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1.
Int Endod J ; 57(7): 815-840, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38441321

RESUMO

Endodontic therapy includes various procedures such as vital pulp therapy, root canal treatment and retreatment, surgical endodontic treatment and regenerative endodontic procedures. Disinfection and tissue repair are crucial for the success of these therapies, necessitating the development of therapeutics that can effectively target microbiota, eliminate biofilms, modulate inflammation and promote tissue repair. However, no current endodontic agents can achieve these goals. Antimicrobial peptides (AMPs), which are sequences of amino acids, have gained attention due to their unique advantages, including reduced susceptibility to drug resistance, broad-spectrum antibacterial properties and the ability to modulate the immune response of the organism effectively. This review systematically discusses the structure, mechanisms of action, novel designs and limitations of AMPs. Additionally, it highlights the efforts made by researchers to overcome peptide shortcomings and emphasizes the potential applications of AMPs in endodontic treatments.


Assuntos
Peptídeos Antimicrobianos , Endodontia , Humanos , Endodontia/métodos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Tratamento do Canal Radicular/métodos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38935006

RESUMO

INTRODUCTION: White spot lesions (WSLs) represent a prominent pathology encountered during orthodontic treatment, originating from enamel demineralization induced by the accumulation of bacterial biofilms. The previously developed bioinspired enamel coating form of self-assembling antimicrobial peptide D-GL13K exhibited antimicrobial activity and enhanced acid impermeability, offering a potential solution to prevent demineralization. The primary aim of this investigation is to assess the in vivo anti-demineralization properties and biocompatibility of the D-GL13K coating. METHODS: A rat model was developed to assess the antimicrobial enamel coating during fixed orthodontic treatment. The anti-demineralization efficacy attributed to the D-GL13K coating was evaluated by employing optical coherence tomography, Vickers microhardness testing, and scanning electron microscopy. The biocompatibility of the D-GL13K coating was investigated through histologic observations of vital organs and tissues using hematoxylin and eosin. RESULTS: The D-GL13K coating demonstrated significant anti-demineralization effects, evidenced by reduced demineralization depth analyzed through optical coherence tomography and enhanced Vickers hardness than in the noncoated control group, showcasing the coating's potential to protect teeth from WSLs. Scanning electron microscopy analysis further elucidated the diminished enamel damage observed in the group treated with D-GL13K. Importantly, histologic examination of vital organs and tissues using hematoxylin and eosin staining revealed no overt disparities between the D-GL13K coated group and the noncoated control group. CONCLUSIONS: The D-GL13K enamel coating demonstrated promising anti-demineralization and biocompatibility properties in a rat model, thereby suggesting its potential for averting WSLs after orthodontic interventions. Further research in human clinical settings is needed to evaluate the coating's long-term efficacy.

3.
Biomacromolecules ; 23(10): 4401-4411, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36173091

RESUMO

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)-diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.


Assuntos
Diabetes Mellitus , Insulina , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos/métodos , Glucose , Hidrogéis , Insulina/química , Agulhas , Polímeros/química , Ratos
4.
Pharm Res ; 39(7): 1523-1534, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35169958

RESUMO

The blood-brain barrier (BBB) hinders therapeutic delivery to the central nervous system (CNS), thereby impeding the development of therapies for brain injury and disease. Receptor-mediated transcytosis (RMT) systems are a promising way to shuttle a targeted therapeutic into the brain. Here, we developed and evaluated an RMT antibody-targeted liposomal system. A previously identified antibody, scFv46.1, that binds to the human and murine BBB and can pass through the murine BBB by transcytosis after intravenous injection was used to decorate the surface of liposomes. Using an in vitro BBB model, we demonstrated the cellular uptake of scFv46.1-modified liposomes (46.1-Lipo). Next, the biodistribution and brain uptake capacity of 46.1-targeted liposomes were assessed after intravenous administration. Our results showed that 46.1-Lipo can lead to increased brain accumulation through targeting of the brain vasculature. Initial rate pharmacokinetic experiments and biodistribution analyses indicated that 46.1-Lipo loaded with pralidoxime exhibited a 10-fold increase in brain accumulation compared with a mock-targeted liposomal group, and this increased accumulation was brain-specific. These studies indicate the potential of this 46.1-Lipo system as a synthetic vehicle for the targeted transport of therapeutic molecules into the CNS.


Assuntos
Barreira Hematoencefálica , Lipossomos , Animais , Anticorpos , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Camundongos , Distribuição Tecidual
5.
Int Endod J ; 55 Suppl 3: 613-636, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35322427

RESUMO

Two fundamental goals of endodontic treatment are to prevent or treat apical periodontitis. From a predictive perspective, several variables can affect the outcome of root canal treatment. Some of these variables depend on intraoperative factors, which include irrigation technique, size of the apical preparation, use of intracanal medicaments or the number of appointments necessary to complete the treatment. However, the outcome may also be affected by host and microbial factors. The intensity of periradicular bone loss or tissue damage, the presence of preoperative pain and associated conditions such as mechanical allodynia and central sensitization, the anatomical complexity of the apical portion of the canal, and the virulence and longevity of the bacterial infection can all have a profound influence on the outcome. Furthermore, numerous medical conditions have been reported to decrease the capability of the immune system to heal the periapical tissues. It is the clinician's responsibility to analyse these variables and incorporate them into the disinfection strategy to maximize the chances of healing. This narrative review will focus on the present status of intracanal medicaments, the clinical indications for their use and future directions for research.


Assuntos
Periodontite Periapical , Irrigantes do Canal Radicular , Hidróxido de Cálcio , Cavidade Pulpar/microbiologia , Desinfecção , Humanos , Periodontite Periapical/tratamento farmacológico , Periodontite Periapical/microbiologia , Tecido Periapical , Irrigantes do Canal Radicular/uso terapêutico , Tratamento do Canal Radicular/métodos
6.
Int Endod J ; 55(10): 1091-1102, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35833329

RESUMO

AIM: The use of high-concentration sodium hypochlorite (NaOCl) as an endodontic irrigant remains controversial because of its potential impact on the fracture strength of endodontically treated teeth. This study evaluated the effects of using different NaOCl concentrations, with 2-min-ethylenediaminetetraacetic acid (EDTA) as the final active irrigant, on the biomechanical and structural properties of root dentine. METHODOLOGY: A new test method, which is more clinically relevant, was utilized to calculate the fracture strength of root dentine. Bovine incisors were used to obtain root dentine discs. The root canals were enlarged to mean diameter of 2.90 mm with a taper of 0.06. The resulting discs were divided into five groups (n = 20) and treated with different concentrations of NaOCl (5.25%, 2.5%, and 1.3%) for 30 min plus 17% EDTA for 2 min. The discs were then loaded to fracture by a steel rod with the same taper through the central hole. The fractured specimens were examined by scanning electron microscopy to evaluate changes in the dimensions of the remaining intertubular dentine and the tubular radius. Micro-hardness was also measured with a Knoop diamond indenter along a radius to determine the depth of dentine eroded by the irrigation. Results were analysed by one-way anova and the Tukey test. The level of significance was set at α = 0.05. RESULTS: The damage by NaOCl increased with its concentration. 5.25% NaOCl greatly reduced the fracture strength of root dentine from 172.10 ± 30.13 MPa to 114.58 ± 26.74 MPa. The corresponding reduction in micro-hardness at the root canal wall was 34.1%. The damages reached a depth of up to 400 µm (p < .05). Structural changes involved the degradation of the intratubular wall leading to enlarged dentinal tubules and the loss of intertubular dentine. Changes in the microstructural parameters showed positive linear relationships with the fracture strength. CONCLUSIONS: With the adjunctive use of EDTA, NaOCl caused destruction to the intratubular surface near the root canal and, consequently, reduced the root dentine's mechanical strength. The higher the concentration of NaOCl, the greater the effect. Therefore, endodontists should avoid using overly high concentration of NaOCl for irrigation to prevent potential root fracture in endodontically treated teeth.


Assuntos
Hipoclorito de Sódio , Dente não Vital , Animais , Bovinos , Cavidade Pulpar , Dentina , Ácido Edético/farmacologia , Humanos , Irrigantes do Canal Radicular/farmacologia , Preparo de Canal Radicular , Hipoclorito de Sódio/farmacologia
7.
Biomacromolecules ; 21(10): 4043-4052, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32786727

RESUMO

Antimicrobial peptides (AMPs) have attracted great interest as they constitute one of the most promising alternatives against drug-resistant infections. Their amphipathic nature not only provides them antimicrobial and immunomodulatory properties but also the ability to self-assemble into supramolecular nanostructures. Here, we propose their use as self-assembling domains to drive hierarchical organization of intrinsically disordered protein polymers (IDPPs). Using a modular approach, hybrid protein-engineered polymers were recombinantly produced, thus combining designer AMPs and a thermoresponsive IDPP, an elastin-like recombinamer (ELR). We exploited the ability of these AMPs and ELRs to self-assemble to develop supramolecular nanomaterials by way of a dual-assembly process. First, the AMPs trigger the formation of nanofibers; then, the thermoresponsiveness of the ELRs enables assembly into fibrillar aggregates. The interplay between the assembly of AMPs and ELRs provides an innovative molecular tool in the development of self-assembling nanosystems with potential use for biotechnological and biomedical applications.


Assuntos
Proteínas Intrinsicamente Desordenadas , Nanoestruturas , Elastina , Polímeros , Proteínas Citotóxicas Formadoras de Poros
8.
Biomacromolecules ; 21(12): 4945-4961, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-32961056

RESUMO

Bioadhesive membranes with controllable and reversible underwater adhesion are desirable for several biomedical applications ranging from biosensing, drug/therapeutic delivery, and tissue regeneration. Here, we present dual soft mucosal and hard bone/enamel tissue adhesive nanofiber membranes composed of chitosan and pectin derivatives for pH-controlled delivery of antimicrobial peptides (AMPs) in the oral cavity. Ex vivo testing with porcine esophagus (soft mucosal mimic) indicated a 2-fold increase in the mucoadhesion of chitosan membranes with 0.05 wt % oxidized pectin coating, while the uncoated membranes exhibited 3-4-fold stronger adhesion to hydroxyapatite discs (enamel/hard bone mimic) compared to the coated membranes. The former is attributed to a synergistic interaction of surface nanofiber topography, intermolecular hydrogen bonding, and aldehyde-amine chemistry between surface polar groups and mucosal proteins, while the latter may arise from electrostatic interactions between cationic amines (-NH3+) in chitosan and anionic phosphates (-PO43-) in hydroxyapatite. Further, the dual hard-soft oral tissue adhesive nanofiber membranes loaded with cationic amphipathic AMPs (D-GL13K and IDR-1018) elicited pH-responsive AMP delivery and antimicrobial action comparable to chlorhexidine (CHX) against oral streptococci. Concurrently, the AMP loaded membranes were cytocompatible to both soft epithelial tissue-derived human oral keratinocytes and hard calvarial murine pre-osteoblast cells. We envision these membranes to function as adhesive gingival grafts and guided bone regeneration (GBR) membranes at the hard-soft tissue interface while simultaneously protecting against oral infections.


Assuntos
Antibacterianos , Nanofibras , Adesivos Teciduais , Adesivos , Animais , Antibacterianos/administração & dosagem , Sistemas de Liberação de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Peptídeos/administração & dosagem , Proteínas Citotóxicas Formadoras de Poros , Suínos
9.
J Oral Maxillofac Surg ; 74(1): 170-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26117379

RESUMO

PURPOSE: To introduce grafting fixed with the periosteum (dumpling technique) as an alternative surgical technique for augmented corticotomy-assisted orthodontics in the lower anterior region and evaluate the preliminary outcomes. MATERIALS AND METHODS: Eleven patients (9 women, 2 men; mean age, 21.4 yr) with a thin alveolus or alveolar defect in the lower anterior region by clinical and radiographic examination underwent an augmented corticotomy using the new dumpling technique. Cone-beam computerized tomography was used to evaluate morphologic changes of the lower anterior ridge before treatment (T0) and 1 week (T1) and 6 months (T2) after the bone-augmentation procedure. Repeated-measures analysis of variance with Bonferroni multiple-comparison test was used to compare variables at each time point. RESULTS: No severe postsurgical complications occurred in any patient. The mean alveolar bone thickness of the labial plate increased from T0 to T1 (P < .001) and decreased from T1 to T2 (P < .001). However, compared with T0, there was still a significant increase in horizontal bone thickness at T2 (P < .05). The vertical alveolar bone level increased from T0 to T1 (P < .001) and was maintained from T1 to T2 (P > .05). No significant differences were found in root length of the lower anterior teeth at these 3 time points (P > .05). CONCLUSIONS: In this preliminary study, the dumpling technique for augmented corticotomy-assisted surgical orthodontics showed alveolar bone augmentation by increasing the vertical alveolar height and the horizontal bone thickness in the labial aspect of the anterior mandibular area. However, long-term follow-up is necessary.


Assuntos
Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Mandíbula/cirurgia , Ortodontia Corretiva/métodos , Osteotomia/métodos , Periósteo/cirurgia , Processo Alveolar/diagnóstico por imagem , Autoenxertos/transplante , Substitutos Ósseos/uso terapêutico , Colágeno , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Seguimentos , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Membranas Artificiais , Minerais/uso terapêutico , Piezocirurgia/métodos , Técnicas de Sutura , Raiz Dentária/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
10.
J Craniofac Surg ; 26(8): e695-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26594976

RESUMO

The juxta-articular myxoma represents a benign mesenchymal neoplasm that arises from tissue within or adjacent to a joint space. There have been a number of reported cases involving myxomas of the knee, shoulder, elbow, wrist, and hip. To our knowledge there, however, have been no reported cases of juxta-articular myxomas of the temporomandibular joint (TMJ). This report describes the case of a 57-year-old woman with a juxta-articular myxoma of the left TMJ extending into the infratemporal fossa (ITF). Access to the tumor was accomplished via a preauricular incision and low condylar osteotomy which allowed for displacement of the condyle for direct visualization and excision of the tumor. The postoperative course was benign and the patient demonstrated no cosmetic or functional limitation. Likewise, follow-up at 30 months showed no evidence of recurrence. Benign encapsulated tumors of the ITF can be effectively accessed by means of a modified preauricular incision, low condylar osteotomy, and anterior meniscal release. This direct approach allows for excellent surgical exposure, minimal surgical site morbidity, and maintenance of physiologic joint function and occlusion.


Assuntos
Mixoma/diagnóstico , Transtornos da Articulação Temporomandibular/diagnóstico , Fossa Craniana Média/patologia , Feminino , Seguimentos , Humanos , Côndilo Mandibular/cirurgia , Pessoa de Meia-Idade , Mixoma/cirurgia , Invasividade Neoplásica , Osteotomia/métodos , Osso Temporal/patologia , Transtornos da Articulação Temporomandibular/cirurgia
11.
Inflammation ; 47(1): 307-322, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37782452

RESUMO

Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif-/-) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif-/- mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.


Assuntos
Pulpite , Animais , Humanos , Camundongos , Polpa Dentária/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Fator Inibidor de Leucemia/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Pulpite/metabolismo
12.
Dent Mater ; 40(4): 608-618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369405

RESUMO

OBJECTIVE: The current dental resin composites often suffer from polymerization shrinkage, which can lead to microleakage and potentially result in recurring tooth decay. This study presents the synthesis of a novel monomer, (3,9-diethyl-1,5,7,11-tetraoxaspiro[5,5]undecane-3,9-diyl)bis(methylene) bis((2-(3-(prop-1-en-2-yl)phenyl)propan-2-yl)carbamate) (DDTU-IDI), and evaluates its effect in the formulation of low-shrinkage dental resin composites. METHODS: DDTU-IDI was synthesized through a two-step reaction route, with the initial synthesis of the required raw material monomer 3,9-diethyl-3,9-dihydroxymethyl-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU). The structures were confirmed using Fourier-transform infrared (FT-IR) spectroscopy and hydrogen nuclear magnetic resonance (1HNMR) spectroscopy. Subsequently, DDTU-IDI was incorporated into Bis-GMA-based composites at varying weight percentages (5, 10, 15, and 20 wt%). The polymerization reaction, degree of conversion, polymerization shrinkage, mechanical properties, physicochemical properties and biocompatibility of the low-shrinkage composites were thoroughly evaluated. Furthermore, the mechanical properties were assessed after a thermal cycling test with 10,000 cycles to determine the stability. RESULTS: The addition of DDTU-IDI at 10, 15, and 20 wt% significantly reduced the polymerization volumetric shrinkage of the experimental resin composites, without compromising the degree of conversion, mechanical and physicochemical properties. Remarkably, at a monomer content of 20 wt%, the polymerization shrinkage was reduced to 1.83 ± 0.53%. Composites containing 10, 15, and 20 wt% DDTU-IDI exhibited lower water sorption and higher contact angle. Following thermal cycling, the composites exhibited no significant decrease in mechanical properties, except for the flexural properties. SIGNIFICANCE: DDTU-IDI has favorable potential as a component which could produce volume expansion and increase rigidity in the development of low-shrinkage dental resin composites. The development of low-shrinkage composites containing DDTU-IDI appears to be a promising strategy for reducing polymerization shrinkage, thereby potentially enhancing the longevity of dental restorations.


Assuntos
Alcanos , Metacrilatos , Ácidos Polimetacrílicos , Metacrilatos/química , Ácidos Polimetacrílicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Polietilenoglicóis/química , Teste de Materiais , Resinas Compostas/química , Bis-Fenol A-Glicidil Metacrilato/química , Polimerização
13.
ACS Biomater Sci Eng ; 10(7): 4437-4451, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38885017

RESUMO

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-ß (TGF-ß) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.


Assuntos
Condrócitos , Homeostase , Lipossomos , Osteoartrite , Condrócitos/metabolismo , Osteoartrite/terapia , Osteoartrite/patologia , Osteoartrite/metabolismo , Lipossomos/química , Humanos , Animais , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Masculino , Fosforilação , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Fator de Crescimento Transformador beta/metabolismo , Matriz Extracelular/metabolismo , Proteína Smad3/metabolismo , Proteína Smad3/genética , Transdução de Sinais , Plasmídeos/genética , Nanopartículas/química , Nanopartículas/uso terapêutico , Proteína Smad2/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética
14.
Int J Biol Macromol ; 267(Pt 1): 131480, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599427

RESUMO

Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. STATEMENT OF SIGNIFICANCE: The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios.


Assuntos
Peptídeos Antimicrobianos , Regeneração Óssea , Colágeno , Membranas Artificiais , Nanofibras , Regeneração Óssea/efeitos dos fármacos , Animais , Ratos , Nanofibras/química , Colágeno/química , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Osteogênese/efeitos dos fármacos , Camundongos , Osteoblastos/efeitos dos fármacos , Streptococcus gordonii/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Fibroblastos/efeitos dos fármacos
15.
Adv Sci (Weinh) ; 11(13): e2307812, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38243646

RESUMO

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.


Assuntos
Ligas , Osteogênese , Implantes Absorvíveis , Ligas/química , Ligas/farmacologia , Teste de Materiais , Mitocôndrias/efeitos dos fármacos , Zinco/química , Disprósio/química , Disprósio/farmacologia , Osteogênese/efeitos dos fármacos , Sirtuínas/efeitos dos fármacos , Humanos , Fraturas Ósseas/tratamento farmacológico
16.
BMJ Open ; 13(5): e064825, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37258076

RESUMO

OBJECTIVES: The purpose of this study was to develop a prediction model to assess the risk of adjacent vertebral compression fractures (AVCFs) after percutaneous kyphoplasty (PKP) surgery. DESIGN: A retrospective chart review. SETTING AND PARTICIPANTS: Patients were collected from the Quzhou People's Hospital, from March 2017 to May 2019. Patients were included if they suffered from osteoporotic vertebral compression fractures (OVCFs), underwent PKP surgery and were followed up for 2 years. INTERVENTIONS: None. METHODS: This was a retrospective cohort study of all PKP surgery procedures of the thoracic, lumbar and thoracolumbar (TL) spine that have been performed for OVCF from 1 March 2017 up to 1 May 2019. The least absolute shrinkage and selection operator (LASSO) regression model was used to optimise feature selection for the AVCF risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the LASSO regression model. The C-index, calibration plot and decision curve analysis were applied to assess this model. RESULTS: Gender, age, the number of surgical vertebrae, cement volume, bone mineral density, diabetes, hypertension, bone cement leakage, duration of anti-osteoporosis treatment after surgery and TL junction were identified as predictors. The model displayed good discrimination with a C-index of 0.886 (95% CI 0.828-0.944) and good calibration. High C-index value of 0.833 could still be reached in the interval validation. Decision curve analysis showed that the AVCF nomogram was clinically useful when intervention was decided at the AVCF possibility threshold of 1%. CONCLUSIONS: This study developed a clinical prediction model to identify the risk factors for AVCF after PKP surgery, and this tool is of great value in sharing surgical decision-making among patients consulted before surgery. TRIAL REGISTRATION NUMBER: researchregistry7716.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cifoplastia/efeitos adversos , Cifoplastia/métodos , Estudos Retrospectivos , Fraturas por Compressão/etiologia , Fraturas por Compressão/cirurgia , Modelos Estatísticos , Resultado do Tratamento , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/complicações , Prognóstico , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Cimentos Ósseos/efeitos adversos , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/etiologia
17.
ACS Macro Lett ; 12(3): 408-414, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36897173

RESUMO

Fibrillar collagen structures mineralized with hydroxyapatite using the polymer-induced liquid precursor (PILP) process have been explored as synthetic models for studying biomineralization of human hard tissues and have also been applied in the fabrication of scaffolds for hard tissue regeneration. Strontium has important biological functions in bone and has been used as a therapeutic agent for treating diseases that result in bone defects, such as osteoporosis. Here, we developed a strategy to mineralize collagen with Sr-doped hydroxyapatite (HA) using the PILP process. Doping with Sr altered the crystal lattice of HA and inhibited the degree of mineralization in a concentration-dependent manner, but did not affect the unique formation of intrafibrillar minerals using the PILP. The Sr-doped HA nanocrystals were aligned in the [001] direction but did not recapitulate the parallel alignment of the c-axis of pure Ca HA in relation to the collagen fiber long axis. The mimicry of doping Sr in PILP-mineralized collagen can help understand the doping of Sr in natural hard tissues and during treatment. The fibrillary mineralized collagen with Sr-doped HA will be explored in future work as biomimetic and bioactive scaffolds for regeneration of bone and tooth dentin.


Assuntos
Biomimética , Colágenos Fibrilares , Humanos , Hidroxiapatitas , Colágeno/química , Durapatita/química , Estrôncio/farmacologia
18.
Head Face Med ; 19(1): 2, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717934

RESUMO

BACKGROUND: Extracting wholly impacted maxillary 3rd molars faces difficulty due to the narrow surgical field, adjacent teeth resistances and risk of oroantral communication. This study is designed to introduce and evaluate the applicability of a novel method-buccal rotation to extract maxillary 3rd molars. MATERIALS AND METHODS: In this cohort study, from October 1st 2020 to September 30th 2021, 72 wholly impacted maxillary 3rd molars were included. Based on the crowns with coronal 1/3, middle 1/3, apical 1/3 of the adjacent teeth roots, teeth were classified into position I, II, III. Based on the angles < 30°, ≥ 30°but < 60°, ≥ 60° to the adjacent teeth, teeth were classified into angulation A, B, C. Traditional method and novel method-buccal rotation were applied based on the surgical simulations. Surgical results were recorded. To analyze the data, Chi-square test was applied. RESULTS: 82.00% of teeth in position I and 50.00% in position II were designed to use traditional method, 83.33% in position III were using the novel method (p < 0.05). 81.25% of teeth in angulation A and 52.63% in angulation B were designed to use traditional method, 80.00% in angulation C were using the novel method (p < 0.05). Four cases got temporary complications. CONCLUSION: Buccal rotation was applicable to extract the deep impacted maxillary third molars with large angles towards the adjacent teeth.


Assuntos
Dente Serotino , Dente Impactado , Humanos , Dente Serotino/cirurgia , Estudos de Coortes , Rotação , Dente Molar , Dente Impactado/diagnóstico por imagem , Dente Impactado/cirurgia
19.
ACS Biomater Sci Eng ; 9(8): 4632-4645, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37486960

RESUMO

Photoactivating dental resin composites have been the most prevailing material for repairing dental defects in various clinical scenarios due to their multiple advantages. However, compared to other restorative materials, the surface of resin-based composites is more susceptible to plaque biofilm accumulation, which can lead to secondary caries and restoration failure. This study introduced different weight fractions (1, 2, 5, 10, and 15%) of magnesium oxide nanoparticles (MgONPs) as antibacterial fillers into dental resin composites. Multifarious properties of the material were investigated, including antibacterial activity against a human salivary plaque-derived biofilm, cytotoxicity on human gingival fibroblasts, mechanical and physicochemical properties as well as the performance when subjected to thermocycling aging treatment. Results showed that the incorporation of MgONPs significantly improved the composites' anti-biofilm capability even at a low amount of 2 wt % without compromising the mechanical, physicochemical, and biocompatibility performances. The results of the thermocycling test suggested certain of aging resistance. Moreover, a small amount of MgONPs possibly made a difference in enhancing photoactivated polymerization and increasing the curing depth of experimental resin composites. Overall, this study highlights the potential of MgONPs as an effective strategy for developing antibacterial resin composites, which may help mitigating cariogenic biofilm-associated secondary caries.


Assuntos
Óxido de Magnésio , Nanopartículas , Humanos , Teste de Materiais , Óxido de Magnésio/farmacologia , Resinas Compostas/farmacologia , Resinas Compostas/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química
20.
J Mech Behav Biomed Mater ; 141: 105783, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36996527

RESUMO

The inherent characteristics of resin composite can lead to micro-leakage after polymerization shrinkage. The bacteria invasion through edge micro-leakage and attachment onto the material surface can cause secondary caries, reducing the service life of resin composites. In this study, magnesium oxide nanoparticles (nMgO) as an inorganic antimicrobial agent and bioactive glass (BAG) as a remineralization agent were simultaneously incorporated into the resin composite. With the addition of both nMgO and BAG, the resin composite showed an excellent antimicrobial effect compared to the resin composite with nMgO or BAG only. The remineralization capacity of demineralized dentin increased with the increasing content of BAG. Vickers hardness, compressive strength, and flexural strength of the resin composite with nMgO-BAG were not significantly affected compared to the ones with the same total filler amount but with BAG only. The depth of cure and water sorption values of the resin composite showed an increasing trend with the increasing total amount of nMgO and BAG fillers. This developed multifunctional resin composite is expected to reduce bacterial invasion and promote remineralization of early caries damage.


Assuntos
Anti-Infecciosos , Vidro , Resinas Compostas , Antibacterianos/farmacologia , Resistência à Flexão , Teste de Materiais , Propriedades de Superfície
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