Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice

Stem cells residing in the periodontal ligament (PDL) support the homeostasis of the periodontium, but their in vivo identity, source(s), and function(s) remain poorly understood. Here, using a lineage-tracing mouse strain, we identified a quiescent Wnt-responsive population in the PDL that became activated in response to tooth extraction. The Wnt-responsive population expanded by proliferation, then migrated from the PDL remnants that remained attached to bundle bone, into the socket. Once there, the Wnt-responsive progeny upregulated osteogenic protein expression, differentiated into osteoblasts, and generated the new bone that healed the socket. Using a liposomal WNT3A protein therapeutic, we showed that a single application at the time of extraction was sufficient to accelerate extraction socket healing 2-fold. Collectively, these data identify a new stem cell population in the intact periodontium that is directly responsible for alveolar bone healing after tooth removal.

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Maresin 1 Promotes Wound Healing and Socket Bone Regeneration for Alveolar Ridge Preservation

Journal of Dental Research ◽

10.1177/0022034520917903 ◽

2020 ◽

Vol 99 (8) ◽

pp. 930-937 ◽

Cited By ~ 1

Author(s):

C.W. Wang ◽

S.H. Yu ◽

T. Fretwurst ◽

L. Larsson ◽

J.V. Sugai ◽

...

Keyword(s):

Wound Healing ◽

Postoperative Pain ◽

Tooth Extraction ◽

Alveolar Bone ◽

Lipid Mediator ◽

Preclinical Model ◽

Alveolar Ridge ◽

Extraction Socket ◽

Socket Healing ◽

Maresin 1

Tooth extraction results in alveolar bone resorption and is accompanied by postoperative swelling and pain. Maresin 1 (MaR1) is a proresolving lipid mediator produced by macrophages during the resolution phase of inflammation, bridging healing and tissue regeneration. The aim of this study was to examine the effects of MaR1 on tooth extraction socket wound healing in a preclinical rat model. The maxillary right first molars of Sprague-Dawley rats were extracted, and gelatin scaffolds were placed into the sockets with or without MaR1. Topical application was also given twice a week until complete socket wound closure up to 14 d. Immediate postoperative pain was assessed by 3 scores. Histology and microcomputed tomography were used to assess socket bone fill and alveolar ridge dimensional changes at selected dates. The assessments of coded specimens were performed by masked, calibrated examiners. Local application of MaR1 potently accelerated extraction socket healing. Macroscopic and histologic analysis revealed a reduced soft tissue wound opening and more rapid re-epithelialization with MaR1 delivery versus vehicle on socket healing. Under micro–computed tomography analysis, MaR1 (especially at 0.05 μg/μL) stimulated greater socket bone fill at day 10 as compared with the vehicle-treated animals, resulting in less buccal plate resorption and a wider alveolar ridge by day 21. Interestingly, an increased ratio of CD206+:CD68+ macrophages was identified in the sockets with MaR1 application under immunohistochemistry and immunofluorescence analysis. As compared with the vehicle therapy, local delivery of MaR1 reduced immediate postoperative surrogate pain score panels. In summary, MaR1 accelerated extraction wound healing, promoted socket bone fill, preserved alveolar ridge bone, and reduced postoperative pain in vivo with a rodent preclinical model. Local administration of MaR1 offers clinical potential to accelerate extraction socket wound healing for more predictable dental implant reconstruction.

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Interspecies comparison of alveolar bone biology: Tooth extraction socket healing in mini pigs and mice

Journal of Periodontology ◽

10.1002/jper.19-0667 ◽

2020 ◽

Vol 91 (12) ◽

pp. 1653-1663 ◽

Cited By ~ 1

Author(s):

Jie Pan ◽

Igor Pilawski ◽

Xue Yuan ◽

Masaki Arioka ◽

Pavla Ticha ◽

...

Keyword(s):

Tooth Extraction ◽

Alveolar Bone ◽

Bone Biology ◽

Extraction Socket ◽

Interspecies Comparison ◽

Socket Healing ◽

Mini Pigs

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Numerical simulation of tooth extraction socket: alveolar bone regeneration

IOP Conference Series Materials Science and Engineering ◽

10.1088/1757-899x/1137/1/012039 ◽

2021 ◽

Vol 1137 (1) ◽

pp. 012039

Author(s):

Rintaro Furukawa ◽

Katsuya Nagayama ◽

Masato Matsuo

Keyword(s):

Numerical Simulation ◽

Bone Regeneration ◽

Tooth Extraction ◽

Alveolar Bone ◽

Extraction Socket

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Effects of pre-extraction intermittent PTH administration on extraction socket healing in bisphosphonate administered ovariectomized rats

Scientific Reports ◽

10.1038/s41598-020-79787-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jae-Young Kim ◽

Hyo-Won Jang ◽

Jung-In Kim ◽

In-Ho Cha

Keyword(s):

Tooth Extraction ◽

Bisphosphonate Therapy ◽

Ovariectomized Rats ◽

Control Group ◽

Micro Ct ◽

Micro Computed Tomography ◽

Extraction Socket ◽

Before And After ◽

Socket Healing ◽

Positive Effect

AbstractThe purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.

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