Early Healing of Oral Soft Tissues: a Clinical and Biomolecular Analysis. Part III

NCT ID: NCT04865952

Last Updated: 2022-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-29

Study Completion Date

2021-07-06

Brief Summary

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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

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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.

Conditions

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Wound Heal Wound Surgical Oral Soft Tissue Conditions Hyaluronic Acid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

split-mouth design
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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HA application (treatment group - HA)

periodontal surgery + HA application + buccal attached gingival (G) biopsies 24 hr after surgical procedure

Group Type EXPERIMENTAL

periodontal surgery + 24 hr buccal attached gingiva (G) biopsy

Intervention Type PROCEDURE

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 application

Intervention Type OTHER

HA will be applied at the end of the surgical procedure, at the level of the vertical released incisions (VRIs) and over VRIs

NO HA application (non treatment group - NT)

periodontal surgery + buccal attached gingival (G) biopsies 24 hr after surgical procedure

Group Type OTHER

periodontal surgery + 24 hr buccal attached gingiva (G) biopsy

Intervention Type PROCEDURE

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).

Interventions

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periodontal surgery + 24 hr buccal attached gingiva (G) biopsy

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).

Intervention Type PROCEDURE

HA application

HA will be applied at the end of the surgical procedure, at the level of the vertical released incisions (VRIs) and over VRIs

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

30 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Andrea Pilloni MD DDS MS

Chairman Section of Periodontics Director of Master Program in Periodontics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andrea Pilloni, MD,DDS,MS

Role: STUDY_DIRECTOR

University of Roma La Sapienza

Locations

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Department of Oral and Maxillofacial Sciences. Section of Periodontics.Sapienza, University of Rome

Roma, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 25473038 (View on PubMed)

Warburton 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.

Reference Type BACKGROUND
PMID: 15659033 (View on PubMed)

Iglesias-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.

Reference Type BACKGROUND
PMID: 30045979 (View on PubMed)

Wang 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.

Reference Type BACKGROUND
PMID: 28005267 (View on PubMed)

Vescarelli 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.

Reference Type BACKGROUND
PMID: 28646601 (View on PubMed)

Marini 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.

Reference Type BACKGROUND
PMID: 30405935 (View on PubMed)

Rojas 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.

Reference Type BACKGROUND
PMID: 33527447 (View on PubMed)

Bansal 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.

Reference Type BACKGROUND
PMID: 21187628 (View on PubMed)

West 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.

Reference Type BACKGROUND
PMID: 2408340 (View on PubMed)

Pilloni 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.

Reference Type BACKGROUND
PMID: 9799448 (View on PubMed)

Fujioka-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.

Reference Type BACKGROUND
PMID: 28093072 (View on PubMed)

Nyman 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.

Reference Type BACKGROUND
PMID: 31333952 (View on PubMed)

Asparuhova 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.

Reference Type BACKGROUND
PMID: 30264516 (View on PubMed)

Other Identifiers

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5315 Prot 0640/2020

Identifier Type: -

Identifier Source: org_study_id

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