基于“免疫微环境调控”的屏障膜研发理念

doi:10.12016/j.issn.2096-1456.2021.08.001

口腔疾病防治 ›› 2021, Vol. 29 ›› Issue (8): 505-514.DOI: 10.12016/j.issn.2096-1456.2021.08.001

基于“免疫微环境调控”的屏障膜研发理念

陈泽涛¹(),林义雄¹,杨杰婷²,黄宝鑫²,陈卓凡³

1.中山大学光华口腔医学院·附属口腔医院口腔研究所/种植科,广东省牙颌系统修复重建技术与材料工程技术研究中心,广东广州（510055）
2.中山大学光华口腔医学院·附属口腔医院种植科,广东省口腔医学重点实验室,广东广州（510055）
3.中山大学光华口腔医学院·附属口腔医院珠江新城门诊,广东省口腔医学重点实验室,广东广州（510055）

收稿日期:2020-10-16 修回日期:2021-01-19 出版日期:2021-08-20 发布日期:2021-05-13
通讯作者: 陈泽涛
作者简介:陈泽涛,研究员,博士研究生导师,就职于中山大学光华口腔医学院·附属口腔医院。现任中山大学科学研究院基地处副处长,广东省牙颌系统修复重建技术与材料工程技术研究中心副主任。担任中华口腔医学会口腔生物医学专业委员会常务委员,广东省口腔医学会口腔种植专业委员会委员,中国生物材料学会青年委员会委员;入选国家海外高层次人才计划。从事口腔种植学、口腔材料学相关医教研工作,聚焦口腔软硬组织再生修复的免疫机制及其调控研究,成果发表于Advanced Functional Materials,ACS Nano,Materials Today,Biomaterials等期刊;共发表SCI学术论文37篇,以第一作者、通信作者发表影响因子大于10的SCI学术论文7篇;主编《口腔基础研究导论》（人民卫生出版社）,参编英语专著《The Immune Response toImplanted Materials and Devices》;主持国家自然科学基金项目（面上、青年）、广东省杰出青年科学基金项目、ITI Research Grant、The Osteology Research Grant等国内国际项目12项。
基金资助:
国家自然科学基金项目(82071167);广东省杰出青年科学基金(2018B030306030);广东省财政高水平医院建设专项资金

Research and development concept of barrier membranes based on “ immune microenvironment regulation”

CHEN Zetao¹(),LIN Yixiong¹,YANG Jieting²,HUANG Baoxin²,CHEN Zhuofan³

1. Laboratory of Stomatology/ Institute of Stomatology and Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, China
2. Institute of Stomatology and Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
3. Zhujiang New Town Clinic, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China

Received:2020-10-16 Revised:2021-01-19 Online:2021-08-20 Published:2021-05-13
Contact: Zetao CHEN
Supported by:
National Natural Science Foundation of China(82071167);Distinguished Young Scholars of Guangdong Province(2018B030306030);Special Fund for High Level Hospital Construction in Guangdong Province

摘要/Abstract

摘要：

引导骨再生技术应用于牙槽骨缺损再生的基础是屏障膜的屏障功能及空间维持作用,因此传统屏障膜的研发策略集中关注其物理屏障功能、降解性能及如何规避免疫原性提高生物相容性。屏障膜不仅能够被动地阻挡结缔组织,其作为“异己”成分植入体内后,会引发宿主持续的免疫反应即异物反应。骨免疫学理论表明免疫系统和骨骼系统联系密切,免疫细胞在骨组织相关的病理生理过程中发挥了重要作用。基于这一研究背景,笔者课题组提出基于“免疫微环境调控”的屏障膜研发理念：通过对屏障膜机械性能、表面性能及理化性能的调控,赋予屏障膜良好的免疫调控能力,诱导良好的局部免疫微环境产生,从而协调成骨与破骨以及屏障膜降解过程,提高引导骨再生中屏障膜成骨效能,满足骨缺损再生修复需求。本文述评了屏障膜的发展沿革及免疫微环境、骨再生、屏障膜三者间的紧密联系,提出基于“免疫微环境调控”的屏障膜研发理念,旨在提高屏障膜的成骨效能,解决牙槽骨缺损再生修复的科学难题。

关键词: 屏障膜, 免疫微环境, 成骨分化, 骨再生, 异物反应, 降解, 免疫细胞, 巨噬细胞

Abstract:

Guided bone regeneration technology applied in alveolar bone defect regeneration is based on the barrier function and space maintenance of the barrier membrane. Therefore, traditional development strategies for barrier membranes focus on their physical barrier function, degradation characteristics and biocompatibility to avoid immunogenicity. However, not only does the barrier membrane passively block connective tissue, it is recognized as a “foreign body”that triggers a persistent host immune response, known as a foreign body reaction. The theories of osteoimmunology reveal a close relationship between the immune system and bone system and emphasize the role of immune cells in bone tissue-related pathophysiological processes. Based on these findings, we propose a novel development strategy for barrier membranes based on immune microenvironment regulation: by manipulating mechanical properties, surface properties and physiochemical properties, barrier membranes are endowed with an improved immunomodulation ability, which helps to regulate immune cell reactions to induce a favorable local immune microenvironment, thus coordinating osteogenesis and osteoclastogenesis as well as barrier membrane degradation to increase the efficiency of barrier membranes in GBR applications. In this paper, we review the development of barrier membranes and their close relationship to the immune microenvironment concerning bone regeneration and membrane degradation. Additionally, the outcomes of research on barrier membranes based on the regulation of the immune microenvironment have been summarized to improve the osteogenesis efficiency of barrier membranes and solve the problem of the regeneration and repair of bone defects, especially alveolar bone defects.

Key words: barrier membrane, immune microenvironment, osteogenic differentiation, bone regeneration, foreign body reaction, degradation, immune cells, macrophage

中图分类号:

陈泽涛,林义雄,杨杰婷,黄宝鑫,陈卓凡. 基于“免疫微环境调控”的屏障膜研发理念[J]. 口腔疾病防治, 2021, 29(8): 505-514.

CHEN Zetao,LIN Yixiong,YANG Jieting,HUANG Baoxin,CHEN Zhuofan. Research and development concept of barrier membranes based on “ immune microenvironment regulation”[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(8): 505-514.

图/表 2

图1 具有骨免疫调控性能的屏障膜

Figure 1 Barrier membrane based on osteoimmunomodulation Based on an osteoimmunomodulation strategy, the development concept of barrier membranes emphasizes the manipulation of both physiochemical characteristics, including mechanical characteristics, and surface properties. Additionally, it introduces bioactive agents, such as metal ions, cytokines and antibiotics, to regulate the activation state and polarization of macrophages, thereby creating a favorable osteoimmunological microenvironment facilitating the osteogenic differentiation of MSCs and improving the osteogenic efficiency of barrier membranes. BMP-2: bone morphogenetic protein-2; TGF-β: transforming growth factor-β; VEGF: vascular endothelial growth factor; M-CSF: macrophage colony-stimulating factor; RANKL: receptor activator of NF-κB ligand; OPG: osteoprotegerin

图2 具有良好“免疫降解”性能的屏障膜

Figure 2 Barrier membrane based on the “immunodegradation” strategy The development concept of an “immunodegradation” strategy emphasizes the modulation of cell-mediated degradation to regulate the degradation characteristics of barrier membranes. Manipulation of key cells and cytokines participating in membrane degradation could regulate the function of T cells and the phagocytosis of both macrophages and FBGCs, achieving efficient regulation of the degradation characteristics and osteogenic improvements of membranes. CXCL8: CXC chemokine ligand 8; CCL: C-C motif chemokine ligand; IL: interleukin

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基于“免疫微环境调控”的屏障膜研发理念

Research and development concept of barrier membranes based on “ immune microenvironment regulation”

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