Injectable Nanocomposite Hydrogel for Accelerating Diabetic Wound Healing Through Inflammatory Microenvironment Regulation

被引：1

作者：

Chen, Yuhui ^{[1
]}

Li, Ying ^{[1
]}

Song, Haoning ^{[1
]}

Liu, Xiaochun ^{[1
]}

Zhang, Hongan ^{[1
]}

Jiang, Jiaxin ^{[2
]}

Liu, Hongsheng ^{[2
]}

Zhuo, Ribo ^{[1
]}

Cheng, Guoyun ^{[1
]}

Fang, Jia ^{[1
]}

Xu, Lei ^{[1
]}

Qi, Yong ^{[1
]}

Sun, Dawei ^{[1
]}

机构：

[1] Jinan Univ, Guangdong Prov Gen Hosp 2, Dept Orthoped & Traumatol, 466 Xingang Middle Rd, Guangzhou 510315, Guangdong, Peoples R China

[2] Guangdong Huayi Biomed Sci & Technol Ctr, Guangzhou 511450, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2025年 / 20卷

关键词：

diabetic wound; thermosensitive hydrogel; inflammatory microenvironment; macrophage polarization; angiogenesis;

D O I：

10.2147/IJN.S505918

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Background: A paramount issue in the realm of chronic wound healing among diabetic patients is the pervasive inflammatory response that persistently thwarts angiogenesis, thereby precipitating protracted delays in the healing process of such wounds. Employing zeolitic imidazolate framework-8 (ZIF-8) as a drug delivery platform, integrated within a temperature-sensitive injectable hydrogel, presents an intriguing strategy for the closure of various irregular wounds, modulation of inflammatory responses, and promotion of angiogenesis. Methods: Herein, ZIF-8 loaded with curcumin (Cur) combined with methylcellulose/carboxymethyl chitosan (MCC) thermosensitive hydrogel was described. The assessment encompassed the temperature-sensitive properties, pH-responsive release, antimicrobial activity, and ROS scavenging capabilities of the MCC@ZIF-8@Cur hydrogel. A series of studies were conducted to explore its biocompatibility, pro-angiogenic effects, and macrophage M2 polarization induction. Additionally, a full-thickness skin defect model of diabetic rat was established to investigate the hydrogel's multifaceted efficacy in facilitating wound repair, mitigating inflammatory responses, and fostering angiogenesis. Results: The thermosensitive MCC@ZIF-8@Cur hydrogel possess the attribute of being injectable and capable of in situ formation (gelation temperature of >= 28 degrees C), thereby establishing an effective physical barrier for a multitude of irregular wound profiles. The incorporation of ZIF-8@Cur confers the hydrogel with exceptional antibacterial properties and the capability to eliminate reactive oxygen species (ROS). Moreover, the pH-responsive MCC@ZIF-8@Cur hydrogel continuously releases Cur and Zn2+, mitigating inflammation, inducing M2 polarization of macrophages, and promoting angiogenesis. This creates a favorable immune microenvironment conducive to skin regeneration, thereby accelerating the healing of diabetic wounds. In vivo studies have demonstrated a markedly accelerated wound healing ratio in rats within the hydrogel group compared to the Control group (p<0.001). By the 14th day of wound healing, the MCC@ZIF-8@Cur hydrogel group achieved a remarkable healing ratio of 97.22%, considerably surpassing the Control group (72.98%), showcasing remarkable potential for treating diabetic wounds. Conclusion: The findings demonstrate the successful creation of a temperature-sensitive hydrogel that exhibits remarkable antibacterial properties and ROS scavenging capabilities. This hydrogel effectively suppresses inflammatory responses, modulates the polarization of macrophages towards the M2 phenotype, and promotes angiogenesis, thus fostering a favorable immune microenvironment for skin regeneration. These attributes collectively augur promising prospects and applications in the healing of diabetic wounds.

引用

页码：1679 / 1696

页数：18

共 49 条

[1] Birkenfeld AL, Mohan V., Prediabetes remission for type 2 diabetes mellitus prevention, Nat Rev Endocrinol, 20, 8, pp. 441-442, (2024)
[2] Taylor R., Understanding the cause of type 2 diabetes, Lancet Diab Endocrinol, 12, 9, pp. 664-673, (2024)
[3] Buch Pranali J, Chai Y, Goluch Edgar D., Treating polymicrobial infections in chronic diabetic wounds, Clin Microbiol Rev, 32, 2, pp. 1-18, (2019)
[4] Chengwei W, Yihao L, Xiaoxiao Y, Et al., In-situ forming hydrogel incorporated with reactive oxygen species responsive and antibacterial properties for diabetic infected chronic wound healing, Chem Eng J, 450, (2022)
[5] Liu C, Lv M, Xu Q, Et al., Chronological adaptive polyoxometalate-based hydrogel for diabetic chronic wounds through synchronous bacterial ferroptosis death and immunomodulation, Nano Today, 58, (2024)
[6] Lou D, Luo Y, Pang Q, Tan W-Q, Ma L., Gene-activated dermal equivalents to accelerate healing of diabetic chronic wounds by regulating inflammation and promoting angiogenesis, Bioact Mater, 5, 3, pp. 667-679, (2020)
[7] Tu Z, Chen M, Wang M, Et al., Engineering bioactive M2 macrophage-polarized anti-inflammatory, antioxidant, and antibacterial scaffolds for rapid angiogenesis and diabetic wound repair, Adv Funct Mater, 31, 30, (2021)
[8] Cao Y, Chen B, Liu Q, Et al., Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment, Bioact Mater, 42, pp. 32-51, (2024)
[9] Yuan Y, Fan D, Shen S, Ma X., An M2 macrophage-polarized anti-inflammatory hydrogel combined with mild heat stimulation for regulating chronic inflammation and impaired angiogenesis of diabetic wounds, Chem Eng J, 433, (2022)
[10] Zhao H, Huang J, Li Y, Et al., ROS-scavenging hydrogel to promote healing of bacteria infected diabetic wounds, Biomaterials, 258, (2020)

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