Wound Healing Following Extraction and Ridge Preservation in Smokers and Non-smokers

The goal of this study is to evaluate bone wound healing following extraction and alveolar ridge preservation (bone graft and membrane) clinically, histologically and in relation to gene expression in smokers and non-smokers. Data from a small group of participants will be analyzed after age-matched subjects undergo extraction and alveolar ridge preservation prior to implant placement. The data obtained in this pilot study will be used to plan a full-fledged study involving a larger number of smoking and non-smoking participants to compare the two groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Wound Healing; Smoking, Cigarette; Alveolar Bone Grafting; Tooth Extraction Site Healing; Bone Healing
• Intervention / Treatment: Other: observational study

Detailed Description

All research procedures will start after IRB approval. Patients of the Graduate Periodontics Clinic in need of extraction, bone graft and membrane will be recruited. There will be two groups (smokers and non-smokers) and their demographic and social, periodontal, surgery-related, anatomical and healing variables as well as patient-reported outcomes will be recorded at different time points (immediately before, during and immediately after surgery and 1, 2, 6 weeks and 4 months) in order to evaluate wound healing outcomes and differences between the groups. The demographic and social variables evaluated are age, gender, race, medical history, medications, smoking (via interview and breath test-smokerlyzer) and alcohol consumption (via interview). The periodontal variables are tooth mobility, probing depth, attachment level, gingival and plaque index. The surgery-related variables include intraoperative complications, duration of procedure, anesthetic amount, type and approach and operator experience. The anatomical variables are bone height and width (buccolingual and buccal dimension), bone density (in Cone Beam Computed Tomographies - CBCTs) and gingival width and thickness. The healing variables include wound opening (tested clinically and in photos), bleeding, grafting material discharge, flap necrosis, loose sutures, and temporary restoration adjustment. The patient-reported outcomes are Oral Health Impact Questionnaire-14 (OHIP-14), Visual Analogue Scale (VAS) for pain, swelling and difficulty of mouth opening. At 4 months during the implant placement appointment, a bone core will be harvested via a 3D printed surgical guide based on virtual CBCT planning. The core willl be used of microCT and histological analysis as well as total RNA extraction and RNA sequencing.

• Study Type: Observational
• Enrollment (Estimated): 12

Contacts and Locations

• Study Contact: Name: Vrisiis Kofina, DDS, MS; Phone Number: 516-817-0393; Email: vrisiis.kofina@marquette.edu
• Study Contact Backup: Name: McKenna Schnack, DDS, MS; Phone Number: 515-822-3552; Email: mckenna.schnack@marquette.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Marquette University School of Dentistry Graduate Periodontics Clinic
      • Contact: Vrisiis Kofina, DDS, MS; Phone Number: 4142886521; Email: vrisiis.kofina@marquette.edu
      • Contact: Arndt Guentsch, DMD, PhD, MHBA, MS; Phone Number: 4142886089; Email: arndt.guentsch@marquette.edu
      • Principal Investigator: Vrisiis Kofina, DDS, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients scheduled for tooth extraction and alveolar ridge preservation (bone graft and membrane) in the Graduate Periodontics Clinic at Marquette University School of Dentistry.

Description

Inclusion Criteria:

• Adult patients (18-75 years)
• Good general health (controlled conditions)
• Smokers (≥10 cigarettes/day for ≥5 years) and never smokers. Confirmation of smoking status will be done via use of a smokerlyzer. The cut-off point for distinguishing smokers from non-smokers is 8 carbon monoxide parts per million (ppm).
• Periodontal status: periodontal health, gingivitis on intact or reduced periodontium, treated periodontitis
• Intact post-extraction bony walls or less than 50% bone dehiscence
• Distance at least 8 mm of vertical bone height between bone crest and anatomical structures (i.e. sinus floor, inferior alveolar nerve (IAN) canal, mental foramen)
• Extracted tooth root in the same three-dimensional position as the future implant placement so that the bone core biopsy can be taken from a site totally within the confines of the former tooth socket without inclusion of surrounding native alveolar bone
• Scheduled for single tooth extraction with bone graft placement and membrane

Exclusion Criteria:

• Uncontrolled periodontal disease
• Uncontrolled systemic disease
• Pregnancy
• Use of therapy and/or medication that impairs wound healing (e.g., bisphosphonates, steroids, chemotherapy, radiotherapy etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Smokers; Subjects are qualified as smokers if they report smoking ≥10 cigarettes/day for ≥5 years, and maintain a 8ppm carbon monoxide concentration or higher via smokerlyzer test.	Other: observational study; Observational study; alveolar ridge preservation
Non-smokers; Subjects qualify as nonsmokers if they have never smoked and upon confirmation by the smokerlyzer test of carbon monoxide concentation of less than 8ppm.	Other: observational study; Observational study; alveolar ridge preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Parameters	bone width	Measured before surgery, during surgery and at 4 months
Clinical Parameters	bone height	Measured before surgery, during surgery and at 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic Parameters	RNA transcriptomic analysis	Bone samples harvested at 4 months
Histological Parameters	Histological analysis of bone cores: %mineralized bone	Samples harvested at 4 months
Histological Parameters	Histological analysis of bone cores: %osteoid	Samples harvested at 4 months
Histological Parameters	Histological analysis of bone cores: %residual bone graft	Samples harvested at 4 months
Histological Parameters	Histological analysis of bone cores: %soft tissue	Samples harvested at 4 months
Histological Parameters	Histological analysis of bone cores: numbers of osteoblasts and osteoclasts	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: bone mineral density	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: tissue mineral density	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: bone volume / tissue volume (BV/TV)	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: trabecular number	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: trabecular separation	Samples harvested at 4 months
Micro-CT Parameters	Histological analysis of bone cores: trabecular thickness	Samples harvested at 4 months
Patient-reported Parameters	Oral Health Impact Profile -14 (OHIP-14). Range from 0 (no impact) to 56 (most severe impact).	Measured before surgery, at 1, 2 and 6 weeks, and 4 months
Patient-reported Parameters	VAS for pain (0-100). Zero indicates no pain and 100 the worst pain imaginable.	Measured before surgery and at 1, 2 and 6 weeks, and 4 months
Patient-reported Parameters	VAS for swelling (0-100). Zero indicates no swelling and 100 the worst swelling imaginable.	Measured before surgery and at 1, 2 and 6 weeks, and 4 months
Patient-reported Parameters	VAS for difficulty of mouth opening (0-100). Zero indicates no difficulty of mouth opening and 100 complete inability to open mouth.	Measured before surgery, at 1, 2 and 6 weeks, and 4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Parameters	gingival width	Measured at baseline (before surgery)
Clinical Parameters	gingival thickness	Measured at baseline (before surgery)
Clinical Parameters	wound opening	Measured immediately after surgery, at 1, 2 and 6 weeks and 4 months
Clinical Parameters	bleeding	Measured at 1, 2 and 6 weeks and 4 months
Clinical Parameters	grafting material discharge	Measured at 1, 2 and 6 weeks and 4 months
Clinical Parameters	flap necrosis	Measured at 1, 2 and 6 weeks and 4 months

Collaborators and Investigators

• Sponsor: Marquette University
• Collaborators: LifeNet Health
• Investigators: Principal Investigator: Vrisiis Kofina, DDS, MS, Marquette University

Study record dates

Study Major Dates

• Study Start (Estimated): January 25, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Smoking; Tobacco Smoking; Tobacco Use; Cigarette Smoking; Investigative Techniques; Methods; Observation
• Other Study ID Numbers: HR-4728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No