The emerging role of fibrin(ogen) in cardiovascular disease.

OBJECTIVE: A coagulation factor called fibrinogen is produced by the liver and is proteolyzed by thrombin to become fibrin. The latest studies have revealed that fibrin(ogen) palys an essential role in the regulation of cardiovascular disease. Understanding the relationship and mechanism between fibrin(ogen) and cardiovascular disease is of great significance for maintaining overall health. The objective of this review is to discuss the specific involvement and underlying mechanisms of fibrin(ogen) in cardiovascular disease. METHODS: A review was conducted using the PubMed database to identify and analyze the emerging role of fibrinogen in cardiovascular disease. RESULTS: The literature review revealed that fibrin(ogen) plays a pivotal role in maintaining cardiovascular disease and are involved in the pathogenesis of cardiovascular disease. Fibrin(ogen) mainly influence various pathophysiological processes, such as participating in thrombosis formation, stimulating the inflammatory response, and other molecular pathways. CONCLUSION: This review focuses on the involvement of fibrin(ogen) in cardiovascular disease, with a particular emphasis on the main functions and underlying mechanisms by which fibrin(ogen) influence the pathogenesis and progression of these conditions. This review underscores the potential of fibrin(ogen) as therapeutic targets in managing cardiovascular disease.

Periodontal Guided Tissue Regeneration Membranes: Limitations and Possible Solutions for the Bottleneck Analysis.

Guided tissue regeneration (GTR) is an important surgical method for periodontal regeneration. By placing barrier membrane on the root surface of the tooth to guide the adhesion and proliferation of periodontal ligament cells, periodontal tissue regeneration can be achieved. This review intends to analyze the current limitations of GTR membranes and to propose possible solutions for developing new ones. Limitations of current GTR membranes include nonabsorbable membranes and absorbable synthetic polymer membranes exhibit weak biocompatibility; when applying to a large defect wound, the natural collagen membrane with fast degradation rate have limited mechanical strength, and the barrier function may not be maintained well. Although the degradation time can be prolonged after cross-linking, it may cause foreign body reaction and affect tissue integration; The clinical operation of current barrier membranes is inconvenient. In addition, most of the barrier membranes lack bioactivity and will not actively promote periodontal tissue regeneration. Possible solutions include using electrospinning (ELS) techniques, nanofiber scaffolds, or developing functional gradient membranes to improve their biocompatibility; adding Mg, Zn, and/or other metal alloys, or using 3D printing technology to improve their mechanical strength; increasing the concentration of nanoparticles or using directional arrangement of membrane fibers to control the fiber diameter and porosity of the membrane, which can improve their barrier function; mixing natural and synthetic polymers as well as other biomaterials with different degradation rates in proportion to change the degradation rate and maintain barrier function; to improve the convenience of clinical operation, barrier membranes that meets personalized adhesion to the wound defect can be manufactured; developing local controlled release drug delivery systems to improve their bioactivity. Impact statement This review provides an up-to-date summary of commonly commercial periodontal guided tissue regeneration membranes, and analyze their limitations in clinical use. Using studies published recently to explore possible solutions from several perspectives and to raise possible strategies in the future. Several strategies have tested in vivo/in vitro, which will guide the way to propel clinical translation, meeting clinical needs.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

Lipidomic analysis reveals altered lipid profiles of gingival tissues with periodontitis.

AIM: The role of lipids in periodontitis has not been well studied. Thus, this study aimed to explore periodontitis-associated lipid profile changes and identify differentially expressed lipid metabolites in gingival tissues. MATERIALS AND METHODS: Gingival tissues from 38 patients with periodontitis (periodontitis group) and 38 periodontally healthy individuals (control group) were collected. A ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based non-targeted metabolomics platform was used to identify and compare the lipid profiles of the two groups. The distribution and expression of related proteins were subsequently analysed via immunohistochemistry to further validate the identified lipids. RESULTS: Lipid profiles significantly differed between the two groups, and 20 differentially expressed lipid species were identified. Lysophosphatidylcholines (lysoPCs), diacylglycerols (DGs), and phosphatidylethanolamines (PEs) were significantly up-regulated, while triacylglycerols (TGs) were downregulated in the periodontitis group. Moreover, the staining intensity of ABHD5/CGI-58, secretory phospholipase A2 (sPLA2), and sPLA2-IIA was significantly stronger in the gingival tissues of patients with periodontitis than in those of healthy controls. CONCLUSIONS: LysoPCs, DGs, and PEs were significantly up-regulated, whereas TGs were down-regulated in gingival tissues of patients with periodontitis. Correspondingly, the immunohistochemical staining of ABHD5/CGI-58, sPLA2, and sPLA2-IIA in gingival tissues was consistent with the downstream production of lipid classes (lysoPCs, TGs, and DGs).

A novel cone-beam CT scanning technique for measuring periodontal soft tissues in the esthetic area.

PURPOSE: This study investigated and tested a novel cone-beam computed tomography (CBCT) scanning technique capable of obtaining clear contours of soft tissues in the esthetic area. METHODS: Twenty-three periodontally healthy participants underwent this novel CBCT scanning technique. Soft tissue morphological parameters were measured on the CBCT images obtained. Intraoral clinical data were also collected at the same locations, and the accuracy of the CBCT method was tested. RESULTS: The median (interquartile range [IQR]) of the supracrestal gingival tissue thickness as 0.91 (0.73-1.13) mm, and the thickness of the central incisors was significantly greater than that of the canines (P < 0.05). The median (IQR) of keratinized tissue thickness was 0.73 (0.55-0.91) mm, which also showed a significantly greater thickness in the central incisors than in the canines (P < 0.05). Bland-Altman analysis suggested that CBCT could be accurate for measuring soft tissues in the esthetic area. CONCLUSION: The novel CBCT technique described yields clear contours of soft tissues in the esthetic area without the need for auxiliary tools. Moreover, measurements of soft tissue morphological parameters on CBCT appear to be accurate.

Evaluation of polydimethylsiloxane-based substrates for in vitro culture of human periodontal ligament cells.

Periodontal ligament (PDL) cells are regarded as the cell type with the highest potential for periodontal regeneration. Biophysical cues of the culture substrate are increasingly identified as vital parameters to affect cell behavior. Compared to traditional tissue culture polystyrene (TCPS), polydimethylsiloxane (PDMS) substrates corroborate more closely the elastic modulus values of the physiological environment. Consequently, the aim of this study was to evaluate the effect of PDMS-based substrates with different stiffness on cellular responses of human PDL cells. PDMS substrates with different stiffness were fabricated by varying the ratio of base to curing component. The influence of PDMS substrates on PDL cell spreading and cytoskeletal morphologies, motility, proliferation, stemness gene expression, and osteogenic differentiation was evaluated and compared to that on conventional TCPS. PDL cells cultured on PDMS substrates exhibited a smaller cell size and more elongated morphology, with less spreading area, fewer focal adhesions, and faster migration than cells on TCPS. Compared to TCPS, PDMS substrates promoted the rapid in vitro expansion of PDL cells without interfering with their self-renewal ability. In contrast, the osteogenic differentiation ability of PDL cells cultured on PDMS was lower in comparison to cells on TCPS. PDL cells on PDMS exhibited similar cell morphology, motility, proliferation, and self-renewal gene expression. The stiffer PDMS substrate increased the osteogenic gene expression of PDL cells compared to the soft PDMS group in one donor. These data indicate that PDMS-based substrates have the potential for the efficient PDL cell expansion.

Cell-Based Approaches in Periodontal Regeneration: A Systematic Review and Meta-Analysis of Periodontal Defect Models in Animal Experimental Work.

Various cell types have been assessed for experimental periodontal tissue regeneration in a variety of animal models. Nonetheless, the efficacy of cell-based approaches for periodontal regeneration is still controversial. Therefore, the purpose of this study was to systematically review cell-based approaches for periodontal regeneration in animal studies including a meta-analysis to obtain more clarity on their efficacy. The results of this systematic review and meta-analysis revealed that cell-based approaches have a favorable effect on periodontal tissue regeneration, as displayed by the positive effect of cell-based approaches on new bone, cementum, and periodontal ligament (PDL) formation in periodontal defects. Moreover, subgroup analysis showed a favorable effect on PDL formation by PDL-derived cells, but not by bone marrow mesenchymal stem cells (BMSCs). However, meta-analysis did not show any statistically significant differences in effect between PDL-derived cells and BMSCs. These results provide important information for the implementation of cell-based approaches in clinical practice as a routine treatment for periodontal regeneration in the future.

Periodontal tissue regeneration using enzymatically solidified chitosan hydrogels with or without cell loading.

This study is aimed to evaluate the in vivo biocompatibility and periodontal regenerative potential of enzymatically solidified chitosan hydrogels with or without incorporated periodontal ligament cells (PDLCs). To this end, chitosan hydrogels, with (n=8; CHIT+CELL) or without (n=8; CHIT) fluorescently labeled PDLCs, were prepared and transplanted into rat intrabony periodontal defects; untreated defects were used as empty controls (n=8; EMPTY). After 4 weeks, maxillae were harvested, decalcified, and used for histological, histomorphometrical, and immunohistochemical assessments. The results showed that PDLCs remained viable upon encapsulation within chitosan hydrogels before transplantation. Histological analysis demonstrated that the chitosan hydrogels were largely degraded after 4 weeks of implantation, without any adverse reaction in the surrounding tissue. In terms of periodontal regeneration, alveolar bone height, alveolar bone area, and epithelial downgrowth were comparable for CHIT, CHIT+CELL, as well as EMPTY groups. In contrast, both CHIT and CHIT+CELL showed a significant increase in functional ligament length compared with EMPTY. From a cellular perspective, the contribution of chitosan hydrogel-incorporated cells to the periodontal regeneration could not be ascertained, as no signal from transplanted PDLCs could be detected at 4 weeks posttransplantation. The results demonstrated that enzymatically solidified chitosan hydrogels are highly biocompatible and biodegradable. Moreover, chitosan hydrogels without cell loading can improve periodontal regeneration in terms of functional ligament length, indicating the great potential of this hydrogel in clinical applications. Further work on the use of chitosan hydrogels as cell carriers is required.

Human periodontal ligament derived progenitor cells: effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior.

OBJECTIVES: STRO-1 positive periodontal ligament cells (PDLCs) and unsorted PDLCs have demonstrated potential for periodontal regeneration, but the comparison between unsorted cells and the expanded STRO-1 sorted cells has never been reported. Additionally, Wnt3a is involved in cell proliferation thus may benefit in vitro PDLC expansion. The aim was to evaluate the effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior of human PDLCs (hPDLCs). MATERIALS AND METHODS: STRO-1 positive hPDLCs were sorted and the sorted cells were expanded and compared with their unsorted parental cells. Thereafter, hPDLCs were treated with or without Wnt3a and the cell proliferation, self-renewal, and osteogenic differentiation were evaluated. RESULTS: No differences were measured between the expanded STRO-1-sorted cells and unsorted parental cells in terms of proliferation, CFU, and mineralization capacity. Wnt3a enhanced the proliferation and self-renewal ability of hPDLCs significantly as displayed by higher DNA content values, a shorter cell population doubling time, and higher expression of the self-renewal gene Oct4. Moreover, Wnt3a promoted the expansion of hPDLCs for 5 passages without affecting cell proliferation, CFU, and osteogenic capacity. CONCLUSIONS: Expanded STRO-1-sorted hPDLCs showed no superiority compared to their unsorted parental cells. On the other hand, Wnt3a promotes the efficient hPDLC expansion and retains the self-renewal and osteogenic differentiation capacity.

Enzymatic control of chitosan gelation for delivery of periodontal ligament cells.

The aim of this study is to optimize enzymatic control over gelation of chitosan-based hydrogels for the delivery of periodontal ligament cells (PDLCs). The results reveal that the gelation time, strength, and degradation rate of the chitosan hydrogels can be controlled precisely by variation of the urea and urease concentrations. PDLCs remain viable inside these hydrogels for up to 30 days. Cells released from the hydrogel upon degradation and collected after 3, 15, and 30 days are able to form colonies and osteogenically differentiate. In conclusion, the enzymatic control over the gelation of chitosan hydrogels offers options for the delivery of PDLCs.

Biomaterial strategies for stem cell maintenance during in vitro expansion.

Stem cells, having the potential for self-renewal and multilineage differentiation, are the building blocks for tissue/organ regeneration. Stem cells can be isolated from various sources but are, in general, available in too small numbers to be used directly for clinical purpose without intermediate expansion procedures in vitro. Although this in vitro expansion of undifferentiated stem cells is necessary, stem cells typically diminish their ability to self-renew and proliferate during passaging. Consequently, maintaining the stemness of stem cells has been recognized as a major challenge in stem cell-based research. This review focuses on the latest developments in maintaining the self-renewal ability of stem cells during in vitro expansion by biomaterial strategies. Further, this review highlights what should be the focus for future studies using stem cells for regenerative applications.

Effects of continuous passaging on mineralization of MC3T3-E1 cells with improved osteogenic culture protocol.

The murine-derived MC3T3-E1 cell line provided by the American Type Culture Collection (ATCC) is a well-known osteogenic cell culture model system to test materials in vitro. However, the effect of passaging on its mineralization capacity has never been described and their culture supplements can be further optimized. Therefore, we evaluated the influence of the passage number and different osteogenic culture supplements, including ascorbic acid (AsAP) and dexamethasone (Dex) on the osteogenic capacity of MC3T3-E1 cells. This capacity was measured by the deposited calcium, the alkaline phosphatase activity, and the expression of osteogenic-related genes, including bone sialoprotein (BSP), osteocalcin (OC), and osteopontin (OPN). The results indicated that the mineralization capacity of MC3T3-E1 cells significantly decreased during passaging and got exhausted at passage 34, as assessed by measuring calcium deposition after 28 days of osteogenic induction. Moreover, the combination of AsAP and Dex triggered significantly more mineralization in MC3T3-E1 cells than the ATCC recommended addition of AsAP alone, as indicated by increased calcium deposition and higher expression of BSP and OPN. However, Dex alone could not trigger this effect, but only in combination with the AsAP, which indicates that Dex has no direct effect on mineralization. In conclusion, the passage number of MC3T3-E1 cells is of great importance and the use of cells above 30 passages should be avoided. In addition, the favored osteogenic supplements providing an improved osteogenic differentiation of MC3T3-E1 cells are the combination of AsAP and Dex.

[Construction and identification of a recombinant lentiviral expression plasmid pLentiTrident1-hBMP2-Neo-hNGF].

PURPOSE: To construct and confirm a recombinant lentiviral vector containing human bone morphogenetic protein 2 (hBMP2) and human nerve growth factor (hNGF). METHODS: The Neomycin gene was digested from pLentiTrident1-EGFP-Neo and then was subcloned into lentiviral vector. The hBMP2 and hNGF genes were amplified by polymerase chain reaction (PCR), and then the PCR product was inserted to proper sites of the vector. Finally, the recombinant vector pLentiTrident1-hBMP2-Neo-hNGF was confirmed by agarose gel electrophoresis and DNA sequence analysis. RESULTS: The construction of recombinant lentiviral vector pLentiTrident-hBMP2 -Neo-hNGF was confirmed through restriction enzyme maping analysis and DNA sequencing. CONCLUSIONS: The recombinant lentiviral vector which can coexpress hBMP2 and hNGF is successfully constructed,which lays a solid foundation of studying the effect of neuro factors on bone regeneration.

A pilot study evaluating the effect of recombinant human bone morphogenetic protein-2 and recombinant human beta-nerve growth factor on the healing of Class III furcation defects in dogs.

BACKGROUND: The quantity of regenerated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP2) is encouraging, but sometimes the quality is inferior. Recombinant human beta-nerve growth factor (rh beta-NGF) plays a major role in bone remodeling. This study evaluates the quality and quantity of regenerated bone in periodontal regeneration following topical application of the two growth factors to Class III furcation defects. METHODS: Thirty-six inflamed Class III furcation defects were created in six beagle dogs at sites of mandibular premolars 2, 3, and 4, and then biodegradable hydrogel incorporating rhBMP2 and rh beta-NGF was topically applied to the defects. The groupings were as follows: G1, untreated (control group A); G2, carrier alone (control group B); G3, 0.4% rhBMP2 + carrier; G4, 2% rh beta-NGF + carrier; G5, 0.4% rhBMP2 + 2% rh beta-NGF + carrier; and G6, 0.2% rhBMP2 + 1% rh beta-NGF + carrier. Eight weeks after application, the quality and quantity of regenerated tissue were evaluated by scanning electron microscopy observation, calcium/phosphorus ratio analysis, and histologic evaluation. RESULTS: The regenerated bone in G5 exhibited the highest calcium/phosphorus ratio among all groups and showed a denser structure with more calcified substances on the collagen fiber surface than that in the other groups. Histomorphometric analysis revealed that 0.4% rhBMP2 + 2% rh beta-NGF promoted the highest percentage of periodontal regeneration among all groups. CONCLUSION: The results of this pilot study suggest that a topical application of rhBMP2 and rh beta-NGF may improve the quality and quantity of regenerated bone in artificially created Class III furcation defects of beagle dogs.

Study on the anti-wear performance of Ni-base composite coating sucker joint that contains nano-diamond and nano-polytetrafluoroethylene.

With the development of oilfields, the problem of eccentric wear between casing and sucker rod in rod-pumped wells operation is more and more severe. Investigations on the eccentric wear show that the abrasion of sucker rod joint is more serious than the sucker rod itself. A new method of producing the Ni-base composite coating that contains nano-diamond and nano-polytetrafluoroethylene (PTFE) on sucker joint obtained by electrodeposition is presented in this paper. The test results show that the anti-wear performance and hardness of the sucker rod improve significantly with the increase of nano-diamond. The addition of nano-PTFE particle is useful in reducing the friction factor. Field tests demonstrate that the life of the sucker rod joint is increased and the maintenance cycle of the rod-pumped well is prolonged.