Evaluating the association between gingival crevicular blood glucose levels and finger capillary blood glucose levels according to periodontal status.

OBJECTIVES: The aim of this study was to evaluate the association between gingival crevicular blood glucose levels (GCBG) and finger capillary blood glucose levels (FCBG) according to the periodontal status of patients. MATERIALS AND METHODS: In this case-control study, 80 patients were divided into 4 groups according to their periodontal status. In these patients, an area of the maxillary gingiva with the highest probing depth was selected for blood sampling. Blood glucose obtained from this area and the right fingertip was measured with a glucometer. Data were analyzed using ANOVA and Pearson correlation coefficient with a significance threshold of 0.05. RESULTS: The groups studied were matched in regard to their sex and age (P > 0.05). The average FCBG and GCBG were not significantly different according to periodontal status (P > 0.05). The correlation between the FCBG and the GCBG showed a significant positive correlation in the total number of participants (P < 0.05, r = 0.531). CONCLUSION: The study observed a positive association between GCBG and FCBG. However, the relationship with periodontal status appeared to be relatively weak. Further research may be needed to determine the potential efficacy of GCBG in diabetes screening during periodontal examinations. CLINICAL RELEVANCE: Most patients with diabetes do not have proper periodontal health, so it may be helpful to screen for diabetes during periodontal examinations.

Site-specific autonomic vasomotor responses and their interactions in rat gingiva.

Blood flow in the gingiva, comprising the interdental papilla as well as attached and marginal gingiva, is important for maintaining of gingival function and is modulated by risk factors such as stress that may lead to periodontal disease. Marked blood flow changes mediated by the autonomic (parasympathetic and sympathetic) nervous system may be essential for gingival hemodynamics. However, differences in autonomic vasomotor responses and their functional significance in different parts of the gingiva are unclear. We examined the differences in autonomic vasomotor responses and their interactions in the gingiva of anesthetized rats. Parasympathetic vasodilation evoked by the trigeminal (lingual nerve)-mediated reflex elicited frequency-dependent blood flow increases in gingivae, with the increases being greatest in the interdental papilla. Parasympathetic blood flow increases were significantly reduced by intravenous administration of the atropine and VIP antagonist. The blood flow increase evoked by acetylcholine administration was higher in the interdental papilla than in the attached gingiva, whereas that evoked by VIP agonist administration was greater in the attached gingiva than in the interdental papilla. Activation of the cervical sympathetic nerves decreased gingival blood flow and inhibited parasympathetically induced blood flow increases. Our results suggest that trigeminal-parasympathetic reflex vasodilation 1) is more involved in the regulation of blood flow in the interdental papilla than in the other parts of the gingiva, 2) is mediated by cholinergic (interdental papilla) and VIPergic systems (attached gingiva), and 3) is inhibited by excess sympathetic activity. These results suggest a role in the etiology of periodontal diseases during mental stress.

Assesment of radiotherapy effects on the blood flow in gingiva and dental pulp - a laser Doppler flowmetry study.

OBJECTIVE: This study aims to determine and compare the dental pulp and gingival blood flow in patients referred for oropharyngeal radiotherapy (RT) at three different time points: before the start, immediately after, and six months following the completion of RT. The aim is also to evaluate the dependence of the pulp and gingival blood flow on the radiation dose. METHODOLOGY: A prospective study included 10 patients referred for intensity-modulated RT (IMRT) in the oropharyngeal region, with at least one intact tooth surrounded by a healthy gingiva. The dose received by each selected tooth and adjacent gingiva was determined according to the map of treatment planning and computer systems. The blood flow measurements were performed using the laser Doppler flowmetry (LDF) method. RESULTS: Comparing vascular flows at three different time points, the median blood flow in the dental pulp showed no statistically significant difference (p=0.325), contrary to gingiva (p=0.011). Immediately after RT completion, the gingival flow significantly increased compared to its starting point (p=0.012). The pulp flow correlated negatively with the radiation dose, whereas a strong correlation was noted 6 months following the RT completion. CONCLUSIONS: RT caused a significant acute gingival blood flow increase, followed by a long-term (over six months) tendency to return to the starting levels. The dental pulp blood flow is differently affected by higher radiation doses (over 50Gy) in comparison to lower doses (below 50Gy). During RT planning, considering the possibility of protecting the teeth localized near the Gross Tumor Volume as a sensitive organ is recommended.

Evaluation of gingival microcirculation in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the possible microcircularity variations at periodontal mucous level in patients with gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Overall 55 periodontally healthy and non-smoker participants were enrolled in the study by whom 30 were diagnosed with GDM (26 to 34 weeks pregnant) and 25 were systemically healthy unpregnant controls. The analysis was performed in the masticatory/gingival mucosa of maxillary anterior region and by the optical probe videocapillaroscopy technique equipped with 200× lenses. The following parameters were recorded: capillary loop visibility, capillary orientation to surface, microhemorrhages, capillary density and tortuosity. RESULTS: The average capillary density was significantly higher in participants with GDM (27 ± 5.46 no. loops/mm2) compared to controls (21.16 ± 3 no. loops/mm2) (P = 0.035) while increased tortuosity scores was observed in controls compared with the GDM group (P = 0.017). There was not any significantly difference between study groups among the other variables (P > 0.05). CONCLUSIONS: Capillary alterations including capillary density and tortuosity were demonstrated in gingival microcirculation of patients with GDM. These microcirculatory changes could provide us new understanding on the dynamics of the relationship between GDM and periodontal tissues.

Effect of physical stimulation (gingival massage) on age-related changes in gingival microcirculation.

The decline in circulatory function with aging may be alleviated by a combination of gingival massage (physical stimulation) and mechanical cleaning. Several studies have reported the systemic effect of physical stimulation on various parts of the body, including its therapeutic effect on pain in the neck and shoulders that becomes evident with age, and improvement in blood circulation. In contrast, few studies have reported on the changes in gingival microcirculation induced by gingival massage, while no previous study has evaluated the effect of gingival microcirculation on age-related changes in the hemodynamics of the oral cavity. This study aimed to investigate how gingival massage affects age-related changes in gingival microcirculation. Male Wistar rats (7-week, 6-month and 1-year old) were prepared for a gingival massage group and a control group. Mechanical stimulation was applied on the maxillary molar gingiva for 5 seconds twice a week for 4 weeks. Subsequently, gingival reactive hyperemia was measured using a laser Doppler flowmeter. In addition, morphological analyses were also performed by hematoxylin and eosin and Indian ink staining and a vascular resin cast model. Base Flow, maximum response (Peak), and time required for the maximum response to halve (T1/2) were reduced in 1-year-old rats compared with the other age groups. In the mechanical stimulated group, T1/2 was increased in 7-week, 6-month, and 1-year-old rats, and total blood flow (Mass) was increased in 6-month and 1-year-old rats. In addition, clear blood vessel networks and loop-like revascularization were only observed in the mechanical stimulated group. Changes in age-related decline in gingival microcirculatory function and vascular construction were reported in this study, and the results suggested that gingival massage activates both the functional and morphological aspects of gingival microcirculation and may be effective for maintaining oral health.

PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis.

Abnormal angiogenesis is one of the significant features in periodontitis leading to progressive inflammation, but angiogenic changes of periodontal ligaments under inflammatory condition were rarely reported. Periodontal ligament stem cells (PDLSCs) were a kind of dental stem cells associated with vascularization. Here we investigated the alteration of angiogenesis of periodontal ligament in periodontitis, and revealed an exosome-mediated pathway to support the effect of PDLSCs on angiogenic improvement. Vascular specific marker CD31 and VEGFA were found to be highly expressed in periodontal ligaments of periodontitis. The VEGFA expression was up-regulated in inflamed PDLSCs compared to control, meanwhile the tube formation of HUVECs was improved when co-cultured with inflamed PDLSCs. Exosomes secretion of PDSLCs was augmented by inflammation, and promoted angiogenesis of HUVECs, whereas blocking secretion of exosomes led to degenerated angiogenesis of HUVECs. Exosome-trasferred VEGFA was proven to be the crucial communicator between PDLSCs and HUVECs. Inflammation inhibited miR-17-5p expression of PDLSCs and relieved its target VEGFA. However, overexpression of miR-17-5p blocked the pro-angiogenic ability of inflamed PDLSCs. In conclusion, the findings indicated that vascularization of periodontal ligaments was enhanced, and inflammatory micro-environment of periodontitis facilitated pro-angiogenesis of PDLSCs through regulating exosome-mediated transfer of VEGFA, which was targeted by miR-17-5p.

Microcirculation changes in gingival tissue after ultrasonic tooth preparation in beagle dogs.

OBJECTIVE: Ultrasonic wave technology is widely used during dental treatments. We previously demonstrated that this method protects the gingival tissue. However, the physiological change on the gingival microvasculature caused by this method remains unclear. The aim of this study was to investigate the relationship between the morphological and physiological effects on gingival microcirculation when preparing teeth, using the conventional dental turbine or ultrasonic method. METHODOLOGY: The lower premolar teeth of beagle dogs were prepared along the gingival margin by using a dental turbine or ultrasonic wave instrument. Gingival vasculature changes were investigated using scanning electron microscopy for corrosion resin casts. Gingival blood flow at the preparation site was determined simultaneously by laser Doppler flowmetry. These assessments were performed immediately (Day 0), at 7 days and 30 days after tooth preparation. RESULTS: At day 0, in the turbine group, blood vessels were destroyed and some resin leaked. Furthermore, gingival blood flow at the site was significantly increased. In contrast, the ultrasonic group demonstrated nearly normal vasculature and gingival blood flow similar to the non-prepared group for 30 days after preparation. No significant alterations occurred in gingival circulation 30 days after either preparation; however, the turbine group revealed obvious morphological changes. CONCLUSIONS: Based on multiple approach analyses, this study demonstrated that ultrasonic waves are useful for microvascular protection in tooth preparation. Compared with a dental turbine, ultrasonic wave instruments caused minimal damage to gingival microcirculation. Tooth preparation using ultrasonic wave instruments could be valuable for protecting periodontal tissue.

Microcirculation changes in gingival tissue after ultrasonic tooth preparation in beagle dogs

Abstract Ultrasonic wave technology is widely used during dental treatments. We previously demonstrated that this method protects the gingival tissue. However, the physiological change on the gingival microvasculature caused by this method remains unclear. Objective The aim of this study was to investigate the relationship between the morphological and physiological effects on gingival microcirculation when preparing teeth, using the conventional dental turbine or ultrasonic method. Methodology The lower premolar teeth of beagle dogs were prepared along the gingival margin by using a dental turbine or ultrasonic wave instrument. Gingival vasculature changes were investigated using scanning electron microscopy for corrosion resin casts. Gingival blood flow at the preparation site was determined simultaneously by laser Doppler flowmetry. These assessments were performed immediately (Day 0), at 7 days and 30 days after tooth preparation. Results At day 0, in the turbine group, blood vessels were destroyed and some resin leaked. Furthermore, gingival blood flow at the site was significantly increased. In contrast, the ultrasonic group demonstrated nearly normal vasculature and gingival blood flow similar to the non-prepared group for 30 days after preparation. No significant alterations occurred in gingival circulation 30 days after either preparation; however, the turbine group revealed obvious morphological changes. Conclusions Based on multiple approach analyses, this study demonstrated that ultrasonic waves are useful for microvascular protection in tooth preparation. Compared with a dental turbine, ultrasonic wave instruments caused minimal damage to gingival microcirculation. Tooth preparation using ultrasonic wave instruments could be valuable for protecting periodontal tissue.

Hematologic Parameters and Blood Cultures from the Gingival Vein Compared with the Cranial Vena Cava in Guinea Pigs.

Blood collection methods in guinea pigs are limited due to the animals' compact neck, short limbs, and lack of a tail. Gingival venipuncture is a recently described blood sampling technique that is minimally traumatic with no significant alterations in hematologic parameters when multiple blood samples were collected weekly for 6 wk. The purpose of this study was to determine whether the gingival vein can be used as an alternative blood collection site in guinea pigs, such that: (1) hematologic parameters would be consistent with samples collected from the cranial vena cava; and (2) no contaminants from the oral cavity would be introduced into the sample. Blood samples were obtained from both the gingival vein and cranial vena cava of anesthetized Dunkin Hartley guinea pigs for CBC (n = 9) and aerobic blood cultures (n = 10). Only MCV was significantly different between sampling sites. Bland-Altman analyses calculated a small mean bias for all hematologic parameters, indicating clinical interpretation is unlikely to be affected by the sampling site. Bacterial growth occurred in all 5 gingival vein blood samples prepared by using saline and 2 of the 5 prepared with dilute chlorhexidine. Bacteria did not grow from any cranial vena caval blood samples prepared with dilute chlorhexidine. No clinical signs of hemorrhage or trauma were detected at either site. These results provide evidence that gingival venipuncture can be used as an alternative blood collection method for guinea pigs for hematologic analysis but should not be used for blood culture.

A Novel Approach to Monitoring Graft Neovascularization in the Human Gingiva.

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids direct contact with the measured area, it is suitable for monitoring blood flow changes during wound healing in human patients. Vestibuloplasty is periodontal surgery to the oral vestibule, aiming to restore vestibular depth with simultaneous enlargement of the keratinized gingiva. In this special clinical case, a split thickness flap was elevated at the first upper premolar and a xenogenic collagen matrix was adapted to the resulting recipient bed. LSCI was used to monitor the re- and neovascularization of the graft and the surrounding mucosa for one year. A protocol is introduced for the correct adjustment of microcirculation measurement in the oral mucosa, highlighting difficulties and possible failures. The clinical case study presented demonstrated that - following the appropriate protocol - LSCI is a suitable and reliable method for following up microcirculation in a healing wound in the human oral mucosa and gives useful information on graft integration.

Immunohistochemical study of CD34 and podoplanin in periodontal disease.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the angiogenesis and lymphangiogenesis in gingival tissue biopsy specimens of individuals with clinically healthy gingiva, chronic gingivitis, and chronic periodontitis (n = 30 per clinical condition). MATERIAL AND METHODS: Histological sections were stained using hematoxylin and eosin as well as immunohistochemically with hematopoietic progenitor cell antigen CD34 and podoplanin (PDPN) antibodies to evaluate the microvascular count, area, and perimeter of blood and lymphatic vessels, respectively. RESULTS: The results revealed a correlation between the microvascular count of blood and lymphatic vessels (P = 0.03; however, in individuals with chronic periodontitis, fewer lymphatic vessels were present than in the clinically healthy gingival tissue (P = 0.01), which was not observed in the case of microvascular area and perimeter. Podoplanin labeling was present in the epithelium, and the intensity of labeling was positively correlated to the intensity of the inflammatory infiltrate (P = 0.03). CONCLUSION: In this study, we concluded that an increase in the number of blood and lymphatic vessels was not observed in bouth gingivitis and periodontitis samples. Podoplanin expression is highly associated with an increased inflammatory infiltration suggesting that PDPN might play an additional role in periodontal disease, other than solely as a lymphangiogenesis marker.

Development and use of a mouth gag for oral experiments in rats.

OBJECTIVE: Rodent models such as mice and rats are often used in investigations of the oral cavity in the fields of periodontology and dental anesthesiology. When various treatments are performed in the oral cavity, it is very important to secure the visual field while keeping the animal's mouth fully opened, in order to ensure the consistency of experimental procedures. Therefore, we developed a standardized gag conforming to various degrees of oral cavity size of different aged rats. DESIGN: The gag was composed of a rectangular incisor-opening frame constructed from a stainless steel wire with retractors and a dial to alter the opening amounts. Wistar rats (n = 5) aged 4, 8, and 12 weeks were used to evaluate the suitability of the gag in oral cavity. As tests for application of gag in intraoral experiments, the ligature placement around the molars, drug injection into the gingiva, measurement of gingival blood flow rate, and installation of stimulation an electrode for somatosensory-evoked potentials into the molar were performed. RESULTS: Adjusting the opening dial enabled both the maintenance of open state and more favorable intraoral observation compared with tweezers as a control device in all different types of rats. Furthermore, our gag made it possible to facilitate the insertion of diverse instruments into the oral cavity and to achieve various experimental purposes. The stainless-steel gag can also be autoclaved and dry-heat sterilized. CONCLUSION: It was revealed that our mouth gag can be widely applied to various oral experiments in different old aged rats.

Age-related changes in gingival blood flow parameters measured using laser speckle flowmetry.

Previous studies have suggested a possible relationship between age-related changes to human gingival hemodynamics and periodontal disease. However, firmly establishing this has been difficult because of a lack of suitable tools. Our study investigated whether a non-invasive laser speckle flowgraphy (LSFG)-based 2-dimensional technique could be used to assess maxillary anterior gingival blood flow under resting conditions. In total, 124 healthy male volunteers aged between 22 and 69 years were included in the study and delineated into young (Y; 22-37 years, n = 45), middle-aged (M; 38-53 years, n = 43), and elderly groups (E; 54-69 years, n = 36). The differences in gingival hemodynamics were compared among age groups and pulse waveform analysis performed to calculate blood flow indices, mean blur rate (MBR), gingival vascular conductance (MBR/mean blood pressure [MBP]), and three pulse waveform parameters (acceleration time index [ATI], falling rate, and blowout time [BOT]). Although no statistically significant differences were observed in the MBR of the three age groups, vascular conductance (MBR/MBP) was lower in groups M and E compared to group Y and correlated negatively with age. ATI and falling rates were also significantly higher in group E relative to group Y, whereas average BOT was significantly lower. All of the assessed parameters correlated with age. These data suggest that there are age-related decreases in the ability to maintain blood flow in the human maxillary anterior gingiva under resting conditions which may impact the likelihood of periodontal disease.

Methodological Proposal to Assess Gingival Thickness in Children.

PURPOSE: Inadequate gingival thickness (GT) may lead to gingival recession. Thus, early identification of patients/teeth at risk would be advantageous. In adults, the probe's visibility through the marginal gingiva (reference test) has been considered a reliable criterion to describe a thin gingiva. This study aimed to evaluate in children two more convenient methods: the whitening of the attached gingiva with coronal labial traction (GW test) and the visibility of the gingival blood supply (BS test). MATERIALS AND METHODS: In 69 children, the GT of primary and/or permanent central and lateral incisors, first primary molars and/or first premolars was assessed with the three tests. The sensitivity and specificity of the GW and BS tests and their odds ratio with probing were calculated. RESULTS: According to probing, 39% of children in the studied population had thin gingiva. The GW and BS tests reported different percentages of GT compared to probing, except for primary teeth, maxillary permanent incisors and mandibular first premolars, where the GW test exhibited a comparable percentage. The sensitivity of GW and BS tests was 37% and 19%, respectively, when compared to probing, while the specificity was 84% and 96%, respectively. CONCLUSION: The GW and BS tests could be used for first-line diagnosis of thin gingiva; if the results are negative, probing should be implemented.

A mixed form of intravascular papillary endothelial hyperplasia in an uncommon location: case and literature review.

Intravascular papillary endothelial hyperplasia (IPEH) is an unusual benign, non-neoplastic vascular lesion that usually occurs in skin, but is uncommon in the oral cavity. Herein, we review the pertinent literature of oraiiPEH and report a new mixed form. A 61-year- old man presented with an ulcerated nodule in the lingual portion of the gingiva related to the left mandibular canine. An excisional biopsy was performed presuming the clinical diagnosis of pyogenic granuloma. Histopathological analysis showed areas of granulation tissue consistent with pyogenic  granuloma. But in  addition, there  were thin-wall dilated vessels with papillary projections of endothelial cells producing vascular channels, associated with  an area of  organizing  thrombus. These microscopic findings led to the diagnosis of pyogenic  granuloma  associated with  IPEH. The immunohistochemical  reactions revealed a diffuse positivity of the vascular cells for CD-34 and smooth muscle actin antibodies.In addition,there was partial positivity for podoplanin and negativity for CD-1OS in the IPEH areas. No signs of recurrence were observed after 6 months of follow-up. The most prevalent site of IPEH in the oral region is the lower lip. IPEH is slightly more common in women and exhibits peaks of prevalence between the fourth and sixth decades of life.

Functional characterization of collaterals in the human gingiva by laser speckle contrast imaging.

OBJECTIVE: The rate of blood flow between the various areas of the gingiva in resting position and under challenge is unknown. In this study, the LSCI method was used to map spatial and temporal changes in gingival blood flow after transient compression. METHODS: Horizontal, vertical, and papilla base compressions were applied on the attached gingiva in 21 healthy patients (13 women, 8 men). LSCI was used to determine dynamic changes in regional blood flow during a five-second occlusion interval and subsequent reperfusion for twenty minutes. RESULTS: Resting blood flow in the attached gingiva apical to the papillae was higher as compared to that in the midbuccal area of the teeth. During short-term horizontal compression, ischemia was greater coronal than apical to the occlusion line. Postocclusive hyperemia was observed not only in the regions affected by ischemia but encompassed a wider area. Hyperemic response was more pronounced and prolonged in male than in female patients. CONCLUSIONS: Blood flow in the attached gingiva shows spatial differences. Our findings corroborate the apicocoronal orientation of blood circulation. Periodontal and papillary collaterals may have little role in the blood supply of the adjacent attached gingiva under physiological conditions.

Assessment of the test-retest reliability of human gingival blood flow measurements by Laser Speckle Contrast Imaging in a healthy cohort.

OBJECTIVE: The reliability of gingival blood flow measured by Laser Speckle Contrast Imaging is unknown. Our aim was to investigate the effect of factors inherent in oral mucosa measurement on intra-day and inter-day reliability. METHODS: Gingival blood flow was measured in seventy healthy subjects. First, measurements were obtained by varying the incidence angle of imaging, using a lip retractor. Second, 3 snapshots were taken with closure of the mouth in-between, and lips were retracted by a dental mirror. These were repeated 1 week later. Third, snapshots were taken either by direct view or using a mirror. Reliability was assessed based on coefficient of variation. RESULTS: Unlike retraction of the lips and the mirror, the incidence angle had an effect on mean blood flow. The coefficient of variation within a subject was 6.4% with the mouth constantly open. With retraction, the intra-session, and the inter-day coefficient of variation were 8.3% and 10.5%, respectively. The coefficient of variation was 11.9% by alternating direct and indirect imaging. CONCLUSIONS: Laser Speckle Contrast Imaging has good short- and long-term reliability regardless of lip retraction or an indirect view. This technique seems to be appropriate for the long-term clinical non-invasive follow-up of gingival microcirculation.

Evaluation of gingival blood as a minimally invasive screening tool for diabetes mellitus among 40-59-year-old adults in dental clinics: A cross-sectional study.

OBJECTIVE: To evaluate a quick, safe, and minimally invasive method to screen for diabetes using gingival blood with the help of self-monitoring glucometer during periodontal examination. MATERIALS AND METHODS: A hospital-based, cross-sectional comparative study was conducted among 40-59-year-old diabetic and nondiabetic population who had come for their master health examination to a private tertiary care hospital (Global Hospital and Health City) in Chennai. Among them, those who fulfilled the inclusion criteria were selected for the study. Thirty diabetic and thirty nondiabetic patients with moderate to severe gingivitis were enrolled and subjected to routine clinical periodontal examination. Blood samples of two sites were analyzed using a glucose self-monitoring device (Accu-Check). Patients were tested for venous fasting blood sugar (VFBS), venous postprandial blood sugar (VPPS), gingival fasting blood sugar (GFBS) level, gingival postprandial blood sugar (GPPS) level, peripheral fingerstick fasting blood sugar (PFBS) level, and peripheral fingerstick postprandial sugar (PPPS) level. Data obtained were statistically analyzed using Student's t-test, ANOVA, and Pearson's correlation test. RESULTS: A significant positive correlation was found between GFBS and VFBS, GFBS and PFBS, GPPS and VPPS, and GPPS and PPPS (P < 0.01) in both diabetic and nondiabetic patients correlation. Using venous blood glucose level as a gold standard, the sensitivity and specificity of GFBS was 93% and 100%, respectively, whereas in GPPS, the sensitivity and specificity was 80% and 96%, respectively. CONCLUSION: Gingival blood glucometry can be used as a minimally invasive screening tool for diabetes mellitus in dental clinics.

Gingival Perfusion and Tissue Biomarkers During Early Healing of Postextraction Regenerative Procedures: A Prospective Case Series.

BACKGROUND: Postextraction alveolar bone loss, mostly affecting the buccal plate, occurs despite regenerative procedures. To better understand possible determinants, this prospective case series assesses gingival blood perfusion and tissue molecular responses in relation to postextraction regenerative outcomes. METHODS: Adults scheduled to receive bone grafting in maxillary, non-molar, single-tooth extraction sites were recruited. Clinical documentation included the following: 1) probing depth (PD); 2) keratinized tissue width (KT); 3) tissue biotype (TB); and 4) plaque level. Wound closure was clinically evaluated. Gingival blood perfusion was measured by laser Doppler flowmetry (LDF). Wound fluid (WF) and gingival biopsies were analyzed for protein levels and gene expression, respectively, of relevant molecular markers. Bone healing outcomes were determined radiographically (cone-beam computed tomography). Healing was followed for 4 months. RESULTS: Data from 15 patients are reported. Postoperatively, neither complications nor changes in PD, KT, or TB were observed. LDF revealed decreased perfusion followed by hyperemia that persisted for 1 month (P ≤0.05). WF levels of angiopoietin-2, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor peaked on day 6 (P ≤0.05) and decreased thereafter. Only IL-8 and TNF-α exhibited increased gene expression. Linear bone changes were negligible. Volumetric bone changes were minimal but statistically significant, with more bone loss when membrane was used (P = 0.05). CONCLUSIONS: Gingival blood perfusion after postextraction bone regenerative procedures follows an ischemia-reperfusion model. Transient increases in angiogenic factor levels and prolonged hyperemia characterize the soft tissue response. These soft tissue responses do not determine radiographic bone changes.