Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Implant treatment in the esthetic area requires stable osseointegration and successful esthetic outcomes. Achieving this goal requires careful consideration of accurate implant axis and ideal three-dimensional position. Owing to the high esthetics and the special anatomical structure of the maxillary, a successful implant means a synthesized deli-beration of the residual bone dimensions, soft-tissue thickness, and the relationship of the residual alveolar ridge with the planned restoration. This article offers an in-depth analysis of the clinical decisions and key factors affecting the implant direction in the esthetic area.
Dental Implantation, Endosseous/methods* ; Dental Implants ; Esthetics, Dental ; Alveolar Ridge Augmentation/methods* ; Osseointegration ; Maxilla/surgery* ; Dental Implants, Single-Tooth

Bioactive glass (BG) has been widely used in the preparation of artificial bone scaffolds due to its excellent biological properties and non-cytotoxicity, which can promote bone and soft tissue regeneration. However, due to the brittleness, poor mechanical strength, easy agglomeration and uncontrollable structure of glass material, its application in various fields is limited. In this regard, most current researches mainly focus on mixing BG with organic or inorganic materials by freeze-drying method, sol-gel method, etc., to improve its mechanical properties and brittleness, so as to increase its clinical application and expand its application field. This review introduces the combination of BG with natural organic materials, metallic materials and non-metallic materials, and demonstrates the latest technology and future prospects of BG composite materials through the development of scaffolds, injectable fillers, membranes, hydrogels and coatings. The previous studies show that the addition of BG improves the mechanical properties, biological activity and regeneration potential of the composites, and broadens the application of BG in the field of bone tissue engineering. By reviewing the recent BG researches on bone regeneration, the research potential of new materials is demonstrated, in order to provide a reference for future related research.
Bone Regeneration ; Bone and Bones ; Freeze Drying ; Glass ; Hydrogels

The gold-standard for bone substitution of large bone defects continues to be autogenous bone graft. Artificial bone substitutes are difficult to replace the autogenous bone grafting due to excessive immune response, fast biodegradation characteristics and inappropriate biocompatibility. Given these drawbacks, osteoimmunology and its advanced functional biomaterials have gained growing attention in recent years. Immune system plays an essential role during bone healing via regulating the shift from inflammatory to anti-inflammation phenotype, and inflammatory cytokines response. The inflammatory reaction mainly include infiltration of immune cells (such as macrophages, neutrophils, T cells, B cells, etc) and release of inflammatory factors (such as IL-1β, IL-6, TNF-α, etc.) at the bone defects, which subsequently affect the step-wised process of bone healing rejuvenation. Hence, advanced bone biomaterials with immunomodulatory properties is of great significance for the treatment of patients with recalcitrant bone defects, especially for delayed healing or non-union. The reciprocal mechanism of immuno-modulated bone healing, however, is not fully understood and more research is required in the future.
Osteogenesis ; Cytokines ; Biocompatible Materials ; Macrophages ; T-Lymphocytes ; Bone Regeneration

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b⁺ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b⁺ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b⁺ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b⁺ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b⁺ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b⁺ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b⁺ macrophages, and suggests a CD301b⁺ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Animals ; Mice ; Bone Regeneration ; Cytokines/metabolism* ; Interleukin-4/therapeutic use* ; Macrophages/physiology* ; Mammals ; Osteogenesis ; Periodontitis/drug therapy*

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.
Platelet-Rich Plasma/metabolism* ; Platelet-Rich Fibrin ; Cell Proliferation ; Bone and Bones ; Intercellular Signaling Peptides and Proteins/metabolism* ; Bone Regeneration

Oligonucleotide drugs have the characteristics of targeting, modifiability and high biosafety. Recent studies have shown that oligonucleotide can be used to make biosensors, vaccine adjuvants, and has the functions of inhibiting alveolar bone resorption, promoting jaw and alveolar bone regeneration, anti-tumor, destroying plaque biofilm, and precise control of drug release. Therefore, it has a broad application prospect in the field of stomatology. This article reviews the classification, action mechanism and research status of oligonucleotide in stomatology. The aim is to provide ideas for further research and application of oligonucleotide.
Humans ; Alveolar Bone Loss ; Biofilms ; Bone Regeneration ; Oligonucleotides ; Oral Medicine

OBJECTIVE: To investigate whether the placement of absorbable collagen membrane increase the stability of alveolar ridge contour after guided bone regeneration (GBR) using buccal punch flap. METHODS: From June 2019 to June 2023, patients who underwent GBR using buccal punch flap simultaneously with a single implant placement in posterior region (from first premolar to second molar) were divided into coverage group, in which particular bone graft was covered by collagen membrane and non-coverage group. Cone beam CT (CBCT) was taken before surgery (T0), immediately after surgery (T1), and 3-7 months after surgery (T2), and the thickness of the buccal bone plate at different levels (0, 2, 4, and 6 mm) below the smooth-rough interface of the implant (BBT-0, -2, -4, -6) was mea-sured after superimposition of CBCT models using Mimics software. RESULTS: A total of 29 patients, including 15 patients in coverage group and 14 patients in non-coverage group, were investigated in this study. At T0, T1, and T2, there was no significant difference in BBT between the two groups (P>0.05). At T1, BBT-0 was (2.50±0.90) mm in the coverage group and (2.97±1.28) mm in the non-coverage group, with corresponding BBT-2 of (3.65±1.08) mm and (3.58±1.26) mm, respectively. At T2, BBT-0 was (1.22±0.55) mm in the coverage group and (1.70±0.97) mm in the non-coverage group, with corresponding BBT-2 of (2.32±0.94) mm and (2.57±1.26) mm, respectively. From T1 to T2, there were no statistically significant differences in the absolute values [(0.47±0.54)-(1.33±0.75) mm] and percentages [(10.04%±24.81%)-(48.43%±18.32%)] of BBT change between the two groups. The thickness of new bone formation in the buccal bone plate from T0 to T2 ranged from (1.27±1.09) mm to (2.75±2.15) mm with no statistical difference between the two groups at all levels. CONCLUSION In the short term, the GBR using buccal punch flap with or without collagen membrane coverage can effectively repair the buccal implant bone defect. But collagen membrane coverage showed no additional benefit on alveolar ridge contour stability compared with non-membrane coverage.
Humans ; Cohort Studies ; Retrospective Studies ; Alveolar Ridge Augmentation ; Collagen ; Cone-Beam Computed Tomography ; Bone Regeneration ; Dental Implantation, Endosseous

Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
Bone Regeneration/physiology* ; Bone and Bones ; Osteogenesis/physiology* ; Osteogenesis, Distraction/methods* ; Tissue Engineering

Ginsenoside Rb1, the effective constituent of ginseng, has been demonstrated to play favorable roles in improving the immunity system. However, there is little study on the osteogenesis and angiogenesis effect of Ginsenoside Rb1. Moreover, how to establish a delivery system of Ginsenoside Rb1 and its repairment ability in bone defect remains elusive. In this study, the role of Ginsenoside Rb1 in cell viability, proliferation, apoptosis, osteogenic genes expression, ALP activity of rat BMSCs were evaluated firstly. Then, micro-nano HAp granules combined with silk were prepared to establish a delivery system of Ginsenoside Rb1, and the osteogenic and angiogenic effect of Ginsenoside Rb1 loaded on micro-nano HAp/silk in rat calvarial defect models were assessed by sequential fluorescence labeling, and histology analysis, respectively. It revealed that Ginsenoside Rb1 could maintain cell viability, significantly increased ALP activity, osteogenic and angiogenic genes expression. Meanwhile, micro-nano HAp granules combined with silk were fabricated smoothly and were a delivery carrier for Ginsenoside Rb1. Significantly, Ginsenoside Rb1 loaded on micro-nano HAp/silk could facilitate osteogenesis and angiogenesis. All the outcomes hint that Ginsenoside Rb1 could reinforce the osteogenesis differentiation and angiogenesis factor's expression of BMSCs. Moreover, micro-nano HAp combined with silk could act as a carrier for Ginsenoside Rb1 to repair bone defect.
Alginates/pharmacology* ; Animals ; Bone Regeneration ; Cell Differentiation ; Durapatite/pharmacology* ; Ginsenosides ; Osteogenesis ; Rats ; Silk/pharmacology* ; Tissue Scaffolds