Search Results (184)

Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin gallate (EGCG). The EDC/NHS and Schiff-base bond connections occurred in the hydrogels, as confirmed by Fourier-transform infrared (FT-IR) analysis. The properties of the fabricated hydrogels, including microstructure, degradation rate, adhesive strength, mechanical strength, and rheological behavior, can be regulated by adjusting the DA-Gel/QCS ratio or by using different crosslinking approaches. In addition, the fabricated hydrogels exhibited self-healing properties and strong adhesion to various materials and organs. Furthermore, the hydrogels performed good antibacterial activity against the typical bacteria, Escherichia coli and Staphylococcus aureus. EGCG encapsulated hydrogels displayed excellent antioxidant activities and good hemocompatibility. The hydrogels also demonstrated excellent cytocompatibility and good cell migration ability. The above results provide a facile approach to fabricate the biomedical hydrogels with a regulated network structure and multifunctional characteristics with potential in biomedical applications. Full article

A critical obstacle in cardiac cell therapy is the unpredictable and poorly understood initial electrophysiological integration of grafted cardiomyocytes into the host tissue, a process that dictates therapeutic success and arrhythmic risk. Current models fail to capture the earliest stages of functional coupling formation. Here, we employed a tailored bioengineering platform, where single cardiomyocytes were stabilized on minimalist electrospun polycaprolactone (PCL) nanofibers, to model the “graft–host” interface and study the dynamics of excitation wave transmission in real-time. Using high-speed optical mapping enhanced by a custom SUPPORT neural network, we achieved the first quantitative insights into the efficiency of nascent intercellular contacts. We determined that within the first 3 h, these initial connections are 39–44 times less effective at conducting excitation than mature contacts within the native monolayer, explaining the observed partial (46%) synchronization of grafted cells. This work provides the first direct measurement of the functional deficit during the initial minutes and hours of graft integration. It establishes that simple, inert polymer fibers can act as a catalytic scaffold to enable this fundamental biological process, offering a powerful strategy to deconstruct and ultimately control the integration of engineered tissues (or cells) for safer cell therapies. Full article

Background: Maxillary sinus floor augmentation is widely used to enable implant placement in the atrophic posterior maxilla, yet comparative data for porcine-derived xenografts remain limited. Objective: To evaluate long-term bone regeneration and implant outcomes following sinus augmentation using a collagenated porcine xenograft. Methods: This paper reports a retrospective case series of three partially edentulous patients (aged 46–56 years) who underwent lateral sinus augmentation with a small-particle collagenated porcine xenograft (THE Graft™, Purgo Biologics, Gyeonggi-do, Republic of Korea) and staged implant placement. In one case, a controlled perforation of the Schneiderian membrane was performed to access and remove a sinus mucocele, followed by repair using a resorbable collagen membrane. Core biopsies were harvested at implant placement for histology (hematoxylin-eosin, Masson–Goldner) and tartrate-resistant acid phosphatase (TRAP) staining. Clinical outcomes included surgical events, vertical bone gain, marginal bone levels, and implant survival at long-term follow-up. Results: Healing was uneventful in all cases. Mean vertical bone gain was 12.0 mm (baseline 1.33 mm to 13.33 mm final). At a mean 46.8-month follow-up (range 38.3–52.2 months), 100% of implants were functional without failure; marginal bone loss remained < 1 mm during the first year and was stable thereafter. Histology at 3.7, 4.7, and 7.5 months showed vascularized new trabecular bone intimately contacting residual xenograft particles (new bone 20–30%, residual biomaterial 30–40%, connective tissue 30–50%). TRAP-positive multinucleated giant cells at 7.5 months indicated ongoing biomaterial degradation without severe inflammatory reactions. Conclusions: Within the limits of a small case series, collagenated porcine xenograft supported predictable bone regeneration and stable long-term implant function after sinus floor elevation, with favorable histologic integration and gradual resorption. Full article

Localized scleroderma (LSc), or morphea, is an autoimmune connective tissue disease causing inflammation and fibrosis of the skin and underlying tissues. While distinct from systemic sclerosis, its clinical presentation is highly diverse. This review summarizes recent advances in the understanding and management of LSc. Pathophysiological insights have evolved significantly; the somatic mosaicism hypothesis is now supported by the observation of all six of Happle’s classic lesion patterns in LSc. Furthermore, recent single-cell RNA sequencing has elucidated key cellular mechanisms, revealing an IFN-γ-driven pro-fibrotic crosstalk between T cells, dendritic cells, and specific inflammatory fibroblast subpopulations. The discovery of a rare monogenic form of LSc caused by a STAT4 gain-of-function mutation provides a powerful human model, solidifying the critical role of the JAK-STAT pathway. Clinically, LSc is classified into subtypes such as circumscribed, linear, and generalized morphea. Extracutaneous manifestations are common, particularly in juvenile LSc, and are associated with higher disease activity and reduced quality of life, necessitating a multidisciplinary approach. Management is becoming standardized, with methotrexate as the first-line systemic therapy for severe disease. For refractory cases, targeted treatments including abatacept, tocilizumab, and JAK inhibitors are emerging as promising options. In addition, reconstructive therapies like autologous fat grafting are crucial for managing atrophic sequelae. These recent advances are paving the way for more effective, targeted therapies to improve outcomes for patients with this complex disease. Full article

Methods: Currently available randomized controlled clinical trials (RCTs) reporting on the adjunctive clinical effects of biomaterials, grafting materials, and grafting techniques on immediate implant placement (IIP) were systematically assessed. Data were qualitatively analyzed and, when appropriate, meta-analysis was performed. Risk of bias and quality of evidence were evaluated using the Cochrane RoB 2 tool and the GRADE framework, respectively. Results: A total of 12 RCTs (484 implants, 6–36 months of follow-up) were included and consistently reported high implant survival rates (96–100%). Data on the use of xenografts, alloplastic and mixed grafts, connective tissue grafts and socket shield technique seem, to different extents, to demonstrate favorable results in terms of peri-implant hard and soft tissue dynamics and esthetic outcomes. Quantitative synthesis conducted on four RCTs demonstrated significantly higher short-term patient-reported postoperative pain, assessed on a 0–100 Visual Analog Scale (VAS) (weighted mean difference 19.45 mm; 95% CI 0.55–38.36; p = 0.04). Most RCTs were rated at moderate to high risk of bias, and certainty of evidence was low to moderate. Conclusions: Regardless of the use of adjunctive materials/approaches, IIP guarantees high implant survival rates. Although different adjunctive strategies to IIP may favor hard and soft tissue stability, they appear to increase short-term patient-reported morbidity. Currently available evidence lacks standardized and patient-centered outcome reporting. Full article

Background/Objectives: To systematically compare the clinical and patient-reported outcomes of soft tissue grafts harvested from the palate and tuberosity, in root coverage surgeries. The primary outcomes assessed were graft dimension, tissue thickness, and postoperative discomfort. Methods: A comprehensive search was conducted in PubMed, Web of Science, OVID Medline, and Scopus databases, covering studies published till December 2023. Eligible studies included clinical studies and clinical trials involving medically fit adults who underwent intraoral soft tissue grafting for mucogingival procedures around teeth. A total of 1209 records were initially identified, with 13 studies meeting the inclusion criteria. Data was extracted and assessed for bias. Results: Graft dimension in terms of thickness was generally higher for tuberosity grafts (2.9 ± 0.5 mm) compared to palatal grafts (2.3 ± 0.6 mm). Tuberosity grafts demonstrate less volume changes in buccolingual thickness. One study reported decreased postoperative pain for tuberosity compared to palate donor sites. Risk of bias assessment using ROB 2 and ROBINS-I tools showed that most included studies exhibited low risk across key domains. Among randomized trials, two studies raised some concerns due to limitations in blinding and allocation concealment. Non-randomized studies showed a moderate risk primarily in confounding and outcome measurement, consistent with inherent observational design limitations. Conclusions: The palate remains a well-established and reliable source of soft tissue grafts. Limited evidence from a single short-term comparative clinical study suggests that tuberosity may offer potential advantages, such as greater graft thickness, reduced volume changes, and less postoperative discomfort. However, the comparative evidence between tuberosity and palatal donor sites is derived from a single short-term study and conclusions must therefore be interpreted with caution. Standardized clinical trials with long-term follow-up are needed to confirm these observations. Clinical Relevance: This review provides clinicians with a preliminary evidence-based perspective into the use of tuberosity as a donor site for soft tissue grafting, an area with limited published data, and highlights its potential to enhance patient outcomes and comfort in mucogingival surgery and emphasizing the need for further research in this area. Full article

Background: To compare the histological and histomorphometrical outcomes after sinus floor elevation using an anorganic bovine bone biomaterial or a biphasic calcium phosphate biomaterial. Material and Methods: Patients who needed maxillary sinus elevation were included in this study. A total of 68 implant sites were evaluated from a total of 42 patients. Twenty patients were treated with anorganic bovine bone, while 22 were treated with biphasic calcium phosphate biomaterial. Morphological and morphometrical studies were performed on the bone samples collected during implant placement. Results: Both biomaterials induced similar relative areas of mineralized tissue overall, particularly if only the area of grafted bone was considered. In turn, a higher proportion of non-mineralized tissue was observed in cases of biphasic calcium phosphate biomaterial with less area of remnant biomaterial particles. None of the implants failed at one year of follow-up. Conclusions: Although both biomaterials induce a similar amount of bone formation, the histopathological characteristics of the grafts are different, with a greater proportion of scar connective tissue with the biphasic calcium phosphate biomaterial. Full article

Background/Objectives: Tooth extraction is known to cause both bone loss and soft tissue collapse, changes that can complicate implant placement. While alveolar ridge preservation techniques have been proposed to limit these alterations, they often fail to maintain both hard and soft tissue dimensions at the same time. Placental-derived extracellular matrices offer a biologically active adjuvant, providing structural proteins that may support healing. The purpose of this study was to assess whether a flowable decellularized Human Placental Connective Tissue Matrix (HPCTM), combined with an allogeneic bone substitute, could improve ridge preservation by addressing changes in soft tissue as the primary outcome and underlying bone volume as the secondary outcome. Methods: In a split-mouth, randomized pilot trial, hopeless teeth in opposite quadrants were atraumatically extracted. Test sockets were grafted with allograft mixed with HPCTM, while control sockets received allograft alone. Healing was followed clinically and digitally using intra-oral scans; standardized photographs at 10, 21, and 30 days post-operatively; and cone-beam computed tomography at 4 months post-operatively. Results: Ten patients completed the study (10 test sites and 10 control sites). Sites treated with HPCTM showed faster and more stable healing. Gingival shrinkage was consistently reduced at test sites, with Hodges–Lehmann median differences of 0.50 mm at Day 10 (95% CI: 0.29–0.62; p = 0.0039), 0.54 mm at Day 21 (95% CI: 0.42–0.65; p = 0.002), and 0.54 mm at Day 30 (95% CI: 0.39–0.68; p = 0.002). Radiographically, test sites lost significantly less bone volume (28.24 ± 2.43%) compared with controls (38.85 ± 1.29%; p = 0.019). Conclusions: Within the limits of this study, HPCTM appears to support better preservation of both gingival architecture and alveolar bone after extraction. Full article

Additive manufacturing has significantly advanced patient-specific medical devices, particularly for hard tissue repair, yet applications in soft tissue remain limited. Existing approaches for 3D-printed soft tissue devices employ mainly biogels and bioinks for regenerative purposes, while synthetic grafts for tendons and ligaments remain non-customizable in shape and mechanics. This study investigates the mechanical performance of 3D-printed thermoplastic polyurethane (TPU) elastomers as a function of printing parameters, informing customizable connective tissue graft designs. Type C dogbone specimens (n = 180) of three replicates each of parameter combinations from material shore hardness, presence of anchoring within the lattice, infill patterns, and infill density were printed and tested following modified ASTM D412 standards for vulcanized rubber and elastomers. The measured mechanical properties are elastic modulus, tensile yield stress, yield strain, ultimate tensile strength, and ultimate strain. Results show that shore hardness and infill density are the strongest predictors of mechanical properties, with positive but modest effects from anchor presence. Infill pattern is only significant through interactions, and its effects depend on other parameters. While all groups underperformed compared to manufacturer-reported TPU strengths and were well below in vitro tendon failure loads, findings highlight material selection and density optimization as critical early considerations for future patient-specific elastomeric graft design. Full article

Background and Objectives: Adequate peri-implant soft tissue dimensions are essential for health, hygiene, and esthetics. When ridge volume is sufficient, phenotype modification may avoid bone grafting. This case report describes a pedicled roll flap performed concurrently with single-stage implant placement after spontaneous socket healing, without bone substitute, and assesses soft-tissue stability with serial intraoral scans. Clinical case: A single-tooth edentulous site underwent prosthetically driven, fully guided implant placement. A modified roll flap with vertical and palatal incisions was prepared; the de-epithelialized crestal connective tissue was elevated and rolled into a buccal envelope to augment thickness. No graft material was used. A provisional crown conditioned the emergence profile. Follow-up included photographs, radiographs, and intraoral scan superimpositions at 2 weeks, 3–4 months, 8 months, and 14 months after implant treatment. Healing was uneventful. Buccal soft-tissue thickness increased, keratinized mucosa was preserved, and midfacial levels remained stable. Emergence profile and papillae integrated harmoniously. Crestal bone levels were stable radiographically. Digital scans corroborated soft-tissue thickness maintenance. No donor-site morbidity occurred. Conclusions: In healed sockets with adequate bone, a modified pedicled roll flap at implant placement can thicken the peri-implant phenotype and achieve stable esthetic integration without bone substitutes. Full article

Objective: This study aimed to compare two protocols for immediate implants with fixed provisional restoration, no grafting (trimodal approach = TA) versus grafting in both the osseous gap and peri-implant mucosa (a trimodal approach with modification of the bony and mucosal compartments = TAOM), by measuring soft tissue changes over time. The periodontal phenotype was noted to investigate the relationship between its thickness and the clinical outcomes. Methods: Thirty-one patients met the inclusion criteria (15 in the TA group and 16 in the TAOM group). The TA group was a historical control group. Measurements were taken using a digital caliper at T0 and 3, 6, and 12 months following the procedure (T3), (T6), and (T12), respectively, from reference points marked in a dental-supported stent. The periodontal phenotype was determined using an analogical caliper. Results: T12: Vertical midfacial change was −0.17 ± 0.37 in the TAOM group and 0.54 ± 0.33 in the TA group, respectively. Statistical significance (p = 0.0001) was found. Papilla vertical change in the TAOM group was −0.16 ± 0.45 mesially and 0.00 ± 0.44 distally. In the TA group, it was 0.55 ± 0.82 mesially and 0.86 ± 0.95 distally. Statistical significance (p = 0.0001) was also found. Conclusions: There were differences in soft tissue change between the two groups, and changes were related to the periodontal phenotype. Studies with more extended follow-up periods are needed to assess the long-term evolution of both protocols. Full article

Background: Gingival recession (GR) is defined as the exposure of the root surface due to the gingival margin shifting apically from the cemento-enamel junction. Current effective management of defects related to GR relies on root coverage periodontal plastic surgery (RCPPS), using the Modified Coronally Advanced Flap (mCAF) with an envelope design. Recent literature also reported the association of different biomaterials to the mCAF procedure. In light of these considerations, a systematic review (SR) was conducted to determine and compare the efficacy of all mCAF adjunctive techniques for the treatment of multiple adjacent GR-type (MAGR) defects. Methods: An electronic search was conducted in 2025 on studies published between 2013 and 2025, using PubMed, Scopus, Web of Science, and Cinahl Complete, to address the focused question: “which is the efficacy of different mCAF adjunctive techniques for the treatment of multiple adjacent GR-type defects, in terms of root coverage (RC), esthetic outcomes, and keratinized tissue (KT) augmentation?”. Randomized controlled trials with a minimum follow-up of 6 months with ≥ 5 patients treated for coverage of MAGR were included. Risk of bias was assessed with RoB 2 Tool. A meta-analysis was performed using RevMan5.4 software and the level of evidence of included studies was analyzed with GRADEPro GDT. Results: A total of 17 studies were included in the SR, 9 of which evaluating mCAF + sCTG (subepithelial connective tissue graft) vs. mCAF adjunctive techniques [Collagen Matrix (CM), xenogeneic acellular dermal matrix (XADM), Platelet-Rich Fibrin (PRF), Enamel Matrix Derivatives (EMD), sCTG harvested double blade scalpel] were then included in the meta-analysis. The primary outcomes of complete root coverage (CRC) and keratinized tissue width variation (ΔKTW) were statistically significant ([CRC: Odds Ratio (OR) 1.70; 95% CI (confidence interval) 1.18, 2.44; p = 0.004]; [ΔKTW: SMD (standardized mean difference) 0.37; 95% CI 0.11, 0.63; p = 0.005]) in favor of mCAF + CTG. Meanwhile, no statistically significant difference was observed in terms of RES. The certainty assessment highlighted relevant results: despite the lack of evidence in the long-term, a high level of evidence showed that sCTG was more effective than XADM in terms of CRC (p = 0.002) and ΔKTW (p = 0.0001). A low level of evidence revealed that sCTG achieved a greater ΔKTW compared to CM (p = 0.0006). Although no significant differences were observed, a low level of evidence suggested that mCAF + EMD and mCAF + sCTG (DBS) may provide good results. To date, only one RCT showed long-term stable results of CTG in terms of RC. Conclusions: The association of sCTG to mCAF demonstrated better results in terms of RC and KTW augmentation in short- and medium-term follow-ups. Long-term studies are needed to confirm the efficacy of the other mCAF adjunctive techniques, considering limitations due to heterogeneity in follow-ups, distribution of techniques analyzed, and different study designs. Registration in PROSPERO (International prospective register of systematic reviews) was performed with ID CRD420251085823. Full article

Background: During maxillary sinus floor augmentation, the elevated sinus mucosa may come into close contact with the pristine mucosa. The presence of xenograft granules can lead to unintended mechanical and biological interactions between the two layers, and the resulting tissue damage remains poorly understood. The aim of this study was to perform a focused histological evaluation of graft-mediated interactions between the elevated and pristine sinus mucosae. Methods: Histological slides from five previously published rabbit sinus augmentation studies using grafts with different resorption rates were retrospectively analyzed. The following main patterns of tissue alteration were identified: (1) Proximity stage, characterized by epithelial thickening, goblet cell hyperactivity, and ciliary shortening; (2) Fusion stage, with epithelial interpenetration and loss of distinct mucosal boundaries; (3) Synechiae stage, featuring connective tissue bridges linking the two mucosae; and (4) Pristine mucosa lesions, caused by direct contact between residual graft particles and the pristine sinus mucosa. Results: A total of 192 sinuses were evaluated. Sinuses augmented with slowly resorbable grafts showed proximity stage in 22.3% of cases, fusion in 7.7%, direct lesions in 9.6%, and only one instance of synechia. In contrast, the faster resorbable xenograft presented only 11.1% of proximity stage, without further alterations. Conclusions: In this rabbit model, xenografts were associated with histological alterations of the sinus mucosa, while synechiae formation was rare. These preclinical findings should not be directly extrapolated to humans but may provide a basis for future investigations. Full article

Background: The aim of this bibliometric study was to evaluate publication trends in the most frequently cited clinical trials on the treatment of gingival recession, taking into account the augmentation materials used. Methods: A Web of Science search was performed among articles published by 30 September 2024. Two independent reviewers evaluated year of publication, journal, authorship country of authors, collaborative relationship, keywords, and the main domains. Results: The top one hundred most-cited clinical trials were published in the span of 26 years from 1993 to 2019, and the total citation counts varied from 44 to 284 (83.69 citations per paper). There was correlation between the time of publication and the number of citations. The articles were authored by 333 researchers representing twenty-two countries. Italy contributed the highest number of articles (n = 36), followed by the USA (n = 28) and Brazil (n = 17). International collaborations were predominantly observed between Italy, the USA, and Switzerland. The type of graft was the most cited field of research (34), followed by guided tissue regeneration (17) and enamel matrix derivative (13). Conclusions: The country that produced the highest number publications among the 100 most-cited clinical trials on gingival recession treatment was Italy. The use of connective tissue graft (CTG) and coronally advanced flap (CAF) was the most prominent trend. Future work should combine bibliometric mapping with critical quality appraisal and explore whether citation trends align with best available evidence. Full article

Mesenchymal stem cells (MSCs) are known to assist liver regeneration. In this study, we show a dose-dependent mode of recovery from liver fibrosis after intravenous injections of MSCs. Male Wistar rats experienced a 42-day-long modeling of liver fibrosis via CCl₄ poisoning and received either a single injection of 2.5 × 10⁶ MSCs on Day 3 after the last CCl₄ dose or two MSC injections on Days 3 and 10. We dynamically monitored levels of liver cytolysis markers and cytokines in the venous blood and performed a histological study of Mallory-stained liver sections. All experimental groups experienced a nearly complete recovery of biochemical markers up to 4 weeks after the end of CCl₄ administration, although we observed anti-inflammatory changes in the cytokine levels only in animals treated by two MSC injections. Histological study revealed minor signs of liver damage up to Day 90 in animals receiving two MSC doses with worse pathology in those who received a single MSC dose. Morphometric values stayed consistent with visual data, demonstrating a significantly larger number of binuclear hepatocytes, a smaller number of false lobules, and a lesser area of connective tissue proper in animals treated by two MSC injections. Our results reflect MSC grafting in applied doses to affect liver fibrosis in a dose-dependent mode. These findings provide a deeper understanding of MSC action in liver fibrosis, and the doses applied may serve as a milestone for further studies in humans. Full article