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

ABSTRACT: 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.

SUBMITTER: Wang CW

PROVIDER: S-EPMC7338694 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe purpose of this study was to prospectively evaluate the efficacy of a demineralized dentin matrix (DDM) in decreasing the initial inflammatory response of the gingiva and facilitating the repair and regeneration of soft tissue in alveolar ridge preservation.MethodsThis clinical study employed a split-mouth design. Fourteen patients with a total of forty-four sites underwent extraction and alveolar ridge preservation (ARP) procedures. A Bilaterally symmetrical extraction operation were conducted on the premolars of each patient. The experimental group received DDM as a graft material for ARP, while the control group underwent natural healing. Within the first month postoperatively, the pain condition, color, and swelling status of the extraction sites were initially assessed at different time points Subsequently, measurements were taken for buccal gingival margin height, buccal-lingual width, extraction socket contour, and the extraction socket area and healing rate were digitally measured. Additionally, Alcian Blue staining was used for histological evaluation of the content during alveolar socket healing.ResultsBoth groups experienced uneventful healing, with no adverse reactions observed at any of the extraction sites. The differences in VAS pain scores between the two groups postoperatively were not statistically significant. In the early stage of gingival tissue healing (3 days postoperatively), there were statistically significant differences in gingival condition and buccal gingival margin height between the two groups. In the later stage of gingival tissue healing (7, 14, and 30 days postoperatively), there were statistically significant differences in buccal-lingual width, extraction socket healing area, and healing rate between the two groups. Furthermore, the histological results from Alcian Blue staining suggested that the experimental group may play a significant role in promoting gingival tissue healing, possibly by regulating inflammatory responses when compared to the control group.ConclusionThe application of DDM in alveolar ridge preservation has been found to diminish initial gingival inflammation after tooth extraction. Additionally, it has shown the ability to accelerate early gingival soft tissue healing and preserve its anatomical contour.Clinical trial registrationchictr.org.cn, identifier ChiCTR2100050650.

Project description:Background:The healing process following tooth extraction results in alveolar ridge resorption. The dimensional changes may complicate the subsequent implant procedure. Socket preservation using absorbable collagen membranes or a combination of membranes with calcium phosphate cement (CPC) particles might ensure that the alveolar ridge retains a suitable morphology for implant placement. Objective:To evaluate the quality and quantity of new bone regenerated after application of either collagen membranes alone covering the sockets or a combination of membranes with CPC particles added into the sockets in dogs. Materials and Methods. Six dogs were included in this study. The mandibular premolars were extracted. For each hemimandible, three premolar extraction sites were randomly assigned to one of the following treatments: a covering collagen membrane, CPC with a covering collagen membrane, and a socket left empty. Cone-beam computed tomography (CBCT) measurements, polyfluorochrome sequential labeling, and histological assessments were performed to investigate the healing ability and repair processes within a 6-month observation period. Results:Buccal bone height in the membrane group was significantly higher than that in the membrane+CPC and blank groups at 4 and 6 months after extraction. The mineral apposition rate over 2-4 months and the alizarin red-stained area in the membrane group were significantly higher than those in the other two groups. Histological analysis after 6 months of healing showed significantly higher amounts of newly formed bone in the membrane group than in the other groups. Conclusion:Extraction sites treated with collagen barrier membranes showed better protection than sites not covered with membranes. And the buccal bone wall of the socket was well preserved by collagen membrane without extra CPC materials. Socket preservation using absorbable membranes alone yielded better quality and quantity of regenerated bone inside the socket site.

Project description:BackgroundThere is limited information on the need for bone augmentation in the context of delayed implant placement whether alveolar ridge preservation (ARP) is previously performed or not. The primary aim of this retrospective cohort study was to evaluate the efficacy of ARP therapy after tooth extraction compared with unassisted socket healing (USH) in reducing the need for ancillary bone augmentation before or at the time of implant placement.MethodsAdult subjects that underwent non-molar single tooth extraction with or without simultaneous ARP therapy were included in this study. Cone beam computed tomography scans obtained before tooth extraction and after a variable healing period were used to record the baseline facial bone thickness and to virtually plan implant placement according to a standard method. A logistic regression model was used to evaluate the effect of facial alveolar bone thickness upon tooth extraction and baseline therapy (USH or ARP) on the need for additional bone augmentation, adjusting for several covariates (i.e., age, sex, baseline KMW, and tooth type).ResultsOne hundred and forty subjects that were equally distributed between both baseline therapy groups constituted the study population. Implant placement was deemed virtually feasible in all study sites. Simultaneous bone augmentation was considered necessary in 60% and 11.4% of the sites in the USH and ARP group, respectively. Most of these sites (64.2% in the USH group and 87.5% in the ARP group) exhibited a thin facial bone phenotype (<1 mm) at baseline. Logistic regression revealed that the odds of not needing ancillary bone augmentation were 17.8 times higher in sites that received ARP therapy. Furthermore, the need for additional bone augmentation was reduced 7.7 times for every 1 mm increase in facial bone thickness, regardless of baseline therapy.ConclusionsBased on a digital analysis, ARP therapy, compared with USH, and thick facial alveolar bone largely reduce the need for ancillary bone augmentation at the time of implant placement in non-molar sites.

Project description:Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen containing BP (N-BP) drug. At present, no clinical procedure is available to prevent or effectively treat MRONJ. Although the pathophysiological basis is not yet fully understood, legacy adsorbed N-BP in jawbone has been proposed to be associated with BRONJ by one or more mechanisms. We hypothesized that removal of the pre-adsorbed N-BP drug common to these pathological mechanisms from alveolar bone could be an effective preventative/therapeutic strategy. This study demonstrates that fluorescently labeled BP pre-adsorbed on the surface of murine maxillo-cranial bone in vivo can be displaced by subsequent application of other BPs. We previously described rodent BRONJ models involving the combination of N-BP treatment such as zoledronate (ZOL) and dental initiating factors such as tooth extraction. We further refined our mouse model by using gel food during the first 7 days of the tooth extraction wound healing period, which decreased confounding food pellet impaction problems in the open boney socket. This refined mouse model does not manifest BRONJ-like severe jawbone exposure, but development of osteonecrosis around the extraction socket and chronic gingival inflammation are clearly exhibited. In this study, we examined the effect of benign BP displacement of legacy N-BP on tooth extraction wound healing in the in vivo model. Systemic IV administration of a low potency BP (lpBP: defined as inactive at 100 μM in a standard protein anti-prenylation assay) did not significantly attenuate jawbone osteonecrosis. We then developed an intra-oral formulation of lpBP, which when injected into the gingiva adjacent to the tooth prior to extraction, dramatically reduced the osteocyte necrosis area. Furthermore, the tooth extraction wound healing pattern was normalized, as evidenced by timely closure of oral soft tissue without epithelial hyperplasia, significantly reduced gingival inflammation and increased new bone filling in the extraction socket. Our results are consistent with the hypothesis that local application of a rescue BP prior to dental surgery can decrease the amount of a legacy N-BP drug in proximate jawbone surfaces below the threshold that promotes osteocyte necrosis. This observation should provide a conceptual basis for a novel strategy to improve socket healing in patients treated with BPs while preserving therapeutic benefit from anti-resorptive N-BP drug in vertebral and appendicular bones.

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

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