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1.
Sci Rep ; 12(1): 18387, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319854

RESUMO

Currently, implants are utilized clinically for bone transplant procedures. However, if infectious osteomyelitis occurs at implant sites, removal of bacteria can be challenging. Moreover, altered blood flow at peri-implant infectious sites can create an anaerobic environment, making it more difficult to treat infection with antibiotics. Thus, it would be beneficial if implants could be modified to exhibit antibacterial activity, even in anaerobic conditions. Here, we show antibacterial activity of silver ions coated on titanium rods, even against the anaerobic bacteria Porphyromonas gingivalis (P. gingivalis), both in vitro and in vivo. Specifically, we implanted silver-coated or control uncoated titanium rods along with P. gingivalis in mouse femoral bone BM cavities and observed significantly inhibited P. gingivalis infection with silver-coated compared with non-coated rods, based on in vivo bio-imaging. Osteonecrosis by infectious osteomyelitis and elevation of the inflammatory factors C-reactive protein and IL-6 promoted by P. gingivalis s were also significantly reduced in the presence of silver-coated rods. Overall, our study indicates that silver ion coating of an implant represents a therapeutic option to prevent associated infection, even in anaerobic conditions or against anaerobic bacteria.


Assuntos
Antibacterianos , Bactérias Anaeróbias , Materiais Revestidos Biocompatíveis , Implantes Experimentais , Osteomielite , Prata , Animais , Camundongos , Antibacterianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Íons/farmacologia , Osteomielite/microbiologia , Osteomielite/prevenção & controle , Prata/farmacologia , Titânio/química , Porphyromonas gingivalis/efeitos dos fármacos , Implantes Experimentais/efeitos adversos , Implantes Experimentais/microbiologia , Fêmur , Proteína C-Reativa
2.
J Endocrinol Invest ; 45(1): 115-124, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34196924

RESUMO

AIM: To compare accuracy, efficacy and acceptance of implantable and transcutaneous continuous glucose monitoring (CGM) systems. METHODS: In a randomized crossover trial we compared 12 weeks with Eversense implantable sensor (EVS) and 12 weeks with Dexcom G5 transcutaneous sensor (DG5) in terms of accuracy, evaluated as Mean Absolute Relative Difference (MARD) vs capillary glucose (SMBG), time of CGM use, adverse events, efficacy (as HbA1c, time in range, time above and below range) and psychological outcomes evaluated with Diabetes Treatment Satisfaction Questionnaire (DTSQ), Glucose Monitoring Satisfaction Survey (GMSS), Hypoglycemia Fear Survey (HFS2), Diabetes Distress Scale (DDS). RESULTS: 16 subjects (13 males, 48.8 ± 10.1 years, HbA1c 55.8 ± 7.9 mmol/mol, mean ± SD) completed the study. DG5 was used more than EVS [percentage of use 95.7 ± 3.6% vs 93.5 ± 4.3% (p = 0.02)]. MARD was better with EVS (12.2 ± 11.5% vs. 13.1 ± 14.7%, p< 0.001). No differences were found in HbA1c. While using EVS time spent in range increased and time spent in hyperglycemia decreased, but these data were not confirmed by analysis of retrofitted data based on SMBG values. EVS reduced perceived distress, without significant changes in other psychological outcomes. CONCLUSIONS: CGM features may affect glycemic control and device acceptance.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico/instrumentação , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Automonitorização da Glicemia/efeitos adversos , Automonitorização da Glicemia/instrumentação , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Implantes Experimentais/efeitos adversos , Insulina/administração & dosagem , Sistemas de Infusão de Insulina/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
3.
J Biomed Mater Res A ; 109(8): 1521-1529, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33590952

RESUMO

The local response of tissue triggered by implantation of degradable magnesium-based implant materials was investigated in vivo in a murine model. Pins (5.0 mm length by 0.5 mm diameter) made of Mg, Mg-10Gd, and Ti were implanted in the leg muscle tissue of C57Bl/6N mice (n = 6). Implantation was generally well tolerated as documented by only a mild short term increase in a multidimensional scoring index. Lack of difference between the groups indicated that the response was systemic and surgery related rather than material dependent. Longitudinal in vivo monitoring utilizing micro-computed tomography over 42 days demonstrated the highest and most heterogeneous degradation for Mg-10Gd. Elemental imaging of the explants by micro X-ray fluorescence spectrometry showed a dense calcium-phosphate-containing degradation layer. In order to monitor resulting surgery induced and/or implant material associated local cell stress, sphingomyelin based liposomes containing indocyanine green were administered. An initial increase in fluorescent signals (3-7 days after implantation) indicating cell stress at the site of the implantation was measured by in vivo fluorescent molecular tomography. The signal decreased until the 42nd day for all materials. These findings demonstrate that Mg based implants are well tolerated causing only mild and short term adverse reactions.


Assuntos
Implantes Absorvíveis , Ligas/análise , Magnésio/análise , Implantes Absorvíveis/efeitos adversos , Ligas/efeitos adversos , Ligas/metabolismo , Animais , Imageamento Tridimensional , Implantes Experimentais/efeitos adversos , Magnésio/efeitos adversos , Magnésio/metabolismo , Teste de Materiais , Camundongos Endogâmicos C57BL , Imagem Óptica , Espectrometria por Raios X
4.
J Biomed Mater Res B Appl Biomater ; 109(4): 584-595, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32935912

RESUMO

Implant-associated soft tissue infections at the skin-implant interface represent the most frequent complications in reconstructive surgery and lead to implant failures and revisions. Titanium implants with deep porosity, called skin-and-bone-integrated-pylons (SBIP), allow for skin ingrowth in the morphologically natural direction, thus restoring a reliable dermal barrier and reducing the risk of infection. Silver coating of the SBIP implant surface using physical vapor deposition technique offers the possibility of preventing biofilm formation and exerting a direct antimicrobial effect during the wound healing phase. In vivo studies employing pig and rabbit dorsum models for assessment of skin ingrowth into the pores of the pylon demonstrated the safety of transcutaneous implantation of the SBIP system. No postoperative complications were reported at the end of the follow-up period of 6 months. Histological analysis proved skin ingrowth in the minipig model without signs of silver toxicity. Analysis of silver release (using energy dispersive X-ray spectroscopy) in the model of intramedullary-inserted silver-coated SBIP in New Zealand rabbits demonstrated trace amounts of silver after 3 months of in-bone implantation. In conclusion, selected temporary silver coating of the SBIP implant surface is powerful at preventing the periprosthetic infections without imparing skin ingrowth and can be considered for clinical application.


Assuntos
Materiais Revestidos Biocompatíveis , Implantes Experimentais , Prata/farmacologia , Infecções dos Tecidos Moles/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Cicatrização , Implantes Absorvíveis , Animais , Materiais Revestidos Biocompatíveis/efeitos adversos , Implantes Experimentais/efeitos adversos , Masculino , Teste de Materiais , Metaloproteinases da Matriz/análise , Microscopia Eletrônica de Varredura , Osseointegração , Porosidade , Desenho de Prótese , Coelhos , Prata/administração & dosagem , Pele/lesões , Infecções dos Tecidos Moles/etiologia , Espectrometria por Raios X , Infecção da Ferida Cirúrgica/etiologia , Suínos , Titânio , Cicatrização/efeitos dos fármacos
5.
J Biomed Mater Res A ; 109(5): 637-648, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32615012

RESUMO

A prosthetic scaffold development using fluorescent nanofiber is reported for an enhanced reepithelialization in wistar albino rats. In this study, a novel approach was followed to construct the biocompatible fluorescent nanofiber that will be helpful to monitor the tissue regeneration process. Here, a multifunctional carbon quantum dots (CQDs)-embedded electrospun polyacrylonitrile (PAN) nanofiber was fabricated and characterized using standard laboratory techniques. The biodegradation ability was assessed by simulated body fluid thereby analyzing porosity and water absorption capacity of the material. The fluorescent scaffold was tested for cytotoxicity and antimicrobial activity using bacterial and fibroblast cells and fluorescent stability was analyzed by bioimaging of animal and bacterial cells. Tissue regeneration capability of the developed scaffold was evaluated using wistar albino rats. Unlike biomicking scaffolds, the CQDs-embedded PAN-based substrate has given dual support by enhancing reepithelialization without growth factors and acted as an antimicrobial agent to provide contamination free tissue regeneration. Scaffolds were examined by using histostaining techniques and scanning electron microscopy to observe the reepithelialization in the regenerated tissues. The novel approach for developing infection free soft tissue regeneration was found to be phenomenal in scaffold development.


Assuntos
Materiais Biocompatíveis , Carbono , Regeneração Tecidual Guiada , Pontos Quânticos/uso terapêutico , Reepitelização/efeitos dos fármacos , Alicerces Teciduais , Resinas Acrílicas , Animais , Materiais Biocompatíveis/efeitos adversos , Adesão Celular , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/efeitos dos fármacos , Implantes Experimentais/efeitos adversos , Implantes Experimentais/microbiologia , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Nanofibras , Pontos Quânticos/administração & dosagem , Ratos , Ratos Wistar , Pele/lesões , Propriedades de Superfície , Alicerces Teciduais/efeitos adversos , Molhabilidade
6.
J Craniofac Surg ; 31(8): 2193-2198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33136853

RESUMO

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.


Assuntos
Implantes Experimentais/efeitos adversos , Arcada Osseodentária/efeitos dos fármacos , Tíbia/efeitos dos fármacos , Titânio/farmacologia , Animais , Feminino , Procedimentos Cirúrgicos Ortognáticos , Osteogênese/efeitos dos fármacos , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ovariectomia , Ratos , Tíbia/cirurgia
7.
Mar Drugs ; 18(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796603

RESUMO

Scaffold material is essential in providing mechanical support to tissue, allowing stem cells to improve their function in the healing and repair of trauma sites and tissue regeneration. The scaffold aids cell organization in the damaged tissue. It serves and allows bio mimicking the mechanical and biological properties of the target tissue and facilitates cell proliferation and differentiation at the regeneration site. In this study, the developed and assayed bio-composite made of unique collagen fibers and alginate hydrogel supports the function of cells around the implanted material. We used an in vivo rat model to study the scaffold effects when transplanted subcutaneously and as an augment for tendon repair. Animals' well-being was measured by their weight and daily activity post scaffold transplantation during their recovery. At the end of the experiment, the bio-composite was histologically examined, and the surrounding tissues around the implant were evaluated for inflammation reaction and scarring tissue. In the histology, the formation of granulation tissue and fibroblasts that were part of the inclusion process of the implanted material were noted. At the transplanted sites, inflammatory cells, such as plasma cells, macrophages, and giant cells, were also observed as expected at this time point post transplantation. This study demonstrated not only the collagen-alginate device biocompatibility, with no cytotoxic effects on the analyzed rats, but also that the 3D structure enables cell migration and new blood vessel formation needed for tissue repair. Overall, the results of the current study proved for the first time that the implantable scaffold for long-term confirms the well-being of these rats and is correspondence to biocompatibility ISO standards and can be further developed for medical devices application.


Assuntos
Antozoários/química , Materiais Biocompatíveis , Colágenos Fibrilares/química , Implantes Experimentais , Procedimentos Ortopédicos/instrumentação , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Alicerces Teciduais , Alginatos/química , Animais , Materiais Biocompatíveis/toxicidade , Modelos Animais de Doenças , Colágenos Fibrilares/isolamento & purificação , Colágenos Fibrilares/toxicidade , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Hidrogéis , Implantes Experimentais/efeitos adversos , Masculino , Procedimentos Ortopédicos/efeitos adversos , Desenho de Prótese , Ratos Wistar , Manguito Rotador/patologia , Lesões do Manguito Rotador/patologia , Fatores de Tempo , Alicerces Teciduais/efeitos adversos , Cicatrização
8.
JBJS Case Connect ; 10(2): e0399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649126

RESUMO

CASE: We describe the case of a 26-year-old man with an infected Radio-Frequency-Identification/Near Field Communication (RFID/NFC) chip in the middle finger. The RFID/NFC chip was removed, the soft tissue debrided, and a pan-sensitive staphylococcus aureus was detected by sonication of the RFID/NFC chip. The patient was postoperatively treated with amoxicillin and clavulanic acid (24 hours iv, total 11 days) and an intrinsic plus splint which led to complete recovery. CONCLUSION: Modern body modifications can lead to infections which shouldn't be underestimated. Interdisciplinary treatment is a key to success.


Assuntos
Reação a Corpo Estranho/etiologia , Implantes Experimentais/efeitos adversos , Dispositivo de Identificação por Radiofrequência , Adulto , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Desbridamento , Reação a Corpo Estranho/tratamento farmacológico , Reação a Corpo Estranho/cirurgia , Humanos , Masculino , Staphylococcus aureus/isolamento & purificação
10.
Methods Mol Biol ; 2140: 43-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32207105

RESUMO

3D bioprinting involves engineering live cells into a 3D structure, using a 3D printer to print cells, often together with a compatible 3D scaffold. 3D-printed cells and tissues may be used for a range of purposes including medical research, in vitro drug testing, and in vivo transplantation. The inclusion of living cells and biomaterials in the 3D printing process raises ethical, policy, and regulatory issues at each stage of the bioprinting process that include the source of cells and materials, stability and biocompatibility of cells and materials, disposal of 3D-printed materials, intended use, and long-term effects. This chapter focuses on the ethical issues that arise from 3D bioprinting in the lab-from consideration of the source of cells and materials, ensuring their quality and safety, through to testing of bioprinted materials in animal and human trials. It also provides guidance on where to seek information concerning appropriate regulatory frameworks and guidelines, including on classification and patenting of 3D-bioprinted materials, and identifies regulatory gaps that deserve attention.


Assuntos
Bioimpressão/ética , Impressão Tridimensional/ética , Experimentação Animal/ética , Experimentação Animal/normas , Animais , Transplante de Células/efeitos adversos , Transplante de Células/ética , Ensaios Clínicos como Assunto/ética , Estudos de Avaliação como Assunto , Experimentação Humana/ética , Humanos , Implantes Experimentais/efeitos adversos , Implantes Experimentais/ética , Propriedade Intelectual , Patentes como Assunto , Políticas , Guias de Prática Clínica como Assunto , Células-Tronco , Engenharia Tecidual/ética , Alicerces Teciduais/efeitos adversos
11.
Clin Exp Dent Res ; 6(1): 107-116, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32067396

RESUMO

OBJECTIVES: Diet-induced metabolic dysfunction such as type 2 diabetes mellitus increases the risk of implant failure in both dental and orthopaedic settings. We hypothesised that a diet high in fat and fructose would adversely affect peri-implant bone structure and function including osseointegration. MATERIALS AND METHODS: Thirty female Sprague-Dawley rats were divided into three groups (n = 10), control group (normal chow) and two intervention groups on a high-fat (60%), high-fructose (20%; HFHF) diet. Titanium implants were placed in the proximal tibial metaphysis in all groups either before commencing the diet (dHFHF group) or 6 weeks after commencing the diet (HFHF group) and observed for an 8-week healing period. Fasting blood glucose levels (fBGLs) were measured weekly. Structural and functional features of the peri-implant bone, including bone-to-implant contact (BIC), were analysed post euthanasia using microcomputed tomography, pull-out tests, and dynamic histomorphometry. RESULTS: The fBGLs were unchanged across all groups. Peri-implant trabecular bone volume was reduced in the HFHF group compared with controls (p = .02). Percentage BIC was reduced in both HFHF group (25.42 ± 3.61) and dHFHF group (28.56 ± 4.07) compared with the control group (43.26 ± 3.58, p < .05) and reflected the lower pull-out loads required in those groups. Osteoblast activity was reduced in both intervention groups compared with the control group (p < .05). CONCLUSION: The HFHF diet compromised osseointegration regardless of whether the implant was placed before or after the onset of the diet and, despite the absence of elevated fBGLs, confirming that changes in bone cell function affected both the initiation and maintenance of osseointegration independent of blood glucose levels.


Assuntos
Implantes Dentários/efeitos adversos , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Osseointegração/fisiologia , Animais , Glicemia/análise , Interface Osso-Implante/diagnóstico por imagem , Interface Osso-Implante/fisiopatologia , Comportamento Alimentar/fisiologia , Feminino , Frutose/efeitos adversos , Implantes Experimentais/efeitos adversos , Modelos Animais , Ratos , Ratos Sprague-Dawley , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Titânio/efeitos adversos , Microtomografia por Raio-X
12.
J Orthop Res ; 38(6): 1216-1227, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31825107

RESUMO

Biomarkers are of interest to identify patients at risk for peri-implant osteolysis and aseptic loosening. We used a rat model of particle-induced peri-implant osteolysis to investigate if early changes in biomarkers were associated with subsequent implant fixation strength. Implants were placed in rat femora, which were then challenged with intra-articular knee injections of either clean polyethylene, lipopolysaccharide-doped polyethylene, or cobalt-chromium alloy particles, with particle-free vehicle serving as control (n ≥ 8 per group). Rats were weighed weekly, blood was collected at weeks 0, 3, 5, and 6, and locomotor behavior was assessed 4 days before study conclusion. Rats were euthanized 6 weeks post surgery. Week 6 serum was analyzed for five bone remodeling markers, while longitudinal serum was assessed for osteocalcin. Bone-implant contact, peri-implant trabecular architecture, and implant fixation strength were measured. Rats challenged with cobalt-chromium particles had a significant reduction in implant fixation strength compared with the vehicle-control group (P = .034). This group also had elevated serum osteocalcin (P = .005), depressed weight gain (P = .001) and less frequent rearing behavior (P = .029). Regardless of group, change in serum osteocalcin at week 3 (r = -.368; P = .046), change in weight at week 2 (r = .586; P < .001), as well as weight change at all other time intervals were associated with fixation strength. The finding that early alterations in serum osteocalcin and body weight were predictive of subsequent implant fixation strength supports continued investigation of biomarkers for early detection of peri-implant osteolysis and implant loosening. Further, change in biomarker levels was found to be more indicative of implant fixation status than any single measurement.


Assuntos
Peso Corporal , Implantes Experimentais/efeitos adversos , Osteocalcina/sangue , Animais , Biomarcadores/sangue , Remodelação Óssea , Lipopolissacarídeos/farmacologia , Masculino , Atividade Motora , Osteólise , Polietileno/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Acta Biomater ; 100: 105-117, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31568879

RESUMO

Synthetic hydrogels, such as poly(ethylene glycol) (PEG), are promising for a range of in vivo applications. However, like all non-biological biomaterials, synthetic hydrogels including PEG elicit a foreign body response (FBR). The FBR is thought to be initiated by adsorbed protein that is recognized by and subsequently activates inflammatory cells, notably macrophages, and culminates with fibrotic encapsulation. However, the molecular mechanisms that drive the FBR are not well understood. Toll-like receptors (TLRs) are key receptors that recognize pathogens, but also recognize altered host proteins that display damage-associated molecular patterns (DAMPs). Thus TLRs may play a role in the FBR. Here, we investigated myeloid differentiation primary response gene 88 (MyD88), a signaling adaptor protein that mediates inflammatory cytokine production induced by most TLRs. An in vitro model was used consisting of macrophages cultured on the surface of synthetic hydrogels, specifically PEG, with pre-adsorbed serum proteins. Our in vitro findings demonstrate that MyD88-dependent signaling is the predominant inflammatory pathway in macrophage activation to synthetic hydrogels. When stimulated with TLR agonists to mimic additional DAMPs present in vivo, MyD88-dependent signaling was also the predominant pathway in macrophage activation. An in vivo model of PEG hydrogels implanted subcutaneously in wild-type and MyD88-/- mice also demonstrated that MyD88 is the key contributor to the recruitment of inflammatory cells and formation of the fibrous capsule surrounding the implanted hydrogel. Taken together, findings from this study identify MyD88-mediated inflammation as being a critical pathway involved not only in the inflammatory response, but in formation of the fibrous capsule to PEG hydrogels. STATEMENT OF SIGNIFICANCE: Synthetic hydrogels are promising for in vivo applications but, like all non-biological biomaterials, synthetic hydrogels elicit a foreign body response (FBR). The molecular mechanisms that drive the FBR are not well understood. This work identifies the myeloid differentiation primary response gene 88 (MyD88) as a central mediator to macrophage activation in response to a poly(ethylene glycol) hydrogel with pre-adsorbed proteins in vitro. Moreover, MyD88 was also central to the recruitment of inflammatory cells, which included neutrophils, monocytes, and macrophages, to implanted PEG hydrogels and to fibrous encapsulation. These findings demonstrate that MyD88-mediated inflammation is responsible in part for the formation of the fibrous capsule of the FBR.


Assuntos
Hidrogéis/efeitos adversos , Implantes Experimentais/efeitos adversos , Inflamação/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , Polietilenoglicóis/efeitos adversos , Transdução de Sinais , Alarminas/metabolismo , Animais , Fibrose , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/patologia , Ativação de Macrófagos , Masculino , Camundongos Endogâmicos C57BL
14.
Acta Biomater ; 89: 242-251, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30880234

RESUMO

Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.


Assuntos
Implantes Experimentais/efeitos adversos , Interleucinas/metabolismo , Macrófagos/metabolismo , Osteólise/metabolismo , Polietilenos/efeitos adversos , Vitamina E/efeitos adversos , Adulto , Animais , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/patologia , Masculino , Camundongos , Osteólise/induzido quimicamente , Osteólise/patologia , Polietilenos/farmacologia , Crânio/metabolismo , Crânio/patologia , Vitamina E/farmacologia
15.
J Biomed Mater Res B Appl Biomater ; 107(8): 2537-2548, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30779430

RESUMO

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag-Y) could extremely enhance the corrosion resistance of these elements, giving the Ex-Mg-1Ag-1Y alloy better anticorrosion rates. Here, we implanted the Ex-Mg-1Ag-1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex-Mg-1Ag-1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C-X-C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2 ) synthesis. Our work revealed that the Ex-Mg-1Ag-1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537-2548, 2019.


Assuntos
Ligas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Implantes Experimentais/efeitos adversos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Magnésio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Prata/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Ítrio
16.
Mater Sci Eng C Mater Biol Appl ; 97: 302-312, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678915

RESUMO

Bionanocellulose (BNC) is a clear polymer produced by the bacterium Gluconacetobacter xylinus. In our current study, "Research on the use of bacterial nanocellulose (BNC) in regenerative medicine as a function of the biological implants in cardiac and vascular surgery", we carried out material analysis, biochemical analysis, in vitro tests and in vivo animal model testing. In stage 1 of the project, we carried out physical and biological tests of BNC. This allowed us to modify subsequent samples of bacterial bionanocellulose. Finally, we obtained a sample that was accepted for testing on an animal model. That sample we define BNC1. Patches of BNC1 were then implanted into pigs' vessel walls. During the surgical procedures, we evaluated the technical aspects of sewing in the bioimplant, paying special attention to bleeding control and tightness of the suture line and the BNC1 bioimplant itself. We carried out studies evaluating the reaction of an animal body to an implantation of BNC1 into the circulatory system, including the general and local inflammatory reaction to the bioimplant. These studies allowed us to document the potential usefulness of BNC as a biological implant of the circulatory system and allowed for additional modifications of the BNC to improve the properties of this new implantable biological material.


Assuntos
Celulose/biossíntese , Celulose/química , Gluconacetobacter xylinus/metabolismo , Implantes Experimentais , Animais , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Procedimentos Cirúrgicos Cardíacos/instrumentação , Celulose/farmacologia , Hemólise/efeitos dos fármacos , Ácido Hialurônico/metabolismo , Implantes Experimentais/efeitos adversos , Inflamação/etiologia , Teste de Materiais , Suínos , Resistência à Tração
17.
J Biomed Mater Res B Appl Biomater ; 107(6): 2091-2101, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30629801

RESUMO

Negative Pressure Wound Therapy (NPWT) has been shown to limit downgrowth around percutaneous devices in a guinea pig model. However, the influence of NPWT on peri-prosthetic tissue characteristics leading to limited downgrowth is still unclear. In order to investigate this, 12 CD hairless rats were assigned into two groups, NPWT and Untreated (n = 6/group). Each animal was implanted with a porous coated titanium percutaneous device and was dressed with a gauze and semi-occlusive base dressing. Post-surgery, animals in the NPWT Group received a regimen of NPWT treatment (-70 to -90 mmHg). After 4 weeks, tissue was collected over the device and stained with CD31 and CD68 to quantify blood vessel density and inflammation, respectively. The device with the surrounding tissue was also collected to quantify downgrowth. NPWT treatment led to a 1.6-fold increase in blood vessel densities compared to untreated tissues (p < 0.05). NPWT treatment also resulted in half the downgrowth as the Untreated Group, although not statistically significant (p = 0.19). Additionally, the results showed a trend toward increased CD68 cell densities in the NPWT Group compared to the Untreated Group (p = 0.09). These findings suggest that NPWT may influence wound healing responses in percutaneous devices by increasing blood vessel densities, limiting downgrowth and potentially increasing inflammation. Overall, NPWT may enhance tissue vascularity around percutaneous devices, especially in patients with impaired wound healing. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2091-2101, 2019.


Assuntos
Interface Osso-Implante , Implantes Experimentais/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa , Neovascularização Fisiológica , Titânio , Cicatrização , Animais , Interface Osso-Implante/irrigação sanguínea , Interface Osso-Implante/patologia , Feminino , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Pelados , Porosidade , Titânio/efeitos adversos , Titânio/química , Titânio/farmacologia
18.
J Mater Chem B ; 7(11): 1951-1961, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255058

RESUMO

Implant infection is one of the most severe complications after orthopedic surgery. The construction of an antibacterial coating on orthopedic implants with release-killing or contact-killing is one of the most efficient strategies to prevent implant-related infections. Here we reported a hydroxypropyltrimethyl ammonium chloride chitosan (HACC) based multilayer modified plasma-sprayed porous titanium coating generated via the layer-by-layer covalent-immobilized method. We demonstrated that the multilayer coating inhibited the colonization and biofilm formation of several bacterial strains, including Staphylococcus aureus (ATCC 25923), methicillin-resistant Staphylococcus aureus (MSRA, ATCC 43300) and clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE 287), in vitro. HACC in the multilayer was released slowly with the degradation of the coating under the action of collagenase, further killing the planktonic bacteria, while the remaining HACC could kill the colonized bacteria. In a rat model of femur implants, the HACC-based multilayer-modified TCs effectively controlled the infection caused by MRSA and prevented bone destruction. Therefore, the HACC-based multilayer modified TCs with multiple antimicrobial properties could be a new potential ideal surface modification strategy to prevent implant associated infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Implantes Experimentais/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Células Cultivadas , Quitosana/análogos & derivados , Quitosana/farmacologia , Feminino , Humanos , Ácido Hialurônico/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Ratos , Ratos Sprague-Dawley , Staphylococcus epidermidis/efeitos dos fármacos , Titânio/farmacologia
19.
J Investig Clin Dent ; 10(1): e12378, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30474243

RESUMO

AIM: The aim of the present study was to evaluate the efficacy on the healing of mechanical decontamination of infected implant surfaces performed with a titanium brush. METHODS: Mandibular premolars and first molars were extracted bilaterally in six dogs. After 3 months, two unsubmerged implants were installed on both sides of the mandible. Three months later, peri-implantitis was induced with ligatures for 3 months and then removed. After 1 month, surgical mechanical decontamination of the surfaces was performed either with a rotatory titanium brush or gauzes soaked in saline. Five month later, biopsies were retrieved. Evaluations on X-rays taken of the mesiodistal plane and on histological slides prepared in a buccal-lingual plane were performed. RESULTS: After the induction of peri-implantitis, a mean marginal bone loss of 2.6 ± 0.6 mm and 1.9 ± 1.0 mm was observed in the brush and gauze groups by X-ray, respectively. Five months after treatment, a mean gain of marginal bone of 0.6 mm was obtained in both groups. The mean closures of the vertical and horizontal defects were 0.6 mm and 0.6 mm for the brush group, and 0.8 mm and 0.5 mm for the gauze group, respectively. Histologically, a loss of attachment at the buccal aspect of 2.2 ± 0.9 mm in the brush group and of 2.3 ± 0.5 mm in the gauze group was found. No statistically-significant differences were found after the treatment. CONCLUSIONS: Mechanical implant surface decontamination performed with a rotatory titanium brush resulted in a marginal bone level gain, yielding a low content of inflammatory infiltrate close to the marginal bone.


Assuntos
Descontaminação/métodos , Peri-Implantite/diagnóstico por imagem , Peri-Implantite/patologia , Peri-Implantite/terapia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/terapia , Animais , Dente Pré-Molar/patologia , Descontaminação/instrumentação , Implantação Dentária Endóssea/efeitos adversos , Implantes Dentários/efeitos adversos , Placa Dentária , Planejamento de Prótese Dentária , Modelos Animais de Doenças , Cães , Implantes Experimentais/efeitos adversos , Mandíbula/patologia , Mandíbula/cirurgia , Peri-Implantite/cirurgia , Radiografia Dentária/métodos , Propriedades de Superfície , Titânio
20.
J Biomed Mater Res A ; 107(1): 187-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30358096

RESUMO

This study investigated the interactive behavior of the particulate and ion forms of cobalt-chromium (Co-Cr) alloy challenged preosteoblasts during the process of prosthetic implant loosening. Preosteoblasts were challenged with Co-Cr particles or Co(II) ions for 72 h, followed by the proliferation and PCR assays. For in vivo test, a titanium pin was implanted into proximal tibia of SCID mice to mimic knee replacement. Co-Cr particles or Co(II) ion challenged preosteoblasts (5 × 105 ) were intra-articularly injected into the implanted knee. The animals were sacrificed 5 weeks post-op, and the prosthetic knees were harvested for biomechanical pin-pullout testing, histological evaluations, and microCT assessment. In vitro study suggested that Co-Cr particles and Co(II) ions significantly suppressed the proliferation of preosteoblasts in a dose-dependent manner. RT-PCR data on the challenged cells indicated overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) and inhibited osteoprotegerin (OPG) gene expression. Introduction of the differently challenged preosteoblasts to the pin-implant mouse model resulted in reduced implant interfacial shear strength, thicker peri-implant soft-tissue formation, more TRAP+ cells, lower bone mineral density, and bone volume fraction. In conclusion, both Co-Cr particles and Co(II) ions interfered with the growth, maturation, and functions of preosteoblasts, and provides evidence that the metal ions as well play an important role in effecting preosteoblasts in the pathogenesis of aseptic loosening. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 187-194, 2019.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ligas de Cromo/toxicidade , Implantes Experimentais/efeitos adversos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteólise/metabolismo , Material Particulado/toxicidade , Falha de Prótese/efeitos adversos , Animais , Linhagem Celular , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos SCID , Osteoblastos/patologia , Osteoclastos/patologia , Osteólise/patologia
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