Effect of Hyaluronic Acid on Oral Mucosal Wound Healing - Focus on Pain and Re-epithelisation

Establishment of a sufficiently wide and thick keratinized gingival/mucosal tissue cuff around teeth/implants is considered of importance for long-term stability. This can more readily be achieved by means of autogenous soft tissue grafts harvested from the palate than with soft tissue substitutes. However, this often implies the creation of an open palatal wound involving secondary intention healing. The aim of this randomized controlled, split-mouth, clinical trial is to assess the effect of a hyaluronic acid containing commercial product on wound healing and patient morbidity after palatal soft tissue harvesting. Altogether, 20 volunteers will be recruited. An individualized splint containing 2 symmetrically located contralateral cylindrical openings will be used for standardized soft tissue harvesting (6 mm in Ø, 2 mm in depth). Soft tissue grafts will be harvested randomly from the right or left side and patients will be monitored for 3 weeks followed by a 1-month wash-out period prior to harvesting the second soft tissue graft from the other side. Participants will randomly start treating the palatal wound either with the test product (GUM Aftaclear Gel, Sunstar Suisse SA, Etoy, Switzerland; 0.3%) or saline solution for 7 days to promote the healing process, which will be reversed for the second round. Patient-related outcomes (morbidity, discomfort, taste alteration, pain killer consumption), frequency of bleeding events, defect closure (area, volume), and microbial colonisation will be recorded and analysed for any differences between the control and test product. Further, in 6 additional volunteers, biopsies of the healing wound are collected in a similar fashion as described above, but with the use of a larger stent in order to harvest also pristine surrounding tissues for histological analysis; biopsies are collected up to 14 days of healing.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Wound Healing
• Intervention / Treatment: Procedure: palatal soft tissue harvesting; Device: Hyaluronic acid; Other: Saline solution (placebo)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Malmo, Sweden
    • Faculty of Odontology, Malmö University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-65 years,
• systemically healthy,
• healthy periodontal conditions at the experimental region or conditions not interfering with proper biopsy harvesting,
• no known sensitivity to HY,
• no uncontrolled diabetes mellitus,
• no radiotherapy or chemotherapy,
• no current pregnancy or breastfeeding,
• no hormonal diseases,
• no infectious diseases,
• no autoimmune diseases or under immunotherapy,
• no systemic bone disease,
• no wound healing disorders or acute inflammatory/infectious processes,
• no systemic diseases with implications on mucous membranes (e.g., Morbus Crohn),
• no increased risk of bleeding (i.e., patient with coagulation disorders or under anticoagulant therapy, and
• no heavy smokers (i.e., no regular tobacco consumption > 10 cigarettes/day).

Exclusion Criteria:

• not meeting the inclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyaluronic acid; Application 3-times per day for 7 days.	Procedure: palatal soft tissue harvesting; A 6x2mm palatal soft tissue graft will be harvested.; Device: Hyaluronic acid; application 3-times per day for 7 days
Placebo Comparator: Saline solution; Application 3-times per day for 7 days.	Procedure: palatal soft tissue harvesting; A 6x2mm palatal soft tissue graft will be harvested.; Other: Saline solution (placebo); application 3-times per day for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain / discomfort (burning) perception by means of a 100 mm VAS	0 indicates no pain, 100 indicates maximum pain	3 days
pain / discomfort (burning) perception by means of a 100 mm VAS	0 indicates no pain, 100 indicates maximum pain	7 days
pain / discomfort (burning) perception by means of a 100 mm VAS	0 indicates no pain, 100 indicates maximum pain	14 days
pain / discomfort (burning) perception by means of a 100 mm VAS	0 indicates no pain, 100 indicates maximum pain	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain killer consumption	amount of pills taken	3 days
pain killer consumption	amount of pills taken	7 days
pain killer consumption	amount of pills taken	14 days
pain killer consumption	amount of pills taken	21 days
disturbance while eating or drinking by means of a 100 mm VAS	0 indicates no disturbance, 100 indicates maximum disturbance	3 days
disturbance while eating or drinking by means of a 100 mm VAS	0 indicates no disturbance, 100 indicates maximum disturbance	7 days
disturbance while eating or drinking by means of a 100 mm VAS	0 indicates no disturbance, 100 indicates maximum disturbance	14 days
disturbance while eating or drinking by means of a 100 mm VAS	0 indicates no disturbance, 100 indicates maximum disturbance	21 days
taste alteration experience by means of a 100 mm VAS	0 indicates no alteration, 100 indicates maximum alteration	3 days
taste alteration experience by means of a 100 mm VAS	0 indicates no alteration, 100 indicates maximum alteration	7 days
taste alteration experience by means of a 100 mm VAS	0 indicates no alteration, 100 indicates maximum alteration	14 days
taste alteration experience by means of a 100 mm VAS	0 indicates no alteration, 100 indicates maximum alteration	21 days
frequency of re-bleeding	number of events	3 days
frequency of re-bleeding	number of events	7 days
frequency of re-bleeding	number of events	14 days
frequency of re-bleeding	number of events	21 days
re-epithelialised defect area (by means of standardized photographs)	mm2	3 days
re-epithelialised defect area (by means of standardized photographs)	mm2	7 days
re-epithelialised defect area (by means of standardized photographs)	mm2	14 days
re-epithelialised defect area (by means of standardized photographs)	mm2	21 days
re-epithelisation by colorimetric digital assessment of the calibrated photographs	colorimetric assessment	3 days
re-epithelisation by colorimetric digital assessment of the calibrated photographs	colorimetric assessment	7 days
re-epithelisation by colorimetric digital assessment of the calibrated photographs	colorimetric assessment	14 days
re-epithelisation by colorimetric digital assessment of the calibrated photographs	colorimetric assessment	21 days
changes in total and specific bacterial counts	log values	3 days
changes in total and specific bacterial counts	log values	7 days
changes in total and specific bacterial counts	log values	14 days
defect volume fill by overlay of the intraoral scans	mm3	3 days
defect volume fill by overlay of the intraoral scans	mm3	7 days
defect volume fill by overlay of the intraoral scans	mm3	14 days
defect volume fill by overlay of the intraoral scans	mm3	21 days
food restrictions (yes/no)		3 days
food restrictions (yes/no)		7 days
food restrictions (yes/no)		14 days
food restrictions (yes/no)		21 days

Collaborators and Investigators

• Sponsor: Malmö University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: October 9, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 2, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: 2020-01018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No