Peri-implant soft tissue volume changes after microsurgical envelope technique with a connective tissue graft. A 5-year retrospective case series.

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.

Endomysium determines active and passive force production in muscle fibers.

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.

Autogenous graft versus collagen matrices for peri-implant soft tissue augmentation. A systematic review and network meta-analysis.

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.

The influence of connective tissue grafting on the reconstruction of a missing facial bone wall using immediate implant placement and simultaneous bone reconstruction: a retrospective long-term cohort study.

PURPOSE: This retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years. METHODS: Sixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB. A subgroup of 34 sites was grafted additionally with CTG using tunnel technique. Primary outcome was the vertical bone regeneration in height and thickness. Secondary outcome parameters were interproximal marginal bone level, recession, soft tissue esthetics (PES), width of keratinized mucosa (KMW) and probing depths (PPD). RESULTS: Mean follow-up period was 60.8 months. In 55 sites a complete vertical bone regeneration was documented. The mean buccal bone level increased by 10.6 mm significantly. The thickness of the buccal bone wall ranged between 1.7 and 1.9 mm, and was significantly thicker in sites without CTG. Interproximal marginal bone level was at implant shoulder level. The mean recession improved significantly by 1.2 mm. In sites with CTG, recessions and PES improved significantly more. CONCLUSIONS: Additional CTG in extraction sites with total buccal bone loss followed by IIP with simultaneous AB grafting led to improved PES and recession, but also to a thinner buccal bone wall compared to sites grafted just with AB.

Histological assessment of a novel de-epithelialization method for connective tissue grafts harvested from the palate. An experimental study in cadavers.

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.

Performance of multiple therapeutic approaches for palatal wound healing after soft tissue graft removal - an overview of systematic reviews.

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.

Treatment of multiple adjacent gingival recessions using leucocyte- and platelet-rich fibrin with coronally advanced flap: a 12-month split-mouth controlled randomized clinical trial.

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.

Is connective tissue massage effective in individuals with fibromyalgia?

OBJECTIVES: The aim of the study was to examine the effectiveness of Clinical Pilates exercises and connective tissue massage (CTM) in individuals with Fibromyalgia (FM) on pain, disease impact, functional status, anxiety, quality of life and biopsychosocial status. METHODS: 32 women were randomly divided into two groups as intervention gorup (CTM + Clinical Pilates exercises, n = 15, mean age = 48.80 ± 7.48) and control gorup (Clinical Pilates exercises, n = 17, mean age = 55.64 ± 7.87). The number of painful regions were assessed with Pain Location Inventory (PLI), disease impact with Fibromyalgia Impact Questionnare (FIQ), functional status with Health Assessment Questionnare (HAQ), anxiety with Beck Anxiety Inventory (BAI), quality of life with Short Form-36 (SF-36) and biopsychosocial status with Biopsychosocial Questionnaire (BETY-BQ) were evaluated. All evaluations were made before and after treatment. Both treatments were applied 3 times a week for 6 weeks. RESULTS: When the pre-treatment and post-treatment results are analyzed; significant difference was observed in PLI (p = 0.007; effect size 1.273), FIQ (p = 0.004; effect size 0.987), SF-36 physical component (p = 0.025; effect size -0.496) and mental component (p = 0.017; effect size -0.761) in the intervention group while the significant difference was observed in FIQ (p = 0.001; effect size 1.096) and BAI (p = 0.043; effect size 0.392), SF-36 physical component (p = 0.008; effect size -0.507) and mental component (p = 0.024; effect size -0.507) in the control group. When the delta values of the groups are compared, the difference was determined only in the PLI (p = 0.023) in favor of the intervention group. CONCLUSIONS: CTM can be effective in reducing the number of painful areas in addition to the positive effects of clinical Pilates exercises in women with FM.

Histological evaluation of the surgical margins of oral soft tissue incisions using a dual-wavelength diode laser and an Er, Cr:YSGG laser; an ex vivo study.

OBJECTIVE: This study compared a dual-wavelength diode laser and an Er, Cr:YSGG laser in oral soft tissue incisions to determine the most effective and safest laser system at the histopathological level. METHODOLOGY: The (810 and 980 nm) dual-wavelength diode laser was used at 1.5 W and 2.5 W (CW) power settings, and the (2780 nm) Er, Cr:YSGG laser was used at 2.5 W and 3.5 W (PW) power settings. Both laser systems were used to incise the tissues of freshly dissected sheep tongue pieces to obtain the following histopathological criteria: epithelial tissue changes, connective tissue changes, and lateral thermal damage extent by optical microscopy. RESULTS: The epithelial and connective tissue damage scores were significantly higher in the dual-wavelength diode laser groups than in the Er, Cr:YSGG laser groups (P<0.001), and there was a significant difference between some groups. The extent of lateral thermal damage was also significantly higher in the diode laser groups than in the Er, Cr: YSGG laser groups (P<0.001), and there was a significant difference between groups. Group 2 (2.5 W) of the diode laser was the highest for all three criteria, while group 3 (2.5 W) of the Er, Cr:YSGG laser was the lowest. CONCLUSION: The Er, Cr:YSGG laser with an output power of 2.5 W is, histologically, the most effective and safest laser for oral soft tissue incision. The dual-wavelength diode laser causes more damage than the Er, Cr:YSGG laser, but it can be used with a low output power and 1 mm safety distance in excisional biopsy.

Ultrasonographic analysis of palatal donor site healing accelerated with platelet-rich fibrin following subepithelial connective tissue harvesting.

OBJECTIVE: Platelet-rich fibrin (PRF) contains a variety of growth factors and bioactive molecules that play crucial roles in wound healing and angiogenesis. We aimed to evaluate the effects of PRF on tissue thickness and vascularization of the palatal donor site by ultrasound (USG) following subepithelial connective tissue harvesting. METHODOLOGY: A subepithelial connective tissue graft was harvested from the palatal region with a single incision for root coverage in 20 systemically healthy patients. In the test group (n = 10), the PRF membrane was placed at the donor site, whereas no material was applied in the control group (n=10). Palatal tissue thickness (PTT) and pulsatility index (PI) were evaluated by USG at baseline and on the 3rd, 7th, 14th, 30th, and 90th days after surgery. The early healing index (EHI) was used to evaluate donor site healing for 30 days. RESULTS: PTT was significantly higher in the PRF group on the 3rd and 14th days after surgery when compared to the controls. In the PRF-treated group, PI levels were significantly higher than in the controls, especially on the 14th day. PTT increased significantly 90 days after surgery compared to the test group baseline, but controls showed a significant decrease. The PRF group showed statistically significant improvements in EHI scores compared to controls on days 3, 7, and 14. This study found a negative correlation between PI values and EHI scores on postoperative days three and seven in the test group. CONCLUSION: USG is a non-invasive, objective method to radiographically evaluate the regenerative effects of PRF on palatal wound healing after soft tissue harvesting. To overcome graft inadequacy in reharvesting procedures, PRF application may enhance clinical success and reduce possible complications by increasing tissue thickness and revascularization in the donor area.

[Long-term result of aortic root remodeling using the Florida sleeve technique in a patient with connective tissue dysplasia and aortic root aneurysm without aortic insufficiency]. / Otdalennyi rezul'tat ekzoprotezirovaniya kornya aorty po metodike Florida Sleeve u bol'nogo s soedinitel'notkannoi displaziei i anevrizmoi kornya aorty bez aortal'noi nedostatochnosti.

Aortic root remodeling using the Florida sleeve technique was proposed as a simpler alternative to classical reconstructive interventions in patients with aortic root aneurysm without aortic insufficiency. We present a 10-year result of valve-sparing surgical treatment using the Florida sleeve technique in a patient with connective tissue dysplasia and aortic root aneurysm.

On Connective Tissue Mast Cells as Protectors of Life, Reproduction, and Progeny.

The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, has been preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MC has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors, enabling its activation via a vast variety of potentially harmful exogenous and endogenous molecules and via reproductive hormones in the female sex organs. Activated MCs release a unique composition of preformed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects-spanning generations-in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell.

CD163+ macrophage density in perimysial connective tissue associated with prognosis in IMNM.

OBJECTIVE: The pathological features of immune-mediated necrotizing myopathy (IMNM) are dominated by the infiltration of macrophages. We aimed to perform a histopathologic semiquantitative analysis to investigate the relationship between macrophage markers and prognosis. METHODS: Semiquantitative analysis of histologic features was performed in 62 samples of IMNM. Independent risk factors were identified through univariate and multivariate regression analysis. Cluster analysis was performed using the partitioning around the medoids (PAM) method. Decision tree modeling was utilized to efficiently determine cluster labels for IMNM patients. The validity of the developmental cohort was assessed by accuracy in comparison with the validation cohort. RESULTS: The most enriched groups in patients with IMNM were macrophages expressing CD206 and CD163. In the multivariate logistic regression model, the high density of CD163+ macrophages in perimysial connective tissue increased the risk of unfavorable prognosis (p = 0.025, OR = 1.463, 95% CI: 1.049-2.041). In cluster analysis, patients in Cluster 1, with lower CD163+ macrophage density and inflammatory burden, had a more favorable prognosis. Conversely, patients in Cluster 3, which were enriched for CD163+ macrophages in the perimysial connective tissue, had the most severe clinical features and the worst prognosis. Correlations were found between the density of CD163+ macrophages in connective tissue and symptom duration (R2 = 0.166, p < 0.001), dysphagia (p = 0.004), cardiac involvement (p = 0.021), CK (R2 = 0.067, p = 0.042), CRP (R2 = 0.117, p < 0.001), and ESR (R2 = 0.171, p < 0.001). CONCLUSION: The density of CD163+ macrophages in perimysial connective tissue may serve as a potential marker for the prediction of IMNM prognosis.

The Effect of Connective Tissue Graft Compared to Concentrated Growth Factor Graft on Buccal Peri-Implant Gingival Thickness: A 12-month Randomized Controlled Clinical Trial.

BACKGROUND: Attached gingival phenotype has a crucial impact on the implant's durability and its future success. PURPOSE: This study aims to measure and compare buccal peri-implant gingival thickness following grafting with connective tissue graft (CTG) and the concentrated growth factor (CGF) graft. STUDY DESIGN, SETTING, SAMPLE: This is a split-mouth designed randomized controlled clinical study in which a total of 20 aged 18 to 55 have bilateral missing teeth in the maxillary premolar region with less than 2 mm of healthy peri-implant gingival thickness. Patients were excluded if they were smokers, had poor oral hygiene, had uncontrolled widespread periodontal disease, or had a history of radiation treatment. The same surgical protocol was followed for each study participant, where an independent blinded medical practitioner assigned the first stage side to be treated with CTG, while the second stage side with CGF 2 weeks later. EXPOSURE VARIABLE: The primary exposure variable of this study was the gingival grafting technique; CTG or CGF. OUTCOME VARIABLE: The primary outcome variable was the buccal peri-implant gingival thickness. Gingival thickness was measured at six different times; immediately before the procedure (T0), after 30 days (T1), after 45 days (T2), after 3 months (T3), after 6 months (T4), and after 12 months (T5). COVARIATES: The covariates were age, sex general health, and periodontal status. ANALYSIS: The statistical analysis; repeated measures analysis of variance test was used to compare the gingival thickness between the studied follow-up times within each group. The level of significance was set at ≤ 0.05. RESULTS: The sample was composed of 40 treatment sites of 20 patients. The mean age of the sample was 32 years and 45% were male. The mean gingival thickness value of the CTG group was 1.62 mm with a (standard deviation = 0.18) compared to 1.28 mm for the CGF group with (standard deviation = 0.20) and an overall P value (0.001) at T5. CONCLUSIONS AND RELEVANCE: CTG showed to have better gingival thickness than CGF in managing peri-implant buccal gingival thickness deficiency.

Effects of the application of low-temperature atmospheric plasma on titanium implants on wound healing in peri-implant connective tissue in rats.

PURPOSE: This study aimed to clarify the effects of surface modification of titanium (Ti) implants by low-temperature atmospheric pressure plasma treatment on wound healing and cell attachment for biological sealing in peri-implant soft tissue. METHODS: Hydrophilization to a Ti disk using a handheld low-temperature atmospheric pressure plasma device was evaluated by a contact angle test and compared with an untreated group. In in vivo experiments, plasma-treated pure Ti implants using a handheld plasma device (experimental group: PL) and untreated implants (control group: Cont) were placed into the rat upper molar socket, and samples were harvested at 3, 7 and 14 days after surgery. Histological evaluation was performed to assess biological sealing, collagen- and cell adhesion-related gene expression by reverse transcription quantitative polymerase chain reaction, collagen fiber detection by Picrosirius Red staining, and immunohistochemistry for integrins. RESULTS: In in vivo experiments, increased width of the peri-implant connective tissue (PICT) and suppression of epithelial down growth was observed in PL compared with Cont. In addition, high gene expression of types I and XII collagen at 7 days and acceleration of collagen maturation was recognized in PL. Strong immunoreaction of integrin α2, α5, and ß1 was observed at the implant contact area of PICT in PL. CONCLUSIONS: The handheld low-temperature atmospheric pressure plasma device provided hydrophilicity on the Ti surface and maintained the width of the contact area of PICT to the implant surface as a result of accelerated collagen maturation and fibroblast adhesion, compared to no plasma application.

Connective tissue disorders in COVID-19: Reply to "People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing".

Connective tissue serves as a framework for other tissues and organs, supporting their functions, shielding them from harmful factors, and aiding repair. In COVID-19, damaged endothelial cells (ECs), increased endothelial permeability, and thrombi contribute to the connective tissue disorders. Even post-recovery, the damage to ECs and connective tissues persists, resulting in long COVID. Individuals with connective tissue disorders are prone to developing severe COVID-19 and experiencing long COVID symptoms. It is advised that these patients receive at least three vaccine doses, undergo early prophylactic antithrombotic therapy during acute COVID-19, and maintain prophylactic anticoagulant treatment in cases of long COVID.

Biomechanical analysis of the human derived soft tissue graft Epiflex for use in oral soft tissue augmentation.

PURPOSE: This study aimed to investigate the biomechanical properties, cell migration, and revascularization of the acellular dermal matrix Epiflex. As a decellularized, freeze-dried human skin graft, Epiflex has broad applications in medical fields, particularly in implantology and dentistry. Understanding its biomechanical characteristics is crucial for its clinical adoption as a novel soft tissue graft option. METHODS: Epiflex (n = 3) was evaluated in comparison to palatal tissue from body donors (n = 3). Key metrics, such as elongation and tear resistance, were quantified. Both graft types underwent histological analysis and scanning electron microscopy. Additionally, the healing properties of Epiflex were assessed using a Chorioallantoic Membrane (CAM) Assay. RESULTS: Biomechanically, Epiflex (mean = 116.01 N) demonstrated the ability to withstand greater forces (p = 0.013) than human palatal tissue (mean = 12.58 N). When comparing the elongation, no significant difference was measured (ASG mean = 9.93 mm, EF mean = 9.7 mm). Histologically, Epiflex exhibited a loosely connected network of collagen fibers with a dense upper layer. The CAM Assay indicated efficient revascularization. CONCLUSION: Epiflex appears to be a viable option for soft tissue augmentation, particularly appealing to patient groups who avoid all or specific animal-derived products due to ethical or religious reasons.

Higher densities of T-lymphocytes in the subsynovial connective tissue of people with carpal tunnel syndrome.

Symptoms in people with carpal tunnel syndrome (CTS) are traditionally attributed to neural tissue, but recent studies suggest that the subsynovial connective tissue (SSCT) may also play a role in CTS. The SSCT undergoes fibrotic thickening which is generally described as "non-inflammatory" based on basic histology. This study uses immunohistochemistry to determine the presence of macrophages and T-cells within SSCT and their relationship with symptoms in people with CTS. SSCT was collected from twenty people with CTS and eight controls undergoing wrist fracture surgery. Immunohistochemical quantification of CD3+ T-cells and CD68+ macrophage densities as well as CD4+/CD8+ T-cell subpopulations were compared between groups using independent t-tests. Spearman correlations were used to identify associations between immune cell densities and CTS symptom scores. The density of CD3+ T-cells was significantly higher in SSCT of people with CTS compared to controls (CTS mean 26.7 (SD 13.7); controls 6.78 (6.3), p = 0.0005) while the density of CD68+ macrophages was lower (CTS mean 9.5 (SD 6.0); controls 17.7 (8.2), p = 0.0058). Neither CD68+ nor CD3+ cell densities correlated with symptom scores. In contrast to previous assumptions, our data show that the SSCT in the carpal tunnel in both people with CTS and controls is not devoid of immune cells. Whereas the higher density of CD68+ macrophages in control participants may be associated with their early recruitment after acute fracture, CD3+ cells within the SSCT may play a role in chronic CTS.

A functional 3D full-thickness model for comprehending the interaction between airway epithelium and connective tissue in cystic fibrosis.

Patients with cystic fibrosis (CF) experience severe lung disease, including persistent infections, inflammation, and irreversible fibrotic remodeling of the airways. Although therapy with transmembrane conductance regulator (CFTR) protein modulators reached optimal results in terms of CFTR rescue, lung transplant remains the best line of care for patients in an advanced stage of CF. Indeed, chronic inflammation and tissue remodeling still represent stumbling blocks during treatment, and underlying mechanisms are still unclear. Nowadays, animal models are not able to fully replicate clinical features of the human disease and the conventional in vitro models lack a stromal compartment undergoing fibrotic remodeling. To address this gap, we show the development of a 3D full-thickness model of CF with a human bronchial epithelium differentiated on a connective airway tissue. We demonstrated that the epithelial cells not only underwent mucociliary differentiation but also migrated in the connective tissue and formed gland-like structures. The presence of the connective tissue stimulated the pro-inflammatory behaviour of the epithelium, which activated the fibroblasts embedded into their own extracellular matrix (ECM). By varying the composition of the model with CF epithelial cells and a CF or healthy connective tissue, it was possible to replicate different moments of CF disease, as demonstrated by the differences in the transcriptome of the CF epithelium in the different conditions. The possibility to faithfully represent the crosstalk between epithelial and connective in CF through the full thickness model, along with inflammation and stromal activation, makes the model suitable to better understand mechanisms of disease genesis, progression, and response to therapy.