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牙周和骨再生的伤口模型:生物学研究的作用。

Wound models for periodontal and bone regeneration: the role of biologic research.

作者信息

Sculean Anton, Chapple Iain L C, Giannobile William V

出版信息

Periodontol 2000. 2015 Jun;68(1):7-20. doi: 10.1111/prd.12091.

Abstract

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.

摘要

牙周治疗的最终目标仍然是用具有相同结构和功能的组织,使那些因破坏性炎症免疫反应或创伤而丧失的牙周组织完全再生,并从以生态失调为特征的生物膜重建可持续促进健康的生物膜。《牙周病学2000》的这一卷讨论了从20世纪60年代末的治疗经验主义向再生疗法转变的多个方面,这种转变建立在对正常结构和功能的生物生理学有更清晰理解的基础上。这篇介绍性文章概述了牙周伤口和骨修复的适当体外实验室模型(如细胞培养)、临床前(即动物)模型和人体研究的要求。实验室研究可能会为伤口修复和再生所涉及的基本机制提供有价值的基础见解,但也存在一维且简单化的方法的问题,这种方法没有考虑到体内情况的复杂性,在体内多种细胞类型和相互作用都对最终结果有贡献。因此,此类实验室研究需要验证性研究,采用专门设计用于证明概念验证疗效、初步安全性以及对人类疾病情况适应性的临床前模型。小动物模型提供了最经济且在后勤上可行的初步方法,但结果不一定能转化到更大动物或人体模型。在规划研究时,需要仔细考虑所有牙周再生模型的优缺点,以确保采用最佳设计来回答所提出的特定研究问题。未来的挑战在于干细胞研究、支架设计、细胞递送和生长因子的选择领域,以及确保适当牙龈覆盖以防止愈合阶段牙龈退缩的研究。

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