The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing

Song, Jianying; Hu, Li‐Xin; Liu, Bo; Jiang, Nan; Huang, Hou-Qiang; Luo, Jiesi; Wang, Long; Zeng, Jing; Huang, Feihong; Huang, Min; Cai, Luyao; Tang, Luping; Chen, Shunli; Chen, Yinyi; Wu, Anguo; Zheng, Silin; Chen, Qi

doi:10.2147/jir.s371939

Cited by 18 publications

(13 citation statements)

References 170 publications

(174 reference statements)

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“…[31] For example, Song et al have highlighted the prominent role of the immune microenvironment in the regulation of diabetic wound healing and summarized the advanced therapies targeting immune cells to promote diabetic wound healing. [32] Therefore, the precise therapeutic strategy based on the regulation of the immune microenvironment will bring new ideas for basic research and clinical translation and treatment of DFUs.…”

Section: Hydrogels-based Immunomodulatory Therapies For Dfusmentioning

confidence: 99%

Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer

Xiong

Qian

Lü

et al. 2023

Adv Funct Materials

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Diabetic foot ulcer (DFU) is one of the most common complications of diabetes, bringing physical and mental challenges for patients due to the lack of efficient curative therapy. Despite considerable advances in pharmacological and surgical approaches, clinical trials for DFU patients remain disappointing due to the local overactive and excessive inflammation. Immunomodulatory hydrogels has significant advantages to overcome the clinical challenge of DFUs therapy. Here, recent fabrication and regenerative advances in the utilization of functional hydrogels for altering the immune microenvironment of DFUs are comprehensively reviewed. The pathological features and the healing processes of DFUs, followed by summarizing the physicochemical properties essential for the design of regenerative hydrogels for immunomodulation in DFUs, are briefly introduced. Then, the potential immuno-therapeutic modalities of hydrogels and emerging trends used to treat DFUs via multitherapeutic approaches and enhanced efficacy and safety are discussed. Taken together, by linking the structural properties of hydrogels to their functions in DFU therapy with a particular focus on immunomodulatory stimuli, this review can promote further advances in designing advanced hydrogels for DFUs, resulting in improved diabetic wound repair through translation into clinical setting in the near future.

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Section: Hydrogels-based Immunomodulatory Therapies For Dfusmentioning

confidence: 99%

Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer

Xiong

Qian

Lü

et al. 2023

Adv Funct Materials

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“…We are all aware that persistent release of inflammatory mediators can initiate an inflammatory cascade, disrupt vascular maturation, and limit collagen deposition (Song et al, 2022), all of which can lead to slow or no wound healing in DW patients. Moreover, in vivo experiments indicate that ESO contributes by preventing abnormal wound inflammation.…”

Section: Resultsmentioning

confidence: 99%

“…All phases of wound healing are dependent on macrophages, the key players in the inflammatory phase (Song et al, 2022). On the basis of their phenotype, macrophages can be roughly classified as M1‐like or M2‐like.…”

Section: Introductionmentioning

confidence: 99%

Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage

Song

Zeng

Zheng

et al. 2023

Phytotherapy Research

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Sanguisorba officinalis L., a traditional Chinese medicine, is frequently used to treat burns and scalds. But even so, it is unknown whether S. officinalis L. can accelerate diabetic wounds (DW) healing. Here, to bridge the gap, we employed in vivo and in vitro evaluations to assess the positive effect of S. officinalis L. ethanol extract (ESO) on DW. Results demonstrated that ESO dramatically improved the DW healing rate. With ESO treatment, the inappropriately elevated levels of IL6, IL1β and TNFα in DW were reduced, while the expression of IL10 was increased, indicating that the abnormal inflammation in DW was also under control. Moreover, the abnormally elevated expression of CD86 was significantly inhibited and the expression of CD206 was significantly up‐regulated following treatment with ESO. The global level of NF‐κB protein was not affected by ESO treatment, but it suppressed the expression of phosphorylated NF‐κB and prevented its nuclear entry. In addition, in RAW264.7 cells activated with lipopolysaccharide (LPS), the expression of NLRP3, Caspase1 and IL1β were significantly diminished following ESO treatment. In conclusion, ESO was proved to be a promising treatment for DW healing due to its potential to accelerate the healing process by suppressing the inflammatory response. This was achieved by increasing the ratio of M2 to M1 polarization through blocking the NF‐κB/NLRP3 signaling pathway.

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“…ROS in the neutrophils stimulate NETosis, capturing and killing pathogens via neutrophils extracellular traps (NETs) [19], through both the NOX-dependent and NOX-independent pathways [16]. Reasonable formation of NETs is beneficial to the normalization of the immune microenvironment, but excessive formation of NETs worsens the abnormal inflammatory response of wounds, which is also the key pathological manifestation of diabetic wounds (DW) that is difficult to heal [20][21][22]. In addition, NETs also reduce the responsiveness of neutrophils to lipopolysaccharide, leading to an imbalance of M1/M2 macrophages [23].…”

Section: Excessive Oxidative Stress Causes Dfu To Stagnate During The...mentioning

confidence: 99%

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

Song¹,

Liu²,

Liu³

et al. 2022

Front. Biosci. (Landmark Ed)

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Difficult or even non-healing diabetic foot ulcers (DFU) are a global medical challenge. Although current treatments such as debridement, offloading, and infection control have resulted in partial improvement in DFU, the incidence, amputation, and mortality rates of DFU remain high. Therefore, there is an urgent need to find new or more effective drugs. Numerous studies have shown that oxidative stress plays an important role in the pathophysiology of DFU. The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway and the advanced glycated end products (AGEs)-receptor for advanced glycation endproducts (RAGE), protein kinase C (PKC), polyol and hexosamine biochemical pathways play critical roles in the regulation of oxidative stress in the body. Targeting these pathways to restore redox balance can control and alleviate the occurrence and development of DFU. Natural biologics are a major source of potential drugs for these relevant targets, and their antioxidant potential has been extensively demonstrated. Here, we discussed the pathophysiological mechanism of oxidative stress in DFU, and identifiled natural biologics targeting these pathways to accelerate DFU healing, in order to provide a new or potential direction for clinical treatment, nursing and related basic research of DFU.

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The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing

Cited by 18 publications

References 170 publications

Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer

Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer

Sanguisorba officinalis L. promotes diabetic wound healing in rats through inflammation response mediated by macrophage

Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

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