Combined Therapeutic Strategy Based on Blocking the Deleterious Effects of AGEs for Accelerating Diabetic Wound Healing

Overview

Journal Regen Biomater

Specialty Biomedical Engineering

Date 2024 Sep 26

PMID 39323743

Authors

Yang Yang

Siwen Huang

Qing Ma

Ning Li

Runchu Li

Yongjun Wang

Hongzhuo Liu

Affiliations

Soon will be listed here.

Abstract

Diabetic foot ulcer is a serious complication of diabetes. Excessive accumulation of advanced glycation end products (AGEs) is one of the critical pathogenic factors in postponing diabetic wound healing. The main pathogenic mechanisms of AGEs include inducing cellular dysfunction, prolonging inflammatory response, increasing oxidative stress and reducing endogenous nitric oxide (NO) production. Combination therapy of blocking the deleterious effects of AGEs and supplementing exogenous NO is hypothesized to promote diabetic wound healing. Here, we presented nanoparticles/hydrogel composite dressings to co-delivery rosiglitazone and S-nitroso glutathione into the wound bed. The designed co-delivery system augmented the survival of fibroblasts, reduced oxidative stress levels, reversed the change of mitochondrial membrane potential and decreased the proinflammatory cytokine expression. Local sustained release of therapeutic agents significantly improved the wound healing of diabetic rats including increasing the wound closure rate, alleviating inflammation, promoting collagen fiber production and angiogenesis. Our finding indicated this local deliver strategy aimed at inhibiting the toxic effects of AGEs has great clinical potential for diabetic wound treatment.

References

Byun K, Yoo Y, Son M, Lee J, Jeong G, Park Y . Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases. Pharmacol Ther. 2017; 177:44-55. DOI: 10.1016/j.pharmthera.2017.02.030. View

Tu C, Lu H, Zhou T, Zhang W, Deng L, Cao W . Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties. Biomaterials. 2022; 286:121597. DOI: 10.1016/j.biomaterials.2022.121597. View

Yang Y, Huang K, Wang M, Wang Q, Chang H, Liang Y . Ubiquitination Flow Repressors: Enhancing Wound Healing of Infectious Diabetic Ulcers through Stabilization of Polyubiquitinated Hypoxia-Inducible Factor-1α by Theranostic Nitric Oxide Nanogenerators. Adv Mater. 2021; 33(45):e2103593. DOI: 10.1002/adma.202103593. View

Wu X, Zhu H, Che J, Xu Y, Tan Q, Zhao Y . Stem cell niche-inspired microcarriers with ADSCs encapsulation for diabetic wound treatment. Bioact Mater. 2023; 26:159-168. PMC: 10008968. DOI: 10.1016/j.bioactmat.2023.02.031. View

Stachura A, Khanna I, Krysiak P, Paskal W, Wlodarski P . Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice-A Mechanistic Systematic Review. Int J Mol Sci. 2022; 23(15). PMC: 9369324. DOI: 10.3390/ijms23158621. View

Shaikh-Kader A, Houreld N, Rajendran N, Abrahamse H . The link between advanced glycation end products and apoptosis in delayed wound healing. Cell Biochem Funct. 2019; 37(6):432-442. DOI: 10.1002/cbf.3424. View

Kharaziha M, Baidya A, Annabi N . Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing. Adv Mater. 2021; 33(39):e2100176. PMC: 8489436. DOI: 10.1002/adma.202100176. View

Zhang C, Biggs T, Devarie-Baez N, Shuang S, Dong C, Xian M . S-Nitrosothiols: chemistry and reactions. Chem Commun (Camb). 2017; 53(82):11266-11277. DOI: 10.1039/c7cc06574d. View

Liang C, Ren Y, Tan H, He Z, Jiang Q, Wu J . Rosiglitazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products. Br J Pharmacol. 2009; 158(8):1865-73. PMC: 2807648. DOI: 10.1111/j.1476-5381.2009.00450.x. View

10.

Xing C, Zhu H, Dou X, Gao L, Baddi S, Zou Y . Infected Diabetic Wound Regeneration Using Peptide-Modified Chiral Dressing to Target Revascularization. ACS Nano. 2023; 17(7):6275-6291. DOI: 10.1021/acsnano.2c10039. View

11.

Zhang Z, Zhang W, Xu Y, Liu D . Efficacy of hyperbaric oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis. Asian J Surg. 2021; 45(1):68-78. DOI: 10.1016/j.asjsur.2021.07.047. View

12.

Gan J, Liu C, Li H, Wang S, Wang Z, Kang Z . Accelerated wound healing in diabetes by reprogramming the macrophages with particle-induced clustering of the mannose receptors. Biomaterials. 2019; 219:119340. DOI: 10.1016/j.biomaterials.2019.119340. View

13.

Gajbhiye S, Wairkar S . Collagen fabricated delivery systems for wound healing: A new roadmap. Biomater Adv. 2022; 142:213152. DOI: 10.1016/j.bioadv.2022.213152. View

14.

Soneja A, Drews M, Malinski T . Role of nitric oxide, nitroxidative and oxidative stress in wound healing. Pharmacol Rep. 2006; 57 Suppl:108-19. View

15.

Wang L, Yu C, Liu W, Cheng L, Zhang Y . Rosiglitazone protects neuroblastoma cells against advanced glycation end products-induced injury. Acta Pharmacol Sin. 2011; 32(8):991-8. PMC: 4002533. DOI: 10.1038/aps.2011.81. View

16.

Yamagishi S, Ueda S, Matsui T, Nakamura K, Imaizumi T, Takeuchi M . Pigment epithelium-derived factor (PEDF) prevents advanced glycation end products (AGEs)-elicited endothelial nitric oxide synthase (eNOS) reduction through its anti-oxidative properties. Protein Pept Lett. 2007; 14(8):832-5. DOI: 10.2174/092986607781483705. View

17.

Peppa M, Stavroulakis P, Raptis S . Advanced glycoxidation products and impaired diabetic wound healing. Wound Repair Regen. 2009; 17(4):461-72. DOI: 10.1111/j.1524-475X.2009.00518.x. View

18.

Cheng F, Wang S, Zheng H, Shen H, Zhou L, Yang Z . Ceria Nanoenzyme-Based Hydrogel with Antiglycative and Antioxidative Performance for Infected Diabetic Wound Healing. Small Methods. 2022; 6(11):e2200949. DOI: 10.1002/smtd.202200949. View

19.

Lim J, Ng N, Thomas C . Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017; 110(3):104-109. PMC: 5349377. DOI: 10.1177/0141076816688346. View

20.

Zhou X, Zhao B, Wang L, Yang L, Chen H, Chen W . A glucose-responsive nitric oxide release hydrogel for infected diabetic wounds treatment. J Control Release. 2023; 359:147-160. DOI: 10.1016/j.jconrel.2023.05.047. View