Antimicrobial delivery systems have undergone extensive development, yet conventional carriers still exhibit limitations such as low loading capacity, inadequate controlled release mechanisms, and cytotoxicity. Recent studies have increasingly demonstrated the potential of Hydrogel Microspheres (HMSs) for antimicrobial delivery. These microspheres exhibit small dimensions, high drug-loading capacity, and the ability to achieve deep-targeted delivery, complemented by adjustable physicochemical properties and biocompatibility that create favorable conditions for antimicrobial transportation. This review systematically examines HMS preparation strategies, characteristic properties, transported antimicrobials, and therapeutic applications. Particular emphasis is placed on critical preparation parameters governing HMS performance, especially those influencing drug delivery dynamics. We conclude by addressing current challenges and proposing actionable strategies for material optimization and clinical translation. This work aims to advance HMS-based antimicrobial delivery systems for more effective infection control.

A material that was able to simultaneously sense a bacterial presence and to release antimicrobial peptides (AMP) on demand in a tunable amount was developed. Simultaneous sensing and release were achieved by the combination of a bacteria-sensing hydrogel with antimicrobial-peptide-carrying mesoporous silica particles or coatings. The mesoporous silica with a mesopore diameter of 22 nm was functionalized with a covalently grafted green light-sensitive linker, to which antimicrobial peptides were covalently attached. The gelatin-based hydrogel, which contains C14R-functionalized mesoporous silica particles, is designed to respond to bacterial presence as it may occur, e.g., in a wound's microbiological environment. In the presence of bacteria and 0.1% trypsin, a protease enzyme simulating bacterial presence, the hydrogel, deposited in a donut shape, undergoes a shape loss as the bacteria cleave cross-linking bonds within the hydrogel. When observing hydrogel shape loss after 2 h as a readout of a bacterial infection, subsequent irradiation triggers the release of antimicrobial peptides on demand with adjustable concentration-time profiles. The sensing and on-demand release are integrated into commercially available wound dressing fabrics, demonstrating an application proof-of-concept. Characterization using ATR-IR spectroscopy, TGA, and BCA validates the successful fabrication and release. The H1.6P composite released antimicrobial agents, reaching concentrations of up to 298 μg/mL at pH 7.4 from a 300 μL sample. The efficacy of the released C14R against E. coli BL21(DE3) is illustrated. Overall, the multifunctionality of this approach presents a promising step toward on-demand wound care and thus for reducing side effects and antibiotic resistance.

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds.

This study evaluates the wound-healing process in horses following the application of two treatment modalities: bacterial cellulose hydrogel with alginate (BCAW) and frog skin (FSW) dressings on experimentally induced skin wounds. Throughout the experiment, no clinical abnormalities were noted in the horses, although initial wound assessments indicated edema and sensitivity. Local hemorrhage was observed in some cases on Day 0, with granulation tissue formation evident by Day 14. Epithelialization began around Day 14 but did not reach complete healing in any group by Day 28. The analysis showed no significant differences in skin wound area or wound contraction rates among the treatment groups compared to control wounds (CWs) over the evaluation periods. Histopathological evaluations also indicated no significant differences in inflammatory responses or healing markers, such as fibroblast proliferation and neovascularization in skin wounds across groups. Despite expectations based on prior research in other species, the treatments with BCAW and FSW did not demonstrate substantial pro-healing effects in horses with induced skin wounds. These findings underscore the complexity of equine wound healing and suggest further investigation is needed to optimize treatment strategies in this species and enhance the translational potential for human clinical applications.

Chronic wounds present a significant healthcare challenge marked by complexities such as persistent bleeding, inhibited cell proliferation, dysregulated inflammation, vulnerability to infection, and compromised tissue remodeling. Conventional wound dressings often prove inadequate in addressing the intricate requirements of chronic wound healing, leading to slow healing and heightened susceptibility to infections in patients with prolonged medical conditions. Bacterial biofilms in chronic wounds pose an additional challenge due to drug resistance. Advanced wound dressings have emerged as promising tools in expediting the healing process. Among these, pH-responsive polysaccharide-based hydrogels exhibit immense prospect by adapting their functions to dynamic wound conditions. Despite their potential, the current literature lacks a thorough review of these wound dressings. This review bridges this gap by meticulously examining factors related to chronic wounds, current strategies for healing, and the mechanisms and potential applications of pH-responsive hydrogel wound dressings as an emerging therapeutic solution. Special focus is given to their remarkable antibacterial properties and significant self-healing abilities. It further explores the pH-monitoring functions of these dressings, elucidating the associated pH indicators. This synthesis of knowledge aims to guide future research and development in the field of pH-responsive wound dressings, providing valuable insights into their potential applications in wound care.

In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO2, and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.

The prevalence of diabetes has been increasing globally, necessitating innovative approaches beyond conventional blood sugar monitoring and insulin control. Diabetes is associated with complex health complications, including cardiovascular diseases. Continuous Glucose Monitoring (CGM) devices, though automated, have limitations such as irreversibility and interference with bodily fluids. Hydrogel technologies provide non-invasive alternatives to traditional methods, addressing the limitations of current approaches. This review explores hydrogels as macromolecular biopolymeric materials capable of absorbing and retaining a substantial amount of water within their structure. Due to their high-water absorption properties, these macromolecules are utilized as coating materials for wound care and diabetes management. The study emphasizes the need for early diagnosis and monitoring, especially during the COVID-19 pandemic, where heightened attention to diabetic patients is crucial. Additionally, the article examines the role of the Internet of Things (IoT) and machine learning-based systems in enhancing diabetes management effectiveness. By leveraging these technologies, there is potential to revolutionize diabetes care, providing more personalized and proactive solutions. This review explores cutting-edge hydrogel-based systems as a promising avenue for diabetes diagnosis, management, and treatment, highlighting key biopolymers and technological integrations.

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.

Since various bioactive substances are unstable and can degrade in the gastrointestinal tract, their stabilization is crucial. This study aimed to encapsulate mango peel extract (MPE) into edible alginate beads using the ionotropic gelation method for the potential oral delivery of bioactive substances. Mango peels, generally discarded and environmentally harmful, are rich in health-promoting bioactive substances. The alginate beads were examined for entrapment efficiency, particle size, morphology, thermal stability, physiochemical interactions, release profile under gastrointestinal conditions, and antibacterial efficacy. The study demonstrated the successful encapsulation of MPE with an efficiency of 63.1%. The in vitro release study showed the stability of the alginate beads in simulated gastric fluid with a maximum release of 45.0%, and sustained, almost complete release (99.4%) in simulated intestinal fluid, indicating successful absorption into the human body. In both fluids, the MPE release followed first-order kinetics. Encapsulation successfully maintained the antibacterial properties of MPE, with significant inhibitory activity against pathogenic intestinal bacteria. This is the first study on MPE encapsulation in alginate beads, presenting a promising oral delivery system for high-added-value applications in the food industry for dietary supplements, functional foods, or food additives. Their production is sustainable and economical, utilizing waste material and reducing environmental pollution.

Bacterial cellulose (BC) has shown high capacity for the treatment of wounds and burns, providing a moisty environment. Calcium alginate can be associated with BC to create gels that aid in wound debridement and contribute to appropriate wound healing. This study is aimed at characterizing and evaluating the use of bacterial cellulose/alginate gel in skin burns in rats.

Cellulose and cellulose/alginate gels were compared regarding the capacity of liquid absorption, moisture, viscosity, and potential cytotoxicity. The 2nd degree burns were produced using an aluminum metal plate (2.0cm) at 120ºC for 20s on the back of rats. The animals were divided into non-treated, CMC(Carboxymethylcellulose), Cellulose(CMC with bacterial cellulose), and Cellulose/alginate(CMC with bacterial cellulose and alginate). The animals received topical treatment 3 times/week. Biochemical (MPO, NAG and oxidative stress), histomorphometry and immunohistochemical assays (IL-1β IL-10 and VEGF) were conducted on the 14th, 21st, 28th, and 35th days.

Cellulose/Alginate gel showed higher absorption capacity and viscosity compared to Cellulose gel, with no cytotoxic effects. Cellulose/alginate presented lower MPO values, a higher percentage of IL-10, with greater and balanced oxidative stress profile.

The use of cellulose/alginate gel reduced neutrophils and macrophage activation and showed greater anti-inflammatory response, which can contribute to healing chronic wounds and burns.

In tissue engineering, 3D printing represents a versatile technology employing inks to construct three-dimensional living structures, mimicking natural biological systems. This technology efficiently translates digital blueprints into highly reproducible 3D objects. Recent advances have expanded 3D printing applications, allowing for the fabrication of diverse anatomical components, including engineered functional tissues and organs. The development of printable inks, which incorporate macromolecules, enzymes, cells, and growth factors, is advancing with the aim of restoring damaged tissues and organs. Polysaccharides, recognized for their intrinsic resemblance to components of the extracellular matrix have garnered significant attention in the field of tissue engineering. This review explores diverse 3D printing techniques, outlining distinctive features that should characterize scaffolds used as ideal matrices in tissue engineering. A detailed investigation into the properties and roles of polysaccharides in tissue engineering is highlighted. The review also culminates in a profound exploration of 3D polysaccharide-based hydrogel applications, focusing on recent breakthroughs in regenerating different tissues such as skin, bone, cartilage, heart, nerve, vasculature, and skeletal muscle. It further addresses challenges and prospective directions in 3D printing hydrogels based on polysaccharides, paving the way for innovative research to fabricate functional tissues, enhancing patient care, and improving quality of life.

Frost damage remains a significant challenge for agricultural practices worldwide, leading to substantial economic losses and food insecurity. Practically, traditional methods for frost management have proven ineffective and come with several drawbacks, such as energy consumption and limited efficacy. Hence, proposing an anti-freezing coating can be an innovative idea. The potential of sodium alginate (SA) to construct anti-freezing hydrogels has been explored in several sciences. SA hydrogels can form protective films around plants as a barrier against freezing temperatures and ice crystals on the plant's surface. Sodium alginate exhibits excellent water retention, enhancing plant hydration during freezing conditions. This coating can provide insulation, effectively shielding the plant from frost damage. The advantages of SA as a coating material, such as its biocompatibility, biodegradability, and non-toxic nature, are highlighted. Therefore, the proposed use of SA as an innovative coating material holds promise for safeguarding plants from frost damage. Following SA potential and frost's huge damage, the present review provides a comprehensive overview of the recent developments in SA-based anti-freezing hydrogels, their applications, and their potential in agriculture as anti-freezing coatings. However, further research and field trials are necessary to optimize the application methods and understand the long-term effects on productivity.

Particles with a porous structure can lead to quick hemostasis and provide a good matrix for cell proliferation during wound healing. Recently, many particle-based wound healing materials have been clinically applied. However, these products show good hemostatic ability but with poor wound healing ability. To solve this problem, this study fabricated APGG composite particles using yeast β-glucan (obtained from Saccharomyces cerevisiae), sodium alginate, and γ-polyglutamic acid as the starting materials. The structure of yeast β-glucan was modified with many carboxymethyl groups to obtain carboxymethylated β-glucan, which could coordinate with Ca2+ ions to form a crosslinked structure. A morphology study indicated that the APGG particles showed an irregular spheroidal structure with a low density (<0.1 g cm-3) and high porosity (>40%). An in vitro study revealed that the particles exhibited a low BCI value, low hemolysis ratio, and good cytocompatibility against L929 cells. The APGG particles could quickly stop bleeding in a mouse liver injury model and exhibited better hemostatic ability than the commercially available product Celox. Furthermore, the APGG particles could accelerate the healing of non-infected wounds, and the expression levels of CD31, α-SMA, and VEGF related to angiogenesis were significantly enhanced.

The precise delivery of growth factors (GFs) in regenerative medicine is crucial for effective tissue regeneration and wound repair. However, challenges in achieving controlled release, such as limited half-life, potential overdosing risks, and delivery control complexities, currently hinder their clinical implementation. Despite the plethora of studies endeavoring to accomplish effective loading and gradual release of GFs through diverse delivery methods, the nuanced control of spatial and temporal delivery still needs to be elucidated. In response to this pressing clinical imperative, our review predominantly focuses on explaining the prevalent strategies employed for spatiotemporal delivery of GFs over the past five years. This review will systematically summarize critical aspects of spatiotemporal GFs delivery, including judicious bio-scaffold selection, innovative loading techniques, optimization of GFs activity retention, and stimulating responsive release mechanisms. It aims to identify the persisting challenges in spatiotemporal GFs delivery strategies and offer an insightful outlook on their future development. The ultimate objective is to provide an invaluable reference for advancing regenerative medicine and tissue engineering applications.

Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high levels of morbidity and is considered a difficult-to-treat infection, often requiring nonstandard treatment regimens and antibiotics. Since over 40% of the emerging antibiotic compounds have insufficient solubility that limits their bioavailability and thus efficacy through oral or intravenous administration, it is crucial that alternative drug delivery products be developed for wound care applications. Existing effective treatments for soft tissue MRSA infections, such as fusidic acid (FA), which is typically administered orally, could also benefit from alternative routes of administration to improve local efficacy and bioavailability while reducing the required therapeutic dose. Herein, we report an antimicrobial poly(oligoethylene glycol methacrylate) (POEGMA)-based composite hydrogel loaded with fusidic acid-encapsulating self-assembled polylactic acid-b-poly(oligo(ethylene glycol) methyl ether methacrylate) (PLA-POEGMA) nanoparticles for the treatment of MRSA-infected skin wounds. The inclusion of the self-assembled nanoparticles (380 nm diameter when loaded with fusidic acid) does not alter the favorable mechanical properties and stability of the hydrogel in the context of its use as a wound dressing, while fusidic acid (FA) can be released from the hydrogel over ∼10 h via a diffusion-controlled mechanism. The antimicrobial studies demonstrate a clear zone of inhibition in vitro and a 1-2 order of magnitude inhibition of bacterial growth in vivo in an MRSA-infected full-thickness excisional murine wound model even at very low antibiotic doses. Our approach thus can both circumvent challenges in the local delivery of hydrophobic antimicrobial compounds and directly deliver antimicrobials into the wound to effectively combat methicillin-resistant infections using a fraction of the drug dose required using other clinically relevant strategies.

Bleeding from uncontrollable wounds can be fatal, and the body's clotting mechanisms are unable to control bleeding in a timely and effective manner in emergencies such as battlefields and traffic accidents. For irregular and inaccessible wounds, hemostatic materials are needed to intervene to stop bleeding. Hemostatic microspheres are promising for hemostasis, as their unique structural features can promote coagulation. There is a wide choice of materials for the preparation of microspheres, and the modification of natural macromolecular materials such as chitosan to enhance the hemostatic properties and make up for the deficiencies of synthetic macromolecular materials makes the hemostatic microspheres multifunctional and expands the application fields of hemostatic microspheres. Here, we focus on the hemostatic mechanism of different materials and the preparation methods of microspheres, and introduce the modification methods, related properties and applications (in cancer therapy) for the structural characteristics of hemostatic microspheres. Finally, we discuss the future trends of hemostatic microspheres and research opportunities for developing the next generation of hemostatic microsphere materials.

Biodegradable polymers, encompassing both natural and synthetic polymers, have demonstrated efficacy as carriers for synthetic drugs, natural bioactive molecules, and inorganic metals. This is due to their ability to control the release of these substances. As a result, various advanced materials, such as nanoparticle- loaded hydrogels, nanofibrous scaffolds, and nanocomposites, have been developed. These materials have shown promise in enhancing processes, such as cell proliferation, vascular angiogenesis, hair growth, and wound healing management. Natural polymers, including hyaluronic acid, collagen, chitosan, gelatin, and alginate, as well as synthetic polymers like polylactic acid, polyglycolic acid, polylactic co-glycolic acid, and PCA, have significant potential for promoting wound healing. This study examines the advancements in biodegradable polymers for wound healing, specifically focusing on each polymer and its distinctive formulations. It also discusses the in vitro experiments conducted using different cell lines, as well as the in vivo studies that explore the numerous uses of these polymers in wound healing. The discussion also included the exploration of modifications or combinations of several polymers, as well as surface changes, in order to produce synergistic effects and address the limitations of individual polymers. The goal was to expedite the healing process of different chronic wounds. Due to this, there have been notable advancements in the technological use of polymeric mixes, including biodegradable polymer-based scaffolds, which have accelerated the process of wound healing.

The increasing demand for probiotic-fortified fruit juices stems from the dietary requirements of individuals with dairy allergies, lactose intolerance, and vegetarian diets. However, a notable obstacle arises from the degradation of probiotics in fruit juices due to their low pH levels and harsh gastrointestinal conditions. In response, this study proposes an innovative approach utilizing a microfluidic chip to create core-shell microcapsules that contain Lactobacillus plantarum Lp90. This method, based on internal-external gelation, forms highly uniform microcapsules that fully enclose the core, which consists of oil-in-water Pickering emulsions stabilized by salmon byproduct protein and sodium alginate. These emulsions remain stable for up to 72 h at a 1% sodium alginate concentration. The shell layer incorporates kelp nanocellulose and sodium alginate, thus improving the thermal properties. Furthermore, compared to free probiotics, the multilayer structure of the core-shell microcapsules provides a robust barrier, resulting in significantly enhanced probiotic stability. These findings introduce a novel strategy for augmenting probiotic delivery in functional fruit juice beverages, promising solutions to the challenges encountered during their development.

In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 μm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%-80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively.

Puerarin is the main isoflavone extracted from Radix Puerariae lobata (Willd.) and exerts a strong protective effect on endothelial cells. This isoflavone also exerts proven angiogenic effects; however, the potential underlying mechanism has not been fully explored. Here in this work, we aimed to determine the proangiogenesis effect of a puerarin-attached lignin nanoparticle-incorporated hydrogel and explore the underlying mechanism.

Puerarin-attached lignin nanoparticles were fabricated and mixed with the GelMA hydrogel. After the hydrogel was characterized, the angiogenic effect was evaluated in a mouse hind-limb ischemia model. To further explore the mechanism of angiogenesis, human endothelial cell line EA.hy926 was exposure to different concentrations of puerarin. Wound healing assays and tube formation assays were used to investigate the effects of puerarin on cell migration and angiogenesis. qPCR and Western blotting were performed to determine the changes in the levels of angiogenesis indicators, autophagy indicators and PPARβ/δ. 3-MA was used to assess the role of autophagy in the puerarin-mediated angiogenesis effect in vivo and in vitro.

The hydrogel significantly improved blood flow restoration in mice with hind-limb ischemia. This effect was mainly due to puerarin-mediated increases in the angiogenic capacity of endothelial cells and the promotion of autophagy activation. A potential underlying mechanism might be that puerarin-mediated activation of autophagy could induce an increase in PPARβ/δ expression.

The puerarin-attached lignin nanoparticle-incorporated hydrogel effectively alleviated blood perfusion in mice with hind-limb ischemia. Puerarin has a prominent proangiogenic effect. The potential mechanisms might be that puerarin-mediated autophagy activation and increase in PPARβ/δ.

Diabetic foot ulcer (DFU), a common complication of diabetes, has become a great burden to both patients and the society. The delayed wound closure of ulcer sites resulting from vascular damage and neutrophil dysfunction facilitates bacterial infection. Once drug resistance occurs or bacterial biofilm is formed, conventional therapy tends to fail and amputation is unavoidable. Therefore, effective antibacterial treatment beyond antibiotics is of utmost importance to accelerate the wound healing process and prevent amputation. Considering the complexity of multidrug resistance, biofilm formation, and special microenvironments (such as hyperglycemia, hypoxia, and abnormal pH value) at the infected site of DFU, several antibacterial agents and different mechanisms have been explored to achieve the desired outcome. The present review focuses on the recent progress of antibacterial treatments, including metal-based medications, natural and synthesized antimicrobial peptides, antibacterial polymers, and sensitizer-based therapy. This review provides a valuable reference for the innovation of antibacterial material design for DFU therapy.

Polysaccharides have emerged as a promising material for hydrogel preparation due to their biocompatibility, biodegradability, and low cost. This review focuses on polysaccharide-based hydrogels' synthesis, characterization, and applications. The various synthetic methods used to prepare polysaccharide-based hydrogels are discussed. The characterization techniques are also highlighted to evaluate the physical and chemical properties of polysaccharide-based hydrogels. Finally, the applications of SAPs in various fields are discussed, along with their potential benefits and limitations. Due to environmental concerns, this review shows a growing interest in developing bio-sourced hydrogels made from natural materials such as polysaccharides. SAPs have many beneficial properties, including good mechanical and morphological properties, thermal stability, biocompatibility, biodegradability, non-toxicity, abundance, economic viability, and good swelling ability. However, some challenges remain to be overcome, such as limiting the formulation complexity of some SAPs and establishing a general protocol for calculating their water absorption and retention capacity. Furthermore, the development of SAPs requires a multidisciplinary approach and research should focus on improving their synthesis, modification, and characterization as well as exploring their potential applications. Biocompatibility, biodegradation, and the regulatory approval pathway of SAPs should be carefully evaluated to ensure their safety and efficacy.

The extracellular microenvironment regulates cell decisions through the accurate presentation at the cell surface of a complex array of biochemical and biophysical signals that are mediated by the structure and composition of the extracellular matrix (ECM). On the one hand, the cells actively remodel the ECM, which on the other hand affects cell functions. This cell-ECM dynamic reciprocity is central in regulating and controlling morphogenetic and histogenetic processes. Misregulation within the extracellular space can cause aberrant bidirectional interactions between cells and ECM, resulting in dysfunctional tissues and pathological states. Therefore, tissue engineering approaches, aiming at reproducing organs and tissues in vitro, should realistically recapitulate the native cell-microenvironment crosstalk that is central for the correct functionality of tissue-engineered constructs. In this review, we will describe the most updated bioengineering approaches to recapitulate the native cell microenvironment and reproduce functional tissues and organs in vitro. We have highlighted the limitations of the use of exogenous scaffolds in recapitulating the regulatory/instructive and signal repository role of the native cell microenvironment. By contrast, strategies to reproduce human tissues and organs by inducing cells to synthetize their own ECM acting as a provisional scaffold to control and guide further tissue development and maturation hold the potential to allow the engineering of fully functional histologically competent three-dimensional (3D) tissues.

Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D-printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D-printing inks comprising DNA from salmon sperm and DNA-induced biosilica inspired by marine sponges, are developed for the machine learning-based 3D-printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D-printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti-inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D-printed hydrogels produce using a DNA-induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair.

Reactive oxygen species (ROS) produced by noble metallic nanoparticles under visible light is an effective way to combat drug-resistant bacteria colonized on the wound. However, the photocatalytic efficiency of noble metallic nanoparticles is limited by its self-aggregation in water media. Moreover, the fast release of noble metallic ions from nanoparticles might engender cellular toxicity and hazardous environmental issues. Herein, we chose AgNPs, the most common plasmonic noble metallic nanoparticles, as an example, modifying the surface of AgNPs with oleic acid and n-butylamine and imbedded them into calcium alginate (CA) hydrogel that holds tissue adhesion, rapid hemostatic, sunlight-sensitive antibacterial and anti-inflammatory abilities, and thus effectively promotes the healing of wounds. Unlike conventional AgNP-based materials, the constrain of colloids and hydrogel networks hinders the leach of Ag⁺. Nonetheless, the CA/Ag hydrogels exhibit on-demand photodynamic antibacterial efficacy due to the generation of ROS under visible light. In addition, the CA/Ag hydrogel can effectively stop the hemorrhage in a mouse liver bleeding model due to their skin-adaptive flexibility and tissue adhesiveness. The potent sunlight-responsive antibacterial activity of the CA/Ag hydrogel can effectively kill multidrug-resistant bacteria both in vitro (>99.999%) and in vivo (>99.9%), while the diminished Ag⁺ release guarantees its biocompatibility. The CA/Ag hydrogel significantly promotes the wound healing process by the downregulation of proinflammatory cytokines (TNF-α and IL-6) in a rodent full-thickness cutaneous wound model. Overall, the proposed multifunctional CA/Ag nanocomposite hydrogel has excellent prospects as an advanced wound dressing.

Drug microcarriers are widely used in disease treatment, and microfluidics is well established in the preparation of microcarrier particles. A proper design of the microfluidic platform toward scalable production of drug microcarriers can extend its application values in wound healing, where large numbers of microcarriers are required. Here, a microfluidic step emulsification method for the preparation of monodisperse droplets is presented. The droplet size depends primarily on the microchannel depth rather than flow rate, making the system robust for high-throughput production of droplets and hydrogel microparticles. Based on this platform, basic fibroblast growth factor (bFGF) is uniformly encapsulated in the microparticles, and black phosphorus (BP) is incorporated for controllable release via near-infrared (NIR) stimulation. The microparticles serve as drug carriers to be applied to the wound site, inducing angiogenesis and collagen deposition, thereby accelerating wound repair. These results indicate that the step emulsification technique provides a promising solution to scalable production of drug microcarriers for wound healing as well as tissue regeneration.

Wound healing is a complex and dynamic process, in which the pH value plays an important role in reflecting the wound status. Wound dressings are materials that are able to accelerate the healing process. Among the multifunctional advanced wound dressings developed in recent years, pH-responsive wound dressings, especially hydrogels, show great potential owing to their unique properties of adjusting their functions according to the wound conditions, thereby allowing the wound to heal in a regulated manner. However, a comprehensive review of pH-responsive wound dressings is lacking. This review summarizes the design strategies and advanced functions of pH-responsive hydrogel wound dressings, including their excellent antibacterial properties and significant pro-healing abilities. Other advanced pH-responsive materials, such as nanofibers, composite films, nanoparticle clusters, and microneedles, are also classified and discussed. Next, the pH-monitoring functions of pH-responsive wound dressings and the related pH indicators are summarized in detail. Finally, the achievements, challenges, and future development trends of pH-responsive wound dressings are discussed.

Convenient and low-cost dressings can reduce the difficulty of wound treatment. Alginate gel dressings have the advantages of low cost and safe usage, and they have obvious potential for development in biomedical materials. Alginate gel dressings are currently a research area of great interest owing to their versatility, intelligent, and their application attempts in treating complex wounds. We present a detailed summary of the preparation of alginate hydrogels and a study of their performance improvement. Herein, we summarize the various applications of alginate hydrogels. The research focuses in this area mainly include designing multifunctional dressings for the treatment of various wounds and fabricating specialized dressings to assist physicians in the treatment of complex wounds (TOC). This review gives an outlook for future directions in the field of alginate hydrogel dressings. We hope to attract more research interest and studies in alginate hydrogel dressings, thus contributing to the creation of low-cost and highly effective wound treatment materials.

Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family's expression patterns in skin and wounds influenced by both diabetes and sex are still unknown.

In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family's expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgf expressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) - a FGFR activation marker gene - in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury).

Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.

Crustaceans and fish scales in the marine food industry are basically thrown away as waste. This not only wastes resources but also causes environmental pollution. While reducing pollution and waste, biological activity and storage of materials are urgent issues to be solved. In this study, by first preparing dry fibers and then making hydrogels, we prepared a fish scale/sodium alginate/chitosan nanofiber hydrogel (FS-P) by cross-linking the nanofibers in situ. From fish and other organisms, fish gelatin (FG), collagen and CaCO₃ were extracted. Fish scale (FS)/sodium alginate/chitosan nanofibers were cross-linked with copper sulfide nanoparticles prepared by a one-step green method to obtain FS-P nanofiber hydrogels under mild conditions without catalyst and additional procedures. These fiber hydrogels not only have good tissue adhesion and tensile properties, but also have the antibacterial effect of natural antibacterial and CuS photothermal synergism, which can achieve 51.32% and 49.96% of the antibacterial effect against Staphylococcus aureus and Escherichia coli respectively, avoiding the generation of superbacteria. The nanofiber hydrogels have 87.56% voidage and 52.68% degradability after 14 days. The combined strategy of using marine bio-based fibers to prepare gels promoted angiogenesis and tissue repair.

Healthy skin protects from pathogens, water loss, ultraviolet rays, and also maintains homeostasis conditions along with sensory perceptions in normal circumstances. Skin wound healing mechanism is a multi-phased biodynamic process that ultimately triggers intercellular and intracellular mechanisms. Failure to implement the normal and effective healing process may result in chronic injuries and aberrant scarring. Chronic wounds lead to substantial rising healthcare expenditure, and innovative methods to diagnose and control severe consequences are urgently needed. Skin tissue engineering (STE) has achieved several therapeutic accomplishments during the last few decades, demonstrating tremendous development. The engineered skin substitutes provide instant coverage for extensive wounds and facilitate the prevention of microbial infections and fluid loss; furthermore, they help in fighting inflammation and allow rapid neo-tissue formation. The current review primarily focused on the wound recovery and restoration process and the current conditions of STE with various advancements and complexities associated with different strategies such as cell sources, biopolymers, innovative fabrication techniques, and growth factors delivery systems.

Nitric oxide is critical for eliminating infection and promoting regeneration in diabetic wounds. However, clinical uses of nitric oxide are limited by its high activity and lack of specificity in targeting infections. Herein, we develop an intelligent nitric oxide nanogenerator comprising isosorbide dinitrate (ISDN)-coated copper sulfide (CuS)/calcium carbonate (CaCO₃) core/shell nanoparticles (CuS@CaCO₃-ISDN) to target the acidic microenvironment of the infected diabetic wounds. Meaningfully, triggered by acid decomposition of CaCO₃, this nanogenerator can achieve a responsive and accelerated release of nitric oxide from ISDN through enzyme-mimicking redox processes that involve CuS nanoparticles and then inactivate biofilm bacteria through the pathways of oxidative stress and disruption of adenosine triphosphate (ATP)-related energy metabolism. Moreover, after eliminating the infection, the pH-responsive release of nitric oxide can promote the proliferation of blood vessels and tissue regeneration and accelerate diabetic wound closure. This study expands the use of nitric oxide donors in wound treatment by developing the enzyme-mimicking release strategy, and the pH-responsive core/shell nanogenerator is promising for a variety of anti-infection therapeutic applications.

Currently, the clinic's treatment of acute/chronic wounds is still unsatisfactory due to the lack of functional and appropriate wound dressings. Intelligent and multifunctional dressings are considered the most advanced wound treatment modalities. It is essential to design and develop wound dressings with required functions according to the wound microenvironment in the clinical treatment. This work summarizes microenvironment characteristics of various common wounds, such as acute wound, diabetic wound, burns wound, scalded wound, mucosal wound, and ulcers wound. Furthermore, the factors of transformation from acute wounds to chronic wounds were analyzed. Then we focused on summarizing how researchers fully and thoroughly combined the complex microenvironment with modern advanced technology to ensure the usability and value of the dressing, such as photothermal-sensitive dressings, microenvironment dressing (pH-sensitive dressings, ROS-sensitive dressings, and osmotic pressure dressings), hemostatic dressing, guiding tissue regeneration dressing, microneedle dressings, and 3D/4D printing dressings. Finally, the revolutionary development of wound dressings and how to transform the existing advanced functional dressings into clinical needs as soon as possible have carried out a reasonable and meaningful outlook.

An effective dressing is essential for wound healing. In fact, the wettability performance is one of the most important factors of a wound dressing. The fundamental functions of a wound dressing involve the absorption of excess exudates and maintenance of optimal moisture at the wound by controlling water evaporation. Here, we designed a type of chitosan (CS) sponge and PCL nanofibrous membrane composite dressing with asymmetric wettability surfaces as wound healing materials for biomedical applications. The hydrophobic surfaces of the composite dressing were waterproof and could efficiently control the water vapor transmission rate, whereas the hydrophilic surface of the CS sponge had good cytocompatibility and water-absorbing capability. Insulin-like growth factor-2 (IGF-2) was added to the CS sponge, and exhibited a stimulatory effect on fibroblasts migration and proliferation. Therefore, the fabricated CS sponge and PCL membrane composite dressing had excellent cytocompatibility, vapor transmission rate, and liquid absorption and asymmetric wettability, suggesting its potential as a promising alternative to traditional wound dressing.

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health. And bacterial contamination could significantly menace the wound healing process. Considering the sophisticated wound healing process, novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients, antibacterial agents included, into biomaterials with different morphologies to improve cell behaviors and promote wound healing. However, a comprehensive review on anti-bacterial wound dressing to enhance wound healing has not been reported. In this review, various antibacterial biomaterials as wound dressings will be discussed. Different kinds of antibacterial agents, including antibiotics, nanoparticles (metal and metallic oxides, light-induced antibacterial agents), cationic organic agents, and others, and their recent advances are summarized. Biomaterial selection and fabrication of biomaterials with different structures and forms, including films, hydrogel, electrospun nanofibers, sponge, foam and three-dimension (3D) printed scaffold for skin regeneration, are elaborated discussed. Current challenges and the future perspectives are presented in this multidisciplinary field. We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.