Clinical trial NCT05191082: Manufacturing, Characterization and Evaluation of the Effect of Silk Fibroin Membranes, Loaded or Not With Neurotensins on Open Wounds in the Palate
Official title: Manufacturing, Characterization and Evaluation of the Effect of Silk Fibroin Membranes, Loaded or Not With Neurotensins on Open Wounds in the Palate: Randomized Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Wound Healing
Palate; Wound
Keywords: Periodontology
Wound healing
Silk fibroin
Randomized clinical trial
Drug Delivery System
Lead sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
Sponsor class: OTHER
First posted: 2022-01-13
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, parallel, superiority, randomized clinical trial with a 3 months of follow-up
Primary purpose: TREATMENT

Brief summary: The aim of the present study will be to manufacture and characterize silk fibroin membranes loaded or not with neurotensin and to evaluate clinical, patient-centered and immunological parameters the effect of using these membranes on open wounds on the human palate.

Detailed description: Surgical procedures for the reconstruction of gingival and peri-Implant tissues with the purpose of restoring function and aesthetics are commonly used in the dental practice. The use of free gingival graft (FGG), despite being considered the gold standard, causes great morbidity and postoperative pain. Thus, in order to reduce these complications, some biomaterials have been explored to accelerate healing and bring greater comfort to the patient. The present study aims to: 1. manufacture silk fibroin membranes (SF), loaded or not with neurotensin (NT); 2. evaluate, clinically and immunologically, the effect of the membranes on open wounds at palate sites. After the manufacture of the membranes they will be characterized by visual aspect, thickness, mechanical properties, surface texture, water vapor permeability, enzymatic degradation and swelling. Posteriorly, sixty six (n = 66) patients requiring exodontia and ridge preservation for future implant placement will be randomly assigned into three groups: Control - Free Gingival Graft (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance; Group SF - Fibroin membrane (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance and placement of the fibroin membrane at the palatal wound site; Group SF + NT - Free Gingival Graft + Neurotensin-loaded Fibroin Membrane (n = 22): extraction and Free Gingival Graft for sealing the alveolus entrance and placement of neurotensin-loaded fibroin membrane at the palatal wound site. The repair of the palatine donor area will be evaluated by clinical parameters such as remaining wound area, tissue thickness, re-epithelialization and early-wound healing index at baseline, 7, 14, 21, 30, 45, and 90 days after the procedure; and patient-centered outcomes by post-operative discomfort, tissue edema and number of analgesic pills used for 14 days after the procedure. In addition, inflammatory cytokines and growth factors will be assessed using the palatal wound inflammatory exudate 3 and 7 days after surgery. For the descriptive statistics, the mean ± standard deviation will be used; Normality: Shapiro-Wilk test; Clinical trials: ANOVA for intra and inter group calculations + Tukey test for multiple comparisons when the Shapiro-Wilk p value ≥ 0.05. If p Shapiro-Wilk \<0.05, will be analyzed using the Friedman test (intragroup) and Mann-Whitney tests (intergroup); Parameters centered on patients: T test.

Eligibility criteria: Inclusion Criteria:

* Patients at least 18 years old, healthy systemically, with good oral hygiene, assessed by means of a plaque index and gingival index less than 25% (O'Leary et al., 1972)
* Patients with no morphological or pathological changes in the donor palatal region;
* Patients who have an indication for extraction and with an indication to preserve the socket for future implant installation;
* The tooth included in the study, as well as the adjacent teeth, must not have loss of periodontal insertion.

Exclusion Criteria:

* Patients with systemic problems (cardiovascular changes, blood dyscrasias, immunodeficiency, diabetes, among others), who contraindicate the surgical procedure;
* Patients who use medications that interfere with wound healing;
* Pregnant or lactating patients;
* Patients who present opportunistic oral lesions, mainly colonizing the palate region;
* Smoking patients;
* Patients undergoing orthodontic treatment;
* Patients already submitted to periodontal surgery in the area of interest in the present study;
* Patients with a history of allergy to any type of material used in the present study.

Primary outcomes:
measure: Change in the Remaining Wound Area (RWA)
timeFrame: baseline, 7, 14, 21, 30, 45 and 90 days after surgery
Secondary outcomes:
measure: Tissue Thickness
timeFrame: baseline, 45 and 90 days after the procedure
measure: Scar and Tissue Colorimetry
timeFrame: 7, 14, 21, 30, 45 and 90 postoperative days
measure: Epithelialization
timeFrame: baseline, 3, 7, 14 and 30 days after the procedure
measure: Early wound healing index
timeFrame: 7 and 14 days after surgery
measure: Tissue edema
timeFrame: 7 days after the surgical procedure
measure: Postoperative discomfort
timeFrame: 7, 14, 21, 30, 45 and 90 days after the surgical procedure
measure: Number of analgesics
timeFrame: until 14 days after surgery
measure: Immunologic Analysis - cytokines
timeFrame: 3 and 7 days after surgery
measure: Immunologic Analysis - growth factors
timeFrame: 3 and 7 days after surgery
measure: Immunologic Analysis - matrix metalloproteinases
timeFrame: 3 and 7 days after surgery
Other outcomes:
Locations:
city: São José Dos Campos
country: Brazil
facility: Mauro Pedrine Santamaria and Ana Carolina Ferreira Bonafe
state: Sao Paulo
Study officials:
affiliation: Sao Paulo States University - Brazil
name: Mauro P Santamaria
role: STUDY_DIRECTOR
affiliation: Sao Paulo States University - Brazil
name: Ana Carolina F Bonafe
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Zheng Z, Liu Y, Huang W, Mo Y, Lan Y, Guo R, Cheng B. Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing. Artif Cells Nanomed Biotechnol. 2018;46(sup2):493-501. doi: 10.1080/21691401.2018.1460372. Epub 2018 Apr 13.
citation: Pereira da Silva L, Miguel Neves B, Moura L, Cruz MT, Carvalho E. Neurotensin decreases the proinflammatory status of human skin fibroblasts and increases epidermal growth factor expression. Int J Inflam. 2014;2014:248240. doi: 10.1155/2014/248240. Epub 2014 Aug 11.