Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing

Chengshi Wang; Tiancheng Li; Xinyi Zeng; Lei Wu; Min Gao; Nanwei Tong; Peipei Duan; Jingping Liu

doi:10.1016/j.dental.2023.03.014

Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing

Dent Mater. 2023 Apr;39(4):418-429. doi: 10.1016/j.dental.2023.03.014. Epub 2023 Mar 15.

Authors

Chengshi Wang¹, Tiancheng Li², Xinyi Zeng², Lei Wu³, Min Gao⁴, Nanwei Tong⁵, Peipei Duan⁶, Jingping Liu⁷

Affiliations

¹ Division of Endocrinology and Metabolism, NHC Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China; Division of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China; West China School of Nursing, Sichuan University, Chengdu, China.
² State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
³ Core facility of West China Hospital, Sichuan University, Chengdu, China.
⁴ West China School of Nursing, Sichuan University, Chengdu, China.
⁵ Division of Endocrinology and Metabolism, NHC Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China.
⁶ State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: duanp@scu.edu.cn.
⁷ Division of Endocrinology and Metabolism, NHC Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liujingping@scu.edu.cn.

PMID: 36931990
DOI: 10.1016/j.dental.2023.03.014

Abstract

Objective: Delayed regeneration of alveolar bone defects because of prolonged inflammation under diabetic conditions remains a challenge for dental rehabilitation in clinic, and effective therapies are required. Cytokines-based immuotherapies might be a potential strategy to regulate inflammation and bone regeneration. Here, we report that local delivery of interleukin-10 (IL-10) by injectable self-assembling peptide (SAP) hydrogel is efficient to promote proinflammatory (M1)-to-anti-inflammatory (M2) phenotype conversion, thereby enhancing bone regeneration in diabetic alveolar bone defects.

Methods: Characteristics of SAP hydrogel were evaluated by morphology, injectable and rheological properties. The loading and release of IL-10 from the SAP hydrogel were evaluated over time in culture. The local inflammatory response and bone repair efficacy of the SAP/IL-10 hydrogel was evaluated in vivo using an alveolar bone defect model of diabetic mice. Finally, the direct effects of M2 macrophage on M1 phenotype and mineralization of MSCs were investigated.

Results: In vitro, encapsulated IL-10 could be sustainedly released by SAP hydrogel with preserved bioactivities. In vivo, SAP/IL-10 hydrogel showed significantly higher efficacy to attenuate M1 polarization and proinflammatory factors levels, and enhance expressions of osteogenic factors. As a result, diabetic bone regeneration induced by SAP/IL-10 hydrogel was significantly faster. Mechanistically, M2 macrophages induced by sustained IL-10 delivery might promote diabetic bone regeneration by reprogramming M1 phenotype, suppressing local inflammation and enhancing the osteogenic differentiation of mesenchymal stem cells (MSCs).

Significance: This study highlights that the SAP hydrogel is a promising drug delivery platform for treatment of alveolar bone defects, which might have translational potential in future clinical applications.

Keywords: Bone regeneration; Controlled release; Inflammation; Macrophage; Self-assembling peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental* / metabolism
Hydrogels* / chemistry
Inflammation / metabolism
Interleukin-10 / metabolism
Interleukin-10 / pharmacology
Macrophages / metabolism
Mice
Osteogenesis
Peptides / metabolism
Rats
Rats, Sprague-Dawley

Substances

Hydrogels
Interleukin-10
Peptides