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The aim of the present study is to evaluate using clinical, patient-centered, immunological, microbiological, and histological parameters, the effect of silk fibroin films loaded or not with insulin in the repair of palatal mucosa open wounds.
There are several types of periodontal and peri-implant soft tissue defects that require surgical treatment to reestablishment function and aesthetics. Therefore, surgical procedures for the reconstruction of the gingival and peri-implant tissues are routinely performed. However, these procedures do not always have predictable outcomes, and problems with the wound healing process can occur, which can impair the outcomes. To overcome this problem, new materials, drugs, and devices have been used to improve the results of surgical procedures. The present study is a controlled clinical trial that will include seventy-five patients with an indication of anterior maxillary tooth extraction for ridge preservation. The ridge preservation will be performed and a free gingival graft harvest from the palatal mucosa will be used to seal the socket entrance. Thereafter, the palatal wound will be randomly assigned into 3 groups: Control Group (C; n=25): open wound on palatal mucosa that will receive no treatment. Blank Film Group (BF; n=25): open wound on palatal mucosa that will receive silk fibroin film as dressing. Insulin-loaded film (IF; n=25): open wound on palatal mucosa that will receive an insulin-loaded silk fibroin film as a delivery system. Clinical, immunological, histological, and microbiome parameters will be analyzed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control Group (CG) | Sham Comparator | The palatal wound area will not receive any treatment |
|
| Blank Film Group (BF) | Experimental | The palatal wound area will receive silk fibroin film as a dressing |
|
| Insulin-loaded film (IF) | Experimental | The palatal wound area will receive an insulin-loaded silk fibroin film as a drug delivery system |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Palatal Wound | Procedure | With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive 4.0 silk sutures. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Remaining wound healing (RWA) | Photographs will be taken from palatal wound with brightness, distance, and angle standardized. A scale will be placed in the palate as a reference to measure the area. These photographs will be exported to an image software (Image J - NIH, Bethesda, USA), and the wound area will be measured in square millimeters (Dias et al., 2015). | 90 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Tissue Thickness (TT) | Tissue thickness of palatine masticatory mucosa will be assessed by a Cone Beam Computed Tomographic (CBCT). In order to standardize the volume measures, the FGG harvested stent, made of 1 mm thick rigid acrylic plates in vacuum plasticizer with radiopaque material, will be used by the patient at the time of the CBCT image acquisition. | 90 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mauro P Santamaria, PhD | Contact | (12) 39479055 | +55 | mauro.santamaria@unesp.br |
| Name | Affiliation | Role |
|---|---|---|
| Mauro P Santamaria, PhD | Sao Paulo State University - Brazil | Study Director |
| Manuela Maria V Miguel, MS | Sao Paulo State University - Brazil | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mauro Pedrine Santamaria and Manuela Maria Viana Miguel | Recruiting | São José dos Campos | São Paulo | 12245000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27756117 | Background | Teuschl AH, Zipperle J, Huber-Gries C, Kaplan DL. Silk fibroin based carrier system for delivery of fibrinogen and thrombin as coagulant supplements. J Biomed Mater Res A. 2017 Mar;105(3):687-696. doi: 10.1002/jbm.a.35940. Epub 2016 Nov 7. | |
| 30475285 | Background | Kamalathevan P, Ooi PS, Loo YL. Silk-Based Biomaterials in Cutaneous Wound Healing: A Systematic Review. Adv Skin Wound Care. 2018 Dec;31(12):565-573. doi: 10.1097/01.ASW.0000546233.35130.a9. |
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Data will be available at the end of the study after a direct request
After the study completion.
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This is a double-blind, parallel, superiority, randomized clinical trial with 3 months of follow-up.
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| Palatal Wound treated with Silk Fibroin Film | Device | With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film and 4.0 silk sutures. |
|
| Palatal Wound treated with Insulin-loaded Silk Fibroin Film | Device | With the goal to harvest the free gingival graft (FGG), an 8mm diameter scalpel will be used to ensure standardized wounds. Thereafter, a 2-mm thick FGG will be removed. The wound area will receive a silk fibroin film loaded with insulin and 4.0 silk sutures. |
|
| Epithelialization (E) | Wound will be colored with Replack (Dentisply - York, Pensilvânia - USA) and quantity measured by Image J program. Then, with the total area of the wound, the epithelization % will be calculated (Ozcelik et al. 2008). | 90 days |
| Early- wound healing index (EWHI) | According to Fickl et al. 2014 any modification in wound healing will be evaluated in five different degrees:
| 14 days |
| Tissue Edema (TE) | Tissue edema will be evaluated with the score: 1 = absent; 2 = slight; 3 = moderate; or 4 = severe (Sanz-Moliner et, 2013). | 7 days |
| Oral Health Impact Profile | Will be evaluated from a questionnaire with 14 questions based on 7 domains: functional limitations, physical pain, psychological discomfort, physical disability, psychological deficiency and social deficiency. The patient should respond to the questions within 14 days after the surgical procedure, performing a postoperative diary. For each question an answer must be given, represented in numbers, being: 0- Never; 1- Almost never; 2-Occasionally; 3-Quite frequent; 4-Very common; 5-I do not know (Tonetti MS et al. 2017) | 14 days |
| Number of analgesics | Number of analgesics used during 14 days after the procedure will be reported at the same postoperative diary (Tonetti et al. 2017). | 14 days |
| Patient Discomfort | By a visual analogic scale (VAS) of 100 mm to assess discomfort, patients will report pain diary during the 14 days after surgery. Scale extremes will be "no pain" to "extreme." (Tonetti et al. 2017). | 14 days |
| Qualitative somatosensory testing (QualST) | This analysis will evaluate somatosensorial profiles and pain conditions. For this, different stimulus will be performed on the wound and the following tests will be applied: (1) Touch stimulus will be applied with a swab by a single application for 1-2 sec in the wound; (2) Cold stimulus will be applied by a stainless steel dental spatula (kept cool in ice water, approximately 0 °C) with wound direct contact during 1-2 sec; (3) The pinprick stimulus will be performed with a periodontal probe with moderate force on the wound area for 1-2 s (Baad-Hansen et al, 2013) Patient will report hypersensitivity, hyposensitivity, or normosensitivity to touch, cold and painful stimulus. | 14 days |
| Immunologic Analysis | With the goal to obtain baseline data for this parameter, crevicular gingival fluid from the gingival area next to the donor area will be collected previous surgery. An absorbent paper (PerioPaper, Oraflow, Plainview, NY, EUA) will be placed at wound edges without pressure during 40s. Collects with blood contamination will be discarded. Samples will be stored into a sterilized Eppendorf containing 100 μL Phosphate Buffer Saline 0.05% Tween 2 (PBS) at - 80 C. Growth factors (VEGF and EGF), chemokines (MIP-1α, MCP-1α), and cytokines (IL1β, IL6, IL10, TNFα) levels will be determinate by the multiplex assay. Moreover, MMP-2, MMP-9, TIMP-1, TIMP-2 will be measured by the same commercial human commercial kit. | 7 days |
| Histological Analysis | CTG will be harvested from the palatal area, the same area that received FGG protocol previously, using the same harvesting stent, during implant therapy. After CTG be harvested, a 2-mm thick will be removed from the graft (Azar et al., 2019) to perform biopsy analysis aiming to observe histological changes during healing process by previously use of silk fibroin film, charged or not with insulin, and spontaneous repair. The specimens will be immersed in 10% formalin for histological analysis which will be stained with hematoxylin-eosin and Masson's trichrome. | 180 days |
| 22564234 | Background | Chen X, Liu Y, Zhang X. Topical insulin application improves healing by regulating the wound inflammatory response. Wound Repair Regen. 2012 May-Jun;20(3):425-34. doi: 10.1111/j.1524-475X.2012.00792.x. |
| 25373688 | Background | Dias SB, Fonseca MV, Dos Santos NC, Mathias IF, Martinho FC, Junior MS, Jardini MA, Santamaria MP. Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial. Lasers Med Sci. 2015 Aug;30(6):1695-702. doi: 10.1007/s10103-014-1685-2. Epub 2014 Nov 6. |
| 39801488 | Derived | Santamaria MP, Mathias-Santamaria IF, Ferreira Bonafe AC, Gonzalez OA, Kirakodu S, Monteiro MF, Casarin RCV, Shaddox LM, Miguel MMV. Microbiome and Inflammatory Biomarkers Associated With Palatal Wound Healing. J Periodontal Res. 2025 Jul;60(7):664-675. doi: 10.1111/jre.13373. Epub 2025 Jan 13. |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D014947 | Wounds and Injuries |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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