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Gingival fenestration is a relatively uncommon soft tissue lesion in which the root apex is exposed in the oral environment after the destruction of the overlying buccal bone plate and mucosa. At present, no clear etiology or treatment guidelines exist for gingival fenestration. This article reports three successfully treated cases of gingival fenestration associated with chronic periapical infection and can help contribute to treatment guidelines for gingival fenestration. All cases were treated with apicoectomy in conjunction with a connective tissue graft (CTG), and the first steps of each case were as follows: endodontic therapy with root-end resection and retrograde filling, then regenerative surgical therapy. However, slightly different regenerative treatment methods were used during the operation according to the different patient conditions. In Case 1, gingival fenestration in the mandibular left first premolar was treated using a xenograft and CTG. In Case 2, gingival fenestration in the maxillary left lateral incisor was treated using advanced platelet-rich fibrin (A-PRF) and CTG. In Case 3, gingival fenestration in the mandibular left second premolar was treated using CTG. Endodontic treatment was combined with periodontal surgery to achieve predictable results. After 13 to 25 months of follow-up, all cases showed well-healed gingival fenestrations and no discomfort. These three cases show the possibility of using apical excision combined with a CTG and/or bone graft/A-PRF in the treatment of gingival fenestration. Reporting these three cases may help advance the field of gingival fenestration treatment. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effect of adding an allogeneic soft tissue graft at the time of single implant placement using a fully digital workflow for implant placement and restoration without making either analog or digital impressions. Materials and Methods: A prospective randomized clinical study was performed enrolling 39 participants requiring single-tooth implants. The patients were randomized into one of two groups: (1) the graft group, which received an allogeneic dermal graft at the time of implant placement (n = 19), or (2) the nongraft group (n = 20). A fully digital surgical and restorative protocol was implemented for both groups. Intraoral scans were taken before implant placement (T0), at the time of final crown delivery (T1), and 1 year after placement (T2). Intraoral scans were aligned using Geomagic Control X 2020 software, and linear and volumetric changes in buccal tissues were measured at T0, T1, and T2. Implant survival, probing depths (PDs), and complications were recorded. Participants were asked to complete an Oral Health Impact Profile (OHIP)-14 survey at T0 and T2. Marginal bone levels were measured at T0 and T2 on periapical radiographs. Results: Overall, 39 participants completed surgery and restoration in the incisor, canine, premolar, and molar sites. Two early failures were recorded in central incisor positions (95% survival). Crown delivery without complication from the digital workflow (impressionless) was achieved for 36 out of 39 cases (92%), and implant depth control was the main challenge. At 1 year, 37 participants attended the follow-up appointment. Both groups showed gain in buccal tissue thickness without significant differences between the two groups for both linear and volumetric measurements (P > .05). Soft tissue grafting was associated with minimal added morbidity. The interproximal marginal bone changes were recorded as follows: -0.16 mm mesial and -0.12 mm distal for the graft group and -0.01 mm mesial and -0.11 mm distal for the nongraft group (P = .07 for mesial and .83 for distal). The OHIP score was significantly reduced at T2 compared to T0 (P = .003) for the entire cohort. Conclusions: Augmentation of the alveolar mucosa on the buccal aspect of single-tooth implants is associated with clinically favorable outcomes. A fully digital workflow has been validated to permit crown delivery on CAD/CAM abutments without implant impressions. [ABSTRACT FROM AUTHOR]

Implants with deficient papillae and black triangles are common findings. The treatment of these esthetic complications is considered to be challenging with limited predictability. Therefore, the present report aims to describe a novel technique for papilla augmentation: the "iceberg" connective tissue graft (iCTG) after extraction and interproximal bone reconstruction in the anterior region. A 35-year-old patient presented with a hopeless tooth with interproximal clinical attachment loss extending to the apical third of the adjacent tooth. Interproximal bone reconstruction was performed through alveolar ridge preservation by directly applying recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to the exposed root surface of the adjacent tooth. A mixture of autogenous bone chips (obtained from the ramus) and bovine bone xenograft particles (previously mixed with the growth factor) was also used. The patient was able to return for implant therapy only 2 years later, at which time an incomplete regeneration of the interproximal bone was observed. Therefore, to compensate the interproximal deficiency, the iCTG approach was utilized, involving a double layer of CTG with different origins. Two small grafts from the tuberosity were sutured to the mesial and distal ends of a wider CTG harvested from the palate, aiming to gain additional volume at the interproximal sites. The composite graft was then sutured on top of the implant platform, and the flap was then released and closed by primary intention. After conditioning the peri-implant tissues, the case was finalized with a satisfactory outcome. The described iCTG could be an effective approach for reconstructing peri-implant papillae following interproximal bone reconstruction. [ABSTRACT FROM AUTHOR]

Mucogingival deformities around implants are frequent findings in clinical practice and often present as inadequate keratinized tissue and insufficient mucosal thickness. Phenotype modification therapy can increase peri-implant mucosal thickness and the amount of keratinized mucosa, improving the long-term clinical outcomes of implants. The free gingival graft (FGG) is considered the gold standard to increase keratinized mucosa; however, FGGs on the lingual aspects of implants are less predictable due to technique sensitivity and often present with insufficient gains in tissue thickness due to a limited blood supply. The semilunar lingualized apically positioned flap (SLAP) with subperiosteal tunnel connective tissue graft (CTG) can increase both peri-implant mucosal thickness and keratinized mucosal width circumferentially. SLAP consists of one full-thickness, semilunar incision within the keratinized mucosa and buccal to the implant, as well as two vertical releasing incisions mesial and distal to the implant, extending lingually into the alveolar mucosa. The tissue is apically positioned lingual to the implant and sutured in place, creating buccal space for a CTG via buccal subperiosteal tunneling. SLAP is a minimally invasive and predictable approach for improving the peri-implant mucosal phenotype. This case report demonstrates gains in peri-implant mucosal thickness and the amount of keratinized mucosa over a 10-month period utilizing SLAP with subepithelial CTG. [ABSTRACT FROM AUTHOR]

This technical report describes the simplified subperiosteal sling (SPS) suture for connective tissue graft (CTG) stabilization in root coverage and phenotype modification of single and multiple recession defects via the vestibular incisional subperiosteal tunnel access (VISTA). The simplified SPS suture engages only the CTG and stabilizes it to the tooth in the coronal-most position, inside the subperiosteal tunnel, independent of the overlying gingival tissue. The simplified SPS suture differs from the original SPS suture in that it engages the CTG first, and the needle and tail of the suture are knotted before the suture is introduced into the subperiosteal tunnel. This allows the needle to pass through the subperiosteal tunnel only once from the vestibular access to the intended gingival sulcus. When multiple teeth are treated, only one simplified SPS suture traverses the vestibular access at a time, as the CTG is incrementally advanced into the tunnel. This prevents suture entanglement and improves the practical application of the technique. [ABSTRACT FROM AUTHOR]

This article defines immunophenotypes of stromal inflammatory and endothelial cells and fibroblasts 3 months after augmentation of the peri-implant soft tissue using a porcine cross-linked collagen matrix (VCMX). Peri-implant soft tissue samples were obtained from 12 patients at the lining mucosa (LM)-masticatory mucosa (MM) junction before (1) and 3 months after (2) augmentation. Immu-nohistochemical stains were performed to identify inflammatory cells (T [CD3] and B [CD20] lymphocytes, plasma cells [CD138]), macrophages (CD68-proinflammatory, CD163-anti-inflammatory/ reparative), endothelial cells (CD31, CD34), and fibroblasts (CD90, TE-7). Differences in the mean positively stained cells pre- and postaugmentation were analyzed by Wilcoxon signed-rank test. CD31+ endothelial cells showed increased mean numbers in MM2 compared to MM1 (P = .025) and in LM2 compared to LM1 (P = .047). CD163+ anti-inflammatory macrophages showed higher mean numbers in MM2 than in MM1 (P = .021) and in LM2 than in LM1 (P = .012). All other cell phenotypes showed nonsignificant changes between pre- and postaugmentation. This molecular study provides novel insight on the frequency of stromal cell phenotypes in the wound healing process at 3 months postaugmentation with VCMX, with anti-inflammatory CD163+ macrophages being predominant. This should be further investigated to help find novel therapeutic approaches to modulate and promote the VCMX-related healing process. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following question: "Do recombinant, purified, and concentrated growth factors enhance the regenerative potential of particulate bone graft substitutes in maxillary sinus floor augmentation (MSA)" Materials and Methods: Human studies comparing histomorphometric data on new bone formation, residual graft material, and fibrous tissue ratio (outcomes of interest) following MSA procedures employing particulate bone grafts/substitutes in combination or not with growth factors were retrieved from PubMed/MEDLINE, Web of Science, Cochrane, and Scopus online databases and complemented with a hand search. Controlled studies published in English up to December 2022 and reporting on histomorphometric data expressed as volume percentage of the outcomes of interest were considered. Risk of bias was assessed, and a meta-analysis was performed to investigate the effects of supplementary growth factors on new bone formation, remaining graft particles, and fibrous tissue ratio. Results: Data were included from 613 samples in 477 patients reported in 22 publications. Meta-analysis showed that platelet-rich plasma or platelet-rich fibrin resulted in 49% more new bone formation than in control group areas (P = .004), and those areas supplemented with growth factors presented 57% less residual graft particles after healing (P < .0001). A significant (P = .03) 1.85-fold increase in connective tissue formation was noted in areas treated with recombinant human bone morphogenetic proteins (rhBMPs) after healing. Conclusions: Selective supplementary growth factors may enhance new bone formation and accelerate particulate graft turnover, while rhBMP may significantly increase connective tissue formation in MSA procedures in humans. [ABSTRACT FROM AUTHOR]

This case series investigated the effect of a combination therapy utilizing connective tissue graft (CTG) in the treatment of periodontal regeneration of mandibular Class III/IV furcation involvement (FI). Six patients diagnosed with periodontitis stage III or IV (grade A to C), presenting with Class III or IV FI, were treated with fibroblast growth factor-2 and carbonate apatite in combination with CTG. The following clinical parameters were evaluated at baseline and after 6, 12, and 18 months: periodontal probing depth, clinical attachment level, furcation invasion, radiographic vertical defect depth, and gingival phenotype. Significant improvements in clinical parameters were observed in all treated FI sites. Four Class III defects and one Class IV defect obtained complete closure, and one Class IV defect was improved to Class I. This case series showed the potential of administering combination regenerative therapy for changing the prognosis of hopeless teeth with severe furcation defects. [ABSTRACT FROM AUTHOR]

Background: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM. Method: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power. Results: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes. Conclusions: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently. [ABSTRACT FROM AUTHOR]

Successful bone augmentation relies on primary wound closure. The labial frenum is a soft tissue that connects the lip to the alveolar mucosa or gingiva. However, the frenum may exert biomechanical forces to the wound edge, causing wound instability. The aim of this study is to review the frenum composition and classifications and to understand the significance of the frenum in wound stability upon bone regeneration. Together with a manual search, an electronic search was conducted through three online databases on studies published until September 2022. A total of 300 articles were identified, and 9 studies were included in this review. Two of the included studies discovered that 35% to 37.5% of the labial frenum had muscle fibers. Other studies showed that the labial frenum was mainly composed of connective tissue with elastic fibers. There are two widely used classifications for the frenum based on its morphology and attachment position. No studies specifically evaluated the impact of the frenum on bone regeneration, but the frenum location intercorrelated with the amount of keratinized tissue, which could influence wound stability. A modified frenum classification for the edentulous ridge and a decision diagram to manage the frenum is proposed for research and evidence-based practice. [ABSTRACT FROM AUTHOR]

Gingival recession treatment is one of the major clinical challenges in periodontics, and various surgical techniques have been proposed to correct it. Most of these techniques are suitable for isolated recession sites and involve harvesting an autogenous tissue graft, which increases patient morbidity and might result in inferior esthetics due to incision design. This study assessed the benefit of adding platelet-rich fibrin (PRF) to the vestibular incision subperiosteal tunneling approach (VISTA) in treating multiple gingival recession compared to using VISTA alone. A total of 41 teeth with Miller Class I and II defects were randomized in a split-mouth design. Multiple clinical parameters were tested, including the change in gingival thickness over time, keratinized tissue width, and gingival phenotype (using the transparency of a periodontal probe). Patient-centered outcomes were also assessed via visual analog scale. Multiple Miller Class I and II recessions in the maxilla can be effectively treated with VISTA. However, when used in conjunction with PRF, no significant differences were detected in any parameter. VISTA has been shown to be associated with a low level of postsurgical pain for patients and can be used for patients with high esthetic demands. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study analyzed radiographic bone levels of 10,871 dental implants in a cohort of 4,247 patients over a 22-year period. The objectives of the study were to assess and explore risk factors associated with the radiographic bone level of dental implants. Method and materials: A longitudinal observational cohort study based on data collected from 1995 to 2019 was conducted on implants placed by a single periodontist. Inclusion criteria included both partially and fully edentulous sites. Exclusion criteria were patients who were considered ASA 3 or greater. Information on medical and dental status prior to implant placement such as diabetes and smoking were included in the analysis. Implant factors such as the implant characteristics (length and diameter) and surgical site were recorded. The outcome assessed was the prevalence of bone loss around implants and any associative factors related to the bone loss. Results: Overall, dental implants lost an average of 0.05 ± 0.38 mm of bone 2 to 3 years after placement and 0.21 ± 0.64 mm 8 years after placement. The soft tissue condition was evaluated using the Implant Mucosal Index (IMI), and bone loss around dental implants was significantly higher when bleeding on probing was multi-point and moderate, multi-point and profuse, and when infection with suppuration was recorded. The mean difference in bone level between smokers and nonsmokers was 0.26 mm (P < .01) over a 4-year period. A mean difference of 0.10 mm (P = .04) in bone loss over 4 years was found between those with an autoimmune disease compared to those without. The diameter of the implant and immediate loading of the dental implant did not influence the radiographic bone levels over time. Conclusions: This large dataset of dental implants highlights predictive risk factors for bone loss around dental implants and the impact these risk factors have on the implant bone level. Consideration of these risk factors by both the dental team and the patient prior to dental implant placement will promote success of the treatment. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) requires a tension-free flap without damaging the collateral circulation in order to secure better surgical outcomes. Topographic knowledge regarding the neurovascular bundles in the posterior aspect of the mandible can prevent complications during lingual flap design. The lingual branch (LB) of the inferior alveolar or maxillary arteries is not sufficiently illustrated or described in the literature. Nevertheless, it has an intimate relationship with the lingual nerve (LN) during ridge augmentation and implant-related posterior mandible surgery. Therefore, this study aimed to clarify the morphology and topography of the LB related to GBR surgeries. In the present human cadaveric study, the LB was analyzed in 12 hemimandibles using latex injection and corrosion casting. Two types of LB were identified based on their origin and course. The LB was found in a common connective tissue sheath close to the LN. The LB assembled several anastomoses on the posterior lingual aspect of the mandible and retromolar area. The LB acted as an anatomical landmark in identifying LN at the posterior lingual aspect of the mandible. [ABSTRACT FROM AUTHOR]

The anterior mandible is the most challenging anatomical site for performing periodontal plastic surgeries. Increased demands for optimal root coverage and esthetic outcomes contribute to the development of pedicle flap-based surgical solutions, in contrast to the predominantly used free gingival graft. The aims of this study were to (1) summarize the current literature to identify the most-used techniques, indications, and their efficacy, and (2) provide a decision table for surgeons to navigate through the selection of appropriate techniques. Four main approaches were identified: free gingival graft, lateral sliding, tunneling, and coronally advanced flap. The flap approaches are mostly combined with a connective tissue graft. The decision table considers the patient's chief complaint, local anatomical factors, and technique sensitivity. The table provides a framework for supporting an evidence-based selection of surgical techniques and for studying novel methods to achieve predictable root coverage in the anterior mandible. [ABSTRACT FROM AUTHOR]

The socket shield technique has been proposed as a surgical method to prevent the collapse of the buccal plate following tooth extraction, leading to excellent soft tissue stability and long-term esthetic outcomes. Despite its success, this technique is still not without potential risks. One of the most common complications is internal exposure of the socket shield, which can present as inner soft tissue inflammation with or without exposure of a portion of the shield. This case series discusses this complication's etiology, diagnosis, treatment, management, and prevention. Data from 10 patients with 12 internally exposed sites are presented. [ABSTRACT FROM AUTHOR]

Objective: Mucogingival surgery involving tissue grafts is commonly employed for cosmetic procedures like root coverage, and is increasingly applied in implant therapy to modulate peri-implant soft tissues and enhance implant survival. These procedures involve harvesting autologous connective or epithelial connective tissue, often from the palate or tuber maxillae. However, this can cause patient morbidity due to postoperative pain. Substitute materials, including animal-derived and xenografts, have been developed but lack qualities of autologous grafts. Method and materials: To address postoperative discomfort, a novel technique, named "palatal shield," using composite resin stabilized on adjacent teeth's palatal surface is proposed as an aid to donor site healing after mucogingival procedures. Two cases are reported where this technique was successfully applied. The first case involves a 53-year-old woman undergoing free gingival graft surgery for peri-implant treatment. The second case features a 58-year-old man receiving subepithelial connective tissue graft surgery for root sensitivity. Results: Ten days post surgery, both patients reported excellent postoperative comfort. The technique's effectiveness is highlighted in these cases, demonstrating its applicability in various surgical cases involving free gingival graft or connective tissue graft harvesting. Conclusion: The proposed "palatal shield" technique offers several advantages, including enhanced patient comfort, ease of application, and cost-effectiveness, making it a promising addition to mucogingival surgical procedures. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the usefulness of ridge augmentation using a customized titanium mesh (CTM) that was preformed by trimming and bending the commercial titanium mesh on a virtually reconstructed 3D acrylic resin model using clinical, radiologic, histologic, and histomorphometric analyses. Materials and Methods: This study was designed prospectively for patients who required vertical ridge augmentation using a staged approach before implant surgery. After installation of the CTM, grafting was performed using deproteinized porcine bone mineral covered with an absorbable membrane. Computed tomography was performed preoperatively and 6 months after simultaneous/staged guided bone regeneration to measure planned, reconstructed, and lacking bone volume, and the reconstruction rate was calculated based on these values. Clinical complications were also recorded, particularly the mesh exposure rate. At re-entry, the bone core was obtained using a trephine bur, and histologic and histomorphometric analyses were performed. Results: A total of 10 sites in eight patients were used for the study analysis. The mean planned bone volume was 1.15 cm3 (range: 0.78 to 1.56 cm3), mean lacking bone volume was 0.13 cm3 (range: 0 to 0.59 cm3), and mean reconstructed bone volume was 1.02 cm3 (range: 0.56 to 1.43 cm3). The exposure rate was 30% (3 out of 10 sites). The reconstruction rate was over 80%, except for one case that showed suppuration. From histomorphometric analysis, 27.52% ± 16.87% of new bone, 7.62% ± 5.19% of residual graft, and 64.86% ± 23.76% of connective tissue were observed. The core biopsy samples demonstrated different pseudoperiosteum layer appearances based on the healing stage of the augmented sites. In the premature bone, the inner osteogenic layer consisted of multiple layers of osteoblast cells with adjacent large blood vessels. However, in the mature augmented site, there was no specific inner osteogenic layer, and the outer fibrous layer was dominant. Conclusions: The fabrication of CTM based on the application of the 3D-printing technique makes vertical ridge augmentation easier and can reduce complications and achieve target bone acquisition. In addition, it is expected that quantitative analysis of the pseudoperiosteum layer will be facilitated using the CTM. [ABSTRACT FROM AUTHOR]

Purpose: To determine the characteristics of dental implant transmucosal surfaces that influence soft tissue attachment and marginal bone loss (MBL). Materials and Methods: The PubMed, Embase, and Cochrane Library electronic databases were searched based on predefined PICO eligibility criteria. Data from animal studies that compared junctional epithelium and connective tissue attachment and MBL from 4 days to 72 weeks were analyzed. The risk of bias was performed with the Systematic Review Centre for Laboratory Animal Experimentation tool. A rank analysis evaluation of data was performed, and the most frequently appearing materials/surfaces for each tissue compartment were identified. Results: The search identified 3,549 studies, 28 of which were eligible for analysis, with an average risk of bias of 28% ± 10%. Machined, polished, etched, sandblasted, or coated titanium and zirconia materials/surfaces were most frequently examined. Several studies investigated lithium disilicate, polyether ether ketone (PEEK) or polyether ketone ketone (PEKK), aluminum oxide, and gold. Based on ranking and frequency of use at different time points, titanium grade IV (Ti-4) microthreads with a polished neck area most frequently supported natural tooth-like junctional epithelial attachment (= 1.5 mm), while machined Ti-4 and machined titanium grade V (Ti-5) most frequently supported connective tissue attachment (= 1.25 mm) and led to the least MBL (= 0.75 mm). Conclusions: Analyzed data suggest that Ti-4 microthreads with a polished neck area and machined Ti-4 and Ti-5 were the materials/surfaces of choice for the transmucosal part of implants. However, the extensive heterogeneity in reported studies precludes solid identification of the best materials/surfaces. [ABSTRACT FROM AUTHOR]

This randomized controlled trial aimed to determine the clinical efficacy of xenogeneic collagen membrane (XCM) derived from porcine peritoneum in combination with a coronally advanced flap (CAF) in the management of gingival recession defects and to compare the outcomes to those of connective tissue grafts (CTGs). A total of 12 systemically healthy individuals presenting with 30 isolated/multiple Cairo RT 1/2 gingival recession defects in maxillary canines and premolars were randomly treated either with CAF + XCM or CAF + CTG. Recession height (RH), gingival biotype (GB), gingival thickness (GT), width of keratinized gingiva (WKG), and width of attached gingiva (WAG) were recorded at baseline and at 3, 6, and 12 months. Patient perceptions of pain and esthetics and the modified root coverage esthetic score (MRES) were also documented. From baseline to 12 months, both groups showed a significant reduction in mean RH (CAF + CTG: 2.73 ± 0.79 mm to 0.33 ± 0.61 mm; CAF + XCM: 2.73 ± 0.88 mm to 1.20 ± 0.77 mm). At 12 months, CAF + CTG sites had a mean root coverage percentage (MRC%) of 85.60% ± 28.74%, whereas CAF + XCM sites had an MRC% of 55.13% ± 31.22%. CAF + CTG-treated sites had significantly better outcomes, with a greater number of sites achieving complete root coverage (n = 11) and higher MRES scores than the porcine peritoneal membrane group (P < .05). [ABSTRACT FROM AUTHOR]

Successful rehabilitation of the anterior maxilla remains a challenge, primarily due to postextraction ridge collapse, which can lead to gingival recession and a nonesthetic appearance. The socket shield technique presents a viable alternative for immediate dental implant placement in the esthetic zone. This pilot study aimed to evaluate the survival, complication rates, and marginal bone loss around body-shift implants placed in fresh extraction sockets with the socket shield technique to replace maxillary incisors. After socket shield preparation, 14 hopeless incisors were extracted and immediately replaced by a body-shift implant (Inverta, Southern Implants) at baseline. Patients were followed up for 12 to 39 months (mean: 18.1 ± 8.2 months). The average age was 52.3 ± 16.9 years, and the survival rate was 100%. One socket shield presented minimal internal exposure that was successfully treated with a connective tissue graft. The mean PES score was 12.9 ± 1.2. Mean interproximal marginal bone loss was -0.4 ± 0.5 mm. Body-shift implants can be a promising alternative for immediate tooth replacement combined with the socket shield technique. The superior esthetic outcomes remained stable, suggesting that the extra space created by the narrow cervical portion of the implant is beneficial for preserving the alveolar bone and limiting internal shield exposure. [ABSTRACT FROM AUTHOR]

Tooth loss or extraction is associated with significant reduction in alveolar ridge volume, extensively expressed in the anterior zone, and immediate implant placement is insufficient to overcome this problem. The proposed approach combined immediate implant placement with buccal tissue enhancement by applying a crosslinked collagen matrix hydrated with crosslinked hyaluronic acid (xHyA). All 10 cases presented with a retained but narrow buccal socket wall, so immediate implant placement with the "tunneled sandwich" technique was performed after tooth extraction. The tunneled sandwich technique helped create a subperiosteal pouch for insertion of the collagen matrix buccal to the alveolar bone crest. The implants healed transmucosally by receiving either a gingiva former or an immediate temporary restoration. Ten sites in 10 patients demonstrated stable, noninflamed peri-implant conditions and suitable ridge volume at the implant neck and achieved high pink esthetic scores 6 months after implant loading. The tunneled sandwich technique is a suitable method to preserve buccal volume, which biologically and esthetically contributes to favorable long-term results. [ABSTRACT FROM AUTHOR]

Purpose: To assess two types of abutment materials routinely used in daily practice--direct polymethyl methacrylate (PMMA) and a zirconia-on--Ti-base abutment--and their effects on peri-implant soft tissues and bone remodeling in a minipig model. Materials and Methods: A total of 40 implants were placed in five minipigs in a single-stage surgery. Four different types of abutment materials (n = 10 per group) were used: (1) titanium (control); (2) zirconia (control); (3) PMMA (test 1); and (4) Ti-base (zirconia bonded to a titanium framework; test 2). After 3 months of healing, the samples were collected and subjected to nondecalcified histology. The soft tissue dimensions (sulcus, junctional epithelium, and connective tissue attachment) were assessed on each abutment mesially and distally, and the distance from the implant margin to the first boneto-implant contact (BIC) was measured. Results: No statistically significant differences were found among the four groups regarding soft tissue dimensions (P = .21), and a long junctional epithelium (mean: 4.1 mm) and a short connective tissue attachment (mean: 0.3 mm) were found in the majority of abutments. In some samples, the junctional epithelium extended all the way to the bone level. The measured peri-implant bone remodeling was similar in all four groups (P = .25). Conclusions: The present findings indicate that both direct PMMA and zirconia-on-Ti-base abutments seem to allow soft tissue integration similar to that of titanium and zirconia abutments. However, clinical studies are warranted to either confirm or refute the observed findings and to further investigate the influence of different materials on mucointegration. [ABSTRACT FROM AUTHOR]

The biggest challenge during periodontal regeneration in the anterior region is the prevention of soft tissue recession. Minimally invasive surgeries, particularly papilla preservation techniques and soft tissue augmentation, may significantly reduce such postoperative soft tissue recession. This article presents the vestibular incision subperiosteal tunnel access (VISTA) approach for periodontal regeneration in the anterior region. A subperiosteal tunnel prepared from a single vertical vestibular incision adjacent to the defect is used for debridement, application of enamel matrix derivative, defect grafting with corticocancellous tuberosity bone, and insertion of the connective tissue graft. Evaluation of six cases with up to 6 years of follow-up showed improvements in all clinical parameters. The probing pocket depth improved from 8.2 ± 0.75 mm initially to 2.7 ± 0.52 mm at follow-up, clinical attachment level improved from 8.5 ± 0.83 mm initially to 2.7 ± 0.52 mm at follow-up, and midfacial gingival recession of 1 mm at two sites was corrected. The papillae were stable at all sites, with an average distance of 4.8 mm from the incisal edge to the papilla tip. This technique seems to be a promising approach for achieving both esthetic and functional goals of periodontal regenerative surgery. However, experience in performing microsurgeries and harvesting tuberosity tissues may be a limitation. [ABSTRACT FROM AUTHOR]

Although connective tissue grafts (CTGs) have been found to increase gingival thickness and reduce facial gingival recession in immediate implant placement and provisionalization (IIPP), they are associated with significant loss of buccal bone thickness. This loss is thought to be related to the preparation of the facial CTG recipient site. This technical report presents a modified dual-zone therapeutic concept in which the bone zone is grafted with bone graft and the tissue zone is grafted with tuberosity CTG without elevation of a facial partial- or full-thickness envelope. [ABSTRACT FROM AUTHOR]

Purpose: This study sought to evaluate the biomechanical properties of the interface between the rotator cuff and the semicircular humeral ligament or rotator cable (RCa) using histological and biomechanical techniques. Methods: Out of 13 eligible cadaver specimens, 5 cadaver shoulders with an intact rotator cuff were included, 8 were excluded due to an injured rotator cuff. The histological study enables us to describe the capsule-tendon interface between the infraspinatus tendon (IST) or supraspinatus tendon (SST) and RCa, and to detect loose connective tissue layers to determine their precise location and measure their length along the interface. The biomechanical study sought to characterize and compare the mechanical strength of the IST-RCa versus SST-RCa interfaces. Results: The average thickness of the RCa was 1.44 ± 0.20 mm. The histological study revealed a loose connective tissue layer at the IST-RCa interface, a finding not observed at the SST-RCa interface. The biomechanical study showed that the rigidity of the SST-RCa interface (72.10–2 N/mm) was 4.5 times higher than for the IST-RCa interface (16.10–2 N/mm) and the average maximum forces reached were 19.0 N and 10.6 N for the SST-RCa and IST- RCa interfaces, respectively. Conclusion: The IST-RCa interface consists of a loose connective tissue layer contrary to the SST-RCa interface. In parallel, two different groups in terms of the mechanical response were identified: the IST-RCa interface group had less rigidity and ruptured more quickly than the SST-RCa interface, therefore emerging as the most vulnerable interface and explaining a potential extension of rotator cuff tears. [ABSTRACT FROM AUTHOR]

Odontogenic Keratocysts (OKCs) are known for their aggressive behavior along with rapid expansion. Subepithelial hyalinization (SEH) is one of the causes of recurrence. The ability to predict this biological behavior histologically may help medical experts choose the best course of action. To investigate the aggressiveness of odontogenic keratocyst caused by SEH and its recurrence tendency in the north Indian population, this study will link differential staining methods with immunohistochemistry biomarkers that can be used in routine investigative procedures. Consequently, the evaluation and grading of SEH were established by measuring from the basement membrane to the extent of connective tissue. The levels were correlated to Ki67, Alcian blue, and O -safranine for validation. Forty OKCs were examined for the histological investigation of SEH using the immunohistochemical marker Ki67 and differential staining with O-safranine and Alcian Blue. The histological trait of separation of epithelium from the connective tissue interface due to SEH was noted. SEH-positive cases that were evaluated with Ki67, had increased proliferative activity. The differential staining techniques were validated with Ki67, cross-tabulations in SPSS, and kappa statistic value was given to analyze the results. Spearman's rank correlation was done between Ki67 vs Alcian blue and O-Safranine. A p value of less than < 0.05 was considered statistically significant. In SEH-positive cases, a higher proliferative index was observed. Additionally, histological metrics were statistically significantly higher in SEH-positive cases. Consequently, SEH is a reliable histopathological indicator in OKC for predicting recurrence. The presence of SEH indicates that OKCs are more likely to recur. [ABSTRACT FROM AUTHOR]

Background: Neuroplasticity induced by mandibular advancement appliance (MAD) in patients with obstructive sleep apnoea (OSA) is poorly documented. Objective: This randomised placebo‐controlled crossover mechanistic study assessed the effects of short‐term use of a MAD on corticomotor excitability of the masseter and tongue in patients with OSA. Methods: Adults (n = 28) with mild or moderate OSA were randomly allocated to sleep with a MAD for 2‐weeks with 40% of the maximal protrusion (MAD active position) and without any jaw protrusion (MAD placebo position). The outcomes were assessed at baseline, and after 2 and 6 weeks, with a 2‐week washout period. The primary outcome was the amplitude of motor evoked potential (MEP) assessed on the right masseter, right side of tongue and right first dorsal interosseous with transcranial magnetic stimulation. Corticomotor map volume of the same muscles was also assessed. Repeated‐measures ANOVAs followed by Tukey test were applied to the data (p <.050). Results: There was a significant increase in the MEP amplitude of the masseter and tongue following the MAD active position compared with the baseline and MAD placebo (Tukey: p <.001). There were no significant MEP amplitude differences between the baseline and placebo positions (p >.050). Moreover, there was a significant increase in corticomotor map volume for the masseter and tongue muscles following the MAD active position compared with baseline and MAD placebo (Tukey: p <.003). Conclusion: Excitability of the masseter and tongue motor pathways is, at least transiently, increased in patients with OSA following a short‐term use of MAD. This novel finding of MAD‐induced neuroplasticity in corticomotor pathways may contribute to a further understanding of the mechanisms of oral appliances for treating OSA. [ABSTRACT FROM AUTHOR]

The article in the Journal of Fish Diseases discusses a case of spontaneous fibromyxoma in senescent turquoise killifish Nothobranchius furzeri, a model organism in aging research. The tumour was predominantly formed by connective tissue and displayed typical traits of fibromyxoma. The research findings suggest that the tumour was not pathogen-induced, and its rapid growth was likely associated with senescence. This report provides valuable insights into spontaneous neoplasia in Nothobranchius furzeri, a species previously not considered tumour-prone. [Extracted from the article]

Fibrosis is characterized by excessive extracellular matrix (ECM) deposition resulting from dysregulated wound healing and connective tissue repair mechanisms. Excessive accumulation of ECM leads to fibrous tissue formation, impairing organ function and driving the progression of various fibrotic diseases. Recently, the role of small ubiquitin‐like modifiers (SUMO) in fibrotic diseases has attracted significant attention. SUMO‐mediated SUMOylation, a highly conserved posttranslational modification, participates in a variety of biological processes, including nuclear‐cytosolic transport, cell cycle progression, DNA damage repair, and cellular metabolism. Conversely, SUMO‐specific proteases cleave the isopeptide bond of SUMO conjugates, thereby regulating the deSUMOylation process. Mounting evidence indicates that SUMOylation and deSUMOylation regulate the functions of several proteins, such as Smad3, NF‐κB, and promyelocytic leukemia protein, which are implicated in fibrotic diseases like liver fibrosis, myocardial fibrosis, and pulmonary fibrosis. This review summarizes the role of SUMO in fibrosis‐related pathways and explores its pathological relevance in various fibrotic diseases. All evidence suggest that the SUMO pathway is important targets for the development of treatments for fibrotic diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the interaction between the NLRP3 inflammasome and superoxide dismutase-2 (SOD2) to provide an insight into the complex host response in periodontitis patients with type 2 diabetes mellitus (T2DM), who have an inherent upregulation of inflammatory cytokines and reactive oxygen species (ROS). Methods: Gingival tissues were collected from 51 patients divided into three groups: group 1, systemically and periodontally healthy; group 2, systemically healthy with periodontitis; and group 3, periodontitis with T2DM. Immunohistochemistry was performed to evaluate the expression of the NLRP3 inflammasome and SOD2 in terms of mean percentage, intensity and staining intensity distribution (SID). Results: The mean percentage levels of NLRP3 and SOD2 expression were statistically significantly higher in group 3 (49.16 ± 6.45% and 48.22 ± 11.66%, respectively) when compared to groups 2 and 1 (p < 0.001). While the groups with periodontitis with or without T2DM had statistically significant differences in these variables, the highest expression was found in the periodontitis patient group with T2DM (p < 0.001). NLRP3 and SOD2 mean percentages were positively correlated in groups 1 and 2 but were negatively correlated in group 3. Conclusion: NLRP3 inflammasome is significantly upregulated in periodontitis patients with T2DM. The negative correlation between SOD2 and NLRP3 in periodontitis patients with T2DM probably indicates insufficient endogenous SOD2 to effectively counteract the excessive oxidative burden and inflammatory state, thereby compounding periodontal destruction in cohorts with T2DM. Further, NLRP3 and SOD2 can be used as biomarkers of periodontal disease progression in periodontitis cohorts modified by DM. [ABSTRACT FROM AUTHOR]

Background Interventions using vibration stimulation have been recognized for their potential for increasing range of motion (ROM) without compromising muscle strength. Handheld vibration massagers can efficiently deliver vibration therapy to the shoulder joint and may be a potential treatment. Purpose To evaluate the effects of vibration massage using a handheld device on the soft tissues of the posterior shoulder joint, particularly on internal rotation (IR) passive ROM and external rotation (ER) muscle strength. Study Design Crossover study design. Methods A crossover study with a 5-min vibration massage and passive control condition was conducted in healthy male volunteers (mean age 20.5 ± 1.7 years). Vibration massage was applied to the posterior shoulder soft tissues of the dominant arm, with no intervention under control conditions. IR-ROM (vertebral level and in abduction) and strength of the external rotators (isometric and isokinetic) were measured before and immediately after the intervention. Vertebral levels were calculated as a ratio of lengths (ratio decreases with increased mobility). IR-ROM in abduction, the angle was measured. Statistical analysis was performed with two-way repeated measures ANOVA and paired t-test (Bonferroni correction). Results Vibration application decreased (improved) vertebral level IR ROM by -4.1% (p < 0.01, d = 0.445) and increased abduction position IR ROM by 11.4° (p < 0.01, d = 0.694). These changes exceeded the 95% confidence interval for the minimum detectable change. By contrast, the control condition produced no changes. IR-ROM (vertebral level and abduction) immediately after the intervention showed significant differences between the control and vibration conditions (p = 0.036, d = 0.273; p = 0.048, d = 0.483, respectively). Muscle strength did not show any interaction, time, or between-condition effects. Conclusions A massage using a handheld vibration massager applied to the posterior shoulder soft tissues increased IR-ROM without negatively affecting muscle strength, suggesting its potential use as a means of warming up. Level of Evidence Level 3 [ABSTRACT FROM AUTHOR]

Background: Umbilical outpouchings (UO) are common in Danish weaners. In slaughter pigs UOs consist of various pathological diagnoses; however, no studies have assessed the pathology in weaners from randomly selected herds, nor the agreement between clinical examination findings and post-mortem results. The primary objective was to estimate the prevalence of UO-related clinical findings in weaners before euthanasia and the pathologic macroscopic findings after euthanasia. A secondary objective was to assess the agreement between the size of the UO, the presence of ulcers, and the diagnosis before and after euthanasia. Pigs were selected for euthanasia and included in the study because the individual farmer believed the pigs were already unfit for transport, would not make it to slaughter, or would become unsellable. Results: In total 214 weaners euthanized due to UOs were examined both clinically and post-mortem. Clinically 65.4% of the UOs were large (≥ 11 cm) and 52.3% were unreducible. In the autopsy 78.5% of the UOs were large, and 54.2% had ulcers on their UO. The most prevalent pathological diagnoses were hernia (36.4%), hernia combined with cysts/abscesses (30.8%), cysts (11.7%), and abscesses (11.2%). Adhesions were found in 32.7%, haemorrhage in 22.7%, incarcerated intestines in 8.9%, and connective tissue related to the UO in 51.9% of the pigs post-mortem. The agreement between the size of the UO in the clinical examination and post-mortem was good, as was the sensitivity and specificity for detecting ulcers in the clinical examination compared to post-mortem. Conclusion: Hernias were the most common pathological diagnosis in weaners euthanized due to UOs, and many pigs had complications related to their UO such as ulcers, adhesions, haemorrhage, or incarcerated intestines—all conditions that could impact the pig's welfare. The presence of connective tissue in the UO in more than half of the pigs indicated that many of the UOs had been present for an extended period. Clinical identification of the umbilical ring is difficult, but the clinical examination is useful for determining the size of the UO and the presence or absence of an ulcer, both critical factors when assessing a pig's welfare and fitness for transport. Clinical examination, however, has limited value in determining the aetiology of UOs. [ABSTRACT FROM AUTHOR]

Tendons are fibrous connective tissues that transmit force from muscles to bones. Despite their ability to withstand various loads, tendons are susceptible to significant damage. The healing process of tendons and ligaments connected to bone surfaces after injury presents a clinical challenge due to the intricate structure, composition, cellular populations, and mechanics of the interface. Inflammation plays a pivotal role in tendon healing, creating an inflammatory microenvironment through cytokines and immune cells that aid in debris clearance, tendon cell proliferation, and collagen fiber formation. However, uncontrolled inflammation can lead to tissue damage, and adhesions, and impede proper tendon healing, culminating in scar tissue formation. Therefore, precise regulation of inflammation is crucial. This review offers insights into the impact of inflammation on tendon–bone healing and its underlying mechanisms. Understanding the inflammatory microenvironment, cellular interactions, and extracellular matrix dynamics is essential for promoting optimal healing of tendon–bone injuries. The roles of fibroblasts, inflammatory cytokines, chemokines, and growth factors in promoting healing, inhibiting scar formation, and facilitating tissue regeneration are discussed, highlighting the necessity of balancing the suppression of detrimental inflammatory responses with the promotion of beneficial aspects to enhance tendon healing outcomes. Additionally, the review explores the significant implications and translational potential of targeted inflammatory modulation therapies in refining strategies for tendon–bone healing treatments. [ABSTRACT FROM AUTHOR]

Background: Tissue engineering techniques offer new strategies to understand complex processes in a controlled and reproducible system. In this study, we generated bilayered human tissue substitutes consisting of a cellular connective tissue with a suprajacent epithelium (full-thickness stromal-epithelial substitutes or SESS) and human tissue substitutes with an epithelial layer generated on top of an acellular biomaterial (epithelial substitutes or ESS). Both types of artificial tissues were studied at sequential time periods to analyze the maturation process of the extracellular matrix. Results: Regarding epithelial layer, ESS cells showed active proliferation, positive expression of cytokeratin 5, and low expression of differentiation markers, whereas SESS epithelium showed higher differentiation levels, with a progressive positive expression of cytokeratin 10 and claudin. Stromal cells in SESS tended to accumulate and actively synthetize extracellular matrix components such as collagens and proteoglycans in the stromal area in direct contact with the epithelium (zone 1), whereas these components were very scarce in ESS. Regarding the basement membrane, ESS showed a partially differentiated structure containing fibronectin-1 and perlecan. However, SESS showed higher basement membrane differentiation, with positive expression of fibronectin 1, perlecan, nidogen 1, chondroitin-6-sulfate proteoglycans, agrin, and collagens types IV and VII, although this structure was negative for lumican. Finally, both ESS and SESS proved to be useful tools for studying metabolic pathway regulation, revealing differential activation and upregulation of the transforming growth factor-β pathway in ESS and SESS. Conclusions: These results confirm the relevance of epithelial-stromal interaction for extracellular matrix development and differentiation, especially regarding basement membrane components, and suggest the usefulness of bilayered artificial tissue substitutes to reproduce ex vivo the extracellular matrix maturation and development process of human tissues. Highlights: 1- Artificial bilayered substitutes developed by tissue engineering allow the spatiotemporal study of extracellular matrix maturation and development. 2- Epithelial tissue substitutes generated on the surface of acellular biomaterials display limited differentiation levels, with limited expression of relevant extracellular matrix components. 3- Full-thickness stromal-epithelial substitutes with a cellular stroma showed significantly higher levels of maturation and differentiation, with higher expression of epithelial (cytokeratin 10, claudin) and stromal markers (collagens, proteoglycans). 4- For the formation and development of the basement membrane, an interaction process between the epithelial and the stromal cells is necessary for the synthesis of most fibrillar and non-fibrillar components of this structure. 5- Our results confirm the intrinsic capability of epithelial cells to synthesize extracellular matrix components and the positive inductive effect of paracrine factors released by stromal cells. [ABSTRACT FROM AUTHOR]

Echinoderms are a diverse phylum with a rich fossil record. The five extant classes of echinoderms are characterised by a pentameral (or pseudo-pentameral) symmetry, a water vascular system, a mesodermal skeleton of calcite stereom, and Mutable Collagenous Tissue (MCT), a unique type of connective tissue. Difficulties in tracing the geologic history of these traits complicates phylogenetic analyses of echinoderms. We present evidence herein of MCT in an extinct class of echinoderms, the Blastoidea. Blastoids have composite hair-like structures, brachioles, which formed a feeding filtration fan. Rare specimens from the Devonian of Germany demonstrate the presence of MCT by preserving brachioles as long rigid structures making a feeding fan with MCT in a rigid state. Specimens show brachioles in different configurations in the same specimen, which may indicate nervous control of MCT in individual brachioles. Other specimens appear to indicate the transition of MCT from a rigid to a compliant state as rigid brachioles begin to curve. Still other specimens show a majority of brachioles as limp hair-like structures swept by currents while a minority of brachioles remain rigid. These remarkable specimens could capture MCT transitioning from its rigid to compliant states in individual specimens indicating rapid burial and preservation. Echinoderms are a diverse phylum of marine invertebrates that possess a unique type of connective tissue: Mutable Collagenous Tissue (MCT); evidence of MCT in the feeding structures of an extinct class of echinoderms, the Blastoidea, is presented. [ABSTRACT FROM AUTHOR]

The post-mortem interval (PMI) is the time elapsed between the death of an individual and its forensic examination. It is a crucial information for judicial authorities, but current techniques still cannot establish a precise time interval. Novel approaches are therefore required. Recently, gingival tissue has emerged as interesting for forensic analysis thanks to the protection offered by lips to this tissue, limiting the influence of environmental factors. It is also easily accessible, and its sampling is minimally invasive even in the presence of rigor mortis. Moreover, the expression of HIF-1α, a master mediator of the hypoxic environment, has been described in gingival samples at different post-mortem (PM) times. We have hypothesized that the time-dependent post-mortem expression of HIF-1α could serve as a biomarker to more accurately predict the PMI. Our analyses were performed in an animal model, the mouse, where environment can be precisely controlled. Therewith, gingival tissue morphology was evaluated through histochemical staining and HIF-1α expression was analyzed by qPCR, western blots and immunofluorescence at different post-mortem times (0h to 100h). Our results showed (a) a global post-mortem stability of gingival tissue (b) a rapid increase in HIF-1α mRNA expression in the short post-mortem times followed by a slow decrease in transcript expression until 100h PM (c) an expression of the HIF- 1α protein and its degradation products, that follows the mRNA pattern (d) the presence of HIF-1α protein in the epithelial and connective layers of the tissue, with signal accumulation in both gingival strata until at least 32h post-mortem. This pilot study thus validated the mouse and the gingival tissue as models for post-mortem analyses, as well as for studying the fate of proteins such as HIF-1α. Transferring these approaches to human subjects may provide a more accurate estimate of PMI. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Clinical Considerations Conclusions Clinical Significance This article describes a clinical protocol utilizing soft tissue augmentation alone or in combination with guided bone regeneration (GBR), introducing simultaneous application of the one abutment one time concept for three‐dimensional reconstruction of the deficient ridge.Soft and hard tissue quality and dimensions are fundamental elements for long lasting results in implant dentistry. Different techniques have been described for soft and hard tissue augmentation at time of implant placement presenting favorable results. However, multiple abutment disconnections during the prosthetic phase of treatment can compromise the results achieved during surgery. The purpose of this article is to present a surgical protocol that allows three‐dimensional ridge reconstruction involving soft tissue augmentation alone, or in combination with hard tissue augmentation in one single step with the use of an one‐time intermediate abutment as an anchorage device for the regenerative materials. Two clinical cases utilizing the proposed protocol are also presented, demonstrating favorable results.The application of the proposed protocol simplifies the surgical phase of treatment, protects the achieved result and enables a favorable outcome in decreased time.Utilising an intermediate abutment as an anchorage device at time of surgery can be proven an easy to apply and biologically favorable alternative way to other methods of soft tissue graft stabilization proposed in the past. [ABSTRACT FROM AUTHOR]

Background: Standard approaches to the treatment of chronic post-radiation proctitis are associated with a high risk of complications and a high percentage of unsatisfactory results due to the reduced regenerative potential of irradiated tissues. Regenerative surgery techniques using the stromal-vascular cell fraction (SVF) based on the patient's autologous adipose tissue are a promising direction for study. Clinical case description: A 76-year-old patient suffering from chronic post-radiation erosive-ulcerative proctitis, grade 4 according to RTOG–EORTC, complicated by recurrent profuse rectal bleeding, underwent local autotransplantation of SVF into the submucosal layer of the rectum and pararectal connective tissue. The follow-up colonoscopies 1 and 6 months after the surgery and histological examination showed the complete epithelialization of ulcerative defects and a decrease in proctitis activity. There were no bleeding episodes during the 12-month postoperative observation period. Conclusion: The proangiogenic, wound-healing, and anti-apoptotic effects of the SVF cell suspension provided reduction of inflammation activity, epithelialization of ulcers, and elimination of defecation-associated hemorrhage, following the SVF injection into the submucosal layer of the rectal wall and pararectal connective tissue in a patient with post-radiation proctitis with ulcers and recurrent bleeding. [ABSTRACT FROM AUTHOR]

Objective: To examine the clinicopathological features, immunohistochemical profiles, and differential diagnosis of sclerosing angiomatiod nodular transformation (SANT). Methods: Three cases of SANT of the spleen, diagnosed between 2014 and 2023 at the Affiliated Hospital of Zunyi Medical University, were analysed. Pathological features were assessed using haematoxylin and eosin staining, followed by immunohistochemistry with the EnVision system. Additionally, a review of relevant literature was conducted. Results: The study included one male and two female patients aged 40–55 years, with a median age of 47.5 years. All lesions were solitary, with tumour diameters ranging from 4 to 7.4 cm (mean 5.7 cm). Gross examination demonstrated that the masses were well-demarcated from the surrounding splenic tissue, with no evident capsule. The cut surfaces of the masses exhibited irregular, porcelain-white nodules that were tough in consistency, with some areas intermingling with splenic tissue. Microscopic examination revealed round or circular nodules comprising multiple slit-like or sinusoidal capillaries, separated by concentric collagen fibres. The nodules exhibited chronic inflammatory cell infiltration, calcification, haemosiderin deposition, and fibrous connective tissue with hyaline or mucoid changes. Immunohistochemical analysis demonstrated differential expression of markers, including cluster of differentiation (CD) 34, CD31, and CD8, within the sinusoidal nodule areas. Periodic acid-Schiff staining was positive for perinodular collagen deposits, while reticulin staining highlighted nodule profiles and intranodular vessels. None of the patients experienced postoperative recurrence or metastasis, and one patient was on aspirin for thrombocytosis. Conclusion: SANT of the spleen is generally considered a rare, benign lesion with angioma-like characteristics. It exhibits exhibiting distinctive histomorphological features within the red pulp. Understanding the differential diagnosis is crucial to prevent missed or incorrect diagnoses. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Key points Plain language summary Platelet concentrates have gained significant attention in periodontology due to their regenerative properties. This randomized clinical trial was aimed to compare the clinical efficacy of advanced platelet‐rich fibrin (A‐PRF) and connective tissue graft (CTG) in the management of recession defects. The objectives were to compare changes in recession height and root coverage percentage between the groups.Systemically healthy individuals presenting Cairo's RT1/RT2 gingival recession defects in the maxilla (n = 40) were treated with either A‐PRF or CTG in combination with coronally advanced flap (CAF). Clinical parameters were measured at baseline, 3 months, and 6 months. Mean and complete root coverage percentages were calculated at 3 and 6 months.In both the test (CAF + A‐PRF) and control (CAF + CTG) groups, a statistically significant reduction in mean recession height was seen from baseline values of 2.90 ± 0.55 mm and 3.15 ± 0.87 mm to 0.80 ± 0.95 mm and 0.15 ± 0.48 mm at 6 months, respectively (p < 0.001). In the test group, 10 sites had complete root coverage at 6 months with mean root coverage of 73.76 ± 29.58%. In the control group, 18 of 20 sites had complete root coverage with mean root coverage of 93.35 ± 23.1%. The control sites had a significantly greater reduction in recession height and higher mean and complete root coverage percentages at 6 months (p < 0.05).The study findings suggest that, the CTG had resulted in superior outcomes than A‐PRF along with CAF. Question: To compare the efficacy of advanced platelet‐rich fibrin (A‐PRF) with connective tissue graft (CTG) in the management of gingival recession defects. Finding: Both interventions showed satisfactory healing. At 6 months, the CTG group demonstrated superior results than the A‐PRF group. Meaning: CTG has a greater therapeutic potential than A‐PRF in the management of gingival recessions. Question: To compare the efficacy of advanced platelet‐rich fibrin (A‐PRF) with connective tissue graft (CTG) in the management of gingival recession defects.Finding: Both interventions showed satisfactory healing. At 6 months, the CTG group demonstrated superior results than the A‐PRF group.Meaning: CTG has a greater therapeutic potential than A‐PRF in the management of gingival recessions.Platelet‐derived membranes are widely used in various dental therapies due to their healing properties. Limited studies have been conducted using the novel platelet preparations in the management of receding gums. This study compared the effects of advanced platelet‐rich fibrin membrane with conventional soft tissue harvested from the palate in the treatment of gum recession. Twenty‐three patients requiring gum augmentation were recruited and treated with either platelet‐derived membrane (test group) or tissue harvested from their palate (control group). Clinical parameters were measured at baseline (before intervention), 3 months, and 6 months. Both treatment modalities resulted in significant gum coverage at the end of 6 months. On comparison, the control sites had significantly greater improvements in all the measured clinical parameters indicating that tissue obtained from the palate had superior therapeutic potential. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities—specifically whether they originate in the inner or outer retina—remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease. [ABSTRACT FROM AUTHOR]

In severe skeletal muscle damage, muscle tissue regeneration process has to face the loss of resident muscle stem cells (MuSCs) and the lack of connective tissue necessary to guide the regeneration process. Biocompatible and standardized 3D structures that can be injected to the muscle injury site, conforming to the defect shape while actively guiding the repair process, holds great promise for skeletal muscle tissue regeneration. In this study, we explore the use of an injectable and porous lysine dendrimer/polyethylene glycol (DGL/PEG) hydrogel as an acellular support for skeletal muscle regeneration. We adjusted the DGL/PEG composition to achieve a stiffness conducive to the attachment and proliferation of murine immortalized myoblasts and human primary muscle stems cells, sustaining the formation and maturation of muscle fibers in vitro. We then evaluated the potential of one selected "myogenic-porous hydrogel" as a supportive structure for muscle repair in a large tibialis anterior muscle defect in rats. This injectable and porous formulation filled the defect, promoting rapid cellularization with the presence of endothelial cells, macrophages, and myoblasts, thereby supporting neo-myogenesis more specifically at the interface between the wound edges and the hydrogel. The selected porous DGL/PEG hydrogel acted as a guiding scaffold at the periphery of the defect, facilitating the formation and anchorage of aligned muscle fibers 21 days after injury. Overall, our results indicate DGL/PEG porous injectable hydrogel potential to create a pro-regenerative environment for muscle cells after large skeletal muscle injuries, paving the way for acellular treatment in regenerative muscle medicine. [ABSTRACT FROM AUTHOR]

Collagen is the most abundant protein found in humans and is fundamental to tissue structure and function. Collagen products used in biomedical research are primarily derived from mammals, and despite being mainly responsible for providing strength to native connective tissue, collagen hydrogels have comparatively low mechanical properties without the use of additional cross‐linking strategies. Alternative sources of collagen, like fish collagen, are emerging as key biomaterials in tissue engineering and regenerative medicine (TERM). By addressing cultural/religious concerns, ease of extraction, absence of mammalian‐derived allergens, and retention of functional motifs, fish collagen has many promising characteristics that make it a suitable alternative to mammalian collagen. Several physical and chemical cross‐linking strategies of fish collagen are explored to create more stable and resilient scaffolds for a variety of TERM applications. This comprehensive review explores how these modifications are optimized in fish collagen hydrogel systems. Herein, the use of fish collagen and their reported sources for TERM research, as well as the types of treatments (including sterilization) used to alter collagen structures and functions, are presented to date. [ABSTRACT FROM AUTHOR]

Ankylosaurs were a group of heavily armored non‐avian dinosaurs (Dinosauria, Ankylosauria), represented by a relatively abundant fossil record from the Cretaceous of North and South America. Their dermal skeleton was characterized by large osteoderms whose development and functional role have been largely investigated. However, interstitial small ossicles, forming between these osteoderms, have been far more overlooked and it remains unknown whether they were formed through the ossification of a preexisting fibrous matrix of connective tissue (i.e., metaplasia) or by a cell‐induced differentiation of new fiber bundles followed by mineralization (i.e., neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147)). Here, we propose a hypothesis on the developmental origin of these small ossicles in the ankylosaurian Antarctopelta oliveroi using light microcopy, scanning electron microscopy and three‐dimensional virtual histology through propagation phase‐contrast synchrotron radiation micro‐computed tomography (PPC‐SRμCT). Ossicles are located in the dermis. They are composed of two layers: (1) a thin external layer, and (2) a thick basal plate, composed of collagen fiber bundles, which forms the main part of the ossicle. The external layer is made of a smooth, vitreous mineralized tissue that does not look like bone. The basal plate, however, is of osseous origin. In this basal plate, the collagen fiber bundles are organized in two orthogonal systems: one horizontal—observable in cross‐sections—and one vertical—observable in the primary plane of sections sensu (Journal of Vertebrate Paleontology, 2004, 24, 874). The horizontal system is itself composed of successive layers of collagen fiber bundles arranged into an orthogonal plywood‐like structure. The bundles of the vertical system radiate from the center of the ossicle at the level of the transition between the external layer and the basal plate and run towards the periphery of the basal plate. Their thickness increases from the center of the ossicle towards its periphery. Numerous bundles of the vertical system form thin threads that interweave and penetrate within the thick bundles of the horizontal system. Our new data suggest that the ossicles were at least partially formed by metaplasia, that is, through the ossification of a preexisting fibrous matrix of connective tissue. This process was probably supplemented by a cell‐induced differentiation of new fiber bundles laid down prior to their incorporation into the fibrous system and its mineralization. This process looks more akin to neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147) than to metaplasia. Consequently, metaplastic and neoplastic processes may coexist in these ossicles with a possible differential expression during ontogeny. [ABSTRACT FROM AUTHOR]

Introduction: Desmoid tumors (DT) are rare, locally invasive tumors originating from connective tissue. Surgical intervention is no longer the standard treatment for DT, as systemic therapy gradually replaces it due to its superior efficacy. Despite the availability of various treatment modalities, there is a need for a first-line systemic treatment regimen that offers both effective disease control and acceptable safety profiles. Methods: To assess the efficacy and safety of different systemic treatment agents for DT, we conducted a systematic review and network meta-analysis. Eligible studies were identified through searches of PubMed, Embase, and the Cochrane Library databases, and data were extracted according to predefined inclusion criteria. Results: Three articles and clinical data from 295 patients with progressive and refractory DT were included in this Bayesian network meta-analysis. When considered by objective response rate (ORR), the efficacy of γ-secretase inhibitor versus placebo (OR 0.12, 95%CI 0.01–1.68) is superior to that of TKI (OR 0.49, 95%CI 0.03–7.62) and chemotherapy (OR 0.90, 95%CI 0.02–40.00). Vascular endothelial growth factor (VEGF)-TKI (OR, 0.09; 95% CI, 0.01–1.79) seemed to have the highest improvement in terms of 1-yr PFS rate, while chemotherapy seemed to have the highest improvement across all therapies in terms of 2-yr PFS rate across all therapies (OR, 0.06; 95 percent CI, 0.01–2.98). In terms of safety, the incidence of AEs is highest for γ-secretase inhibitor versus placebo (OR 0.16, 95%CI 0.02–1.55), while TKI is associated with the least AEs (OR 0.62, 95%CI 0.06–6.97). Conclusion: γ-secretase inhibitor provides superior local control of tumors, while chemotherapy and TKI may offer better long-term survival benefits. Among the three regimens, TKI demonstrated better treatment-related safety. These findings have important implications for guiding clinical practice in systemic treatment of DT. Highlights: The study conducted a systematic review and Bayesian network meta-analysis to evaluate the efficacy and safety of systemic treatment options for progressive and refractory desmoid tumors. The analysis included 3 RCT studies, and the primary clinical endpoints were progression-free survival and objective response rate. The network meta-analysis showed that γ-secretase inhibitors have better tumor response and more severe toxicity, while chemotherapy and TKI may have better long-term survival benefits. [ABSTRACT FROM AUTHOR]

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient's fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis. [ABSTRACT FROM AUTHOR]

Three-dimensional organotypic models benefit from the ability to mimic physiological cell–cell or cell–matrix interactions and therefore offer superior models for studying pathological or physiological conditions compared to 2D cultures. Organotypic models consisting of keratinocytes supported by fibroblasts embedded in collagen matrices have been utilised for the study of oral conditions. However, the provision of a suitable model for investigating the pathogenesis of periodontitis has been more challenging. Part of the complexity relates to the different regional epithelial specificities and connective tissue phenotypes. Recently, it was confirmed, using 3D organotypic models, that distinct fibroblast populations were implicated in the provision of specific inductive and directive influences on the overlying epithelia. This paper presents the organotypic model of the dentogingival junction (DGJ) constructed to demonstrate the differential fibroblast influences on the maintenance of regionally specific epithelial phenotypes. Therefore, the review aims are (1) to provide the biological basis underlying 3D organotypic cultures and (2) to comprehensively detail the experimental protocol for the construction of the organotypic cultures and the unique setup for the DGJ model. The latter is the first organotypic culture model used for the reconstruction of the DGJ and is recommended as a useful tool for future periodontal research. [ABSTRACT FROM AUTHOR]

This systematic review investigates the efficacy of using connective tissue grafting (CTG) versus an acellular dermal matrix (ADM) for soft tissue management in immediate implant placement (IIP). The study focuses on comparing the soft tissue thickness (STT) and keratinized tissue width (KTW) changes post-implantation. Adhering to the PRISMA guidelines, a comprehensive literature search was conducted, targeting randomized clinical trials and cohort studies involving soft tissue grafting in conjunction with IIP. Data extraction and analysis focused on STT and KTW measurements from baseline to follow-up intervals of at least 6 months. The statistical analyses included the weighted mean differences and heterogeneity assessments among the studies. The meta-analysis revealed no significant difference in the STT gain between CTG and ADM at 12 months, with the weighted mean differences favoring the control group but lacking statistical significance (CTG: 0.46 ± 0.53 mm, p = 0.338; ADM: 0.33 ± 0.44 mm, p = 0.459). The heterogeneity was high among the studies, with discrepancies notably influenced by individual study variations. Similarly, the changes in KTW were not significantly different between the two grafting materials. Conclusions: Both CTG and ADM are viable options for soft tissue management in IIP, with no significant difference in efficacy regarding the soft tissue thickness and keratinized tissue width outcomes. Future research should aim to minimize the heterogeneity and explore the long-term effects to better inform clinical decisions. [ABSTRACT FROM AUTHOR]

Aim: To assess the impact of the timing of soft‐tissue augmentation (STA) on mean buccal bone changes following immediate implant placement (IPP) in the anterior maxilla. Materials and Methods: Patients with a failing tooth and intact buccal bone wall in the anterior maxilla (15–25) were enrolled in this randomized controlled trial. Following single IIP and socket grafting, they were randomly allocated to the control group (immediate STA performed during the same surgical procedure) or the test group (delayed STA performed 3 months later). Implants were placed with a surgical guide and immediately restored with an implant‐supported provisional crown. Changes in bone dimensions were assessed using superimposed CBCT images taken prior to surgery and at 1‐year follow‐up. Clinical outcomes were registered at 1‐year follow‐up. Results: Twenty patients were randomized to each group (control: 16 females, 4 males, mean age 57.6; test: 9 females, 11 males, mean age 54.2). Ten patients in the control group and 13 patients in the test group had a thick bone wall phenotype. Estimated marginal mean horizontal buccal bone loss at 1 mm below the implant shoulder was −0.553 and −0.898 mm for the control and test group, respectively. The estimated mean difference of 0.344 mm in favour of the control group was not significant (95% CI: −0.415 to 1.104; p = 0.363). Also at all other horizontal and vertical levels, no significant differences could be observed between the groups. The combination of socket grafting and STA enabled counteraction of any buccal soft‐tissue loss (≥ 0 mm) at 1 mm below the implant shoulder in 82% of the patients in the control group and in 75% of the patients in the test group (p = 1.000). The clinical outcome was favourable in both groups, yet implants in the control group demonstrated slightly less marginal bone loss (median difference 0.20 mm; 95% CI: 0.00–0.44; p = 0.028). Conclusion: In patients with an intact and mainly thick buccal bone wall in the anterior maxilla, the timing of STA following IIP had no significant impact on mean buccal bone loss. Trial Registration: ClinicalTrials.gov identifier: NCT05537545 [ABSTRACT FROM AUTHOR]

Aim: To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum. Materials and Methods: Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer‐shaped bony defect was created on each side of the mandible. After 3 months of healing, full‐thickness muco‐periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra‐orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro‐CT. Results: New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups. Conclusions: Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials. [ABSTRACT FROM AUTHOR]