Wound ulceration caused by diabetes is a typical chronic wound wherein healing the local tissue is difficult due to lack of blood vessels and tissue necrosis caused by the long-term accumulation of free radicals. Near-field electrospinning (NFES) is an innovative technology used to produce micro-nano-scaled, controllable sequencing fibers. In this study, we constructed a novel wound dressing based on the NFES polycaprolactone (PCL) fiber network and modified gelatin with methacrylic anhydride (GelMA) hydrogel to promote angiogenesis and the re-epithelialization of diabetic wounds. An angiogenic and antioxidant drug named deferoxamine (DFO) was encapsulated in a GelMA hydrogel to achieve a slow-release effect that is more suitable for chronic wounds. The cell adhesion experiment showed that the cells could attach to the fibers in the dressing group having a network of PCL fibers on the surface and grow along the direction of the fibers, which in turn, effectively regulates cell behavior from the physical structure. Additionally, the large pore size (~ 500 μm) of the network allowed the cells to penetrate the pores and enter the surface of the hydrogel without being blocked out. Besides, the composite dressing had a notable effect on angiogenesis. Furthermore, antioxidation experiments confirmed that the DFO-loaded hydrogel exhibited antioxidant activity. Experimental animal models of diabetes showed that rats treated with the PCL-GelMA-DFO (PGD) hydrogel had faster ability of hemostasis, scab formation, and wound healing. In conclusion, the PGD hydrogel effectively promoted the repair of chronic wounds.

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients. Therefore, a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds. In this study, chitosan methacrylate-gallic acid (CSMA-GA) polymer with antioxidant activity, antimicrobial activity, and ultraviolet (UV)-triggered gelling properties was developed as a hydrogel precursor. Meanwhile, amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle (NP) with strong antibacterial activity. Subsequently, F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity. The hybrid hydrogel platform (CSMA-GA/F127/chlorhexidine (CMGFC)) exhibited high antibacterial efficiency (> 99.9%) and strong reactive oxygen species (ROS) scavenging ability (> 80.0%), which effectively protected cells from external oxidative stress (upregulated superoxide dismutase (SOD) and glutathione/oxidized glutathione disulfide (GSH/GSSG) levels and downregulated malondialdehyde (MDA) levels). Moreover, in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses (downregulated interleukin-6 (IL-6) and upregulated interleukin-10 (IL-10) levels), promoted angiogenesis (upregulated vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD 31) levels), and wound healing (enhanced collagen deposition and tissue remodelling). Overall, the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.

Polyphenols, as widely existing natural bioactive products, provide a vast array of advanced biomedical applications attributing to their potential health benefits that linked to antioxidant, anti-inflammatory, immunoregulatory, neuroprotective, cardioprotective function, etc. The polyphenol compounds could dynamically interact and bind with diverse species (such as polymers, metal ions, biomacromolecules, etc.) via multiple interactions, including hydrogen bond, hydrophobic, π–π, and cation–π interactions due to their unique chemical polyphenolic structures, providing far-ranging strategies for designing of polyphenol-based vehicles. Natural polyphenols emerged as multifaceted players, acting either as inherent therapeutics delivered to combat diverse diseases or as pivotal assemblies of drug delivery vehicles. In this review, we focused on the rational design and application of metal-phenolic network (MPN) based delivery systems, polyphenol-based coating films, polyphenol hollow capsules, polyphenol-incorporated hydrogels, and polymer-polyphenol-based nanoparticles (NPs) in various diseases therapeutic, including cancer, infection, cardiovascular disease, neurodegenerative disease, etc. Additionally. the versatility and mechanisms of polyphenols in the field of biomacromolecules (e.g., protein, peptide, nucleic acid, etc.) delivery and cell therapy have been comprehensively summarized. Going through the literature review, the remaining challenges of polyphenol-containing nanosystems need to be addressed are involved, including long-term stability, biosafety in vivo, feasibility of scale-up, etc., which may enlighten the further developments of this field. This review provides perspectives in utilizing natural polyphenol-based biomaterials to rationally design next generation versatile drug delivery system in the field of biomedicine, which eventually benefits public health.

Electrospinning is a popular and effective method of producing porous nanofibers with a large surface area, superior physical and chemical properties, and a controllable pore size. Owing to these properties, electrospun nanofibers can mimic the extracellular matrix and some human tissue structures, based on the fiber configuration. Consequently, the application of electrospun nanofibers as biomaterials, varying from two-dimensional (2D) wound dressings to three-dimensional (3D) tissue engineering scaffolds, has increased rapidly in recent years. Nanofibers can either be uniform fiber strands or coaxial drug carriers, and their overall structure varies from random mesh-like mats to aligned or gradient scaffolds. In addition, the pore size of the fibers can be adjusted or the fibers can be loaded with disparate medicines to provide different functions. This review discusses the various structures and applications of 2D fiber mats and 3D nanofibrous scaffolds made up of different one-dimensional (1D) fibers in tissue engineering. In particular, we focus on the improvements made in recent years, especially in the fields of wound healing, angiogenesis, and tissue regeneration.