Nanofiber/hydrogel core–shell scaffolds with three-dimensional multilayer patterned structure for accelerating diabetic wound healing

Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Herein, a nanofiber/hydrogel core–shell scaffold with three-dimensional (3D) multilayer patterned structure (3D-PT-P/GM) was introduced for promoting diabetic wound healing with improved angiogenesis. The results showed that the 3D-PT-P/GM scaffolds possessed multilayered structure with interlayer spacing of about 15–80 μm, and the hexagonal micropatterned structures were uniformly distributed on the surface of each layer. The nanofibers in the scaffold exhibited distinct core–shell structures with Gelatin methacryloyl (GelMA) hydrogel as the shell and Poly (d, l-lactic acid) (PDLLA) as the core. The results showed that the porosity, water retention time and water vapor permeability of the 3D-PT-P/GM scaffolds increased to 1.6 times, 21 times, and 1.9 times than that of the two-dimensional (2D) PDLLA nanofibrous scaffolds, respectively. The in vitro studies showed that the 3D-PT-P/GM scaffolds could significantly promote cell adhesion, proliferation, infiltration and migration throughout the scaffolds, and the expression of cellular communication protein-related genes, as well as angiogenesis-related genes in the same group, was remarkably upregulated. The in vivo results further demonstrated that the 3D-PT-P/GM scaffolds could not only effectively absorb exudate and provide a moist environment for the wound sites, but also significantly promote the formation of a 3D network of capillaries. As a result, the healing of diabetic wounds was accelerated with enhanced angiogenesis, granulation tissue formation, and collagen deposition. These results indicate that nanofiber/hydrogel core–shell scaffolds with 3D multilayer patterned structures could provide a new strategy for facilitating chronic wound healing. Graphical Abstract

Diabetic wound healing approaches: an update

Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.

Correction: Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds

Correction for ‘Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds’ by Cheng Hu et al., J. Mater. Chem. B, 2021, 9, 9684–9699, DOI: 10.1039/D1TB02170B.

Hierarchically Porous MOF-Based Microneedles for Glucose-Responsive Infected Diabetic Wounds Treatment

Elaborately designed stimuli-responsive antibacterial systems are highly desirable for infected diabetic wounds treatment. Herein, a hierarchically porous metal-organic framework (MOF)-based glucose-responsive microneedles (MNs) was designed for painless transdermal wounds treatment....

In vivo study of Centella asiatica (L.) Urban as a drug gel for diabetes wounds

Background: Centella asiatica L. Urban is a tropical plant whose spread is quite broad as Indonesia. One of the ingredients of Centella asiatica L. Urban is asiaticoside which has excellent wound healing abilities. However, research on diabetic wound healing with Centella asiatica L. Urban extract formulation in the form of a gel has not been found. Therefore, it is necessary to look at the healing activity of diabetic wounds using Centella asiatica L. Urban extract in the form of a gel.Objective: This experimental study aims to explore the effect of gel extract derived from the Centella asiatica L. Urban on the length of time for wound healing.Methods: The subjects in this study were eight weeks old Balb-C mice conditioned to hyperglycemia and were divided into five groups. The Centella asiatica L. Urban extract is provided in three concentration levels, with 3%, 5%, and 7%. As a form of negative control, used gel without Centella asiatica L. Urban extract and positive control without gel, only hydrocolloid dressing.Results: Centella asiatica L. Urban at concentrations of 3% (with the value of Sig. > 0.05), 5%, and 7% showed the ability to heal wounds.Conclusions: Centella asiatica L. Urban gel extract with a concentration of 3% had a significant effect on wound healing compared to other preparations.

Accelerative Effect of Cinnamon Nanoparticles as well as HAMLET on Healing of Wounds Infected with MRSA in Diabetic Rats

Objective. The aim of the present study was to investigate the effect of cinnamon nanoparticles (CNPs) on healing of wounds infected with methicillin-resistant Staphylococcus aurous with human alpha-lactalbumin made lethal to tumor cells sensitization in diabetic rats. Methods. We included fifty diabetic male rats and divided them into 5 groups. There were 10 rats in each group as follows: CONTROL group: we did not infect the CONTROL group. The wound was only covered with sterile saline 0.9% solution (0.1 mL). INFCTD group: in this group, the wounds were infected with MRSA and covered with sterile saline 0.9% solution (0.1 mL). INFCTD-HMLT group: in this group, the wounds were infected with MRSA and HAMLET (100 μg). INFCTD-CNM group: in this group, the wounds were infected with MRSA and 0.1 mL CNPs (1 mg/mL) were applied topically to wounds. INFCTD-HMLT-CNM group: in this group, the wounds were infected with MRSA, HAMLET (100 μg), and 0.1 mL CNPs (1 mg/mL). Results. Bacteriology, wound area reduction measurements, biochemistry, histomorphometrical studies, hydroxyproline levels, and reverse transcription polymerase chain reaction for caspase-3, Bcl-2, and p53 showed significant difference between rats in the INFCTD-HMT-CNM group in comparison with other groups ( P < 0.05 ). Conclusions. Accelerated healing of diabetic wounds infected with MRSA showed that local application of cinnamon nanoparticles along with HAMLET sensitization on S. aureus-infected wound could be taken into consideration.

Collagen/Chitosan Gels Cross-Linked with Genipin for Wound Healing in Mice with Induced Diabetes

Diabetes mellitus continues to be one of the most common diseases often associated with diabetic ulcers. Chitosan is an attractive biopolymer for wound healing due to its biodegradability, biocompatibility, mucoadhesiveness, low toxicity, and hemostatic effect. A panel of hydrogels based on chitosan, collagen, and silver nanoparticels were produced to treat diabetic wounds. The antibacterial activity, cytotoxicity, swelling, rheological properties, and longitudinal sections of hydrogels were studied. The ability of the gels for wound healing was studied in CD1 mice with alloxan-induced diabetes. Application of the gels resulted in an increase in VEGF, TGF-b1, IL-1b, and TIMP1 gene expression and earlier wound closure in a comparison with control untreated wounds. All gels increased collagen deposition, hair follicle repair, and sebaceous glands formation. The results of these tests show that the obtained hydrogels have good mechanical properties and biological activity and have potential applications in the field of wound healing. However, clinical studies are required to compare the efficacy of the gels as animal models do not reproduce full diabetes pathology.

mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype

Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polarization. However, the differentially expressed miRNAs involved in wound healing and their effects on diabetic wounds remain to be further explored. In this study, we first identified differentially expressed miRNAs in the inflammation, tissue formation and reconstruction phases in wound healing using Illumina sequencing and RT-qPCR techniques. Thereafter, the expression of musculus (mmu)-miR-145a-5p (“miR-145a-5p” for short) in excisional wounds of diabetic mice was identified. Finally, expression of miR-145a-5p was measured to determine its effects on macrophage polarization in murine RAW 264.7 macrophage cells and wound healing in diabetic mice. We identified differentially expressed miRNAs at different stages of wound healing, ten of which were further confirmed by RT-qPCR. Expression of miR-145a-5p in diabetic wounds was downregulated during the tissue formation stage. Furthermore, we observed that miR-145a-5p blocked M1 macrophage polarization while promoting M2 phenotype activation in vitro. Administration of miR-145a-5p mimics during initiation of the repair phase significantly accelerated wound healing in db/db diabetic mice. In conclusion, our findings suggest that rectifying macrophage function using miR-145a-5p overexpression accelerates diabetic chronic wound healing.