Charge and receptor functional injectable hydrogels as cytokine-releasing reservoirs for wound healing

Mao, Jiayi; Cai, Zhengwei; Liu, Zhimo; Qian, Shutong; Zhao, Binfan; Yu-yu, Zhang; Zhuang, Yaping; Zhang, Liucheng; Mao, Xiyuan; Zhang, Yuguang; Cui, Wenguo; Sun, Xiaoming

doi:10.1016/j.cej.2022.137880

Cited by 15 publications

(6 citation statements)

References 53 publications

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“…As shown in Figure 4k, L929 cells tolerated the 3D embedding and proliferated continuously during the 3 days, which might be due to the glycopeptide hydrogel that mimicked the glycoprotein composition and nanofibrous structure of cutaneous ECM, and is beneficial to cell adhesion, proliferation and migration. [ 22a,36 ] These results indicated that the EPEG‐OA@PHMS hydrogel exhibited excellent cytocompatibility and hemocompatibility and could be used in biological applications.…”

Section: Resultsmentioning

confidence: 94%

“…As a precursor of the EPEG‐OA hydrogel, EPEG was synthesized by a two‐step method (Figure S6, Supporting Information). First, according to a previously described method, [ 36 ] EPL‐PBA was obtained by reducing the Schiff base reaction with sodium cyanoborohydride. Then, EGCG was grafted onto EPL‐PBA through boronic ester bonds or to form the EPEG precursor.…”

Section: Resultsmentioning

confidence: 99%

“…The glycopeptide hydrogel based on sodium alginate and polylysine mimicked the natural ECM. [ 36 ] Sodium alginate is a natural polysaccharide composed of β‐D‐mannuronic and α‐L‐guluronic acids, sodium alginate‐based hydrogels have been used extensively in biological applications owing to their low cost, renewability, biocompatibility and biodegradability. [ 41 ] Polylysine as a natural antibacterial peptide has excellent biocompatibility and broad‐spectrum antibacterial activity, making the EPEG‐OA hydrogel potentially an excellent biomedical material, especially for the preparation and functionalization of wound dressings.…”

Section: Resultsmentioning

confidence: 99%

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A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

Wang

Cheng

et al. 2023

Adv Funct Materials

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Chronic refractory wounds have become a severe threat to public health and are characterized by repeated bacterial infections, persistent hypoxia, abnormal immune regulation, and obstruction of angiogenesis. However, current treatment strategies usually perform only one or two therapeutic functions and cannot satisfy the dynamic and complex demands of chronic wound healing. Herein, a versatile dynamic Schiff base and borate ester cross‐linked glycopeptide hydrogel is prepared from phenylboronic acid‐grafted ε‐polylysine (EPBA), epigallocatechin‐3‐gallate (EGCG), and oxidized alginate. Customized polydopamine‐coated honeycomb MnO2 nanoparticles loaded with herb‐derived salvianolic acid B (PHMS) are embedded into the hydrogel before gelation. Under the distinct acidic and oxidative microenvironment of chronic refractory wounds, the hydrogel gradually dissociates, and the released EPBA effectively eliminates bacteria, while the released EGCG and PHMS eradicates reactive oxygen and nitrogen species, promotes M2 polarization of macrophages, and continuously generates oxygen. Then PHMS further disintegrates, and the released salvianolic acid B promotes angiogenesis through the PI3K/Akt pathway. The versatile glycopeptide hydrogel accelerates Staphylococcus aureus‐infected diabetic cutaneous wound repair in vivo and is a promising candidate dressing for chronic refractory wound healing.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

Wang

Cheng

et al. 2023

Adv Funct Materials

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“…We speculated that HucMSC-Exo might reprogram neutrophils into a beneficial phenotype, much like the tissue-repairing M2 macrophage phenotype, which is recognized for tempering inflammation and facilitating tissue repair. 18,37,[39][40][41][42][43][44] Cutting-edge research in oncology has revealed that neutrophils within tumor environments can manifest a pro-tumor N2 phenotype by expressing Arg1, CCL2, and CCL5, mainly regulated by the transforming growth factor-β within the tumor milieu. 45 Extending this concept to wound healing, we found a diverse array of neutrophils at the injury site, with a notable fraction expressing M2 markers-Arg1-marking the first reported occurrence of N2 neutrophils in skin tissue.…”

Section: Discussionmentioning

confidence: 99%

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

Yang,

Xie,

Xia

et al. 2024

IJN

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Background Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes. Methods HucMSC-Exo were isolated via ultracentrifugation and subsequently administered through subcutaneous injection into full-thickness cutaneous wounds in mice. To determine the impact of host neutrophils on the healing effects of HucMSC-Exo in skin injuries, strategies including neutrophil depletion and adoptive transfer were employed. Flow cytometry was used to evaluate the proportion of N2 subtype neutrophils in both normal and diabetic wounds, and the effect of HucMSC-Exo on this proportion was assessed. Furthermore, the mitochondrial metabolic reprogramming driven by HucMSC-Exo during N2 polarization was investigated through JC1 staining, ATP quantification, fatty acid uptake assays, and assessment of FAO-related genes ( Cpt1b, Acadm, and Acadl ). Results Depleting host neutrophils strikingly dampened prohealing effect of HucMSC-Exo on skin injury, while adoptive transfer of bone marrow neutrophils rescued this process. During normal healing process, some neutrophils expressed N2 markers, in contrast, diabetic wounds exhibited a reduced expression of N2 markers. After treatment with HucMSC-Exo, most neutrophils increased the phosphorylation of STAT6, leading to mitochondrial metabolic reprogramming and thus acquired an N2 phenotype. These N2 neutrophils, polarized by HucMSC-Exo, boosted the release of proangiogenic factors, particularly BV8, a myeloid cell-derived proangiogenic factor, and induced angiogenesis thereby favoring tissue restoration. Conclusion This research uniquely demonstrates the identification of N2 neutrophils in skin injury and shows that HucMSC-Exo could skew neutrophils toward N2 phenotype, enhancing our insight into how cells react to HucMSC-Exo.

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“…Besides, polysaccharides, such as HA and alginate, can be modified with aldehyde groups by chemoselective oxidation of vicinal diols with sodium periodate. [ 38 ]…”

Section: Design Of Hydrogels For Immunomodulationmentioning

confidence: 99%

Designing Hydrogels for Immunomodulation in Cancer Therapy and Regenerative Medicine

Zhang,

He,

Chen

2023

Advanced Materials

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The immune system not only acts as a defense against pathogen and cancer cells, but also plays an important role in homeostasis and tissue regeneration. Targeting immune systems is a promising strategy for efficient cancer treatment and regenerative medicine. Current systemic immunomodulation therapies are usually associated with low persistence time, poor targeting to action sites and severe side effects. Due to their ECM‐mimetic nature, tunable properties and diverse bioactivities, hydrogels are intriguing platforms to locally deliver immunomodulatory agents and cells, as well as provide an immunomodulatory microenvironment to recruit, activate and expand host immune cells. In this review, we focus on the design considerations, including polymer backbones, crosslinking mechanisms, physicochemical nature, and immunomodulation‐related components, of the hydrogel platforms. The immunomodulatory effects and therapeutic outcomes in cancer therapy and tissue regeneration of different hydrogel systems are emphasized, including hydrogel depots for delivery of immunomodulatory agents, hydrogel scaffolds for cell delivery, and immunomodulatory hydrogels depending on the intrinsic properties of materials. Finally, the remained challenges in current systems and future development of immunomodulatory hydrogels are discussed.This article is protected by copyright. All rights reserved

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Charge and receptor functional injectable hydrogels as cytokine-releasing reservoirs for wound healing

Cited by 15 publications

References 53 publications

A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

HucMSC-Exo Induced N2 Polarization of Neutrophils: Implications for Angiogenesis and Tissue Restoration in Wound Healing

Designing Hydrogels for Immunomodulation in Cancer Therapy and Regenerative Medicine

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