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BACKGROUND: Patients with skeletal angle Class III malocclusion usually have inadequate hard and soft tissue volume at the mandibular anterior teeth. The labial proclination at the teeth may lead to gingival recession. The purpose of this study was to explore whether periodontal phenotype modification therapy with soft tissue augmentation (PhMT-s) can prevent gingival recession in these patients. METHODS: Four patients with skeletal Class III malocclusion and a thin periodontal phenotype underwent surgical-orthodontic treatment. Prior to tooth movement, they underwent a minimally invasive vestibular incision with subperiosteal tunnel access combined with autogenous connective tissue grafts for periodontal phenotype modification with soft tissue augmentation (PhMT-s). The labial gingival thickness of the anterior mandibular teeth was measured at three distinct levels: at the cementoenamel junction (GT0), 3 mm apical to the CEJ (GT3), and 6 mm apical to the CEJ (GT6). These measurements were taken at baseline, three months following PhMT-s, and after tooth decompensation. Additionally, a biopsy sample was obtained from the PhMT-s site of one patient. All sections were subsequently stained using hematoxylin and eosin, Masson trichrome, Sirius Red, and immunohistochemistry. RESULTS: The thickness of the labial gingiva was increased about 0.42 to 2.00 mm after PhMT-s. At the end of pre-orthognathic surgical orthodontic treatment, the thickness of the labial gingiva was increased about - 0.14 to 1.32 mm compared to the baseline and no gingival recession occurred after the pre-orthognathic surgical orthodontic treatment. The histologic results demonstrated that the grafts obtained from the PhMT-s site exhibited increased deposition of collagen fibers. Moreover, the proportion of type III collagen increased and the grafts displayed significantly reduced positive expression of CD31 and OCN. CONCLUSIONS: PhMT-s increased the thickness of the soft tissue, stabilizing the gingival margin for teeth exhibiting a thin periodontal phenotype and undergoing labial movement. This is attributed to the increased deposition of collagen fibers.

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This case report describes the use of the modified laterally positioned flap (LPF) technique associated with a subepithelial connective tissue graft (SCTG) for root coverage of homologous mandibular molars with deep gingival recession (GR). A 25-year-old woman with deep GR affecting the mandibular right and left second molars (teeth 31 and 18, respectively) reported bilateral dentinal hypersensitivity. The defect in tooth 31 was 5 mm deep and 4 mm wide. In tooth 18, the defect was 6 mm deep and 5 mm wide. There was 1 mm of keratinized tissue at tooth 31, and no keratinized tissue was present at tooth 18. The modified LPF-SCTG technique with mesial to distal positioning of the flap was selected to treat the defects. The flap was modified by a submarginal incision in the tooth farthest from the GR to preserve the integrity of the donor site. One year postsurgery, tooth 31 had 80.0% coverage, a 66.6% gain in clinical attachment, and a 5-mm increase in keratinized tissue width. Tooth 18 had 83.3% root coverage, a 71.4% gain in clinical attachment, and a 5-mm increase in keratinized tissue width. The patient's complaints of hypersensitivity were resolved, and the tissue gain provided better access and more comfort during cleaning of the teeth. The flap donor sites demonstrated no clinical signs of GR. Based on the 1-year follow-up assessments, the modified LPF-SCTG technique was effective for the treatment of deep single-tooth GR in mandibular molars without causing adverse affects on the flap donor sites.

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The growing demand for sustainable and ethical food options has led to significant advancements in plant-based meat substitutes (PBMS). PBMS have made considerable progress in simulating the taste, texture, and sensory properties of animal meat. Connective tissue is a fundamental component of animal meat that significantly influences tenderness, texture, and sensory properties. However, the imitation of realistic connective tissues has received relatively less attention in the PBMS industry. The current work focuses on exploring materials and techniques for the replication of plant-based connective tissues (PBCT). By understanding the structural and functional characteristics of animal connective tissues (ACT), it is possible to replicate these characteristics in PBCT. Hydrogels, with their ability to simulate certain properties of ACT, present a viable material for the creation of PBCT. To achieve the desired simulation, their mechanical and structural properties need to be enhanced by using several materials and several physical techniques.

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INTRODUCTION: The varicose vein affects more than 30% of the general population. Significantly increased rates were noticed in women and older population. From the histopathological point of view, venous arterialization, smooth muscle cell hypertrophy, and hyperplasia are the main changes noticed in varicose vein disease. Some of the main therapeutic methods used in the management of varicose disease are injection sclerotherapy, conservative, surgical, saphenous vein inversion and removal, high saphenous ligation, ambulatory phlebectomy, transilluminated powered phlebectomy, endovascular management, cryostripping. AIM: The aim of this study was to evaluate the morphology of connective fibers from the wall of the varicose veins extirpated by cryostripping. PATIENTS, MATERIALS AND METHODS: The study included 109 samples taken by cryostripping method. Hematoxylin-Eosin, Masson's trichrome, Silver and Orcein staining were applied. The assessment of fibers was made according to score values between 0 and 3. RESULTS: It was found no major structural differences in terms of alterations of collagen fibers induced by the applied surgical procedure. It was noticed duplications and multiplications of the internal elastic lamina, as diffuse and nodular forms. Depletion of elastic fibers at the media was a lesion identified in most of the specimens. The depletion of reticulin fibers correlates with the accumulation of collagen fibers, which partially or completely replace the network in the media and intima. No correlation was found between changes in the reticulin network and the time between prelevation and buffered formalin fixation, the maximum time investigated being five days. CONCLUSIONS: The Orcein staining in the venous vessel evaluation panel may be a useful investigation.

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OBJECTIVES: Coenzyme Q10 (CoQ10) or ubiquinone is one of a cell's most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG). MATERIALS AND METHODS: Thirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months. RESULTS: EHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups. CONCLUSION: CoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months. CLINICAL RELEVANCE: Early wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

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OBJECTIVE: The aim of this study was to evaluate the effectiveness of a novel biomaterial (FG) for alveolar ridge preservation compared to CTG in terms of soft tissue thickness and bone dimensional changes. MATERIALS AND METHODS: A randomized clinical trial was conducted on 30 patients who required extraction of 30 hopeless mandibular posterior teeth. All patients went through atraumatic tooth extraction, and then, they were randomly allocated to either a CTG, an FG, or a spontaneous healing (SH) group (1:1:1). All patients received a dental implant placed 6 months postoperatively. The soft tissue thickness and bone dimensional changes were measured before and 6 months after the procedure. RESULTS: The study's analysis revealed statistically significant differences in buccal gingival thickness and dimensional bone changes across the three examined groups after 6 months (p < 0.05). The SH group had lower gingival thickness (1.31 ± 0.65 mm) and higher vertical resorption (-1.46 ± 1.67 mm at the buccal aspect) compared with the CTG and FG groups. The CTG and FG groups had similar gingival thickness (2.42 ± 0.70 and 3.00 ± 0.71 mm, respectively) and bone width reduction (+0.86 ± 2.31 and +0.93 ± 2.38 mm, respectively), whereas the CTG group had lower vertical bone loss (-0.30 ± 1.09 mm at the buccal aspect) than the FG group (-0.47 ± 2.30 mm at the buccal aspect). CONCLUSION: FG and CTG demonstrate equivalent soft tissue thickness and comparable horizontal bone dimension outcomes in ARP.

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Soft tissue deficiency in a tooth extraction site in the aesthetic area is a common and challenging clinical situation. This case report demonstrates the successful treatment of extensive gingival recession and buccal bone dehiscence associated with a hopeless tooth. Initially, a connective tissue graft was used to cover the root and thicken the soft tissue. After 2 months, the tooth was extracted, an implant was immediately placed, and a temporary restoration was installed. After 3 months, the soft tissue exhibited a natural and harmonious architecture. A custom zirconia abutment and crown were then fabricated and placed. At the 4-year follow-up, the peri-implant tissue displayed satisfactory aesthetics, with a well-structured buccal bone plate and healthy peri-implant indicators. This two-stage approach, addressing gingival recession first and proceeding with immediate implant placement after soft tissue healing, proved to be a safe and effective method with stable long-term results.

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The various connective tissues of the body have different functions, which result from their specific structure and composition. The identification of this structure-function relationship is of great importance for various disciplines such as medicine, biology or tissue engineering. Connective tissue consists mainly of an extracellular matrix (ECM) and a limited number of cells. It is extremely adaptable because the activity of the cells remodels the composition and structure of the ECM in order to adapt the mechanical properties (functions) to the new demands (e.g. an increased mechanical stimulus).

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Connective tissue is an important component of meat products that provides support to animal muscles. Hydrogels are considered a promising alternative to connective tissues and simulate actual products by adjusting the gel texture and mouthfeel. This study used soybean protein isolate (SPI), corn starch (CS), konjac glucomannan (KGM), and seaweed powder (SP) as raw materials to examine the effect of different added SP and KGM concentrations on the gel texture. The G' of the gel increased five-fold when the SP and KGM concentration was increased from 1 % to 3 %. The results of mechanical property tests showed that with the addition of SP, the gel hardness increased from 316.00 g to 1827.23 g and the tensile strength increased from 0.027 MPa to 0.089 MPa. Sensory evaluation showed that the samples with 2 % SP and KGM presented the highest overall acceptability score and the most significant similarity to real connective tissue. The connective tissue simulants exhibited excellent water-holding capacity (>90 %), significantly increasing their juiciness. SEM indicated that 2 % KGM addition improved gel network structure stability. The results demonstrate the potential of seaweed polysaccharide-derived hydrogels as connective tissue mimics. This provides a new strategy for the preparation of high mechanical strength hydrogels and lays the foundation for structural diversification of plant-based meat.

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Fascia is a specialized connective tissue system that encapsulates and interconnects between tissues and organs throughout the body. The fascia system regulates pain sensation, organ inflammation, trauma, and fibrotic diseases. This mini-review summarizes recent findings from animal models, which reveal the inter-dependency between tissues/organs and the fascia system. Special mechanisms are explored of fascia response to skin inflammatory processes and fibrotic microenvironments in trauma models. We highlight the functionally diverse communities of its fascia-born fibroblasts and the significance of their stage-specific differentiation and communication to disease progression. Understanding the molecular mechanisms and cellular processes within the fascia microenvironment may serve as a basis for future clinical translation.

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BACKGROUND: Connective tissue serves a role beyond mere spatial filling. Furthermore, there is increasing evidence that connective tissue plays an important role in the pathogenesis of conditions such as carpal tunnel syndrome (CTS). According to our hypothesis, the median nerve (MN) is surrounded by a system of connective tissue distal to the pronator teres and extending up to, and including, the carpal tunnel. METHODS: To visualize the connective tissue surrounding the median nerve, we dissected the forearms of 15 body donors from pronator teres to the carpal tunnel, created plastination slices stained with Periodic Acid-Schiff (PAS), and injected ink into the seen spaces. We verified our findings with a segmentational analysis of radiological data of 10 healthy individuals. RESULTS: We macroscopically describe the median nerve´s system of connective tissue (MC) distal to the pronator teres and up to and including the carpal tunnel. This system creates, connects, and separates spaces. At least from the pronator teres to the carpal tunnel it also creates subspaces from proximal to distal. For the MC, we established a mean cross-sectional area of 153.1 mm2 (SD=37.15) in the carpal tunnel. The median nerve consistently resides at the center of this MC, which further connects to flexor muscles of the forearm, and to the radius bone. In the carpal tunnel, the MC creates subspaces inside. There, it also acts as the outermost internal layer enveloping flexor tendons, and the MN. DISCUSSION: The term MC does not negate but orders the existence of other "connectives", like subsynovial connective tissue, endo-, epi- or perineuria, epimysia, periostea, or peritendinea, to a hierarchy related to the median nerve. Diseases of the MN are common. Knowing the anatomy of the MC and how it relates to MN function may help clinicians recognize and understand conditions like CTS.

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Peri-implant soft tissue deficiency (PSTD) is a significant factor impacting aesthetics, particularly in the anterior zone, where labial bone resorption and thin peri-implant phenotypes are common. The occurrence of a gray color around the implant fixture due to PSTD can be aesthetically concerning in the esthetic zone. In cases involving natural teeth, autogenous soft tissue grafts such as subepithelial connective tissue grafts (SCTGs), free gingival grafts (FGGs), and coronally advanced flaps (CAFs) are commonly utilized. However, there are limited reports of using bone grafts in conjunction with these techniques for modifying the gingival phenotype around both teeth and implants. In the presented cases where PSTD resulted in visible gray coloration of the implant fixture in the esthetic zone, mechanical and chemical decontamination of the exposed implant surface was performed using a titanium brush and tetracycline (Tc) HCl. Subsequently, to enhance peri-implant mucosa thickness and mask the titanium color, simultaneous SCTG and bone grafting procedures were conducted. Within the limitations of these case reports, successful esthetic outcomes were achieved and maintained without recurrence for 3-6 years following the simultaneous subepithelial connective tissue graft and bone graft procedures. These findings suggest the potential efficacy of this combined approach in addressing PSTD and enhancing aesthetic results around dental implants, though further studies are needed to validate these outcomes.

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The musculoskeletal system, crucial for movement and support, relies on the delicate balance of connective tissue homeostasis. Maintaining this equilibrium is essential for tissue health and function. There has been increasing evidence in the past decade that shows the circadian clock as a master regulator of extracellular matrix (ECM) homeostasis in several connective tissue clocks. Very recently, exercise has emerged as a significant entrainment factor for cartilage and intervertebral disk circadian rhythms. Understanding the implications of exercise on connective tissue peripheral clocks holds promise for enhancing tissue health and disease prevention. Exercise-induced factors such as heat, glucocorticoid release, mechanical loading, and inter-tissue cross talk may play pivotal roles in entraining the circadian rhythm of connective tissues. This mini review underscores the importance of elucidating the mechanisms through which exercise influences circadian rhythms in connective tissues to optimize ECM homeostasis. Leveraging exercise as a modulator of circadian rhythms in connective tissues may offer novel therapeutic approaches to physical training for preventing musculoskeletal disorders and enhancing recovery.

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OBJECTIVE: The primary objective of this review is to compare autogenous soft tissue grafts (connective tissue graft - CTG and free gingival graft-FGG) with different type of matrices (acellular dermal matrix-ADM, xenograft collagen matrix-XCM, volume-stable collagen matrix-VCMX) used to increase peri-implant soft tissues. MATERIALS AND METHODS: A search on electronic databases was performed to identify randomized and non-randomized controlled trials (RCTs and CCTs, respectively) with either parallel or split-mouth design, and treating ≥ 10 patients. A network meta-analysis (NMA) was used to compare different matrices. Soft tissue thickness dimensional changes and keratinized width (KMW) changes were the primary outcome measures. The secondary outcomes were to evaluate: a) PROMs; b) volumetric changes; c) surgical operating time; and d) different periodontal measurements. RESULTS: A total of 23 studies were included in the qualitative analysis, and 16 studies (11 RCTs and 5 CCTs) in the quantitative analysis. A total of N = 573 sites were evaluated for NMA. CTG resulted the best material for increasing peri-implant soft tissue thickness, at 180 and 360 days after surgery. The use of an ADM showed good results for buccal thickness increase, primarily in the first three months after surgery. Vestibuloplasty + FGG resulted in the most effective technique for peri-implant KMW augmentation, after 180 days. CONCLUSIONS: While CTG demonstrated better performance in all the comparison and FGG showed to be the best graft to increase keratinized mucosa up to 90 days, ADM and VCMX may be used to increase soft tissue horizontal thickness with lower patients' morbidity. LIMITATIONS: The limits of this NMA are the following: a) limited number of included studies; b) high heterogeneity among them (number of patients, treatment sites, surgical techniques, outcome measures, and follow-ups). CLINICAL RELEVANCE: Many studies compared the efficacy of autogenous and non-autogenous grafts in terms of gingival thickness, volume, and keratinized width increase. However, there is still not clear overall evidence on this topic. This NMA helps clinicians to choose the right material in different peri-implant soft tissue procedures. Recommendations for future studies are mandatory.

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Connective tissues can be recognized as an important structural support element in muscles. Recent studies have also highlighted its importance in active force generation and transmission between muscles, particularly through the epimysium. In the present study, we aimed to investigate the impact of the endomysium, the connective tissue surrounding muscle fibers, on both passive and active force production. Pairs of skeletal muscle fibers were extracted from the extensor digitorum longus muscles of rats and, after chemical skinning, their passive and active force-length relationships were measured under two conditions: (i) with the endomysium between muscle fibers intact, and (ii) after its dissection. We found that the dissection of the endomysium caused force to significantly decrease in both active (by 22.2 % when normalized to the maximum isometric force; p < 0.001) and passive conditions (by 25.9 % when normalized to the maximum isometric force; p = 0.034). These findings indicate that the absence of endomysium compromises muscle fiber's not only passive but also active force production. This effect may be attributed to increased heterogeneity in sarcomere lengths, enhanced lattice spacing between myofilaments, or a diminished role of trans-sarcolemmal proteins due to dissecting the endomysium. Future investigations into the underlying mechanisms and their implications for various extracellular matrix-related diseases are warranted.

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AIM: The aim of the present retrospective case series was to longitudinally assess soft tissue volume changes on the vestibular aspect of implants in relation to keratinized mucosa thickness (KMT) and width (KMW) after the application of the microsurgical envelope technique combined with a connective tissue graft (CTG). MATERIALS AND METHODS: A total of 12 healthy patients received 12 dental implants placed either in the posterior maxilla or mandible. The study involved the harvesting of 12 CTGs with a minimally invasive single-incision technique, grafted to the vestibular peri-implant soft tissue utilizing the envelope technique, followed by the insertion of 12 screw-retained IPS e.max crowns. RESULTS: The healing process was uneventful across all areas, and all patients were followed up for a period of 5 years. The evaluation of KMT showed the highest decrease in the first 6 weeks after surgery (5.5 ± 0.79 to 4.59 ± 0.62 mm), then dropped slightly to 4 ± 0.85 mm, after which it maintained at 4 ± 0.36 mm until the 2-year time point. Between the second and third years after surgery, a further decrease of 3.59 ± 0.42 mm was recorded for KMT, which then remained constant until the end of the 5-year research period. The observations regarding KMW were slightly different, with the measurements demonstrating the greatest decrease in first 6 weeks (from 2.5 ± 0.42 to 1.5 ± 0.42 mm), which was maintained until the 1-year time point. Between the first and second years after surgery, the KMW increased to 2 ± 0.60 mm and remained level for the next 3 years, at 2 ± 0.85 mm. CONCLUSIONS: The current research demonstrated the advantages of using a combination of a minimally invasively harvested CTG and the microsurgical envelope technique for a duration of 5 years.

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OBJECTIVE: This split-mouth randomized study aimed to assess efficacy of leucocyte-platelet-rich fibrin (L-PRF) versus connective tissue graft (CTG) in achieving root coverage (RC) for multiple adjacent gingival recessions (MAGRs) throughout 12-month period. MATERIALS AND METHODS: The study enrolled 59 teeth from 12 patients with Miller Class I MAGRs ≥ 2 mm on bilateral or contralateral sides. Patients were randomly assigned to receive coronally advanced flap (CAF) with either CTG (control) or L-PRF (test) treatment. Various parameters, including plaque and gingival index, clinical attachment level, recession depth, probing depth, recession width (RW), papilla width (PW), keratinized tissue width (KTW), gingival thickness (GT), percentage of RC, complete root coverage (CRC), and location of the relative gingival margin concerning the cemento-enamel junctions (GMCEJ) after CAF, were recorded at baseline, 3-, 6-, and 12-months post-surgery. On June 29, 2021 the study was registred to ClinicalTrials.gov (NCT04942821). RESULTS: Except KTW and GT gain, all clinical parameters, RC, and CRC were similar between the groups at all follow-up periods (p > 0.05). The higher GT and KTW gains were detected in the control group compared to test group at 12 months (p < 0.05). Both RC and CRC were positively associated with initial PW and GMCEJ, but negatively with initial RW (p < 0.05). CONCLUSIONS: The current study concludes that L-PRF were equally effective as CTG in treating MAGRs in terms of RC and CRC. Additionally, RC and CRC outcomes appeared to be influenced by GMCEJ, PW, and RW. CLINICAL RELEVANCE: L-PRF could represent a feasible substitute for CTG in treating MAGRs.

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OBJECTIVES: This study aims to compare the histological outcomes of three distinct de-epithelialization methods used in (connective tissue grafts) CTG harvested from the palate. MATERIALS AND METHODS: An experimental study using nine cadaver head specimens was carried out to compare 3 different de-epithelialization techniques for CTG. Eighteen samples were randomly allocated to three study groups: bone scraper, diamond bur and extraoral removal with a scalpel. The main outcome variable was the graft surface percentage without epithelium remains. Additionally, the time employed, and the graft thickness were also measured. RESULTS: Sixteen CTGs were analyzed. The extraoral scalpel group presented a total surface area with no epithelium of 58.84% (22.68) and a mean de-epithelialization time of 3.7 min; the intraoral diamond bur group had 88.24% (41.3) of the surface with no epithelium and took 1.455 min, and the intraoral bone scraper showed 97.98% (5.99) of surface without epithelium and a mean time of 0.815 min (P < 0.05). Histological analysis showed significant differences between the bone scraper and the extraoral group (P = 0.009). CONCLUSION: The de-epithelialization technique with a bone scraper seems to be the most effective and fastest de-epithelialization technique for CTG. These findings need to be confirmed in future clinical studies with larger samples. CLINICAL RELEVANCE: The use of bone scrapers, could be a simple, effective and fast technique to de-epithelialize connective tissue grafts harvested from the palatal area for both novice and experienced surgeons.

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OBJECTIVE: To overview the literature to answer the following question: "What is the performance of different therapies on wound healing and postoperative discomfort after palatal ASTG removal?" METHODS: SRs that evaluated the wound healing (WH), postoperative pain, bleeding, and analgesic consumption of patients submitted to de-epithelialized/free gingival grafts (FGG) or subepithelial connective tissue grafts (SCTG) removed from the palate were included. The searches were conducted on six white and two gray databases up to December 2023. Methodological quality was evaluated through AMSTAR 2. The synthesis of results was described as a narrative analysis. RESULTS: Ten SRs (involving 25 randomized clinical trials) related to low-level laser therapy (LLLT) (3), platelet-rich fibrin (PRF) (4), cyanoacrylate tissue adhesives (CTA) (2), and ozone therapy (OT) (1) were included in this overview. All techniques demonstrated improvements in WH. LLT, PRF, and CTA reduced pain and analgesic consumption. PRF and CTA reduced bleeding. Regarding methodological quality, the SRs were classified as critically low (2), low (5), moderate (2), or high quality (1). CONCLUSIONS: In SRs related to LLLT, PRF, CTA, and OT, the use of different therapies after palatal ASTG removal improved WH and postoperative discomfort. Due to the studies' low methodological quality and high heterogeneity, data should be interpreted with caution. CLINICAL RELEVANCE: The present overview compiles the evidence of SRs related to different therapies for WH and patients' postoperative experience and reveals that different treatments can significantly improve the clinical outcomes of patients who require ASTG removal for periodontal or peri-implant surgeries. REGISTRATION: PROSPERO registration number: CRD42022301257.

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