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. 2025 May 22;6:1587821. doi: 10.3389/fdmed.2025.1587821

Table 2.

Wound healing assessment by Laser Doppler flowmetry.

Author (year) Study design Aim Indication Time evaluated Results Clinical relevance
Heitzer et al., 2025 Pre-clinical Compare the hemostyptic properties and gingival healing after tooth extraction in rodent under rivaroxaban therapy over 10 days Hemostyptic properties and gingival healing between novel polyurethane based adhesive VIVO and gelatin sponge (GESP) 1 time point Increase mean blood flow for both treatments VIVO demonstrated effective hemostasis and favorable gingival healing following tooth extraction under continuous rivaroxaban therapy
Katz et al., 2024 Clinical Evaluate peri-implant tissue perfusion (blood flow) in implants placed in pristine bone, avascular, and microvascular grafts Gingiva; perfusion in different bone types in dental implants 1 time point No differences found in gingival blood flow in either pristine or avascular bone or microvascular grafts Perfusion was similar between implants in native and augmented sites, though those in avascular or microvascular grafts showed increased peri-implant inflammation
Diehl et al., 2022 Clinical Assess microcirculation and the expression patterns of wound-healing related implants in type 2 diabetes mellitus patients Periodontitis 3 months Wound healing after implant surgery was similar in healthy patients and T2DM Considered hydrophilic surface titanium zirconium with reduced diameter for T2DM patients
Liu et al., 2022 Pre-clinical Measure changes in blood flow rate using advanced PRF in early-stage gingival regeneration after tooth extraction Gingival tissue regeneration 1 time point Gingival blood flow was higher with A-PRF A-PRF may be beneficial for gingival tissue regeneration
Miron et al., 2022 Clinical Evaluate microcirculation at marginal gingiva after change of toothbrush Periodontal health 14 days New toothbrushes in adolescents with healthy gingiva can increase gingival blood flow Changing the toothbrush in less than a month could be a factor in gingival micro irritation
Svetlana et al., 2022 Clinical Determine and compare dental pulp and gingival blood flow Radiotherapy 6 months RT cause a significant acute gingival blood flow Protect teeth before radiotherapy to avoid ischemia of soft tissues
Komaki et al., 2022 Clinical Investigate the hemodynamics of gingival microcirculation Occlusal trauma During and after clenching Ischemia was present during clenching followed by reactive hyperemia by the release of clenching Occlusal trauma should be prevented to avoid detrimental effects on periodontal tissues due to compression of the vascular network of the periodontal membrane
Laredo-Naranjo et al., 2021 Clinical Identify gingival microcirculation Orthodontic treatment 30 days Longitudinal evaluation showed increased perfusion in Nitinol arches three times greater than basal flow Identification of inflammatory process in treatment is crucial to discontinue the use of harmful methods
Yamamoto et al., 2021 Pre-clinical Assess changes in peri-implant vascular network and blood flow Peri-implant tissue inflammation 90 days Significant increase in blood flow around implants with an inflamed blood vessels invade the bone marrow through the bone margin of the alveolar bone Analysis of gingival microcirculation of tissues may aid the pathological analysis in clinical setting
Kuraji et al., 2019 Pre-clinical Evaluate temporal changes in gingival blood flow during disease progression Periodontitis 28 days Levels of alveolar bone loss, gene expression and immunostained VEGF- positive vessels correlated with increase changes in gingival blood flow. Dynamic alteration of gingival blood flow was demonstrated during disease progression, inflammation, vasculogenesis and alveolar bone resorption
Alssum et al., 2017 Clinical Assess gingival blood perfusion and wound fluid Post extraction regenerative 120 days Transient increases in angiogenic and prolonged hyperemia of soft tissue Soft tissue ischemia-reperfusion model does not determine radiographic bone changes
Kaner et al., 2017 Clinical Characterize early phase of wound healing after periodontal surgery with and without Enamel matrix derivative (EMD) Early wound healing after periodontal surgery 2 weeks before surgery and 14 days after surgery Significantly decrease at the papillary base with increased blood flow until day 14. Group without EDM showed decreased blood flow at day 1 when compared Detection of changes in microcirculation after surgery with differentiation between surgical techniques
Ogino et al., 2017 Clinical Examined the extent of reactive hyperemia effect on GBF in denture-supporting mucosa during chewing Biting force After simulated biting or chewing for 30 s at 8 time points Significant correlation between GBF chewing and the extent of reactive hyperemia Slow chewing induced less GBF than regular or fast chewing in denture-supporting mucosa. Subject with less reactive hyperemia had less GBF in denture-supporting mucosa
Tatarakis et al., 2017 Clinical Assess early healing process using a xenogenic collagen matrix (CMX) or connective tissue graft (CTG) Root recession coverage 30 days CTG showed a vascular homogeneous pattern whereas CMX had a second phase of increased blood flow at 14 days Identify early vascular response and assessing maturity of surgical wound
Le Bars et al., 2016 Clinical Measure the microcirculation of the healthy palatal mucosa at three specific points, and to test the reproducibility and sensitivity of the LDF Palatal mucosa (median raphe (MR), Schroeder area (SA), retro incisive papilla (RP) 3 min Palatal blood flow differed significantly from other surfaces. SA showed the highest GBF values followed by RP and MR LDF can help to detect the onset of pathological alterations of the palatal mucosa
Reuther et al., 2016 Clinical Investigate the effect of electronic cigarettes (with nicotine and without) on blood flow in the buccal mucosa Electronic cigarette smoking After 5 min of vaping. Intervals at 5 min for 30 min Wide variation in results and a small but significant rise in nicotine vaping but fell to baseline within 30 min Electronic cigarettes may influence blood flow in the oral mucosa
Svalestad et al., 2014 Clinical Evaluate the effect of hyperbaric oxygen therapy (HBOT) on vascular function Gingival mucosa 6 months Vascular capacity increased by HBOT, and effect persists up to 6 months A significant increase in maximal blood flow may indicate a vascular bed with improved healing capacity
Kawaai et al., 2013 Clinical Assess the oral mucosal blood flow during sedation with dexmedetomidine Palatal 0, 5, 10, 12, 22 and 32 min after the start of the infusion GBF decreased significantly after the start of the infusion of dexmedetomidine LDF showed decreased levels of GBF by the mediating effect of dexmedetomidine on a-2 adrenoceptors
Kozlov and Ibragim 2011 Clinical Examine GBF in patients with varying degrees of inflammation in health, gingivitis and periodontitis Periodontal disease 1 time point Changes in micro vessels lead to the development of blood flow stagnation in post capillaries and local stasis in the gingival tissues LDF can estimate the severity of the disorders of the microcirculation in the gingiva in the development of periodontitis
Okada et al., 2010 Clinical Determine the effect of the number of biting forces on change in blood flow in denture-supporting maxillary mucosa. Biting force BL, at rest (1, 4, 8, 12 min) GBF showed statistically significant differences at pre-loading and loading There was an increase in mean blood flow during intermittent loading relative to at pre-loading
Sakr et al., 2010 Clinical Characterize the buccal microvascular response in patients with septic shock Septic shock Every 2 s for 5 min and after 1 week GBF increased during the 2nd day of septic shock and decreased after. Non septic patients GBF was significantly greater superficially LDF may be useful for tracing microvascular alterations in critically ill patients
Svalestad et al., 2010 Clinical Evaluate reproducibility of LDF for assessing microvascular blood flow after radiotherapy and hyperbaric oxygen therapy Mandibular mucosa 6 weeks Blood flow increased when compared to basal flow after heat provocation LDF showed reproducibility in longitudinal studies
Singh et al., 2008 Clinical Comparison between blood flow in the tongue and oral mucosa with 2 LDF probes Intraoral cavity 3 time points (0, 6 and 24 h) Measurements by the 2 probes were correlated significantly but the standard deviations were large LDF measurements showed large variations between probes
Retzpei et al., 2007a Clinical Compared gingival blood flow responses followed simplified papilla preservation (test) and modified Widman flap (control) Periodontal access flap 60 days Results present an ischemia-reperfusion flap model with papilla preservation flap with faster recovery. A peak hyperemic response resolved by day 4 (test) but persisted until day 7 (control) LDF may present clinical applicability in recording dynamic changes in the microcirculatory blood perfusion. Papilla preservation flap may be associated with faster recovery of gingival blood flow post-operatively
Retzepi et. 2007b Clinical Investigate pattern of gingival blood flow changes after periodontal access flap surgery Periodontal access flap surgery 60 days Different areas of the flaps consistently showed an ischemic-hyperemia patterns of perfusion alteration during wound healing This technique may be useful in representing the dynamic nature of flaps blood flow reperfusion
Rodriguez-Martinez et al., 2006 Clinical Explore possible association between an index of gingival microvascular perfusion response to compression of alveolar mucosa Periodontitis 2 measurements 4 min apart Microvascular density, dilation, elongation and organize capillary network has a positive correlation with clinical measurement and increased reactive hyperemia Increase or decrease in gingival perfusion could indicate clinical predominance of gingivitis or periodontitis
Donos et al., 2005 Clinical Evaluate the applicability of the LDF in recording changes in gingival blood flow Periodontal surgery 60 days GBF increases in comparison to baseline values until the 7th day. By the 15th day, 30th, and 60th gingival blood flow values were similar to the baseline LDF might present clinical applicability in recording changes in gingival blood flow following periodontal surgery
Kocabalkan and Turgut 2005 Clinical Investigate the influence resin base materials on the blood flow of underlying mucosa Biting forces Baseline (BL), 1 week, 1, 3 and 6 months Soft lining and hard acrylic: Mean GBF in mucosa after 1 week was significantly lower than baseline and at 6 months after return to normality
Hard: GBF in molar region increased after 6 months compared to BL
Dentures hinders blood flow to supporting tissues
Patino-Marin et al., 2004 Clinical Systematize a procedure that allows characterization of perfusion response pattern to topical and transitory compression Attached gingiva 2 measurements 5 min apart Gingival compression propitiated an induced flow debt followed by increased flow after compression is released Microvascular responses are reproducible indices of perfusion response whose validation under pathological circumstances remains to be evaluated
Kerdvongbundit et al., 2003 Clinical Evaluate dynamic changes in the micromorphology and microcirculation of healthy and inflamed human gingiva Gingival surfaces (free and attached gingiva, interdental papilla and alveolar mucosa) 15 min with 90 s intervals GBF in healthy and gingivitis was significantly different. After treatment at 1 and 3 months GBF showed significant differences LDF can be used to record GBF before and after inflammation reduction
Kemppainen et al., 2003 Clinical Study capsaicin-evoked blood flow responses in maxillary gingiva Alveolar mucosa and attached gingiva 4–15 s Significant higher blood flow during the stimulation period and 3 min after Alveolar mucosa is more sensitive to chemical irritants than attached gingiva
Akazawa and Sakurai 2002 Clinical Investigate the influence of the continuous compression because of light clenching on the GBF of the denture underlying mucosa in tissue-supported or tooth-tissue-supported dentures Biting force Baseline and 5, 10, 20, 30 and 60 s GBF in mucosa underlying the denture showed statistically significant correlation between recovery and loading time Continuous clenching results in ischemia and delays the recovery of GBF in the mucosa after the release of compression
Ambrosini et al., 2002 Clinical Evaluation of the modifications occurring in human gingival blood flow following periosteal stimulation Surface of the gingival graft Intervals of 1 week Increased blood flow was shown at 7 days after periosteal stimulation Detects alterations of the vascularization several hours before the clinical symptoms become apparent during wound healing monitoring
Vag and Fazekas 2002 Clinical Monitor reactions of marginal gingiva during prosthetic rehabilitation Prosthetic rehabilitation 6 weeks Significant correlation was found between gingival index and increased blood flow Monitoring gingival blood flow may provide valuable information of the healing process of inflamed marginal gingiva
Kerdvongbundit and Vongsavan et al., 2002 Clinical Evaluate the microcirculation in the gingiva of healthy and gingivitis patients Gingival surfaces (free gingiva, interdental gingiva, attached gingiva, and alveolar mucosa) 90 s intervals for 15 min Blood flow in the maxillary anterior gingiva showed significant differences from the mandibular anterior gingiva in the interdental gingiva, attached gingiva, and alveolar mucosa GBF in the maxillary anterior gingiva was greater than that in the mandibular anterior gingiva. GBF was lower in free gingiva and higher in alveolar mucosa
Kerdvongbundit and Vongsavan et al., 2002 Clinical Evaluate the microcirculation in patients with moderate gingivitis, periodontitis, and healthy gingiva Gingival surfaces (free and attached gingiva, interdental papilla and alveolar mucosa) 90 s intervals for at least 15 min GBF in moderate gingivitis and periodontitis showed similar values and were higher than those in healthy gingiva GBF in patients with periodontitis and gingivitis revealed significant differences when compared to healthy patients
Heckmann et al., 2001 Clinical Study oral mucosal blood flow in burning mouth syndrome (BMS) patients Hard palate, the tip of the tongue, midline of the oral vestibule, and lip 2 min BMS patients exhibited a higher significantly response on the hard palate compared to healthy patients Higher vascular reactivity in patients with burning mouth syndrome when compared to healthy patients
Matsuki et al., 2001 Clinical Measure gingival blood flow under different water temperatures and evaluate reproducibility Marginal gingiva 5 days Warm water (36 and 50°C showed a significant increase in blood flow and flow went to baseline (after 3 and 4 min, respectively). Cold water (4°C) showed decreased blood flow and level went to baseline after 2 min. LDF showed acceptable reproducibility with no significant effect from the probe angle
Heckmann et al., 2000 Clinical Study the changes of blood flow after the effects of painful stimulation using dry ice (CO2) Hard palate, lip and oral vestibule Baseline and 2 min Mucosal blood flow increased significantly at all sited after dry ice application Mucosal blood flow varies at different mucosal sites. Tongue blood flow changes were the least pronounced
Ahn and Pogrel 1998 Clinical Determine if 2% lidocaine with 1:100,000 epinephrine decreases the blood flow in gingival tissues Gingival margin Recording during 15 min and 1 min at 10 intervals Significant decrease of GBF (maximum decrease 51%) with gradual return to baseline up to 35 min. Gingival effects may be of relevance with soft tissue surgical procedures
Perry et al., 1997 Clinical Quantify changes in blood flow following tooth brushing Tooth brushing 4 weeks Tooth bruising for 3 and 10 s significantly increased blood flow LDF showed to be a non-invasive tool to understand dynamics of blood flow
Ketabi and Hirsch 1997 Clinical Determine vascular responses in the gingiva of smokers and non-smokers after anesthetic injection Local anesthetic 15 min Significant decrease of GBF (average 46%) in the gingiva. Statistically significance for GBF recovery between smokers and non-smokers LDF showed that recovery of GBF is longer in smokers than in non-smokers.
Schmid-Schönbein et al., 1997 Clinical Identify vascular temporal patterns in mucosal microcirculation in maxillary gingiva with laser Doppler anemometry (LDA) Gingivitis 12.5 min Dynamic fluctuation relates to physiological events synchronized to neurodynamic activity or ventilatory influences, gravitational effects or arterial o venous pressure Analysis of data obtained in the study allows temporal pattern characteristics for future diagnostic procedures
Herlofson et al., 1996 Clinical Test the oral mucosa irritant potential of toothpaste detergent (sodium lauryl sulfate) Gingiva 10–15 min GBF increased significantly from the second to ninth minute LDF may be a useful non-invasive technique for intraoral testing of different agents of intraoral use
Hinrichs et al., 1995 Clinical (1) Determine gingival blood flow in the gingival sulcus after probing and injection of local anesthetic.
(2) Determine reproducibility of measurements
Periodontal probing and after local anesthetic injection Baseline, 1 and 2 months (1) Increased blood flow was seen after probing whereas blood flow decreased after local anesthetic injection with vasoconstrictor.
(2) Intrasulcular measurements were reproducible at 1 and 2 months
LDF is a non-invasive and reproducible tool capable of detecting alterations in blood flow in different time points
Dodson et al., 1994 Clinical Assess value of intraoperative maxillary blood perfusion and describe pattern of blood flow changes during Le Fort I osteotomy Orthognathic surgery Intraoperative (10 s intervals) Significant decrease of GBF of 64% during the fracture and mobilization compared to preoperative values LDF is a feasible and valuable tool for measuring intraoperative maxillary blood flow dynamics
Hoke et al., 1994 Clinical Develop a protocol for quantification of blood flow Intraoral cavity 30 s intervals in 3 time points High flows were in the buccal mucosa, vestibule and tongue. Medium flows were found in the attached gingiva Intraoral tissue blood flow varies by site and be quantified non-invasively
Matheny and Johnson et al., 1993 Clinical Determine the changes that occur in the gingival microcirculation during the development of experimental gingivitis Gingivitis 2 time points Significant decrease in gingival regional BF in gingivitis patients Gingival microcirculation exhibited a dynamic change in response to the development and progression of gingivitis
Baab et al., et al., 1990 Clinical Gingival blood flow and temperature were monitored continuously before and after cooling via a twin probe placed in the gingival sulcus Periodontitis 5 min Patients with periodontitis Periodontitis patients showed significantly faster recovery of GBF than controls
Baab and Öberg 1987 Clinical Study the acute effects of cigarette smoking on gingival blood flow Tobacco smoking 5 min after smoking Higher GBF during smoking GBF increased significantly after smoking and stayed high during 5 min after
Baab et al., 1986 Clinical Measure gingival blood flow after different stimuli: warm and cold water, pressure and biting force Soft tissue measurements (free and attached gingiva, interdental papilla, alveolar mucosa) Intervals of 30 s for water, 3 min for pressure and 1 min after biting force No significant differences of blood flow after water stimuli (warm or cold), and pressure. Significant difference with occlusal biting force of 5 N LDF is a non-invasive promising tool to study GBF