Wound HealNCT04865952
Early Healing of Oral Soft Tissues: a Clinical and Biomolecular Analysis. Part III
A study testing periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and HA application in people with Wound Heal and Wound Surgical, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
The purpose of the present study is to evaluate the effect of Hyaluronic acid application in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues. Read more about this study
- Who is it for?
- Ages 30 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Wound Heal, Wound Surgical, Oral Soft Tissue Conditions
- What is being tested?
- periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and HA application
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteItaly
- Study dates
- 29 Apr 2021to 6 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- patients that required periodontal surgery;
- patients age between 30-60 years;
- patients with full mouth plaque score and full mouth bleeding score < 15%;
- patients with a good general healthy status;
- patients without any medicaments or drug consumption that can affect the healing process;
- non-smoking patients.
Who cannot join
- patients in pregnancy;
- patients in lactation period;
- patients with consumption of antibiotics or anti-inflammatory drugs in the previous six months;
- patients with systemic diseases.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Oral and Maxillofacial Sciences. Section of Periodontics.Sapienza, University of Rome
Roma, 00161
About this study
Official title: Effect of Hyaluronic Acid Application in Gene Expression and Cellular Behavior 24-hours After Injury
The purpose of the present study is to evaluate the effect of Hyaluronic acid application in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues.
Read the detailed description
Although it has been demonstrated the role of HA in many different biological process related with tissue repair and regeneration, specific mechanisms involved in the early wound healing process in the oral soft tissues remains unclear.
A recent in vitro study evaluated the effects of two HA formulations on human oral fibroblasts involved in soft tissue wound healing/regeneration. The authors demonstrated that the investigated HA formulations maintained the viability of oral fibroblasts and increased their proliferative and migratory abilities. Moreover, enhanced expression of genes encoding type III collagen and transforming growth factor-β3, characteristic of scarless wound healing. Interestingly, TGFB1 remains unchanged. Moreover, compared to untreated control cells, either HA preparation upregulated the expression levels of COL3A1 in both HPFs and HGFs at 24 hour, whereas no effect on COL1A1 mRNA levels was detected The HAs upregulated the expression of genes encoding pro-proliferative, pro-migratory, and pro-inflammatory factors, with only a moderate effect on the latter in gingival fibroblasts. However, in vitro experiments have certain limitations. HA would undergo degradation to lower MW molecules following hyaluronidase activity during the post-operative period and will thus exert additional or even opposing effects on the wound repair process.28
To highlight, is the fact that in the latest years, the translational medicine focuses in research concerning scar-free wound healing tissues repair mechanisms and regarding this, it has been proposed that HA plays an important role in the fast and scarless fetal wound healing seeing during the first and second trimester.
Therefore, the aim of the present pilot study will be to evaluate the effect of hyaluronic acid application on gene expression and cellular behavior in the early wound healing process of gingival tissues. The second aim of the present work will be to evaluate the effect of HA in the wound healing clinical response.
Our hypothesis is that HA modifies the expression of genes related with the early wound healing response and the behavior of the main cells involved in this biological process: fibroblasts; stimulating and accelerating their wound healing potential.
- Being tested
- periodontal surgery + 24 hr buccal attached gingiva (G) biopsy, HA application
- Keywords
- early wound healing, gingival tissue, wound healing, hyaluronic acid, soft tissue injury
- Medical subject headings
- Surgical Wound, Soft Tissue Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
periodontal surgery + 24 hr buccal attached gingiva (G) biopsyProcedure or surgery
Periodontal surgery will be performed and 24 hr after the surgical procedure a 2mm punch biopsy will be harvested at the level of the buccal attache gingiva (G).
HA applicationOther
HA will be applied at the end of the surgical procedure, at the level of the vertical released incisions (VRIs) and over VRIs
| Study group | Role | What they receive |
|---|---|---|
| HA application (treatment group - HA) | Experimental | periodontal surgery + HA application + buccal attached gingival (G) biopsies 24 hr after surgical procedure Receives: Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy; Other: HA application |
| NO HA application (non treatment group - NT) | Other | periodontal surgery + buccal attached gingival (G) biopsies 24 hr after surgical procedure Receives: Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline fold regulation wound healing related genes at 24 hours HA application
Total RNA from biopsies or cell cultures was extracted using TRIzol reagent Quantitative real-time PCR (qRT-PCR) cDNA was generated and cDNA obtained were used for amplification of wound healing related genes using the appropriate TaqMan gene expression assay kits.
Measured: 24 hours after surgery (T24 hours)
Clinical evaluation of early wound healing
Assessed with a clinical index (EHS- Early wound healing score). This score assessed clinical signs of re-epithelialization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Since complete wound epithelialization was the main outcome, the CSR score was weighted to be 60% of the total final score. Accordingly, a score of 0, 3, or 6 points was possible for the assessment of CSR, whereas scores of 0, 1, or 2 points were possible for CSH and CSI. Higher values indicated better healing. Accordingly, the score for ideal early wound healing was 10.
Measured: 24 hours after surgery (T24 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2021
- Study start29 Apr 2021
- Primary completion5 Jul 2021
- Study completion6 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Wound HealStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- split-mouth design
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Pilloni MD DDS MS, University of Roma La Sapienza
- Investigators
- Andrea Pilloni, MD,DDS,MS, Study director, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04865952
- Sponsor's protocol ID
- 5315 Prot 0640/2020
- Status last verified
- Oct 2022
- First submitted
- 25 Apr 2021
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014 Dec 3;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
PubMed 25473038Warburton G, Nares S, Angelov N, Brahim JS, Dionne RA, Wahl SM. Transcriptional events in a clinical model of oral mucosal tissue injury and repair. Wound Repair Regen. 2005 Jan-Feb;13(1):19-26. doi: 10.1111/j.1067-1927.2005.130104.x.
PubMed 15659033Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL, Edwards D, Doci C, Asselin-Labat ML, Onaitis MW, Moutsopoulos NM, Gutkind JS, Morasso MI. Transcriptional signature primes human oral mucosa for rapid wound healing. Sci Transl Med. 2018 Jul 25;10(451):eaap8798. doi: 10.1126/scitranslmed.aap8798.
PubMed 30045979Wang Y, Tatakis DN. Human gingiva transcriptome during wound healing. J Clin Periodontol. 2017 Apr;44(4):394-402. doi: 10.1111/jcpe.12669. Epub 2017 Feb 11.
PubMed 28005267Vescarelli E, Pilloni A, Dominici F, Pontecorvi P, Angeloni A, Polimeni A, Ceccarelli S, Marchese C. Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa. J Clin Periodontol. 2017 Oct;44(10):1039-1050. doi: 10.1111/jcpe.12767. Epub 2017 Aug 25.
PubMed 28646601Marini L, Rojas MA, Sahrmann P, Aghazada R, Pilloni A. Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds. J Periodontal Implant Sci. 2018 Oct 24;48(5):274-283. doi: 10.5051/jpis.2018.48.5.274. eCollection 2018 Oct.
PubMed 30405935Rojas MA, Ceccarelli S, Gerini G, Vescarelli E, Marini L, Marchese C, Pilloni A. Gene expression profiles of oral soft tissue-derived fibroblast from healing wounds: correlation with clinical outcome, autophagy activation and fibrotic markers expression. J Clin Periodontol. 2021 May;48(5):705-720. doi: 10.1111/jcpe.13439. Epub 2021 Feb 17.
PubMed 33527447Bansal J, Kedige SD, Anand S. Hyaluronic acid: a promising mediator for periodontal regeneration. Indian J Dent Res. 2010 Oct-Dec;21(4):575-8. doi: 10.4103/0970-9290.74232.
PubMed 21187628West DC, Hampson IN, Arnold F, Kumar S. Angiogenesis induced by degradation products of hyaluronic acid. Science. 1985 Jun 14;228(4705):1324-6. doi: 10.1126/science.2408340.
PubMed 2408340Pilloni A, Bernard GW. The effect of hyaluronan on mouse intramembranous osteogenesis in vitro. Cell Tissue Res. 1998 Nov;294(2):323-33. doi: 10.1007/s004410051182.
PubMed 9799448Fujioka-Kobayashi M, Muller HD, Mueller A, Lussi A, Sculean A, Schmidlin PR, Miron RJ. In vitro effects of hyaluronic acid on human periodontal ligament cells. BMC Oral Health. 2017 Jan 16;17(1):44. doi: 10.1186/s12903-017-0341-1.
PubMed 28093072Nyman E, Henricson J, Ghafouri B, Anderson CD, Kratz G. Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model. Plast Reconstr Surg Glob Open. 2019 May 1;7(5):e2221. doi: 10.1097/GOX.0000000000002221. eCollection 2019 May.
PubMed 31333952Asparuhova MB, Kiryak D, Eliezer M, Mihov D, Sculean A. Activity of two hyaluronan preparations on primary human oral fibroblasts. J Periodontal Res. 2019 Feb;54(1):33-45. doi: 10.1111/jre.12602. Epub 2018 Sep 27.
PubMed 30264516
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Hyaluronic Acid Application in Gene Expression and Cellular Behavior 24-hours After Injury
- ClinicalTrials.gov ID
- NCT04865952
- Acronym / sponsor ID
- 5315 Prot 0640/2020
- Keywords
- early wound healing, gingival tissue, wound healing, hyaluronic acid, soft tissue injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- 5 Jul 2021 (actual)
- Study completion
- 6 Jul 2021 (actual)
- First posted
- 29 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the present study is to evaluate the effect of Hyaluronic acid application in the gene expression profile and cellular behavior in the early wound healing process -24 hours after injury- of the oral soft tissues.
Detailed description
Although it has been demonstrated the role of HA in many different biological process related with tissue repair and regeneration, specific mechanisms involved in the early wound healing process in the oral soft tissues remains unclear.
A recent in vitro study evaluated the effects of two HA formulations on human oral fibroblasts involved in soft tissue wound healing/regeneration. The authors demonstrated that the investigated HA formulations maintained the viability of oral fibroblasts and increased their proliferative and migratory abilities. Moreover, enhanced expression of genes encoding type III collagen and transforming growth factor-β3, characteristic of scarless wound healing. Interestingly, TGFB1 remains unchanged. Moreover, compared to untreated control cells, either HA preparation upregulated the expression levels of COL3A1 in both HPFs and HGFs at 24 hour, whereas no effect on COL1A1 mRNA levels was detected The HAs upregulated the expression of genes encoding pro-proliferative, pro-migratory, and pro-inflammatory factors, with only a moderate effect on the latter in gingival fibroblasts. However, in vitro experiments have certain limitations. HA would undergo degradation to lower MW molecules following hyaluronidase activity during the post-operative period and will thus exert additional or even opposing effects on the wound repair process.28
To highlight, is the fact that in the latest years, the translational medicine focuses in research concerning scar-free wound healing tissues repair mechanisms and regarding this, it has been proposed that HA plays an important role in the fast and scarless fetal wound healing seeing during the first and second trimester.
Therefore, the aim of the present pilot study will be to evaluate the effect of hyaluronic acid application on gene expression and cellular behavior in the early wound healing process of gingival tissues. The second aim of the present work will be to evaluate the effect of HA in the wound healing clinical response.
Our hypothesis is that HA modifies the expression of genes related with the early wound healing response and the behavior of the main cells involved in this biological process: fibroblasts; stimulating and accelerating their wound healing potential.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- split-mouth design
| Arm | Type | Receives |
|---|---|---|
| HA application (treatment group - HA) | Experimental | Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsy, Other: HA applicationperiodontal surgery + HA application + buccal attached gingival (G) biopsies 24 hr after surgical procedure |
| NO HA application (non treatment group - NT) | Other | Procedure: periodontal surgery + 24 hr buccal attached gingiva (G) biopsyperiodontal surgery + buccal attached gingival (G) biopsies 24 hr after surgical procedure |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- patients that required periodontal surgery;
- patients age between 30-60 years;
- patients with full mouth plaque score and full mouth bleeding score < 15%;
- patients with a good general healthy status;
- patients without any medicaments or drug consumption that can affect the healing process;
Key exclusion criteria (4 listed)
- patients in pregnancy;
- patients in lactation period;
- patients with consumption of antibiotics or anti-inflammatory drugs in the previous six months;
- patients with systemic diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| periodontal surgery + 24 hr buccal attached gingiva (G) biopsyPeriodontal surgery will be performed and 24 hr after the surgical procedure a 2mm punch biopsy will be harvested at the level of the buccal attache gingiva (G). | Procedure or surgery | HA application (treatment group - HA), NO HA application (non treatment group - NT) |
| HA applicationHA will be applied at the end of the surgical procedure, at the level of the vertical released incisions (VRIs) and over VRIs | Other | HA application (treatment group - HA) |
Primary outcome
Changes from baseline fold regulation wound healing related genes at 24 hours HA application
Time frame: 24 hours after surgery (T24 hours)
Total RNA from biopsies or cell cultures was extracted using TRIzol reagent Quantitative real-time PCR (qRT-PCR) cDNA was generated and cDNA obtained were used for amplification of wound healing related genes using the appropriate TaqMan gene expression assay kits.
Clinical evaluation of early wound healing
Time frame: 24 hours after surgery (T24 hours)
Assessed with a clinical index (EHS- Early wound healing score). This score assessed clinical signs of re-epithelialization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Since complete wound epithelialization was the main outcome, the CSR score was weighted to be 60% of the total final score. Accordingly, a score of 0, 3, or 6 points was possible for the assessment of CSR, whereas scores of 0, 1, or 2 points were possible for CSH and CSI. Higher values indicated better healing. Accordingly, the score for ideal early wound healing was 10.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- Background: PubMed 25473038Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014 Dec 3;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
- Background: PubMed 15659033Warburton G, Nares S, Angelov N, Brahim JS, Dionne RA, Wahl SM. Transcriptional events in a clinical model of oral mucosal tissue injury and repair. Wound Repair Regen. 2005 Jan-Feb;13(1):19-26. doi: 10.1111/j.1067-1927.2005.130104.x.
- Background: PubMed 30045979Iglesias-Bartolome R, Uchiyama A, Molinolo AA, Abusleme L, Brooks SR, Callejas-Valera JL, Edwards D, Doci C, Asselin-Labat ML, Onaitis MW, Moutsopoulos NM, Gutkind JS, Morasso MI. Transcriptional signature primes human oral mucosa for rapid wound healing. Sci Transl Med. 2018 Jul 25;10(451):eaap8798. doi: 10.1126/scitranslmed.aap8798.
- Background: PubMed 28005267Wang Y, Tatakis DN. Human gingiva transcriptome during wound healing. J Clin Periodontol. 2017 Apr;44(4):394-402. doi: 10.1111/jcpe.12669. Epub 2017 Feb 11.
- Background: PubMed 28646601Vescarelli E, Pilloni A, Dominici F, Pontecorvi P, Angeloni A, Polimeni A, Ceccarelli S, Marchese C. Autophagy activation is required for myofibroblast differentiation during healing of oral mucosa. J Clin Periodontol. 2017 Oct;44(10):1039-1050. doi: 10.1111/jcpe.12767. Epub 2017 Aug 25.
- Background: PubMed 30405935Marini L, Rojas MA, Sahrmann P, Aghazada R, Pilloni A. Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds. J Periodontal Implant Sci. 2018 Oct 24;48(5):274-283. doi: 10.5051/jpis.2018.48.5.274. eCollection 2018 Oct.
- Background: PubMed 33527447Rojas MA, Ceccarelli S, Gerini G, Vescarelli E, Marini L, Marchese C, Pilloni A. Gene expression profiles of oral soft tissue-derived fibroblast from healing wounds: correlation with clinical outcome, autophagy activation and fibrotic markers expression. J Clin Periodontol. 2021 May;48(5):705-720. doi: 10.1111/jcpe.13439. Epub 2021 Feb 17.
- Background: PubMed 21187628Bansal J, Kedige SD, Anand S. Hyaluronic acid: a promising mediator for periodontal regeneration. Indian J Dent Res. 2010 Oct-Dec;21(4):575-8. doi: 10.4103/0970-9290.74232.
- Background: PubMed 2408340West DC, Hampson IN, Arnold F, Kumar S. Angiogenesis induced by degradation products of hyaluronic acid. Science. 1985 Jun 14;228(4705):1324-6. doi: 10.1126/science.2408340.
- Background: PubMed 9799448Pilloni A, Bernard GW. The effect of hyaluronan on mouse intramembranous osteogenesis in vitro. Cell Tissue Res. 1998 Nov;294(2):323-33. doi: 10.1007/s004410051182.
- Background: PubMed 28093072Fujioka-Kobayashi M, Muller HD, Mueller A, Lussi A, Sculean A, Schmidlin PR, Miron RJ. In vitro effects of hyaluronic acid on human periodontal ligament cells. BMC Oral Health. 2017 Jan 16;17(1):44. doi: 10.1186/s12903-017-0341-1.
- Background: PubMed 31333952Nyman E, Henricson J, Ghafouri B, Anderson CD, Kratz G. Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model. Plast Reconstr Surg Glob Open. 2019 May 1;7(5):e2221. doi: 10.1097/GOX.0000000000002221. eCollection 2019 May.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Pilloni, MD,DDS,MS study director
University of Roma La Sapienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing periodontal surgery + 24 hr buccal attached gingiva (G) biopsy and HA application in people with Wound Heal and Wound Surgical, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline fold regulation wound healing related genes at 24 hours HA application (time frame: 24 hours after surgery (T24 hours)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04865952, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.