocompatible synthetic polymers used as wound dressing materials, such as PVA, PCL, PLA, PLGA, PU, and PEO/PEG, focusing on their composition, fabrication techniques, and functions promoting wound healing. Additionally, the future development prospects of synthetic biodegradable polymer-based wound dressings are put forward. Our review aims to provide new insights for the further development of wound dressings using synthetic biodegradable polymers.

Bacterial infection in the most mobile area usually leads to delayed healing and functional restriction, which has been a long-term challenge in clinic. Developing hydrogel-based dressings with mechanical flexibly, high adhesive and anti-bacterial properties, will contribute to the healing and therapeutic effects especially for this typical skin wound. In this work, composite hydrogel named PBOF through multi-reversible bonds between polyvinyl alcohol, borax, oligomeric procyanidin and ferric ion demonstrated a 100 times ultra-stretch ability, 24 kPa of highly tissue-adhesive, rapid shape-adaptability within 2 min and self-healing feature within 40 s, was designed as the multifunctional wound dressing for the Staphylococcus aureus-infected skin wound in the mice nape model. Besides, this hydrogel dressing could be easily removed on-demand within 10 min by water. The rapid disassembly of this hydrogel is related to the formation of hydrogen bonds between polyvinyl alcohol and water. Moreover, the multifunctional properties of this hydrogel include strong anti-oxidative, anti-bacteria and hemostasis derived from oligomeric procyanidin and photothermal effect of ferric ion/polyphenol chelate. The killing ratio of the hydrogel on Staphylococcus aureus in infected skin wound reached 90.6% when exposed to 808 nm irradiation for 10 min. Simultaneously, reduced oxidative stress, suppressed inflammation, and promoted angiogenesis all together accelerated wound healing. Therefore, this well-designed multifunctional PBOF hydrogel holds great promise as skin wound dressing especially in the high mobile regions of the body. STATEMENT OF SIGNIFICANCE: An ultra-stretchable, highly tissue-adhesive, and rapidly shape-adaptive, self-healing and on-demand removable hydrogel based on multi-reversible bonds among polyvinyl alcohol, borax, oligomeric procyanidin and ferric ion is designed as dressing material for infected wound healing in the movable nape. The rapid on-demand removal of the hydrogel relates to the formation of hydrogen bonds between polyvinyl alcohol and water. This hydrogel dressing shows strong antioxidant capacity, rapid hemostasis and photothermal antibacterial ability. This is derived from oligomeric procyanidin and thephotothermal effect of ferric ion/polyphenol chelate, which eliminates bacterial infection, reduces oxidative stress, regulates inflammation, promotes angiogenesis, and finally accelerates the infected wound healing in movable part.

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH₂-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1-6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency. However, the inadequate durability, deficient pro-secretion of extracellular matrix (ECM) and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect. Herein, a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism (photo-triggered and dynamic covalent bonds). Owing to its characteristic networks, the synergistic effect of the hydrogel for vocal folds (VFs) vibration and phonation is adequately demonstrated. Notably, owing to its inherent bioactivity of polysaccharides, the hydrogel could significantly enhance the secretion of major components (type I/III collagen and elastin) in the lamina propria of the VFs both in vivo and in vitro. In a rabbit model for glottic insufficiency, the optimized hydrogel (C1A1) has demonstrated a durability far superior to that of the commercially made hyaluronic acid (HA) Gel. More importantly, owing to the ECM-inducing bioactivity, the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel, and were similar to those of the normal VFs. Taken together, through a simple-yet-effective strategy, the novel hydrogel has demonstrated outstanding durability, ECM-inducing bioactivity and physiological function preservation, therefore has an appealing clinical value for treating glottic insufficiency.

Massive damage to the skin can lead to heavy bleeding and potential wound infection. Therefore, the preparation of low-cost wound dressings that meet these requirements by simple methods has a good application prospect. In the study, a shape memory cryogel prepared at low temperatures by mixing chitosan (CS) and citric acid (CA). Silver nanoparticles (Ag NPs) introduced into the cryogel through the reduction of Ag⁺ with tannic acid (TA) as a reducing agent. The CS/CA/Ag cryogel has good mechanical properties and interconnected macroporous structures. The results of hemostasis tests show that CS/CA/Ag cryogel can absorb a large amount of blood and promote blood cell adhesion compared with commercial gelatin sponges and gauze. Meanwhile, CS/CA/Ag cryogel has a good antibacterial ability against S. aureus and E. coli. Furthermore, CS/CA/Ag cryogel significantly promotes wound healing in the full-thickness wound model infected with S. aureus. In conclusion, the cryogel prepared by the simple method has great advantages in rapid hemostasis and promoting wound healing.

Management of diabetic wound has long been a clinical challenge due to pathological microenvironment of excessive inflammation, persistent hyperglycemia, and biofilm infection caused by overdue reactive oxygen species (ROS) production and defective blood vessels. Herein, a multifunctional hydrogel with ROS scavenging and photothermal antibacterial activity based on oxidized dextran (Odex), gallic acid-grafted gelatin (GAG) and Ferric ion, named OGF, was developed for treatment of infected wound in a diabetic mouse. This hydrogel was double-crosslinked by the dynamically Schiff-base bonds formed between aldehyde groups in Odex and amino groups in GAG and the metal coordination bonds formed between Ferric ion and polyphenol groups or carboxyl groups in GAG, which endowed the resulted OGF hydrogel with well injectable, self-healing and adhesive properties. Due to the high-efficiency photothermal effect of Ferric ion/polyphenol chelate, this hydrogel killed Staphylococcus aureus and Escherichia coli rapidly and completely within 3.5 min under near-infrared light radiation. Furthermore, this composed hydrogel presented good antioxidation, hemostasis and biocompatibility. It also remarkably accelerated the complete re‑epithelialization of Staphylococcus aureus‑infected wound in diabetic mice within 18 days by eliminating infection, mitigating oxidative stress and inflammation, and facilitating angiogenesis. Therefore, the proposed multifunctional hydrogel exerts a great potential for translation in the clinical management of diabetic wounds. STATEMENT OF SIGNIFICANCE: High reactive oxygen species (ROS) levels and vascular defects in diabetic wounds can lead to excessive inflammation, persistent hyperglycemia, biofilm infection and other pathological microenvironments, which can further develop to the chronic wounds. In this study, we designed a multifunctional hydrogel with ROS-scavenging ability and photothermal antibacterial activity for the treatment of infected diabetic wound. As expected, this multifunctional hydrogel dressing highly accelerated the complete re‑epithelialization of Staphylococcus aureus‑infected wound in diabetic mouse by eliminating infection, mitigating oxidative stress and inflammation, as well as facilitating angiogenesis. This work provides a promising therapeutic strategy for infected diabetic wound by inhibition of oxidative stress and biofilm infection.

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.

Hydrogels have been widely used in wet tissues. However, the insufficient adhesion of hydrogels for wound hemostasis remains a grand challenge. Herein, a facile yet effective strategy is developed to fabricate tough wet adhesion of hydrogen-bond-based hydrogel (PAAcVI hydrogel) using copolymerization of acrylic acid and 1-vinylimidazole in dimethyl sulfoxide followed by solvent exchange with water. The PAAcVI hydrogel shows equally robust adhesion (>400 J m^-2) to both wet and dry tissues. Moreover, the PAAcVI hydrogel also exhibits strong long-term stable adhesion underwater and in various wet environments. Meanwhile, the adhesion of PAAcVI hydrogel can be adjusted through Zn²⁺-ion-mediated on-demand debonding, which makes it easy to peel off from the tissue reducing pain during dressing removal and avoiding secondary injury. The PAAcVI hydrogel displays efficient hemostasis in the mice-tail docking model and mice-liver bleeding model. This hydrogen-bond-based hydrogel shows tough wet adhesion, and its adhesion is controllable, demonstrating its promising application in moisture-resistant adhesives, medical adhesives, and hemostatic materials.