Nanofiber scaffolds have emerged as a revolutionary drug delivery platform for promoting wound healing, due to their unique properties, including high surface area, interconnected porosity, excellent breathability, and moisture absorption, as well as their spatial structure which mimics the extracellular matrix. However, the use of nanofibers to achieve controlled drug loading and release still presents many challenges, with ongoing research still exploring how to load drugs onto nanofiber scaffolds without loss of activity and how to control their release in a specific spatiotemporal manner. This comprehensive study systematically reviews the applications and recent advances related to drug-laden nanofiber scaffolds for skin-wound management. First, we introduce commonly used methods for nanofiber preparation, including electrostatic spinning, sol–gel, molecular self-assembly, thermally induced phase separation, and 3D-printing techniques. Next, we summarize the polymers used in the preparation of nanofibers and drug delivery methods utilizing nanofiber scaffolds. We then review the application of drug-loaded nanofiber scaffolds for wound healing, considering the different stages of wound healing in which the drug acts. Finally, we briefly describe stimulus-responsive drug delivery schemes for nanofiber scaffolds, as well as other exciting drug delivery systems.

/pdf/nanofiber-scaffolds-as-drug-delivery-systems-promoting-wound-3qg6rk40.pdf

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing

Accelerating chronic wound healing is of great clinical significance. In this study, a bilayer pad (PCL-TH/PVA-Alg@CUR) with tetracycline hydrochloride (TH) loaded polycaprolactone (PCL) nanofiber as the outer layer (PCL-TH), and poly (vinyl alcohol) (PVA) hydrogel loaded with sodium alginate microspheres (Alg) encapsulating of curcumin (CUR) as the inner layer (PVA-Alg@CUR) was prepared to accelerate the chronic wound healing. The prepared bilayer pad shows a porous structure and can release CUR specifically according to the pH of chronic wounds. Moreover, it has good water vapor transmittance and water absorption ability, and its mechanical properties can meet the daily expansion and contraction of the skin. The antimicrobial and antioxidant properties of the bilayer pads were verified by the inhibition zone, co-culture method and in vitro free radical scavenging experiments. In addition, in vivo experiments have shown that the bilayer pad can inhibit the bacteria at the wound site and accelerate the healing of the chronic diabetic wound infected by bacteria. This study indicates the prepared antibacterial and antioxidant bilayer dressing with pH responsive release property have potential clinical applications. 

Antibacterial and antioxidant wound dressings with pH responsive release properties accelerate chronic wound healing

Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity. When examining acute infected wounds characterized by a low pH environment, the engineered Alg/CuP composite hydrogels demonstrated high bacterial eradication efficacy against both planktonic bacteria and biofilms, attributed to the combined action of catalytically generated hydroxyl radicals and the sustained release of Cu ions. In contrast, when applied to chronic diabetic wounds, which typically have a high pH environment, these composite hydrogels exhibit significant angiogenic performance. This is driven by the provision of catalytically generated dissolved oxygen and a beneficial supplement of Cu ions released from the degradable CuP nanozyme. Further, a mild thermal effect induced by NIR irradiation amplifies the catalytic activities and bioactivity of Cu ions, thereby enhancing the healing process of both infected and diabetic wounds. Our study validates that the synergistic integration of photothermal effects, catalytic activity, and released Cu ions can concurrently yield high antibacterial efficiency and tissue regenerative activity, rendering it highly promising for various clinical applications in wound healing.

pH-Responsive Wound Dressing Based on Biodegradable CuP Nanozymes for Treating Infected and Diabetic Wounds.

With the great success of coronavirus disease (COVID-19) messenger ribonucleic acid (mRNA) vaccines, mRNA therapeutics have gained significant momentum for the prevention and treatment of various refractory diseases. To function efficiently in vivo and overcome clinical limitations, mRNA demands safe and stable vectors and a reasonable administration route, bypassing multiple biological barriers and achieving organ-specific targeted delivery of mRNA. Nanoparticle (NP)-based delivery systems representing leading vector approaches ensure the successful intracellular delivery of mRNA to the target organ. In this review, chemical modifications of mRNA and various types of advanced mRNA NPs, including lipid NPs and polymers are summarized. The importance of passive targeting, especially endogenous targeting, and active targeting in mRNA nano-delivery is emphasized, and different cellular endocytic mechanisms are discussed. Most importantly, based on the above content and the physiological structure characteristics of various organs in vivo, the design strategies of mRNA NPs targeting different organs and cells are classified and discussed. Furthermore, the influence of administration routes on targeting design is highlighted. Finally, an outlook on the remaining challenges and future development toward mRNA targeted therapies and precision medicine is provided. 

mRNA nanodelivery systems: targeting strategies and administration routes

Smart hydrogels have shown great potential applications in disease treatment due to their controlled and local drug-release ability. Herein, a smart hydrogel with pH-responsive, injectable, and self-healing properties for controlled release of taxifolin (TFL) was prepared by freezing-thawing and photo-crosslinking methods. The crosslinking network of hydrogels (CS-CA hydrogels) was constructed by the hydrogen bonds, Schiff base bonds, and cyclobutane rings using chitosan (CS) and coumarin (CA) as raw materials. The CS-CA hydrogel demonstrated a compressive strength of 1.04 MPa, a self-healing efficiency of 99.9 %, and could maintain structural and functional integrity after injection. In addition, the drug release rate and shape of the CS-CA hydrogels were tunable due to its pH sensitivity. The TFL cumulative release reached 60 % within 12 h at pH = 4, and after equilibration, the cumulative release of TFL at pH = 4 (80 %) was significantly higher than at pH = 9.2 (50 %). The CCK8 experiment showed that the resulting hydrogel had no cytotoxicity. Meanwhile, subcutaneous implantation experiments in mice showed that the CS-CA hydrogels had favorable biodegradability and compatibility. 

A pH-responsive, injectable and self-healing chitosan-coumarin hydrogel based on Schiff base and hydrogen bonds.

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.

pH-Responsive wound dressings: advances and prospects.

Abstract To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19 F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H 6 ) to form H 6 -PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H 6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19 F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis. 

A pH-responsive nanoplatform with dual-modality imaging for enhanced cancer phototherapy and diagnosis of lung metastasis

A versatile nanoplatform with excellent biofilm permeability and spatiotemporal ROS regulation for peri-implantitis treatment

Recent progress in ROS-responsive biomaterials for the diagnosis and treatment of cardiovascular diseases

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