Department of Diagnosis and Surgery, Institute of Science and Technology, São Paulo State University, São José dos Campos, SP, Brazil.
Dental Research Division, Guarulhos University, Guarulhos, SP, Brazil.
Braz Dent J. 2024 Oct 25;35:e246133. doi: 10.1590/0103-6440202406133. eCollection 2024.
Craniofacial bone defects caused by tumors, trauma, long-term tooth loss, or periodontal disease are a major challenge in the field of tissue engineering. In periodontitis and peri-implantitis, reconstructive therapy is also a major challenge for the dental surgeon. Lipoxins, resolvins, protectins, and maresins, known as specialized pro-resolving lipid mediators (SPMs), have been widely studied in the field of dental, oral, and craniofacial research for bone regeneration for their actions in restoring tissue homeostasis and promoting tissue healing and regeneration. Therefore, this study focuses on a survey of the use of SPMs for craniofacial and alveolar bone regeneration. Thus, electronic searches of five databases were performed to identify pre-clinical studies that evaluated the actions of SMPs on craniofacial and alveolar bone regeneration. Of the 523 articles retrieved from the electronic databases, 19 were included in the analysis. Resolvin (Rv) E1 was the mostly assessed SPM (n=8), followed by maresins (Ma) R1 (n=3), lipoxins (Lx) A4 (n=3), RvD1 (n=3), RvD2 (n=1), LxB4 (n=1), and maresin (M)-CTR3 (n=1). Meta-analysis showed that SPMs increased the newly formed bone by 14.85% compared to the control group (p<0.00001), decreased the area of the remaining defect by 0.35 mm2 (p<0.00001), and decreased the linear distance between the defect to the bone crest by 0.53 mm (p<0.00001). RvE1 reduced inflammatory bone resorption in periodontal defects and calvarial osteolysis and enhanced bone regeneration when RvE1 was combined with a bovine bone graft. RvD2 induced active resolution of inflammation and tissue regeneration in periapical lesions, while RvD1 controlled the inflammatory microenvironment in calvarial defects in rats, promoting bone healing and angiogenesis. MaR1 induced the proliferation and migration of mesenchymal stem cells, osteogenesis, and angiogenesis in calvarial defects, and benzo (b)-LxA4 and LxA4 promoted bone regeneration calvarial and alveolar bone defects in rats, inducing regeneration under inflammatory conditions. In summary, SPMs have emerged as pivotal contributors to the resolution of inflammation and the facilitation of bone neoformation within craniofacial and alveolar bone defects. These results are based on pre-clinical studies, in vivo and in vitro, and provide an updated review regarding the impact of SPMs in tissue engineering.
由肿瘤、创伤、长期牙齿缺失或牙周病引起的颅面骨缺损是组织工程领域的一大挑战。在牙周炎和种植体周围炎中，重建治疗也是牙科医生的一大挑战。脂氧素、分辨率素、保护素和maresin 被称为专门的促解决脂质介质 (SPM)，它们在口腔和颅面研究中的骨再生方面得到了广泛研究，因为它们在恢复组织内稳态和促进组织愈合和再生方面发挥作用。因此，本研究重点调查 SPM 在颅面和牙槽骨再生中的应用。因此，进行了五个数据库的电子检索，以确定评估 SPM 对颅面和牙槽骨再生作用的临床前研究。从电子数据库中检索到的 523 篇文章中，有 19 篇被纳入分析。解析素 (Rv) E1 是评估最多的 SPM(n=8)，其次是maresin (Ma) R1(n=3)、脂氧素 (Lx) A4(n=3)、RvD1(n=3)、RvD2(n=1)、LxB4(n=1) 和maresin (M)-CTR3(n=1)。荟萃分析显示，与对照组相比，SPM 使新形成的骨增加了 14.85%(p<0.00001)，使剩余缺陷面积减少了 0.35mm2(p<0.00001)，使缺陷与骨嵴之间的线性距离减少了 0.53mm(p<0.00001)。RvE1 减少牙周缺损中的炎症性骨吸收和颅盖骨骨溶解，并与牛骨移植物结合时增强骨再生。RvD2 在根尖病变中诱导炎症和组织再生的主动解决，而 RvD1 在大鼠颅盖骨缺损中控制炎症微环境，促进骨愈合和血管生成。MaR1 诱导颅盖骨缺损中间充质干细胞的增殖和迁移、成骨和血管生成，而 benzo(b)-LxA4 和 LxA4 促进大鼠颅盖骨和牙槽骨缺损中的骨再生，在炎症条件下诱导再生。总之，SPM 已成为解决颅面和牙槽骨缺损中炎症和促进新骨形成的关键因素。这些结果基于临床前研究、体内和体外研究，并提供了关于 SPM 在组织工程中的影响的最新综述。
