Diabetic Wound Healing Research Articles

Assembly of Recombinant Proteins into β-Sheet Fibrillating Peptide-Driven Supramolecular Hydrogels for Enhanced Diabetic Wound Healing.

Supramolecular hydrogels offer a noncovalent binding platform that preserves the bioactivity of structural molecules while enhancing their stability, particularly in the context of diabetic wound repair. In this study, we developed protein-peptide-based supramolecular hydrogels by assembling β-sheet fibrillizing peptides (designated Q11) with β-tail fused recombinant proteins. The Q11 peptides have the ability to drive the gradated assembly of N- or C-terminal β-sheet structure (β-tail) fused recombinant proteins. We first investigated the assembly properties of Q11 and assessed its stability under varying pH and temperature conditions by combining Q11 with two β-tail fused fluorescent proteins. The results showed that Q11 enhanced the tolerance of the fluorescent proteins to changes in pH and temperature. Building upon these findings, we designed collagen-like proteins and Sonic Hedgehog-fused recombinant proteins (CLP-Shh) that could be assembled with Q11 to form peptide-protein supramolecular hydrogels. These hydrogels demonstrated the ability to improve cell viability and migration and upregulate key markers of cell growth. Further in vivo studies revealed that the Q11-driven supramolecular hydrogel effectively enhances diabetic wound healing and epidermal regeneration by promoting the expression of epidermal-related proteins and immune factors. This study highlights the potential of supramolecular hydrogels for clinical applications and their promise in the development of biofunctional hydrogels for therapeutic use.

Magnetically Actuated Microrobot Equipped with Electron‐Extracting Nanohooks for Enhanced Photothermal Fungal Eradication

AbstractFungal infections pose a formidable challenge in the healing of diabetic wounds due to complex inflammatory microenvironments, high resistance, and recurrence risks, particularly during fungal aggregation and germination stages. Inspired by controllable fishhooks, this work presents a magnetically actuated microrobot (Co@NCNH/NC) that leverages carbon nanohooks to enhance localized photothermal therapy. This microrobot features controllable navigation capabilities to pathogens in the magnetic field, enabling precise fungal capture and thermally promoted penetration even in high‐viscosity environments. With impact force and high conductivity, the microrobot's nanohooks induce disruption of cell envelopes and facilitate electron extraction from membranes, collectively compromising fungal integrity and enhancing fungal vulnerability. Thus, in situ, heat ablation further eradicates aggregated spores and causes irreversible damage to germinated fungi by aggravating cellular lysis, metabolic dysfunction, and destruction of actin cytoskeletons, inhibiting fungal self‐repair and growth. Moreover, Co@NCNH/NC with good biocompatibility exhibits catalase‐like activity that helps alleviate wound inflammation during therapy. This dual‐action approach accelerates critical wound healing processes including angiogenesis and epidermalization, ultimately improving healing outcomes in chronic diabetic wounds. By combining targeted fungal eradication with inflammation reduction and tissue regeneration, this adaptable microrobotic technology shows considerable promise for advancing therapeutic efficacy and prevention of recurrence in diabetic wound healing.

Impact of Moringa oleifera Hydro-Alcoholic Bark Extract on Diabetic Wound Healing: A Topical Approach.

The current study was aimed to evaluate the potential of Moringa oleifera against diabetic foot ulcer, where the wound healing is impaired and susceptible to infection. The effects of M. oleifera hydroalcoholic bark extract (MOHE) on different parameters influencing diabetic wound healing were comprehensively investigated including: anti-inflammatory effects, antibacterial properties, antioxidant activity, anti-diabetic properties, and fibroblast proliferation and migration. Furthermore, in vivo studies were conducted in diabetic rats and Zebrafish to investigate the topical effects of MOHE on wound healing. The findings of this study demonstrated that MOHE has strong anti-diabetic effect, including a significant inhibition of α-amylase activity (IC50 = 0.043 mg/mL) and 2.92-fold increase in 2-NBDG uptake in McCoy cells. MOHE demonstrated considerable antioxidant activity, inhibiting DPPH (IC50: 0.046 mg/mL) and ABTS (IC50: 0.04 mg/mL) free radicals. In in vitro wound healing studies employing MOHE revealed a significant increase in McCoy fibroblast proliferation (148.83%) and improved migration, resulting in a wound closure rate of 46.3%. MOHE exhibited significant antibacterial activity against pathogenic bacteria species. It efficiently reduced heat-induced RBC hemolysis, with anti-inflammatory effect of 73% at 0.2 mg/mL. Furthermore, MOHE demonstrated better results in the treatment of diabetic wounds in Wistar rats and fin regeneration in Zebra fish compared to Calendula cream. This evidence based pharmacological study highlights the promising potential of MOHE in facilitating the healing of diabetic wounds, offering a topical approach to address this challenging healthcare issue.

Injectable Nanocomposite Hydrogel with Synergistic Biofilm Eradication and Enhanced Re-epithelialization for Accelerated Diabetic Wound Healing.

Diabetic wounds remain a critical clinical challenge due to their harsh microenvironment, which impairs cellular function, hinders re-epithelialization and tissue remodeling, and slows healing. Injectable nanocomposite hydrogel dressings offer a promising strategy for diabetic wound repair. In this study, we developed an injectable nanocomposite hydrogel dressing (HDL@W379) using LAP@W379 nanoparticles and an injectable hyaluronic acid-based hydrogel (HA-ADH-ODEX). This dressing provided a sustained, pH-responsive release of W379 antimicrobial peptides, effectively regulating the wound microenvironment to enhance healing. The HDL@W379 hydrogel featured multifunctional properties, including mechanical stability, injectability, self-healing, biocompatibility, and tissue adhesion. In vitro, the HDL@W379 hydrogel achieved synergistic biofilm elimination and subsequent activation of basal cell migration and endothelial cell tube formation. Pathway analysis indicated that the HDL@W379 hydrogel enhances basal cell migration through MEK/ERK pathway activation. In methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds, the HDL@W379 hydrogel accelerated wound healing by inhibiting bacterial proliferation and promoting re-epithelialization, regenerating the granulation tissue, enhancing collagen deposition, and facilitating angiogenesis. Overall, this strategy of biofilm elimination and basal cell activation to continuously regulate the diabetic wound microenvironment offers an innovative approach to treating chronic wounds.

Heterojunction Nanozyme Hydrogels Containing Cu-O-Zn Bonds with Strong Charge Transfer for Accelerated Diabetic Wound Healing.

The complex microenvironment of persistent inflammation and bacterial infection is a major challenge in chronic diabetic wounds. The development of nanozymes capable of efficiently scavenging reactive oxygen species (ROS) is a promising method to promote diabetic wound healing. However, many nanozymes show rather limited antioxidant activity and ROS-dependent antibacterial effects under certain circumstances, further weakening their ability to scavenge ROS. To meet these challenges, electronically regulated bioheterojunction (E-bio-HJ) nanozyme hydrogels derived from metal-organic frameworks (MOFs) were designed and prepared via an interface engineering strategy. Owing to the electron transfer and redistribution effects of the abundant and highly dispersed Cu-O-Zn sites at the heterogeneous interface, the E-bio-HJ nanozymes exhibited catalase (CAT)-like activity with ultrahigh hydrogen peroxide affinity (Km = 25.76 mM) and sustained ROS consumption. In addition, owing to the enhanced interfacial effect of E-bio-HJ and the good biocompatibility and cell adhesion of the methacryloylated gelatin (Gel) hydrogel, the E-bio-HJ gelatin hydrogel (E-bio-HJ/Gel) further reduced inflammation by inducing macrophage transformation to the M2 phenotype, accompanied by excellent antimicrobial properties and enhanced cell migration, angiogenesis, and collagen deposition, which synergistically promoted diabetic wound healing. This highly effective and comprehensive strategy offers a new approach for the rapid healing of diabetic wounds.

Novel cocktail therapy based on multifunctional supramolecular hydrogel targeting immune-angiogenesis-nerve network for enhanced diabetic wound healing

Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution. The therapeutic efficacy of the hydrogel is realized through its integration with adipose-derived stem cells (ADSCs) and lipid nanoparticles encapsulating ginsenoside RG1 and Stromal cell-derived factor-1 (SDF-1). This strategic combination directs ADSCs to the injury site, guiding them toward neurogenic specialization while establishing an advantageous immunomodulatory environment through macrophage reprogramming. The synergistic effects of the newly differentiated nerve cells and the regenerative cytokines secreted by ADSCs contribute significantly to enhanced angiogenesis, ultimately expediting the diabetic wound healing process. To summarize, this innovative hydrogel-based therapeutic system represents a novel perspective for the management of diabetic wounds by concurrently targeting immune response, angiogenesis, and nerve regeneration—a pivotal advancement in the quest for effective solutions in diabetic wound care.

CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing

BackgroundDelayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds. MethodsIn vivo, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and Clec14a−/− diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. In vitro, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs. ResultsCLEC14A expression was suppressed in diabetic wounds. Deletion of the Clec14a inhibited angiogenesis and activated inflammatory responses in vivo. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels in vitro. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose. ConclusionCLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.

Antimicrobial Effects of Thonningianin a (TA)-Loaded Chitosan Nanoparticles Encapsulated by a PF-127hydrogel in Diabetic Wound Healing.

Diabetic wounds are serious chronic complications of diabetes and can lead to amputation and death. Although considerable progress has been made in drugs and materials for treating it, it's still an urgent clinical problem as the materials and drugs have potential therapeutic drawbacks, such as low delivery efficiency and poor tissue permeability. To promote diabetic wound healing, a composite of thonningianin A (TA)-loaded chitosan nanoparticles (CNPS) encapsulated by a Pluronic F-127 (PF-127) hydrogel (TA-CNPS-PF) was developed in this study. TA-CNPS was prepared by ionic gelation method and TA-CNPS was thoroughly dispersed into PF-127hydrogel to prepare TA-CNPS-PF. The particle size, hydrogel structure, encapsulation ratio, release ratio, antimicrobial properties of TA-CNPS-PF were determined and the effect of TA-CNPS-PF on diabetic wounds was assessed. The effect of TA on macrophage polarization was also examined in vitro. The particle size was approximately 100 nm of TA-CNPS-PF and the hydrogel had a homogeneous three-dimensional reticulation structure. The encapsulation efficiency of TA in the CNPS were 99.3% and the release ratio of TA-CNPS-PF was approximately 86% and has antimicrobial properties. TA-CNPS-PF promoted diabetic wound healing significantly. Histopathology confirmed that TA-CNPS-PF promoted complete re-epithelialization and adequate collagen deposition. TA promoted the polarization of M1 macrophages into M2 macrophages via light microscopy, immunocytometry and flow cytometry. TA-CNPS-PF also promoted an increase in the number of M2 macrophages in diabetic wounds. TA promotes diabetic wound healing by promoting the polarization of M1 macrophages into M2 macrophages and TA-CNPS-PF has good antimicrobial activity and a good drug release ratio in this study, which provides a new direction for the treatment of diabetic wounds and is expected to be highly advantageous in clinical diabetes wound therapy.

Corrole-based Photothermal Nanocomposite Hydrogel with Nitric Oxide Release for Diabetic Wound Healing.

The management of chronic diabetic wounds remains a significant challenge due to persistent bacterial infections and impaired angiogenesis. Herein, we reported a nanocomposite hydrogel (M/P-SNO/G) incorporated with M/P-SNO nanoparticles engineered by supramolecular assembly of the photosensitizing mono-carboxyl corrole (MCC) and S-nitrosothiol-modified polyethylene glycol (mPEG-SNO) for synergistic photothermal therapy (PTT)/nitric oxide (NO) treatment of diabetic wounds. The strong π-π interaction among aggregated MCC in M/P-SNO enhances the optical absorption and photothermal ability, thereby facilitating the precise release of NO upon laser irradiation. The hydrogel matrix, composed of oxidized hyaluronic acid and carboxymethyl chitosan crosslinked by Schiff-base, demonstrates good injectability and self-healing characteristics, providing an ideal environment for wound repair. As expected, M/P-SNO/G exhibits a desirable photothermal performance and a controlled laser-responsive NO release, realizing enhanced bactericidal effect and anti-biofilm ability in vitro. In a full-thickness skin defect model on diabetic mice, M/P-SNO/G has proven effective in bacteria clearance and angiogenesis, significantly accelerating wound healing. This study presents a feasible supramolecular strategy to develop diabetic wound dressings with synergistic PTT/NO treatment. STATEMENT OF SIGNIFICANCE: Developing advanced dressings that simultaneously eliminate bacteria and accelerate wound recovery is essential for treating diabetic wounds. This study developed a nanocomposite hydrogel (M/P-SNO/G) featuring the synergistic effect of photothermal therapy (PTT) and nitric oxide (NO) treatment to accelerate infected diabetic wound healing. M/P-SNO NPs within the hydrogel are self-assembled through the hydrophobic photosensitizing mono-carboxyl corrole (MCC) and the hydrophilic NO-releasing polymer (mPEG-SNO), where highly aggregated MCC molecules ensure superior photothermal performance. Meanwhile, the temperature increase induced by the photothermal effect activates NO release from the hydrogel. Under 660 nm laser irradiation, M/P-SNO/G demonstrates a PTT/NO synergy to effectively inhibit bacterial proliferation and promote angiogenesis, offering significant benefits in diabetic wound repair and further expanding the biomedical applications of corroles.

Antibacterial carboxymethyl chitosan hydrogel loaded with antioxidant cascade enzymatic system for immunoregulating the diabetic wound microenvironment

Diabetic wound healing faces several complex challenges, such as hypoxia, oxidative stress, and bacterial infections, which severely inhibit the wound-healing process. Herein, a quaternary ammonium salt-crosslinked carboxymethyl chitosan hydrogel (TPC) with excellent antioxidant and antibacterial properties was developed to immunoregulate the diabetic wound microenvironment. The TPC hydrogel was prepared by first mixing carboxymethyl chitosan (CMCS) and protocatechualdehyde (PA), followed by the addition of a quaternary ammonium cross-linker (TSPBA) and a superoxide dismutase (SOD)–catalase (CAT) cascade system. The immobilized SOD and CAT retained their activity, continuously converting endogenous ·O2− and H2O2 to O2 and H2O. PA also provided the TPC hydrogel excellent oxygen and nitrogen radical scavenging capacity. The quaternary ammonium groups in TSPBA significantly enhanced the inherent antibacterial ability of CMCS-based hydrogels. In diabetic wound-healing experiments, this porous and adhesive TPC hydrogel effectively closed wounds and regenerated skin tissue, resulting in shorter wound edges, thicker granulation, and higher collagen deposition levels compared with other groups. The TPC hydrogel also promoted macrophage polarization toward the M2 phenotype, accelerating wound healing by upregulating IL-10 expression, downregulating IL-6 expression, and enhancing angiogenesis. These results demonstrate the great potential of TPC hydrogel as a promising therapeutic dressing for treating diabetic wounds.

536 Sodium butyrate promotes healing of diabetic wounds through modulation of the epigenome in dysfunctional macrophages

536 Sodium butyrate promotes healing of diabetic wounds through modulation of the epigenome in dysfunctional macrophages

Engineered biomimetic nanovesicles-laden multifunctional hydrogel enhances targeted therapy of diabetic wound

Angiogenesis is essential for diabetic wound healing. Endothelial progenitor cell-derived extracellular vesicles (EPC-EVs) are known to promote wound healing by enhancing angiogenesis, while the low yield and lack of effective targeting strategies limit their therapeutic efficacy. Here, the biomimetic nanovesicles (NVs) prepared from EPC (EPC-NV) through an extrusion approach were reported, which functioned as EV mimetics to deliver contents from EPC to the wound. Besides, the cRGD peptide was coupled to the surface of EPC-NV (mEPC-NV) to achieve active endothelial cells (ECs)-targeting. Furthermore, we developed a dual hydrogel network by combining Fe3+@ Protocatechualdehyde (PA) complex-modified Acellular Dermal Matrix (ADM) with light-cured gelatin (GelMA), to enrich and sustainably release mEPC-NV. The hydrogel system with antioxidant and antibacterial properties also made up for the deficiency of mEPC-NV, reducing reactive oxygen species (ROS) and inhibiting infection in diabetic wound. Taken together, this study established a novel bioactive delivery system with angiogenesis, antioxidant and antibacterial activities, which might be a promising strategy for the treatment of diabetic wound.

Gene-engineered polypeptide hydrogels with on-demand oxygenation and ECM-cell interaction mimicry for diabetic wound healing

The treatment of infected diabetic wounds remains a significant clinical challenge due to pathogen infection, excessive inflammation, and impaired angiogenesis with troubled extracellular matrix (ECM) - cell and cell - cell interaction. Herein, we prepared a Janus polypeptide-engineered hydrogel with programmable function driven by self-assembly of the same A domain. The hydrogel was composed of a V8-degradable AC10A layer loaded with hybrid phages for precise bacterial inhibition (ABC) and a PC10ARGD layer loaded with Mn-based mineralized erythrocyte for continuous supply oxygen on demand (PEM). The results of laser speckle contrast imaging, photoacoustic imaging, and hyperspectral imaging demonstrated that the AC10A@BP-Ce6/PC10AR@EM hydrogel (ABC/PEM) accelerated the reconstruction of normal skin structure by breaking the oxygen diffusion barrier and supplying oxygen on demand to promote angiogenesis and functionalization. In addition, in vitro and in vivo experiment results showed that the ABC/PEM hydrogel can mimic positive ECM - cell interaction to inhibit the polarization of macrophage towards M1-type to slow down the inflammatory process by down-regulated yes-associated protein (YAP), and relieve the mechanical tension of fibroblasts to reduce scar formation. Finally, the ABC/PEM hydrogel promotes a healing rate of 98.83% on day 21 and results in the number of dermal appendages being eight times that of the negative group. This work presents an effective strategy for diabetes-related chronic infected wound management.

Chondroitin sulfate sponge scaffold for slow-release Mg2+/Cu2+ in diabetic wound management: Hemostasis, effusion absorption, and healing

The management of diabetic wounds presents significant challenges due to persistent inflammation, microenvironmental disruptions, and impaired angiogenesis. To address these issues, this study developed a multifunctional chondroitin sulfate sponge (CSP@Cu-Mg) with anti-inflammatory properties, hemostatic effects, effusion absorption, and enhanced healing promotion. Through ion crosslinking, MgO and CuO were incorporated into the interpenetrating network structure of chondroitin sulfate and acellular dermal matrix, resulting in a sponge with impressive liquid absorption capacity (3450 %) and porosity (83 %). This sponge enabled sustained release of Mg2+/Cu2+ ions, with approximately 40 % cumulative release over 7 days. This release helped reduce inflammation, promote the proliferation and migration of skin repair-related cells, and stimulate angiogenesis. In vivo studies demonstrated that the CSP@Cu-Mg sponge significantly improved diabetic wound healing by modulating inflammation and accelerating collagen deposition, angiogenesis, and re-epithelialization. This extracellular matrix sponge, which synergistically releases Mg2+/Cu2+, presents a promising strategy for comprehensive diabetic wound management with substantial clinical implications.

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

A multi-purpose dressing based on resveratrol-loaded ionic liquids/gelatin methacryloyl hydrogel for enhancing diabetic wound healing

Diabetic wound (DW) is a multifaceted challenge, characterized by persistent bacterial infections and compromised angiogenesis. To address these issues and enhance DW healing, we developed a novel strategy using a photo-crosslinked hydrogel system composed of ionic liquids (ILs) and gelatin methacryloyl (GelMA) loaded with resveratrol (Res). The ILs/GelMA hydrogel was fabricated via a simple photo-crosslinking process, resulting in desirable mechanical properties, biocompatibility, and controlled release kinetics. Res was incorporated into the hydrogel matrix (ILs/GelMA@Res) to ensure sustained release, facilitating angiogenesis and accelerating wound healing. In vitro studies demonstrated that the ILs/GelMA@Res hydrogel exhibited potent antibacterial activity against Staphylococcus aureus and Escherichia coli, inhibiting bacterial growth and biofilm formation. Furthermore, the sustained release of Res from the hydrogel promoted angiogenesis by activating the PI3K/AKT signaling pathways associated with VEGF and FGF, enhancing endothelial cell proliferation, migration, and tube formation. In a DW mice model, the ILs/GelMA@Res hydrogel demonstrated accelerated wound closure, reduced inflammation, and robust neovascularization. This multifunctional hydrogel-based delivery system holds considerable potential for clinical translation, offering a safe and effective treatment modality for diabetic patients with chronic wounds.

Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing

Abstract: Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca2+ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for Understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

Cratylia mollis lectin reduces inflammatory burden induced by multidrug-resistant Staphylococcus aureus in diabetic wounds.

In diabetes, tissue repair is impaired, increasing susceptibility to Staphylococcus aureus infections, a pathogen commonly found in wounds. The emergence of S. aureus strains that are highly resistant to antimicrobial agents highlights the urgent need for alternative therapeutic options. One promising candidate is Cramoll (Cratylia mollis seed lectin), known for its immunomodulatory, mitogenic, and healing properties. However, its efficacy in infected diabetic wounds remains unexplored. This study evaluated the effects of topical Cramoll treatment on diabetic wounds infected by S. aureus. Diabetic Swiss mice (induced by streptozotocin) were subjected to an 8-mm wound on the back and subsequently infected with a suspension of multidrug-resistant S. aureus. During the treatment period, the wounds were clinically evaluated for inflammation and the area of injury. After seven days, samples were collected from the wounds to quantify the bacterial load and histopathological and immunological analyses. Wounds infected by S. aureus exhibited more pronounced areas and severity indices, which were significantly reduced by Cramoll treatment (p < 0.05). Histopathological analysis revealed a reduction in inflammatory cells and an increase in revascularization with Cramoll treatment (p < 0.05). Cramoll also promoted greater collagen production compared to controls (p < 0.05). Furthermore, Cramoll treatment significantly reduced the S. aureus load in wounds (p < 0.0001), decreased TNF-α and IL-6 levels in infected wounds, and increased ERK pathway activation (p < 0.05). In conclusion, Cramoll lectin improves the healing of diabetic wounds, and these results contribute to the understanding of Cramoll healing mechanisms, reinforcing its potential as a healing agent in various clinical conditions.

Photobiomodulation studies on diabetic wound healing: An insight into the inflammatory pathway in diabetic wound healing.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Neurotensin Conjugated Polymeric Porous Microparticles Suppress Inflammation and Improve Angiogenesis Aiding in Diabetic Wound Healing.

Neurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 - 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 - 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.