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The purpose of the present study is to observe and compare -through a biomolecular analysis- the differences in the gene expression and cellular behavior in the early wound healing process -24 hours after injury- between the following three oral tissues: alveolar mucosa, buccal gingiva and palatal tissue.
The main hypothesis is that there is a difference in the gene expression and in the cellular behaviour between the three oral tissues studied and this difference can be observed at 24 hours post-injury.
The wound healing is an extremely complex process. It has been observed that oral wounds mechanisms present special features. In fact, mucosal wounds demonstrated accelerated healing compared to cutaneous wounds.
Numerous comparative studies have described important differences of cellular behavior and genes expression between oral mucosal and dermal tissues. Moreover, it has been observed that the behavior of the cells is autonomous, i.e., that greatest differences seen in the genomic response after injury in skin and mucosa are derived, in part, from intrinsic differences in the genetic regulation of the cells at each site. Also, it is important to highlight the fact that it has been observed that the cellular response after wound is early, showing the first and greatest changes at 12-24 hours post injury. Moreover, a recent study has been raised the possibility of that the transcriptional regulatory networks responsible for the accelerated healing in oral mucosa are already present in the unwounded state.
In the oral mucosal tissues, the mechanisms underlying scar-less wound healing have been studied. Most studies have focused on the cellular characteristics and the molecular expression as growing factors, inflammatory mediators, etc., and have evaluated the process in later periods.
Therefore, while the biomolecular basis of the differences in oral mucosal and dermal tissues wound healing have been described, this is less well understood in the different oral soft tissue wounds.
The following points must be considered:
The main questions are:
Twenty-four hours after injury: Are there differences in the gene expression and cellular behaviour between the three studied tissues?
The transcriptional regulatory networks responsible for the accelerated oral tissues healing:
Deepen the knowledge in the early wound healing process of these tissues and the difference between them -evaluating the genes expression and the behavior of the cells- could allow the generation of new approaches to improve the healing of oral wounds.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Biopsies | Other | Oral soft tissues biopsies (alveolar mucosa, buccal gingiva, and palatal tissue) at T0 and T24 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral soft tissues biopsies | Other | Oral soft tissues biopsies (alveolar mucosa, buccal gingiva, and palatal tissue) will be harvested by the examiner at the time of the surgery (immediately before to start the surgical procedure -T0) and 24 hours after surgery (T24) at the level of the vertical released incisions (VRIs) with a biopsy punch with plunger of 2.0 mm diameter. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes from baseline fold regulation wound healing related genes at 24 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. | Baseline (T0) and 24 hours after surgery (T24) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrea Pilloni, MD,DDS,MS | University of Roma La Sapienza | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Oral and Maxillofacial Sciences. Section of Periodontics.Sapienza, University of Rome | Rome | 00161 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25473038 | Background | 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. | |
| 11276871 | Background | Bartold PM, McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000. 2000 Oct;24:253-69. doi: 10.1034/j.1600-0757.2000.2240113.x. No abstract available. |
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| ID | Term |
|---|---|
| D000072836 | Surgical Wound |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
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| 24 hours and 1 week after surgery |
| 15790734 | Background | Szpaderska AM, Walsh CG, Steinberg MJ, DiPietro LA. Distinct patterns of angiogenesis in oral and skin wounds. J Dent Res. 2005 Apr;84(4):309-14. doi: 10.1177/154405910508400403. |
| 15659033 | Background | 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. |
| 19769724 | Background | Wong JW, Gallant-Behm C, Wiebe C, Mak K, Hart DA, Larjava H, Hakkinen L. Wound healing in oral mucosa results in reduced scar formation as compared with skin: evidence from the red Duroc pig model and humans. Wound Repair Regen. 2009 Sep-Oct;17(5):717-29. doi: 10.1111/j.1524-475X.2009.00531.x. |
| 19854029 | Background | Mak K, Manji A, Gallant-Behm C, Wiebe C, Hart DA, Larjava H, Hakkinen L. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci. 2009 Dec;56(3):168-80. doi: 10.1016/j.jdermsci.2009.09.005. Epub 2009 Oct 24. |
| 18460641 | Background | Roy S, Khanna S, Rink C, Biswas S, Sen CK. Characterization of the acute temporal changes in excisional murine cutaneous wound inflammation by screening of the wound-edge transcriptome. Physiol Genomics. 2008 Jul 15;34(2):162-84. doi: 10.1152/physiolgenomics.00045.2008. Epub 2008 May 6. |
| 17244330 | Background | Chen W, Fu X, Ge S, Sun T, Zhou G, Han B, Li H, Sheng Z. Profiling of genes differentially expressed in a rat of early and later gestational ages with high-density oligonucleotide DNA array. Wound Repair Regen. 2007 Jan-Feb;15(1):147-55. doi: 10.1111/j.1524-475X.2006.00195.x. |
| 30045979 | Background | 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. |
| 28005267 | Background | 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. |
| 16841303 | Background | Kantarci A, Black SA, Xydas CE, Murawel P, Uchida Y, Yucekal-Tuncer B, Atilla G, Emingil G, Uzel MI, Lee A, Firatli E, Sheff M, Hasturk H, Van Dyke TE, Trackman PC. Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis. J Pathol. 2006 Sep;210(1):59-66. doi: 10.1002/path.2000. |
| 28646601 | Background | 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. |
| 30405935 | Background | 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. |
| 33527447 | Derived | 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. |