Enhanced MSC spheroid adhesion on 3D-printed leaf-stacked scaffolds for functional tracheal regeneration.

To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. German Clinical Trials Register: DRKS00017484.

Background/Objectives: Preclinical studies of head and neck squamous cell carcinoma (HNSCC) commonly use subcutaneous heterotopic (flank) tumor models for simplicity; however, orthotopic models may better reflect the native tumor environment. Direct comparisons of the tumor immune microenvironments (TIME) and tumor-draining lymph nodes (tdLNs) between these models remain limited. Better understanding of site-specific immune differences could improve model selection and interpretation of translational HNSCC studies. Methods: ROC1 tumors were established in murine heterotopic and orthotopic sites, followed by assessment of tumor growth kinetics, survival, and the tumor microenvironment. Immune composition of tumors, blood, tdLNs, and spleen was evaluated at three tumor progression timepoints using multiparameter spectral flow cytometry. Results: Heterotopic and orthotopic tumor models showed similar growth kinetics and survival. Immune profiling revealed increased infiltration of CD3+ T-cells, natural killer (NK) cells, and myeloid populations in both models. Heterotopic tumors were enriched in dendritic cells (DCs), plasmacytoid DCs, and monocytic myeloid-derived suppressor cells (M-MDSCs), whereas orthotopic tumors showed increased macrophages, granulocytic MDSCs, and M-MDSCs. Despite temporal variation, both TIMEs were dominated by macrophages, DCs, and CD3+ T-cells. Late-stage heterotopic tumors contained more CD4+ T-cells. Reduced T-cell cytotoxicity (PD-1, CD107a) and increased immune checkpoint expression across myeloid cells indicated an immunosuppressive TIME. Systemically, effector cells were preserved despite suppressive cell trafficking, and tdLNs in both models exhibited immunosuppressive PD-L1 expression. Conclusions: Heterotopic and orthotopic ROC1 tumors share key immune features, but site-specific differences in the TIME and tdLNs reveal tissue-dependent regulation. These local effects align with systemic changes, supporting global tumor-associated immunosuppression.

Influence of litter size on placental stereological characteristics and its relationship with neonatal outcome in dogs.

The Y-incision technique enables implantation of larger prosthetic valves by facilitating effective aortic annular enlargement. Although this approach improves hemodynamic outcomes, rare and clinically significant complications may occur and remain insufficiently described. A patient undergoing surgical aortic valve replacement with concomitant Y-incision annular enlargement developed early postoperative severe central mitral regurgitation. Standard transthoracic and transesophageal echocardiography demonstrated abnormal aorto-mitral geometry and annular distortion. Reoperation revealed deformation of the mitral annulus adjacent to the patch implantation site. Based on intraoperative findings, imaging data, and schematic analysis, we hypothesized that turbulent flow within the pouch-like neo-aortomitral curtain combined with patch sutures placed near the mitral annulus contributed to annular distortion and subsequent mitral valve incompetence. Severe mitral regurgitation represents a rare but clinically important complication of the Y-incision technique. Patient-specific aorto-mitral anatomy, including annular distance and aorto-mitral angle, may play a critical role in this mechanism. Careful preoperative anatomical assessment and meticulous intraoperative patch positioning are essential to minimize this risk and improve procedural safety.

Advanced gentamicin-loaded chitosan/hydroxyapatite/mesoporous SiO2 scaffold: A comprehensive investigation of drug delivery and cellular interactions.

Evaluation of 3D bioprinted pancreatic islets for insulin secretion in diabetic rats.

Successful embryo development, acquisition of uterine receptivity, implantation, and decidualization during the peri-implantation window are essential events that ensure a healthy pregnancy. While ovarian aging has long been considered the primary cause of age-related decline in fertility, emerging evidence demonstrates that uterine aging also compromises the ability to support pregnancy. The chromosomal passenger complex, composed of pIncenp, Aurora B, Survivin, and Borealin, is a critical regulator of cell cycle progression, particularly in chromosome condensation, mitotic spindle organization, and cytokinesis. We investigated age-associated changes in the expression and localization of those members, as well as the proliferation marker Ki-67, at implantation sites in mice during the peri-implantation period. Female mice aged 12, 20, and 26-32 weeks were used, and uterine tissues were collected on Days 5, 6, and 8 of pregnancy. Immunohistochemistry was performed to determine the localization of those proteins and Ki-67, while Western blotting was used to quantify protein expression levels. Our results revealed dynamic and age-dependent alterations in protein expression throughout pregnancy. Ki-67 expression decreased with advancing age in the luminal and glandular epithelium on Day 5, whereas pIncenp and Survivin levels were elevated in the stromal compartment of older mice. On Day 6, pIncenp, Borealin, and Survivin expression increased in the luminal epithelium of aging groups, and Aurora B expression was higher in older mice on Day 8. These findings highlight a potential role for complex dysregulation in impaired implantation/decidualization with maternal aging and may provide insight into mechanisms underlying implantation failure and recurrent pregnancy loss.

This study aimed to characterize evolving causes and outcomes of cochlear implant (CI) revision surgeries in the post-2012 era, a period marked by improved device reliability and changing patient expectations. We retrospectively reviewed 1,449 CI procedures performed at a tertiary referral center between 2012 and 2024, identifying 48 revision surgeries. Cases were categorized by implantation site (in-house vs. referral) and classified by revision indication. Device survival was evaluated with Kaplan-Meier and competing risks analyses. Auditory outcomes and electrode positioning were assessed before and after revision. The in-house revision rate was 1.9%, with a 7-year cumulative device survival of 96.1%. Functional performance concerns (n = 20) emerged as the leading cause of revision, exceeding infection/flap problems (n = 19) and device failure (n = 6). Referral patients more often underwent elective reimplantation for performance optimization, frequently converting from lateral wall to modiolar-hugging arrays. These revisions consistently achieved superior modiolar proximity and significant gains in speech perception, with postoperative imaging confirming successful reinsertion trajectories despite fibrous tracts. Infection remained the predominant early complication, while functional revisions increased gradually over time. Revision cochlear implantation in the modern era reflects both reduced device failures and the rise of patient-driven revisions for functional optimization. Strategic electrode selection and pursuit of bilateral symmetry can yield meaningful auditory improvements. These findings underscore the evolving role of revision surgery in enhancing CI outcomes, highlighting the importance of individualized decision-making in contemporary practice.

Comparative Effects of Porous Tantalum and Porous Titanium: A Systematic Review and Meta-Analysis.

PurposeTo examine the visual outcomes and complication rates for IOL (intraocular lens) exchange, analysed by combination of surgical indication and secondary IOL implantation site.DesignRetrospective case series of IOL exchange procedures performed between June 1998 and July 2018 from a single tertiary referral centre, London, United Kingdom.MethodsConsecutive IOL exchange procedures with pre-operative and 6-month post-operative visual acuity and complication data were eligible.Results318 eyes from 288 patients were included. Mean best-corrected visual acuity (BCVA) improved from 0.82 ± 0.77 to 0.47 ± 0.60 LogMAR at 6 months (p < 0.001), in particular following complete IOL dislocation (adjusted p < 0.001), partial IOL dislocation (adjusted p = 0.001), refractive indications (adjusted p = 0.02), and pseudophacodonesis (adjusted p = 0.02). The most performed and the greatest BCVA improvement was found with subsequent anterior chamber IOL implantation (-0.44 ± 0.72 LogMAR, n = 214, 67%). The poorest BCVA at 6 months was following IOL exchange for corneal oedema (1.13 ± 0.81 LogMAR, n = 16, 5%). 26% of cases underwent concurrent pars plana vitrectomy, and 15% underwent anterior vitrectomy, with 8% experiencing post-operative cystoid macular oedema.ConclusionsIOL exchange is safe and effective, however careful patient selection and pre-operative counselling assisted by such data should determine when surgery should be undertaken.

Purpose of the study: to analyze and systematize the modern possibilities of contouring in the repair of cranial bones based on the literature data. Material and methods . Scientific articles in PubMed, eLibrary, Scopus, Medscape, and Cyberleninka databases were analyzed by keywords “repair”, “skull bones”, “contouring”, “implant”, “autograft”, “alloimplant”, “cell-free regenerative technologies”, “microvesicles” over the past 15 years. Data from 95 foreign and 47 domestic articles were selected on the topic under consideration. Results . Based on a review of the literature on the topic under study, it was found that despite enormous efforts to develop alternatives to autografts, no ideal bone graft substitute has been created. The surgeon must know the individual properties of each bone graft substitute in order to apply it correctly to a particular patient. The main synthetic bone substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate or a combination of these minerals, they have a number of advantages over allografts, including unlimited supply, ease of sterilization and storage. However, they also have disadvantages, such as fragility, different resorption rates, and low efficacy in some clinical cases. Recently, osteoinductive materials, such as demineralized bone matrix (DCM) and bone morphogenetic proteins, have attracted attention, but polymer and biocomposite matrices today seem to be the most promising materials in comparison with DCM. Special attention in the development of new types of matrices is paid to the possibility of fixation of osteogenic factors and targeted pharmaceutical substances on a carrier material for their controlled and prolonged release at the surgical implantation site. The use of composite carriers of various compositions in vivo demonstrates high rates of osteogenesis, promotes the launch of biomineralization and allows varying the rate of degradation of the material. Conclusion . Currently, the operating surgeon has a wide range of materials for performing plastic surgery of a bone defect of the skull using auto-, allo- or xenografts. Each of these options has its own strengths and weaknesses, and the choice of material and method of implantation should be decided individually for each patient. Scientists associate great prospects with the creation of bioactive skeletal materials with fixed osteogenic factors that are released directly in the area of the bone defect and accelerate regeneration. The development of this technology will allow cell-free regenerative medicine to cross the boundary of laboratory research on the replacement of bone defects and enter clinical use.

Background: Implant site preparation affects primary stability and early osseointegration of dental implants. Conventional subtractive drilling is widely used in routine clinical practice. Osseodensification has been introduced to compact bone and improve mechanical engagement, but comparative evidence remains inconsistent. Purpose: To compare implant stability (ISQ) and insertion torque for implants placed with osseodensification versus conventional drilling across time points and anatomical sites. Methods: Five electronic databases were searched from inception to June 2025. Human clinical and in vitro comparative studies were eligible when they reported ISQ and/or insertion torque for osseodensification and conventional drilling. Risk of bias was assessed using validated tools for randomized and non-randomized studies. Meta-analysis was performed in Stata 17 using a random-effects model. Mean differences with 95% confidence intervals were calculated, and heterogeneity was assessed with I². Results: Six studies were included. Osseodensification produced higher ISQ values than conventional drilling immediately after placement (MD +5.96; 95% CI 2.78 to 9.13) and at six months (MD +4.45; 95% CI 1.17 to 7.74). Insertion torque values were also higher with osseodensification with the largest differences reported in posterior and maxillary sites. Heterogeneity was substantial across several comparisons. Conclusion: Osseodensification improves mechanical stability compared with conventional drilling. Further trials with standardized drilling protocols and outcome assessment are required. Clinical implications: Osseodensification may be considered to enhance primary stability particularly in lowdensity bone and posterior maxillary regions.

Damage-Associated Molecular Patterns (DAMPs) or alarmins are endogenous molecules that activate immune cells and drive an inflammatory response. Derangements in DAMP levels are associated with pregnancy disorders. Our previous study demonstrated that an excess of High Mobility Group Box 1 (HMGB1), an alarmin, in the uterine cavity leads to implantation failure in rats. The present study investigated whether HMGB1-induced implantation failure was associated with perturbations in the uterine immune microenvironment. Recombinant HMGB1 with/without its inhibitor glycyrrhizin was administered on day 3 post-coitum (p.c.) in Wistar rats. Uterine fluid, uterine horns, and lymph nodes were collected on day 5 p.c. HMGB1-associated implantation failure was found to be associated with altered proportions of uNK cells, Tregs; altered phenotype of macrophages, and impaired decidualization. While total CD68+ macrophage proportion did not change significantly, the proportion of M2 macrophages (CD68+CD163+) was reduced at the implantation sites in the HMGB1-treated uterine horns. The proportion of activated M2 macrophages (CD68+CD163+CD86+MHCIIlow) was also reduced in the HMGB1-treated animals. This was accompanied by a significant increase in IL-1β and IL-5 cytokine levels in the uterine fluid. Further, our studies demonstrated that some of these effects, such as a decrease in the uNK cell proportion and modulation in the macrophage phenotype, result from the direct effect of excess HMGB1 on the endometrium. These effects were not observed in animals receiving both HMGB1 and glycyrrhizin. Thus, an excess of HMGB1 in the uterine cavity alters the proportion/phenotype of uterine immune cells and thereby compromises the implantation competence of the endometrium.

Aortic dissection is a potentially life-threatening condition that occurs when the aortic wall ruptures. Acute aortic dissection is the most common type of potentially catastrophic aortic disease and, if left untreated, carries a high risk of early mortality. Stanford type B or DeBakey type III aortic dissections begin in the descending thoracic aorta without retrograde extension into the ascending aorta. Rupture of the thoracic aorta as a complication of acute type B dissection is a life-threatening condition with a high mortality rate. Such critical situations require urgent treatment, ideally in an experienced aortic center. Open surgery to repair the descending aorta in such patients is associated with a high mortality rate of approximately 20%, and up to 15% of survivors suffer complications such as paraplegia, stroke, or renal failure. Endovascular thoracic aortic repair (TEVAR) has become a valuable treatment alternative in emergency situations. In fact, under certain clinical and radiographic conditions, such as an appropriate implantation site, and with surgical experience, TEVAR is the method of choice in these critical situations. Right-sided secondary hemothorax is extremely rare in this condition. In this case report, we report the successful treatment of a patient with acute type B aortic dissection complicated by aortic rupture and right-sided hemothorax using TEVAR. Contrast-enhanced multislice computed tomography confirmed massive right-sided hemothorax and acute type B aortic dissection, with the primary fenestration located slightly distal to the left subclavian artery. Furthermore, a possible site of rupture of the false lumen in the descending aorta at the level of ThVI was identified. Endovascular aortic grafting with open surgical switching of the left subclavian artery was then performed. The postoperative period was uneventful. At a six-month follow-up, the patient showed no complications.

Introduction. The results of surgical treatment of inguinal hernias indicate significant progress in the treatment of this pathology, thanks to the introduction of alloplasty and laparoscopic operations. At the same time, the recurrence rate of inguinal hernia after alloplasty in primary hernioplasty is 1.5-11.6%, and in recurrent hernioplasty 3.5% – 22%, which is of concern. Aim. To increase the effectiveness of surgical treatment of patients with recurrent inguinal hernia by studying the causes of recurrence and choosing a pathogenetically justified method of surgery. Materials and methods. The paper presents the results of surgical treatment of 125 patients with recurrent inguinal hernia aged 21 to 79 years. According to the Campanelli G. classification, recurrent oblique inguinal hernias were R1 in 60 (48%), direct R2 in 51 (40.8%), and R3 in 14 (11,2%) patients. Hernia recurrence occurred in 26 (20.8%) patients in the first year after alloplasty, in 52 (41.6%) after 2 years, in 47 (37.6%) after 3 years. When choosing a method of reconstruction of the inguinal canal, the EHS recommendations were followed. Results. It was found that the main reasons for the re-recurrence of inguinal hernia after open alloplasty according to Lichtenstein and TAPP were: non-adherence to the technique of implant placement and fixation, which contributed to cicatricial-atrophic changes in the muscular-aponeurotic structures of the inguinal canal in 62.4% of patients, and insufficient implant overlap of the hernial orifice due to the use of a small implant in 34.4% of patients. In case of recurrence of R1 and R2 after the Lichtenstein method, TAPP was performed, provided that there were no complications of the previous operation that required revision of the implantation site. In case of recurrence after open alloplasty, when it was necessary to revise the inguinal canal to remove the implanted mesh or perform neurolysis, Lichtenstein plastic surgery was performed. In case of recurrence after TAPP, Lichtenstein allohernioplasty was performed. In case of R3 with a destroyed posterior wall of the inguinal canal, open preperitoneal allohernioplasty was performed. In the postoperative period, inflammatory complications were observed in 10 (8%) patients. Long-term treatment results were studied in 124 patients over a period of 1 to 5 years. Hernia recurrence occurred in 1 (0.8%) patient as a result of wound suppuration. Conclusions. Improving the results of surgical treatment of patients with inguinal hernias can be achieved through individual selection of a modern, pathogenetically justified method of allohernioplasty and technically correct performance of the operation itself.

To address challenges associated with the uptake of daily oral pre-exposure prophylaxis (PrEP) by young women at high risk of acquiring HIV, a range of novel, long-acting, slow-release products are being developed and clinically evaluated. One such technology is an annual implant of tenofovir alafenamide (TAF). This study explores the perspectives of participants from a first-in-human trial of an annual TAF implant to inform considerations for future PrEP implant innovation. The study, conducted in Durban, South Africa between 2022 and 2023, included 29 in-depth interviews (IDIs) and three focus group discussions (FGDs) with 18 participants. All participants experienced some form of implant site reaction (ISR). In some instances, these were minor, and in others, the implant removal process left longer-lasting and more severe skin changes. Participants' perceptions of these ISRs were influenced by concerns about their appearance, social stigma, and associations between scars and gender-based violence. Mild skin changes were deemed acceptable, while severe scarring and discolouration caused concerns about attracting negative attention. Few participants expressed concerns about their own scars, however, visible scars which might be mistaken for a contraceptive implant caused concern. Despite the ISRs experienced, there was positive feedback for this type of technology, and many considered that other women would be interested in adopting a sub-dermal implant should it be effective in preventing HIV. Continued enhancements of next generation implants to enhance drug release rates should consider how to minimise the severity and visibility of ISRs.

To analyse the effect of implantoplasty on the efficacy of brushing dental implants. Acrylic hemi-arches were made to simulate a horizontal bone loss condition in an implant in position 46, exposing 3 mm of its cervical intra-osseous portion. Implantoplasty was performed on the implant surfaces of the test group, and no surface modification was performed on the control group. The exposed portion of both groups was coated with carbon spray to simulate dental biofilm. Each site was analysed before and after brushing for a carbon-free area. Buccal/oral sites were brushed with toothbrushes while mesial/distal sites were brushed with interdental brushes. The analysed area consisted of a 6 mm2 rectangle divided into three thirds (cervical, middle and apical) on each of the four sites. On buccal/oral sites of the test group (implantoplasty), brushing removed an average of 43.11% of the biofilm. In contrast, on the buccal/oral sites of the control group (no implantoplasty), brushing removed 36.09% (p < 0.001). On proximal sites of both test and control groups, brushing removed an average of 32.1% and 32.29% of the biofilm, respectively (p = 0.728). Implantoplasty positively influenced the removal of simulated biofilm on buccal/oral sites of dental implants.

When a skull base defect occurs, reconstruction is typically performed using a variety of autologous grafts, flaps, or synthetic materials. Failure to achieve appropriate management and closure can lead to serious consequences, such as cerebrospinal fluid (CSF) leakage and subsequent meningitis. Current grafts and synthetic patches often lack biological activity, mechanical integration, and sealing capacity. Here, we developed a multifunctional, injectable composite scaffold composed of collagen/silk-fibroin (S-F) and α-tricalcium phosphate (α-TCP), designed for simultaneous CSF sealing and tissue regeneration. The upper S-F-rich layer forms a dense, non-porous barrier to prevent CSF egress, while the lower α-TCP-containing layer promotes osteointegration and mechanical support. The scaffold is fabricated via a cryogelation-inspired process, enabling shape-memory behavior for minimally invasive deployment. In vitro studies confirmed favorable cell adhesion, matrix protein expression, and osteogenic activation. In vivo evaluation further indicated stable integration of the composite at the implantation site without severe adverse tissue responses. Overall, these results support the potential of this layered, shape-memory composite as a dual-functional platform for cranial base reconstruction.

Surgical site infections (SSIs) remain a major clinical challenge, particularly due to bacterial adhesion and biofilm formation on suture materials. In this study, we developed a dual drug-eluting suture incorporating chlorhexidine (CHX) and dexamethasone (DEX), with lauric acid used as a binding agent to enhance drug adhesion. The exact composition of the system was CHX/DEX/Lauric Acid, designed to enable localized delivery of both therapeutic agents at the implantation site. Vicryl sutures were dip-coated and characterized by means of FTIR-ATR and HPLC to confirm drug incorporation and release. Mechanical integrity was preserved, with no significant difference in tensile strength between coated and uncoated sutures. Antimicrobial activity was confirmed against Gram-positive and -negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in addition to the yeast Candida albicans. Cell viability assays demonstrated acceptable biocompatibility, with values exceeding 70%. These findings support the potential of dual-functionalized sutures to reduce SSIs and modulate inflammation, offering a promising strategy for improving postoperative outcomes.