Biochemical and biomechanical characterization of an autologous protein-based fibrin sealant for regenerative medicine.

Accidental events or surgical procedures usually lead to tissue injury. Fibrin sealants have proven to optimize the healing process but have some drawbacks due to their allogeneic nature. Autologous fibrin sealants present several advantages. The aim of this study is to evaluate the performance of a new autologous fibrin sealant based on Endoret®PRGF® technology (E-sealant). One of the most widely used commercial fibrin sealants (Tisseel®) was included as comparative Control. E-sealant´s hematological and biological properties were characterized. The coagulation kinetics and the microstructure were compared. Their rheological profile and biomechanical behavior were also recorded. Finally, the swelling/shrinkage capacity and the enzymatic degradation of adhesives were determined. E-sealant presented a moderate platelet concentration and physiological levels of fibrinogen and thrombin. It clotted 30 s after activation. The microstructure of E-sealant showed a homogeneous fibrillar scaffold with numerous and scattered platelet aggregates. In contrast, Control presented absence of blood cells and amorphous protein deposits. Although in different order of magnitude, both adhesives had similar rheological profiles and viscoelasticity. Control showed a higher hardness but both adhesives presented a pseudoplastic hydrogel nature with a shear thinning behavior. Regarding their adhesiveness, E-sealant presented a higher tensile strength before cohesive failure but their elastic stretching capacity and maximum elongation was similar. While E-sealant presented a significant shrinkage process, Control showed a slight swelling over time. In addition, E-sealant presented a high enzymatic resorption rate, while Control showed to withstand the biodegradation process in a significant way. E-sealant presents optimal biochemical and biomechanical properties suitable for its use as a fibrin sealant with regenerative purposes.

Sleep bruxism and sleep respiratory disorders in children and adolescents: A systematic review.

OBJECTIVE: Sleep bruxism (SB) is a repetitive rhythmic and nonrhythmic activity. It can be a comorbid condition for other disorders, such as sleep breathing disorders (SBD). However, a clear causal link between these factors is yet to be established. Moreover, this relationship is even more unknown in children. Thus, this systematic review aimed to determine the relationship between SB and SBD in children and teenagers and consolidate the current knowledge about the possible association between both phenomena at the pediatric age. MATERIALS AND METHODS: Advanced searches were performed in five electronic databases with the last search updated on February 1, 2023. The methodological quality of the selected studies was analyzed using the quality assessment tool for experimental bruxism studies. RESULTS: Twenty-nine of 6378 articles were selected for detailed analyses. Most articles found a comorbid relationship between SB and SBD, though no study analyzed a temporary relationship. Due to the heterogeneity of the studies, a meta-analysis could not be performed. CONCLUSION: Despite the limitations of this systematic review, it can be concluded that there is an association between SB and SBD in children. However, the level of evidence is low.

Clinical Performance of Implant-Supported Prostheses in the Rehabilitation of Patients Previously Treated for Medication-Related Osteonecrosis of the Jaws (MRONJ): A Systematic Review.

There is a lack of consensus on managing resultant bone and soft tissue defects or on restoring oral function and aesthetics following medication-related osteonecrosis of the jaws (MRONJ) lesion healing. This clinical challenge presents a dilemma for practitioners. Removable prostheses pose a recurrence risk if poorly fitted and may inadequately restore function or aesthetics in cases of significant bone defect. Dental implant-supported prostheses could enhance function and quality of life, though their risks and indications are not well-defined. This systematic review examines the clinical outcomes and complications associated with implant-supported rehabilitations post-MRONJ surgery. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations and it was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO) (CRD42023492539).

Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response.

Background: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.

Plasma Rich in Growth Factors in Bone Regeneration: The Proximity to the Clot as a Differential Factor in Osteoblast Cell Behaviour.

The osteogenic differentiation process, by which bone marrow mesenchymal stem cells and osteoprogenitors transform into osteoblasts, is regulated by several growth factors, cytokines, and hormones. Plasma Rich in Growth Factors (PRGF) is a blood-derived preparation consisting of a plethora of bioactive molecules, also susceptible to containing epigenetic factors such as ncRNAs and EVs, that stimulates tissue regeneration. The aim of this study was to investigate the effect of the PRGF clot formulation on osteogenic differentiation. Firstly, osteoblast cells were isolated and characterised. The proliferation of bone cells cultured onto PRGF clots or treated with PRGF supernatant was determined. Moreover, the gene expression of Runx2 (ID: 860), SP7 (ID: 121340), and ALPL (ID: 249) was analysed by one-step real-time quantitative polymerase chain reaction (RT-qPCR). Additionally, alkaline phosphatase (ALPL) activity determination was performed. The highest proliferative effect was achieved by the PRGF supernatant in all the study periods analysed. Concerning gene expression, the logRGE of Runx2 increased significantly in osteoblasts cultured with PRGF formulations compared with the control group, while that of SP7 increased significantly in osteoblasts grown on the PRGF clots. On the other hand, despite the fact that the PRGF supernatant induced ALPL up-regulation, significantly higher enzyme activity was detected for the PRGF clots in comparison with the supernatant formulation. According to our results, contact with the PRGF clot could promote a more advanced phase in the osteogenic process, associated to higher levels of ALPL activity. Furthermore, the PRGF clot releasate stimulated a higher proliferation rate in addition to reduced SP7 expression in the cells located at a distant ubication, leading to a less mature osteoblast stage. Thus, the spatial relationship between the PRGF clot and the osteoprogenitors cells could be a factor that influences regenerative outcomes.

Clinical performance of additively manufactured subperiosteal implants: a systematic review.

PURPOSE: The aim of this study was to assess implant survival and complications rate of modern subperiosteal implants (CAD designed and additively manufactured). METHODS: A systematic review was conducted using three electronic databases; Medline (Pubmed), Cochrane library, and SCOPUS, following the PRISMA statement recommendations to answer the PICO question: "In patients with bone atrophy (P), do additively manufactured subperiosteal implants (I), compared to subperiosteal implants manufactured following traditional approaches (c), present satisfactory implant survival and complication rates (O)? The study was pre-registered in PROSPERO (CRD42023424211). Included articles quality was assessed using the "NIH quality assessment tools". RESULTS: Thirteen articles were finally selected (5 cohort studies and 8 case series), including 227 patients (121 female / 106 male; weighted mean age 62.4 years) and 227 implants. After a weighted mean follow-up time of 21.4 months, 97.8% of implants were in function (5 failures reported), 58 implants (25.6%) presented partial exposure, 12 patients (5.3%) suffered soft tissue or persistent infection. Fracture of the interim prosthesis was reported in 8 of the155 patients (5.2%) in which the use of a provisional prosthesis was reported. A great heterogeneity was found in terms of study design and methodological aspects. For this reason, a quantitative analysis followed by meta-analysis was not possible. CONCLUSIONS: Within the limitations of this study, modern additively manufactured subperiosteal implants presented a good survival in the short-time, but a noticeable number of soft-tissue related complications were reported. Further studies are needed to assess the clinical behavior in the medium- and long-term.

Efficacy of plasma rich in growth factors for healing chronic skin ulcers: a systematic review of randomized controlled trials with meta-analysis.

BACKGROUND: Chronic skin ulceration is a serious pathological condition for which the adjuvant use of platelet-rich plasma (PRP) has been indicated. However, evidence for the use of PRP in patients with chronic skin ulcers remains insufficient due to a large heterogeneity in experimental designs, PRP composition, and preparation protocols. OBJECTIVE: To assess previously published reports of the clinical effect of plasma rich in growth factors (PRGF) on chronic skin wounds. METHODS: A comprehensive search of the PubMed, Cochrane Library, and Scopus databases was performed to identify randomized controlled trials (RCTs) assessing the effect of PRGF on chronic ulcer healing, with no limitation regarding publication date (up to September 1, 2022). Percentage area reduction and probability of complete healing in chronic ulcers, pain reduction, infection risk, and cost savings were analyzed. A meta-analysis was performed, and the overall evidence was qualified using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 113 studies were identified. After full-text screening, 5 RCTs met the inclusion criteria. The meta-analysis showed a significant effect of PRGF on both wound area reduction (mean difference, 56.90% [95% CI, 52.28-61.51], I² = 0%; P = .56) and on the probability of complete healing (RR, 7.07 [95% CI, 1.84-27.16], I² = 0%; P = .53) in chronic ulcers. The overall risk of bias rating was "some concerns," whereas the certainty of evidence was high for both outcomes. A qualitative analysis suggested that PRGF did not increase infection risk and was able to reduce wound pain. CONCLUSION: The use of PRGF significantly enhances wound area reduction and also the probability of complete healing in chronic ulcers. More studies are needed to assess the effect of PRGF on pain and infection, as well as its cost-effectiveness.

Effect of Health Status and Heat-Induced Inactivation on the Proteomic Profile of Plasma Rich in Growth Factors Obtained from Donors with Chronic Inflammatory Skin Conditions.

Atopic dermatitis, psoriasis and lichen sclerosus are among the most challenging conditions treated by dermatologists worldwide, with potentially significant physical, social and psychological impacts. Emerging evidence suggests that autologous-platelet-rich plasma could be used to manage skin inflammation. However, the presence of soluble autoimmune components could hinder their therapeutic potential. The aim of this study was to analyze the proteomic profile of plasma rich in growth factors (PRGFs) obtained from donors with inflammatory skin conditions to evaluate the impact of skin health status on the composition and bioactivity of PRGF-based treatments. Venous blood from healthy volunteers and patients with psoriasis, lichen sclerosus and atopic dermatitis was processed to produce PRGF supernatant. Half of the samples were subjected to an additional thermal treatment (56 °C) to inactivate inflammatory and immune molecules. Proteomic analysis was performed to assess the protein profile of PRGFs from healthy and non-healthy patients and the effect of Immunosafe treatment. Differential abundance patterns of several proteins related to key biological processes have been identified, including complement activation, blood coagulation, and glycolysis- and gluconeogenesis-related genes. These results also demonstrate that the thermal treatment (Immunosafe) contributes to the inactivation of the complement system and, as a consequence, reduction in the immunogenic potential of PRGF products.

Mouth Breathing and Its Impact on Atypical Swallowing: A Systematic Review and Meta-Analysis.

The aim of this systematic review is the assessment of the effect of mouth breathing on the prevalence of tongue thrust. The review was performed according to the PRISMA 2020 checklist guidelines, and the protocol was registered with PROSPERO (CRD42022339527). The inclusion criteria were the following: studies of clinical trials and cross-sectional and longitudinal descriptive studies that evaluate the appearance of tongue thrust in patients with mouth breathing; healthy subjects of any age, race or sex; and studies with a minimum sample group of five cases. The exclusion criteria were the following: studies with syndromic patients, articles from case reports, and letters to the editor and/or publisher. Searches were performed in electronic databases such as The National Library of Medicine (MEDLINE via PUBMED), the Cochrane Central Register of Controlled Trials, Web of Science and Scopus, including studies published until November 2023, without a language filter. The methodological quality of the included case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) tool was used for descriptive cross-sectional studies and cross-sectional prevalence studies. A meta-analysis was conducted on studies that provided data on patients' classification according to mouth breathing (yes/no) as well as atypical swallowing (yes/no) using Review Manager 5.4. From 424 records, 12 articles were selected, and 4 were eligible for meta-analysis. It was shown that there is no consensus on the diagnostic methods used for mouth breathing and tongue thrust. The pooled risk ratio of atypical swallowing was significantly higher in the patients with mouth breathing (RR: 3.70; 95% CI: 2.06 to 6.66). These studies have several limitations, such as the heterogeneity among the individual studies in relation to the diagnostic tools and criteria for the assessment of mouth breathing and atypical swallowing. Considering the results, this systematic review shows that patients with mouth breathing presented higher risk ratios for atypical swallowing.

Enhancing the correlation between in vitro and in vivo experiments in dental implant osseointegration: investigating the role of Ca ions.

This study delves into the osteogenic potential of a calcium-ion modified titanium implant surface, unicCa, employing state-of-the-art proteomics techniques both in vitro (utilizing osteoblasts and macrophage cell cultures) and in vivo (in a rabbit condyle model). When human osteoblasts (Hobs) were cultured on unicCa surfaces, they displayed a marked improvement in cell adhesion and differentiation compared to their unmodified counterparts. The proteomic analysis also revealed enrichment in functions associated with cell migration, adhesion, extracellular matrix organization, and proliferation. The analysis also underscored the involvement of key signalling pathways such as PI3K-Akt and mTOR. In the presence of macrophages, unicCa initially exhibited improvement in immune-related functions and calcium channel activities at the outset (1 day), gradually tapering off over time (3 days). Following a 5-day implantation in rabbits, unicCa demonstrated distinctive protein expression profiles compared to unmodified surfaces. The proteomic analysis highlighted shifts in adhesion, immune response, and bone healing-related proteins. unicCa appeared to influence the coagulation cascade and immune regulatory proteins within the implant site. In summary, this study provides a comprehensive proteomic analysis of the unicCa surface, drawing correlations between in vitro and in vivo results. It emphasizes the considerable potential of unicCa surfaces in enhancing osteogenic behavior and immunomodulation. These findings significantly contribute to our understanding of the intricate molecular mechanisms governing the interplay between biomaterials and bone cells, thereby facilitating the development of improved implant surfaces for applications in bone tissue engineering.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors.

OBJECTIVE: The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS: Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS: The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS: hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE: These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.

Efficacy and Safety of Plasma Rich in Growth Factor in Patients with Congenital Aniridia and Dry Eye Disease.

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms. METHODS: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed. RESULTS: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss. CONCLUSION: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

[5.5 mm implant. A solution for severe atrophies without sacrificing predictability]. / Implante de 5,5 mm. Una solución para atrofias severas sin renunciar a la predictibilidad.

The rehabilitation of areas of the maxilla and mandible with extreme resorption is a fact of increased presence in our dental practice. Surgical techniques such as short and extra-short implants facilitate the resolution of these clinical cases. In this clinical case report we develop a case rehabilitated using a 5.5 mm long implant and we provide a biomechanical study of the behaviour of implants with these characteristics.

Confección de férulas de descarga personalizadas por CAD-CAM / Customized CAD-CAM fabrication of occlusal splints

La elaboración de férulas de descarga con la utilización de la técnica convencional, basada en la mezcla de un monómero y polímero con el posterior curado de la mezcla, puede dejar restos de monómero que generen reacciones de hipersensibilidad en algunas personas sensibles a estos químicos. Así, el uso de la tecnología CAD-CAM (Diseño Asistido por Ordenador - Fabricación Asistida por Ordenador), puede mejorar el ajuste y confort relacionado con el uso del dispositivo por el paciente. En el siguiente artículo se presenta un método de elaboración de férulas basado en esta tecnología.

The production of occlusal splints using the conventional technique based on a monomer and polymer mixing with subsequent curing of the mixture may leave traces of monomer that generate hypersensitivity reactions in allergic people to these chemicals. Hence, the use of CAD-CAM technology can improve the fit and comfort related to the use of the device on the patient. In this article a splint elaboration method is shown based on this technology.

Rehabilitación mediante implante dental tras un caso de osteomielitis focal esclerosante. A propósito de un caso / Rehabilitation by dental implant following a case of focal sclerosing osteomyelitis. A case report

La osteomielitis focal esclerosante es un cuadro de poca frecuencia ante el cual no existen demasiadas opciones terapéuticas, al margen del tratamiento de conductos del diente afectado. En caso de no encontrarse el diente vital, los tratamientos se reducen y, respecto del hueso afectado, no existen evidencias científicas sobre la colocación de implantes. Presentamos un caso clínico en el que se maneja este cuadro eliminando el hueso y regenerándolo con PRGF-Endoret®, para colocar posteriormente un implante dental. (AU)

Focal sclerosing osteomyelitis is a rare condition with few therapeutic options other than root canal treatment of the affected tooth. If the tooth is not vital, the treatments are reduced, and there is little scientific evidence of the benefits of the placement of implants in the affected bone. We present a clinical case in which this condition is managed by removing the affected bone, regenerating it with PRGF-Endoret® and subsequently placing a dental implant in the treated area. (AU)

Retratamiento de un caso con atrofia ósea compleja combinada unida a periimplantitis. Importancia de la reversibilidad de los tratamientos implantológicos / Retreatment of a case with bone atrophy combined complex together with peri-impiantitis. importance of the reversibility of the implant treatments

Los implantes dentales son un tipo más de tratamiento para la resolución de casos de edentulismo. Desde su inicio, en los años 70, han sido una alternativa creciente para rehabilitar pacientes, sobre todo en casos en los que las rehabilitaciones convencionales no eran posibles. Cada vez de forma más frecuente nos enfrentamos a retratamientos de implantes y casos con atrofias más complejas. En el siguiente caso, mostramos un retratamiento de implantes fracasados unido a una situación de atrofia extrema vertical y horizontal combinada. En casos de atrofia severa maxilar y mandibular, el uso de los implantes cortos puede acortar los tiempos de tratamiento y simplificar las técnicas quirúrgicas sin renunciar a la predictibilidad como en el caso mostrado. (AU)

Dental implants are an alternative treatment for extended the resolution of cases of edentulism. Since its inception in the year 70 have been a growing alternative to rehabilitate patients, especially in cases where conventional rehabilitations were not possible. Every time, in the dental office were more often we re-treatments of implants and cases with more complex atrophies. In the following case we show a re-treatment of failed implants attached to a situation of extreme atrophy combined vertical and horizontal. In cases of severe maxillary and mandibular atrophy, the use of short implants can shorten treatment times and simplify surgical techniques without sacrificing predictability as in the case shown. (AU)

Implantes extracortos en mandíbulas con extrema reabsorción vertical: serie de casos / Extra-short implants in vertical atrophy: case series

Introducción: el uso de los implantes extracortos permite la rehabilitación de extremas reabsorciones. Esto obliga en ocasiones a la utilización de prótesis sobre los mismos con una proporción corona-implante desfavorable llegando a ratios de 2:1 o de 3:1 en los casos más extremos. Materiales y métodos: se realizó un análisis de casos clínicos donde se insertaron implantes extracortos con un reborde residual (menor o igual a 5,5mm) y tiempo de carga mínimo de seis meses. Se realizó una prueba de chi-cuadrado para las variables categóricas y una t de Student para las variables continuas. Posteriormente, se realizaron modelos de regresión lineal ajustados. Resultados: fueron reclutados seis casos a los que se les insertaron implantes extracortos. El 21,2% de los pacientes incluidos en el estudio fueron hombres y el 78,8% mujeres, con una edad media de 57 años. La proporción corona-implante medio fue de 3,19 (+/- 0,24). La media de la pérdida ósea mesial de los implantes estudiados fue de 0,86mm (+/- 0,33) y la media de la pérdida ósea prodistal fue de 0,83mm (+/- 0,47). Cuando se analizó la pérdida ósea mesial y distal en función proporción no se encontraron diferencias estadísticamente significativas (p=0,224). Conclusiones: el uso de implantes extracortos no es un factor de riesgo para la pérdida ósea crestal o para el fracaso de la prótesis o del implante según los datos aportados por este estudio aun cuando la proporción corona-implante sea superior a tres.

Introduction: the use of extra-short implants in oral implantology it allows us to rehabilitate extremly resorbed bone. The clinical use of these implants generate a Crown-implant ratio desfavorable (2:1 or 3:1 in some cases). Materials and methods: we carry aut a retrospective study with extra-short implants (residual bone height ≤ 5 mm) and follow-up after loading up to 6 months. We was conducted a chi-square test for categorical variables and Student t test for continuous variables. Finally, linear regression models adjusted was performed. Results: finally 6 patients were included in the study. The 212% of the patiens were male and the mean age was 57 years. The mean of Crown-implant ratio was 3.19 (+/- 0,24).The mean of bone loss in the mesial area was 0,86 mm (+/- 0,33) and in the distal area was 0,83 (+/- 0,47). When analyze the bone loss in relation with the crown-implant ratio no significative statistical differences were found. Conclusions: the use of extra-short implants is not a risk for crestal bone loss, implant survival or prosthesis survival, even when the Crown-implant ratio was up to 3.