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Scientific Reports May 2024Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental...
Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.
Topics: Animals; Rabbits; Femur; Bone Transplantation; X-Ray Microtomography; Absorbable Implants; Bone Regeneration; Osteogenesis
PubMed: 38816454
DOI: 10.1038/s41598-024-63067-y -
BMC Oral Health May 2024Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the...
BACKGROUND
Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated.
METHODS
A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes.
RESULTS
Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117-1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001-1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849-13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632).
CONCLUSIONS
This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.
Topics: Humans; Diabetes Mellitus, Type 2; Computational Biology; Periodontitis; Mendelian Randomization Analysis; Genome-Wide Association Study
PubMed: 38811930
DOI: 10.1186/s12903-024-04408-1 -
Scientific Reports May 2024Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has...
Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100's nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants.
Topics: Calcium Phosphates; Humans; Aortic Valve; Osteopontin; Calcinosis; Collagen; Durapatite; Aortic Valve Stenosis; Cholesterol
PubMed: 38806601
DOI: 10.1038/s41598-024-62962-8 -
Scientific Reports May 2024Polyetheretherketone (PEEK) is considered as an excellent biomaterial for bone grafting and connective tissue replacement. The clinical potential is, however, limited by...
Polyetheretherketone (PEEK) is considered as an excellent biomaterial for bone grafting and connective tissue replacement. The clinical potential is, however, limited by its bioinertness, poor osteoconduction, and weak antibacterial activity. These disadvantages can be overcome by introducing suitable additives to produce mineral-polymer composites or coatings. In this work, a PEEK-based bioactive composite has been obtained by blending the polymer with magnesium phosphate (Mg(PO)) particles in amounts ranging from 1 to 10 wt.% using the hot press technique. The obtained composite exhibited improved mechanical and physical properties, above the lower limits set for bone engineering applications. The tested grafts were found to not induce cytotoxicity. The presence of magnesium phosphate induced the mineralisation process with no adverse effects on the expression of the marker crucial for osteoblastic differentiation. The most promising results were observed in the grafts containing 1 wt.% of magnesium phosphate embedded within the PEEK matrix. The improved bioactivity of grafts, together with suitable physical-chemical and mechanical properties, indicate this composite as a promising orthopaedic implant material.
Topics: Benzophenones; Ketones; Polymers; Polyethylene Glycols; Biocompatible Materials; Phosphates; Humans; Magnesium Compounds; Materials Testing; Osteoblasts
PubMed: 38806564
DOI: 10.1038/s41598-024-61941-3 -
Minerva Cardiology and Angiology Aug 2024The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties...
Safety and efficacy of the latest generation biodegradable polymer-coated ultrathin sirolimus-eluting stent in the treatment of coronary artery disease in a European all-comer population with or without high bleeding risk: The Cruz HBR Registry.
BACKGROUND
The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties and represents an attractive percutaneous coronary intervention (PCI) device in a high bleeding risk (HBR) population. The aim of this Cruz HBR registry was to assess safety and efficacy of the Supraflex Cruz SES in a large cohort of all-comer patients, of whom about one third were patients at HBR.
METHODS
Patients undergoing PCI were enrolled in this prospective, multi-centre, open label registry and stratified into non-HBR and HBR groups. The primary endpoint was a device-oriented composite endpoint (DOCE), a composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel and clinically driven target lesion revascularization within 12 months after PCI. The predefined aims were to show non-inferiority of the non-HBR group to the Supraflex arm of the TALENT Trial, and of the HBR group to polymer-free biolimus-coated stent arm of LEADERS FREE Trial.
RESULTS
A total of 1203 patients were enrolled across 26 European centers, including a significant proportion (38.7%; N.=466) of HBR patients. A total of 1745 lesions were treated in 1203 patients and 2235 stents were implanted. The DOCE occurred within the total cohort in 5.8% of patients with a significant difference between HBR patients and non-HBR patients (8.1% vs. 4.4%; P<0.001). All-cause mortality at 12 months was significantly (P<0.0001) different among HBR (9.0%) and non-HBR patients (1.7%), respectively. At 12 months, the overall incidence of definite and probable stent thrombosis was 1.0%. Major bleeding occurred in 5.9% patients of the HBR group. These results met the non-inferiority criteria with respect to the TALENT trial for the non-HBR group (P<0.0001), and the LEADERS FREE trial for the HBR group (P<0.0001).
CONCLUSIONS
The Cruz HBR registry confirms that PCI with the Supraflex Cruz SES is associated with a favorable clinical outcome in an all-comer population, including complex patients with HBR.
Topics: Humans; Drug-Eluting Stents; Sirolimus; Male; Registries; Female; Coronary Artery Disease; Prospective Studies; Percutaneous Coronary Intervention; Aged; Middle Aged; Polymers; Hemorrhage; Treatment Outcome; Europe; Absorbable Implants; Prosthesis Design; Risk Factors
PubMed: 38804621
DOI: 10.23736/S2724-5683.24.06462-7 -
International Journal of Nanomedicine 2024There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and...
INTRODUCTION
There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth.
METHODS
A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca, P, and Sr ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen.
RESULTS
The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity.
DISCUSSION
In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.
Topics: Titanium; Silver; Strontium; Anti-Bacterial Agents; Acetabulum; Animals; Coated Materials, Biocompatible; Osseointegration; Mice; Surface Properties; Fractures, Bone; Durapatite; Osteoblasts; Hydroxyapatites; Prostheses and Implants; Ions; Humans; Cell Line
PubMed: 38803996
DOI: 10.2147/IJN.S464905 -
Clinical and Experimental Dental... Jun 2024This study aimed to evaluate the impact of silver nanoparticles (AgNPs) synthesized from propolis on the formation of Porphyromonas gingivalis biofilms.
OBJECTIVE
This study aimed to evaluate the impact of silver nanoparticles (AgNPs) synthesized from propolis on the formation of Porphyromonas gingivalis biofilms.
MATERIAL AND METHODS
AgNPs were synthesized from propolis, and their inhibitory effect on P. gingivalis biofilm formation was assessed. Different concentrations of AgNPs (0.1%, 0.3%, and 0.5%) were tested to determine the dose-dependent antibacterial activity.
RESULTS
The results of this study indicated that AgNPs exhibited an inhibitory effect on P. gingivalis biofilm formation. The antibacterial activity of AgNPs was dose-dependent, with concentrations of 0.1%, 0.3%, and 0.5% showing effectiveness. Notably, the concentration of 0.5% demonstrated the most significant anti-biofilm formation activity.
CONCLUSION
The results of this study suggest that AgNPs synthesized from propolis have potential as an effective option for enhancing periodontal treatment outcomes. The inhibitory effect of AgNPs on P. gingivalis biofilm formation highlights their potential as alternative antimicrobial agents in the management of periodontal diseases.
Topics: Porphyromonas gingivalis; Biofilms; Silver; Metal Nanoparticles; Anti-Bacterial Agents; Green Chemistry Technology; Propolis; Microbial Sensitivity Tests; Dose-Response Relationship, Drug; Humans
PubMed: 38798089
DOI: 10.1002/cre2.887 -
Clinical and Experimental Dental... Jun 2024Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures,...
Optimizing esthetic zone periodontal regeneration in a 1-2-wall infrabony defect using recombinant human platelet-derived growth factor BB and β-tricalcium phosphate: A case report.
OBJECTIVE
Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and β-tricalcium phosphate (β-TCP).
MATERIALS AND METHODS
At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with β-TCP, without the use of a membrane.
RESULTS
At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21.
CONCLUSION
These results demonstrate the efficacy of rh-PDGF-BB with β-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.
Topics: Humans; Male; Calcium Phosphates; Adult; Becaplermin; Guided Tissue Regeneration, Periodontal; Recombinant Proteins; Alveolar Bone Loss; Periodontitis; Proto-Oncogene Proteins c-sis; Bone Regeneration; Esthetics, Dental
PubMed: 38798052
DOI: 10.1002/cre2.908 -
International Journal of Biological... Jun 2024Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive...
Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive glaucoma surgeries. Here, by controlling mAb passive diffusion, we developed a polymeric, rate-controlling membrane reservoir loaded with poly(lactic-co-glycolic acid) microspheres to deliver mAb for several weeks. Different parameters were tested to ensure that the microspheres achieved a good quality characteristic, and our results showed that 1 %W/V emulsifier with 5 %W/V NaCl achieved mAb-loaded microspheres with the highest stability, encapsulation efficiency and minimal burst release. Then, we fabricated and compared 10 types of microporous films based on polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG). Our results revealed distinct pore characteristics and degradation patterns in different films due to varying polymer properties, and all the polymeric film formulations showed good biocompatibility in both human trabecular meshwork cells and human conjunctival fibroblasts. Finally, the optimized microspheres were loaded into the reservoir-type polymeric implant assembled by microporous membranes with different surface coating modifications. The implant formulation, which was fabricated by 60 PCL: 40 PEG (3 %W/V) polymer with 0.1 %W/V poly(lactic-co-glycolic acid) barrier, exerted the best drug release profile that can sustained release mAb (83.6 %) for 4 weeks.
Topics: Humans; Glaucoma; Antibodies, Monoclonal; Microspheres; Minimally Invasive Surgical Procedures; Polylactic Acid-Polyglycolic Acid Copolymer; Polyesters; Drug Delivery Systems; Drug Liberation; Polymers; Polyethylene Glycols; Porosity; Drug Carriers
PubMed: 38797299
DOI: 10.1016/j.ijbiomac.2024.132655 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and... (Review)
Review
BACKGROUND
Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth.
AIM
The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient.
METHODS
Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects.
RESULTS
The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures.
CONCLUSIONS
Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes.
PubMed: 38794131
DOI: 10.3390/ph17050561