Del-1 nanoparticles/silk fibroin hydrogel accelerates the healing of chronic skin wounds by promoting inflammation regression

Xuewei KAN; Pingping YAO; Jiaqi CHEN; Jun TANG

doi:10.16016/j.2097-0927.202401069

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Del-1 nanoparticles/silk fibroin hydrogel accelerates the healing of chronic skin wounds by promoting inflammation regression

Basic Medicine | 更新时间：2026-01-09

- Del-1 nanoparticles/silk fibroin hydrogel accelerates the healing of chronic skin wounds by promoting inflammation regression
- Journal of Army Medical University Vol. 46, Issue 9, Pages: 988-996(2024)
- 作者机构：
  
  230001 合肥，中国科学技术大学附属第一医院(安徽省立医院)皮肤科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82273516)
- DOI：10.16016/j.2097-0927.202401069
  CLC： R364.5;R640.5;R977.6
- Received：17 January 2024，
  
  Revised：2024-02-29，
  
  Published：15 May 2024
- 稿件说明：
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Xuewei KAN, Pingping YAO, Jiaqi CHEN, et al. Del-1 nanoparticles/silk fibroin hydrogel accelerates the healing of chronic skin wounds by promoting inflammation regression[J]. Journal of Army Medical University, 2024, 46(9): 988-996.
DOI：

Xuewei KAN, Pingping YAO, Jiaqi CHEN, et al. Del-1 nanoparticles/silk fibroin hydrogel accelerates the healing of chronic skin wounds by promoting inflammation regression[J]. Journal of Army Medical University, 2024, 46(9): 988-996. DOI： 10.16016/j.2097-0927.202401069.

摘要

目的

探讨负载发育内皮基因座-1(developmental endothelial locus-1，Del-1)纳米颗粒的丝素水凝胶对小鼠慢性皮肤伤口愈合的影响。

方法

在6~8周BALB/c小鼠背部皮肤用磁铁挤压12 h放松12 h，循环4 d，形成慢性压疮; 小鼠分为3组，每组8只，分别给予皮肤创面PBS、丝素水凝胶或Del-1纳米颗粒/丝素水凝胶治疗，拍照并计算创面愈合率，连续治疗9 d，HE、Masson染色检测皮肤组织愈合；通过CD14和TNF-α的免疫荧光检测创面巨噬细胞和炎症因子表达；过氧叔丁醇(tert-butyl hydroperoxide，TBHP)体外刺激小鼠巨噬细胞系RAW 264.7和小鼠血管内皮细胞系C166；在C166细胞中过表达Del-1，结晶紫染色检测巨噬细胞迁移；RT-qPCR检测炎症因子IL-6表达。

结果

小鼠实验证实Del-1纳米颗粒/丝素水凝胶组的创面愈合快于丝素水凝胶组和PBS组(

＜0.01)；Del-1纳米颗粒/丝素水凝胶组创面的TNF-α及CD14的表达低于丝素水凝胶组和PBS组(

＜0.01)，但胶原沉积和组织修复高于PBS和丝素水凝胶组(

＜0.01)。体外实验证实TBHP激活巨噬细胞向内皮细胞迁移，但Del-1过表达组巨噬细胞迁移率显著下降(

＜0.01)；RT-qPCR显示Del-1抑制了IL-6表达(

＜0.01)。

结论

Del-1纳米颗粒/丝素水凝胶能够加速小鼠压疮愈合，其机制可能是通过促进炎症消退和组织修复。

Abstract

Objective

To investigate the effect of silk fibroin hydrogel loaded with developmental endothelial locus-1 (Del-1) nanoparticles on the healing of chronic skin wounds in mice.

Methods

The back skin of BALB/c mice (6-8 weeks old) was pressed with a magnet for 12 h and then relaxed for 12 h

for 4 consecutive days to establish a chronic pressure ulcer wound. After infliction

the mice were randomly di

vided into 3 groups (

=8)

and the skin wounds were treated with PBS

silk fibroin hydrogel or Del-1 nanoparticles/silk fibroin hydrogel. The wound healing was recorded with camera to calculate the wound healing rate. In 9 d after treatment

HE and Masson staining were used to observe the wound healing

and immunofluorescence staining for CD14 and TNF-α was used to compare the appearance frequency of skin macrophages and the expression of inflammatory factors. After Tert-butyl peroxide (TBHP) was used to stimulate mouse macrophage RAW 264.7 cells and mouse vascular endothelial C166 cells

C166 cells were transfected with lentival vector to overexpress Del-1. Crystal violet staining was used to observe the migration of macrophages. RT-qPCR was used to detect the expression of inflammatory factor IL-6.

Results

The wound healing was significantly faster in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group (

0.01). The expression levels of TNF-α and CD14 in the wound surface were lower (

0.01)

but collagen deposition and tissue repair were better in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group (

0.01).

In vitro

experiments

macrophages migrated to endothelial cells stimulated by TBHP

but the migration rate of macrophages was significantly lower in the Del-1 overexpression group (

0.01). RT-qPCR confirmed that Del-1 inhibited the transcription of IL-6 (

0.01).

Conclusion

Del-1 nanoparticles/silk fibroin hydrogel can significantly accelerate the healing of skin wounds

and its mechanism may be through promoting the regression of inflammation and tissue repair.

关键词

Keywords

references

MERVIS J S, PHILLIPS T J. Pressure ulcers: Pathophysiology, epidemiology, risk factors, and presentation[J]. J Am Acad Dermatol, 2019, 81(4): 881-890. DOI: 10.1016/j.jaad.2018.12.069.

OLSSON M, JÄRBRINK K, DIVAKAR U, et al . The humanistic and economic burden of chronic wounds: a systematic review[J ] . Wound Repair Regen, 2019, 27(1): 114-125. DOI: 10.1111/wrr.12683.

BEYENE R T, DERRYBERRY S L JR, BARBUL A. The effect of comorbidities on wound healing[J]. Surg Clin North Am, 2020, 100(4): 695-705. DOI: 10.1016/j.suc.2020.05.002.

ZHENG H Y, ZUO B Q. Functional silk fibroin hydrogels: preparation, properties and applications[J]. J Mater Chem B, 2021, 9(5): 1238-1258. DOI: 10.1039/D0TB02099K.

GHOLIPOURMALEKABADI M, SAPRU S, SAMADIKU-CHAKSARAEI A, et al . Silk fibroin for skin injury repair: where do things stand?[J ] . Adv Drug Deliv Rev, 2020, 153: 28-53. DOI: 10.1016/j.addr.2019.09.003.

MAZUREKŁ, SZUDZIK M, RYBKA M, et al . Silk fibroin biomaterials and their beneficial role in skin wound healing[J ] . Biomolecules, 2022, 12(12): 1852. DOI: 10.3390/biom12121852.

BHAR B, CHAKRABORTY B, NANDI S K, et al . Silk-based phyto-hydrogel formulation expedites key events of wound healing in full-thickness skin defect model[J ] . Int J Biol Macromol, 2022, 203: 623-637. DOI: 10.1016/j.ijbiomac.2022.01.142.

LIU Y K, FAN J C, LV M Q, et al . Photocrosslinking silver nanoparticles-aloe vera-silk fibroin composite hydrogel for treatment of full-thickness cutaneous wounds[J ] . Regen Biomater, 2021, 8(6): rbab048. DOI: 10.1093/rb/rbab048.

WANG R F, RUAN L M, JIANG G H, et al . Fabrication of curcumin-loaded silk fibroin and polyvinyl alcohol composite hydrogel films for skin wound healing[J ] . ACS Appl Bio Mater, 2022. DOI: 10.1021/acsabm.2c00548.

CHAALA M, SEBBA F Z, FUSTER M G, et al . Accelerated simple preparation of curcumin-loaded silk fibroin/hyaluronic acid hydrogels for biomedical applications[J ] . Polymers, 2023, 15(3): 504. DOI: 10.3390/polym15030504.

RUIZ-ALCARAZ A J, NÚÑrEZ-SÁNCHEZ MÁ, ASENSIO RUIZ M A, et al . Optimizing the preparation of silk fibroin nanoparticles and their loading with polyphenols: towards a more efficient anti-inflammatory effect on macrophages[J ] . Pharmaceutics, 2023, 15(1): 263. DOI: 10.3390/pharmaceutics15010263.

MONTALBÁN M G, COBURN J M, LOZANO-PÉREZ A A, et al . Production of curcumin-loaded silk fibroin nanoparticles for cancer therapy[J ] . Nanomaterials, 2018, 8(2): 126. DOI: 10.3390/nano8020126.

ESKAN M A, JOTWANI R, ABE T, et al . The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss[J ] . Nat Immunol, 2012, 13(5): 465-473. DOI: 10.1038/ni.2260.

CHOI E Y, LIM J H, NEUWIRTH A, et al . Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination[J ] . Mol Psychiatry, 2015, 20(7): 880-888. DOI: 10.1038/mp.2014.146.

KANG Y Y, KIM D Y, LEE S H, et al . Deficiency of developmental endothelial locus-1(Del-1) aggravates bleomycin-induced pulmonary fibrosis in mice[J ] . Biochem Biophys Res Commun, 2014, 445(2): 369-374. DOI: 10.1016/j.bbrc.2014.02.009.

YAN S, CHEN L, ZHAO Q, et al . Developmental endothelial locus-1(Del-1) antagonizes interleukin-17-mediated allergic asthma[J ] . Immunol Cell Biol, 2018, 96(5): 526-535. DOI: 10.1111/imcb.12023.

LUO L W, ZHANG H Y, ZHANG S Y, et al . Extracellular vesicle-derived silk fibroin nanoparticles loaded with MFGE8 accelerate skin ulcer healing by targeting the vascular endothelial cells[J ] . J Nanobiotechnol, 2023, 21(1): 455. DOI: 10.1186/s12951-023-02185-7.

LI M R, HOU Q, ZHONG L Z, et al . Macrophage related chronic inflammation in non-healing wounds[J ] . Front Immunol, 2021, 12: 681710. DOI: 10.3389/fimmu.2021.681710.

WILLENBORG S, SANIN D E, JAIS A, et al . Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing[J ] . Cell Metab, 2021, 33(12): 2398-2414. e9. DOI: 10.1016/j.cmet.2021. 10.004.

XIONG Y, LIN Z, BU P Z, et al . A whole-course-repair system based on neurogenesis-angiogenesis crosstalk and macrophage reprogramming promotes diabetic wound healing[J ] . Adv Mater, 2023, 35(19): e2212300. DOI: 10.1002/adma.202212300.

HASSANSHAHI A, MORADZAD M, GHALAMKARI S, et al . Macrophage-mediated inflammation in skin wound healing[J ] . Cells, 2022, 11(19): 2953. DOI: 10.3390/cells11192953.

WLASCHEK M, SINGH K, SINDRILARU A, et al . Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds[J ] . Free Radic Biol Med, 2019, 133: 262-275. DOI: 10.1016/j.freeradbiomed.2018.09.036.

WU Y K, CHENG N C, CHENG C M. Biofilms in chronic wounds: pathogenesis and diagnosis[J]. Trends Biotechnol, 2019, 37(5): 505-517. DOI: 10.1016/j.tibtech.2018.10.011.

RAZIYEVA K, KIM Y, ZHARKINBEKOV Z, et al . Immunology of acute and chronic wound healing[J ] . Biomolecules, 2021, 11(5): 700. DOI: 10.3390/biom11050700.

DIPIETRO L A, WILGUS T A, KOH T J. Macrophages in healing wounds: paradoxes and paradigms[J]. Int J Mol Sci, 2021, 22(2): 950. DOI: 10.3390/ijms22020950.

NIU X P, LI X H, FENG Z P, et al . EDIL3 and VEGF synergistically affect angiogenesis in endothelial cells[J ] . Clin Cosmet Investig Dermatol, 2023, 16: 1269-1277. DOI: 10.2147/CCID.S411253.

SHINDE R, HEZAVEH K, HALABY M J, et al . Apoptotic cell-induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans[J ] . Nat Immunol, 2018, 19(6): 571-582. DOI: 10.1038/s41590-018-0107-1.

KOURTZELIS I, LI X F, MITROULIS I, et al . DEL-1 promotes macrophage efferocytosis and clearance of inflammation[J ] . Nat Immunol, 2019, 20(1): 40-49. DOI: 10.1038/s41590-018-0249-1.

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