Wang Chengshi, Li Tiancheng, Zeng Xinyi, Wu Lei, Gao Min, Tong Nanwei, Duan Peipei, Liu Jingping
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.
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.
Dent Mater. 2023 Apr;39(4):418-429. doi: 10.1016/j.dental.2023.03.014. Epub 2023 Mar 15.
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.
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.
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).
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.
糖尿病条件下，由于炎症持续时间延长导致牙槽骨缺损延迟再生，这仍然是临床牙科修复面临的一项挑战，因此需要有效的治疗方法。基于细胞因子的免疫疗法可能是调节炎症和骨再生的一种潜在策略。在此，我们报告通过可注射自组装肽（SAP）水凝胶局部递送白细胞介素-10（IL-10）可有效促进促炎（M1）向抗炎（M2）表型转化，从而增强糖尿病牙槽骨缺损中的骨再生。
通过形态、可注射性和流变学特性评估SAP水凝胶的特征。在培养过程中随时间评估IL-10从SAP水凝胶中的负载和释放情况。使用糖尿病小鼠牙槽骨缺损模型在体内评估SAP/IL-10水凝胶的局部炎症反应和骨修复效果。最后，研究M2巨噬细胞对M1表型和间充质干细胞（MSC）矿化的直接影响。
在体外，封装的IL-10可由SAP水凝胶持续释放并保留生物活性。在体内，SAP/IL-10水凝胶在减弱M1极化和促炎因子水平以及增强成骨因子表达方面显示出显著更高的效果。因此，由SAP/IL-10水凝胶诱导的糖尿病骨再生明显更快。从机制上讲，持续递送IL-10诱导的M2巨噬细胞可能通过重编程M1表型、抑制局部炎症和增强间充质干细胞（MSC）的成骨分化来促进糖尿病骨再生。
本研究强调SAP水凝胶是治疗牙槽骨缺损的一种有前景的药物递送平台，可能在未来临床应用中具有转化潜力。
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