Bifunctional cellulose nanocrystal-MoS2 nanosheets for NIR-activated fluid management and antibacterial protection in wound microenvironments.

Designing pullulan phosphates with tunable structure-property relationships via a multicomponent reaction system for potential biomedical applications.

BackgroundImpaired wound healing in diabetic patients remains a major clinical challenge due to oxidative stress, chronic inflammation, and compromised tissue regeneration.ObjectiveThis study aimed to develop and evaluate a novel nanocomposite hydrogel system incorporating lipoic acid and melatonin to enhance diabetic wound healing.MethodsChitosan nanoparticles co-loaded with lipoic acid and melatonin (LAMELCNPs) were embedded within a calcium alginate hydrogel to form a bioactive wound dressing (LAMELCNPHYD). The system was characterized in terms of its microstructure, swelling behavior, drug release profile, cytocompatibility, antioxidant capacity, anti-inflammatory activity, and hemocompatibility. In vivo wound healing efficacy was assessed using a streptozotocin-induced diabetic rat model.ResultsScanning electron microscopy (SEM) confirmed the porous hydrogel structure. LAMELCNPHYD showed sustained drug release, excellent cytocompatibility, and enhanced antioxidant and anti-inflammatory activity. In vivo, LAMELCNPHYD significantly improved wound closure, collagen deposition, epithelial regeneration, and modulation of inflammatory markers (reduced interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9); increased transforming growth factor-beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF)).ConclusionThe LAMELCNPHYD hydrogel demonstrated potent wound healing efficacy through combined antioxidative, anti-inflammatory, and regenerative mechanisms, offering a promising therapeutic strategy for diabetic wound management.

A multidrug-loaded biosponge based on chitosan and polyvinyl alcohol as efficient wound dressings for diabetic wounds treatment

Scar formation after skin injury remains a major clinical challenge because most conventional wound dressings promote closure rather than tissue regeneration, often resulting in fibrosis. Although several biomaterials, such as collagen, chitosan, alginate, gelatin, and zein, have been explored to improve healing outcomes, the attainment of truly scar-free regeneration remains a significant challenge. In this study, we developed a bioactive nanocomposite wound dressing by incorporating hyaluronic acid nanoparticles (HANs) into a natural mucilage matrix extracted from chia seeds. The HANs were synthesized via flash nanoprecipitation, resulting in a uniform particle size of 173 ± 1 nm. When embedded into the chia mucilage film via solvent casting, the resulting dressing exhibited tunable hydrophilicity and adequate mechanical integrity (tensile strength of 2.2 MPa). In vitro assessments demonstrated excellent cytocompatibility and the promotion of wound healing activities. Furthermore, chick chorioallantoic membrane (CAM) assays revealed significantly enhanced angiogenesis in the bioactive films compared to controls, indicating superior regenerative potential. Crucially, in vivo studies using a full-thickness rat wound model evidenced accelerated re-epithelialization and tissue regeneration within 17 days. Collectively, this naturally derived, nanoengineered platform offers a cost-effective and biologically active strategy for promoting skin regeneration.

Medium/low internal phase Pickering emulsion gels stabilized by biopolymer: Stability mechanism, material design, and application.

Silk fibroin nanofibers-GelMA hydrogel composite loaded with embryonic fibroblasts: A strategy for enhanced wound healing.

Pathological scarring following skin trauma remains a formidable clinical challenge. Hydrogel dressings can promote wound closure by providing wet healing environment, yet the role of the dressing's mechanical microenvironment on the scar formation is overlooked. Herein, a series of mechanically-tunable hydrogels were produced from the same concentrations of polyvinyl alcohol (PVA) and poly(polyethylene glycol methacrylate-co-glycidyl methacrylate) (PPG) without or with the addition of hyperbranched poly-l-lysine (HBPL) via a cyclic freeze-thaw method. All the hydrogels could maintain their mechanical strength under physiological conditions. Culture with fibroblasts on the hydrogels in vitro showed that the high-stiffness environment triggered the Piezo1 ion channel (the mechanosensitive ion channel), inducing a calcium influx, conveying severe scarring potential. The low-modulus hydrogels (∼20-29 kPa) significantly reduced scar elevation index, α-smooth muscle actin expression and collagen I/III ratios in a rabbit ear ventral full-thickness wound model in vivo. While the mechanical modulus of the hydrogel played a dominant role in scar suppression, the incorporation of HBPL provided a modest yet synergistic anti‑scarring benefit by effectively adsorbing key inflammatory factors. The material system demonstrated its great potential as a ready-to-use wound dressing for clinical translation. By identifying a mechanical adaptive window for wound dressings, this study provides a framework for the rational design of mechanotherapeutic biomaterials to achieve better scar-less tissue regeneration. STATEMENT OF SIGNIFICANCE: Pathological scarring following skin trauma remains a formidable clinical challenge. Hydrogel dressings can promote wound closure by providing a wet healing environment, yet the role of the dressing's mechanical microenvironment on the scar formation is overlooked. Herein, mechanically-tunable polyvinyl alcohol-based hydrogels with the same chemical compositions were prepared via a cyclic freeze-thaw method. The substrate stiffness modulated the Piezo1 mechanosensitive axis, triggering a stiffness-dependent calcium influx. The low-modulus dressings effectively suppressed pathological hyperplasia with the smallest scar elevation index, downregulated α-smooth muscle actin expression, and a transition toward a regenerative type III/I collagen ratio. By silencing the Piezo1-mediated mechanotransduction pathway through a low-modulus interface, this study provides a robust material design framework that optimizes the regenerative microenvironment, offering a promising dual-strategy approach for clinical wound management and the prevention of pathological fibrosis.

Wound infections pose a substantial clinical challenge and an escalating healthcare burden, further complicated by the rapid increase in multidrug-resistant bacteria. Antimicrobial peptides (AMPs) offer an alternative to conventional antibiotics, but their rapid degradation, hemolytic activity, and potential cytotoxicity complicate systemic delivery and can have negative impact on wound healing. Here we show a bacterial nanocellulose hyaluronan (BC-HA) hybrid hydrogel wound dressing functionalized with mesoporous silica nanoparticles (MSNs) for localized, enzyme responsive delivery of a sequence optimized antimicrobial peptide (SOAP) for treatment of infected wounds. The dressings provide moisture retention and excellent skin conformability while enabling infection-triggered AMP release by bacterial and host proteases. In vitro, SOAP-loaded dressings showed potent activity against clinical wound pathogens while remaining compatible with human primary dermal fibroblasts and keratinocytes. In a contaminated porcine wound model, the dressings significantly reduced bacterial load while accelerating wound re-epithelialization and epithelial maturation compared to the controls. By integrating a dual-function hydrogel that promotes healing and provides on-demand antimicrobial activity, critical limitations in the use of AMPs in wound care can be addressed, providing new possibilities to treat infected wounds.

Injectable photo-crosslinked hyaluronic acid/carboxymethyl cellulose hydrogel for the sustained delivery of rhFGF2 and accelerated wound healing.

Time-ordered crosslinked hydrogel for full-cycle therapy of chronic wounds.

Chronic wounds require multifunctional dressings capable of simultaneously controlling infection, managing exudate, and promoting tissue regeneration. This study develops CuO nanoparticles incorporated alginate/chitosan hydrogel dressing reinforced onto nonwoven fabrics of pure cotton, pure hemp, and 50:50 cotton: hemp blend fabricated via full factorial design for wound dressing applications. The composites were characterized by surface morphology, chemical structure, mechanical properties, antibacterial activity, air permeability, and water absorbency. Morphological analysis confirms uniform hydrogel coating and successful CuO deposition. Mechanical strength and water absorbency increased with hydrogel concentration, with a maximum tensile strength of 115.61 N for the hemp reinforced sample at 2%. All CuO-loaded hydrogel composite dressings exhibited effective antibacterial performance. Although higher hydrogel concentrations reduce air permeability, blended substrates achieve a balanced combination of strength, breathability, and exudate management. This eco-friendly, cost-effective composite demonstrates strong potential for infection control for wound healing applications.

Diabetic wounds are a severe complication of diabetes, imposing a significant economic burden on patients and their families. Egg white (EW) is a natural, cost-effective, and easily accessible nutrient that contains various bioactive compounds with anti-inflammatory and pro-angiogenic properties. Carbon dots (CDs) exhibit excellent biocompatibility and low toxicity. This study introduces a CDs-crosslinked EW hydrogel (CEWH), prepared using CDs as crosslinkers for EW. Our previous study has established CEWH as a multifunctional biomaterial for tissue engineering. In this study, we further demonstrate that CEWH acts as a scaffold for diabetic wound healing in a mouse model by recruiting macrophages and promoting their polarization toward the M2 phenotype, thereby improving the local wound microenvironment. Its large pore size and extended degradation profile facilitate vascular infiltration into the wound site. Moreover, CEWH not only enhances the proliferation of skin tissue cells but also promotes the regeneration of hair follicles, sebaceous glands, and nerves while facilitating collagen deposition, ultimately restoring normal skin architecture and accelerating wound closure in diabetic mice. Overall, our findings underscore CEWH's potential as an effective and affordable wound dressing, providing a safe and economically viable solution for diabetic wound treatment.

Wounds can result from a variety of causes, including burns, traumas, surgeries, and long-term conditions like diabetes. The development of biofilms has detrimental consequences as well. Wound healing is also impacted by ageing, hypertrophic scarring, and recurrent injuries. With rising death rates and related costs, wound healing is a serious global concern. The severity of wound healing is caused by microbial infection, inflammation, and a lack of cell migration, proliferation, and angiogenesis. The many phases of wound healing include hemostasis, inflammation, proliferation, and remodeling to restore the integrity of the skin and subcutaneous tissue with its anti-microbial, anti-angiogenic, and anti-inflammatory effects. The development of biomaterials for wound dressings has reached a new benchmark and improved understanding. The extraordinary outcomes are caused by more recent discoveries and patents that concentrate on the wound microenvironments, such as pH, temperature, and reactive oxygen species. Because they can adjust to the current microenvironment at the injured surface, wound dressing materials that can function as theranostics also have significant advantages. The wound healing products should concentrate on cell-cell interactions, cell proliferation, cell signaling, and vascularization in order to make the therapy effective. The main advantages are also explained by the wound-healing material's penetrating effect. This review endeavored to throw light on different aspects of wounds and the latest advances in bioproducts effective for wound healing. Further, the clinical trials for wound healing products have been addressed.

Bacterial cellulose (BC), a renewable microbially produced biocompatible polymer, is widely studied as a wound dressing given its nanofibrillar structure, mechanical strength, and high water retention capacity. However, pristine BC is largely biologically inert and does not actively stimulate tissue regeneration, highlighting the need for its biofunctionalization. Effective wound care requires dressings that both protect the wound environment and actively promote healing, driving growing interest in advanced and affordable bioactive wound dressings. FucoPol (FP), a fucose-containing, polyanionic microbial polysaccharide with proven wound-healing, antioxidant, and photoprotective properties, offers an attractive strategy to impart bioactivity to BC. In this study, BC membranes were functionalized by impregnation with an FP solution, enabling efficient diffusion and loading of the bioactive polysaccharide. The resulting FP-functionalized membranes presented reduced crystallinity (CI = 47 vs 56%) and water-holding capacity (41 ± 2.1 vs 75 ± 0.9 g/g). However, they outperformed neat BC in biological properties; BC/FP membranes promoted keratinocyte proliferation and metabolic activity and accelerated wound closure (28.3 ± 7.5% at 24 h). Overall, FP-functionalized BC membranes emerge as promising materials for developing bioactive wound dressings with clear enhanced therapeutic potential, particularly for early-stage wound management.

Diabetes, old age, infections, and malnutrition are some of the causes of chronic wounds, which are a major global health problem. These wounds affect millions of people and put an elevated demand on the health systems worldwide. Traditional wound dressings are often incapable of counteracting the main pathological features of chronic wounds, which include continuous biofilm formation, prolonged inflammation, and deficient tissue regeneration. The primary aim of this review is to outline the growing pharmaceutical potential of nanomaterials in the management of advanced and chronic wounds. Specifically, this work evaluates how nanotechnology improves healing through advanced drug delivery systems and antibacterial agents, and it proposes new hybrid solutions such as combining nanomaterials with bioactive scaffolds and 3D bioprinted dressings to shift wound care toward precise, responsive treatments for hard-to-heal injuries. This includes examining how the structural dimensionality of these nanomaterials, categorized into zero-dimensional nanoparticles, one-dimensional electrospun nanofibers, and two-dimensional graphene oxide-based composites, enhances their therapeutic efficacy. These nanomaterials provide benefits such as a large surface area, high biocompatibility, the ability to regulate drug release, and the capability to perform multiple functions. Thus, they make it possible to treat different pathological conditions of wounds by means of antibacterial, anti-inflammatory, and pro-regenerative activities. There is an increasing focus on plant-derived nanomaterials for their antioxidant capabilities as well as for their potential for largescale, environmentally friendly manufacturing. The results from animal studies and small clinical trials indicate that nanomaterial-based dressings can, in some cases, speed up wound healing compared to traditional methods, although the efficacy differs among wound types and experimental models. Moving forward, the principal focus in this area of wound nanomedicine is on personalization, where microbiome analysis, inflammatory biomarker tracking, and wound sensor devices will help to continuously adapt the therapeutic materials. New techniques for production, such as microfluidic nanoparticle creation and AI-aided toxicology testing, combined with flexible clinical trial protocols, are expected to overcome the issues of safety testing, production at scale, and clinical application.

A self-powered ZnMo hydrogel battery patch for synergistic electrochemical wound healing.

Poly(lactic acid) (PLA)-based piezoelectric materials are considered promising candidates for smart wound dressings. However, the low crystallinity of PLA limits the ordered arrangement of dipoles, resulting in insufficient piezoelectric output for effective electrical stimulation therapy. In this work, star-shaped poly(ethylene glycol)-poly(L-lactic acid) (sPEG-PLLA) copolymers are synthesized and electrospun into nanofiber membranes. The star-shaped structure can serve as a nucleation site, enabling sPEG-PLLA with a molecular weight of 25k (sPEG-PLLA-25k) to form α-crystals with higher crystallinity. Thus, the sPEG-PLLA-25k nanofiber membrane exhibits the best piezoelectric performance, with a voltage of up to 9 V, which is three times higher than that of the poly(L-lactic acid) (PLLA) membrane (3 V). Both in vitro cell experiments and in vivo wound healing assessments confirm that ultrasound (US)-activated sPEG-PLLA-25k membranes significantly promote cell proliferation and migration, and achieve a higher wound closure rate compared to the PLLA-US group. This work has made breakthroughs in the first attempt to enhance the piezoelectricity of PLA-based materials by a molecular design strategy and developed a dressing with excellent piezoelectric properties and biocompatibility, which provides new materials and strategies for a self-driven electrical stimulation wound healing system.

The growing prevalence of chronic and infected wounds represents a major clinical challenge that conventional passive dressings fail to adequately address. Bioinspired pH-responsive hydrogels have emerged as intelligent biomaterials capable of dynamically interacting with the wound microenvironment. However, the field still faces major translational barriers, with many laboratory prototypes not yet progressing to clinically or commercially established products. Unlike descriptive literature compilations, this review provides a critical analytical evaluation focused on synthesizing fundamental engineering principles and quantitative design considerations that govern smart hydrogel performance. We systematically classify pH trigger mechanisms, discuss model-based relationships among crosslinking density, mesh size, swelling behavior, and release kinetics, and delineate multifunctional synergies. Particular analytical weight is dedicated to the practical constraints of terminal sterilization, large-scale fabrication controls, and regulatory pathways. By defining a hierarchical decision framework and introducing standardized benchmarking metrics, this review aims to bridge the gap between polymer synthesis and clinical reality, offering a design-oriented framework for next-generation regenerative wound dressings.

Chronic wounds constitute a major global clinical challenge, whereas traditional dressings lack real-time monitoring and active therapeutic capabilities. Self-powered thermoelectric gel dressings that integrate thermoelectric conversion and flexible gel networks have emerged as a transformative platform for wound care, enabling the seamless integration of sensing and therapy. This review systematically summarizes the fundamental energy conversion mechanisms and multi-scale material design strategies of thermoelectric gels, along with the essential fabrication processes, electrode engineering, and integration technologies for practical applications. It further highlights two core functions of these dressings: self-powered multimodal monitoring of wound temperature, pressure, and biomarkers, and in situ pro-healing effects through electrical stimulation that modulates inflammation, cellular behavior, and angiogenesis. Recent advances in the personalized management of diabetic foot ulcers, infected wounds, and athletic injuries using these dressings are also summarized. Finally, the key existing challenges and future development trends are critically analyzed, providing a comprehensive theoretical and technical framework for the advancement of next-generation intelligent wound dressings.