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1.
Arthrosc Tech ; 10(2): e481-e486, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33680782

ABSTRACT

Periprosthetic joint infection of the shoulder is a challenging clinical situation to manage owing to the fastidious organisms often present and delayed clinical presentation. While several treatment options have been described, the mainstay of treatment remains a staged revision with the use of a humeral antibiotic cement spacer. Such spacers are commercially available or can be made by hand. When an extended humeral osteotomy is required to remove a well-fixed long stem humeral component, it may be advantageous to place an antibiotic spacer with a stem length approximately as long as the hardware being removed. This technique demonstrates creation of a custom length, humeral antibiotic cement spacer for use in treatment of shoulder periprosthetic joint infection.

2.
J Arthroplasty ; 36(4): 1462-1469, 2021 04.
Article in English | MEDLINE | ID: mdl-33199093

ABSTRACT

BACKGROUND: Recent studies have suggested clinical superiority with robotic-assisted arthroplasty compared to traditional techniques. However, concerns exist regarding the author's financial conflicts of interest (COI), which may influence research outcomes. This study aimed to determine whether COI relating to robotic-assisted arthroplasty influences the results of published outcomes following total hip (THA), total knee (TKA), and unicompartmental knee arthroplasty (UKA). METHODS: We performed a systematic review to identify all studies evaluating the use of robotics in THA, TKA, and UKA. An author's financial COI was identified if they reported a relevant disclosure through the American Academy of Orthopedic Surgeons or within the study article. We then queried the Open Payments website to record all payments made from a robotic company in the year prior to publication. Each study was categorized as either favoring robotics (n = 42), neutral (n = 10), or favoring traditional techniques (n = 2). We then compared the number of conflicted authors, journal impact factor, level of evidence, and mean annual industry payment to each author. RESULTS: Of the 54 studies meeting inclusion criteria, 49 (91%) had an author financial COI. Conflicted studies were more likely to report favorable results of robotics than nonconflicted studies. When compared to studies favoring conventional techniques, those demonstrating favorable robotics outcomes had a higher number of conflicted authors and a higher mean industry payment per author. There was no difference in the level of evidence or journal impact factor. DISCUSSION: Nearly all studies comparing robotic THA, TKA, and UKA to conventional techniques involve financially conflicted authors. Further studies without COI may provide unbiased results.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Robotic Surgical Procedures , Conflict of Interest , Disclosure , Humans , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Treatment Outcome
3.
J Mech Behav Biomed Mater ; 103: 103588, 2020 03.
Article in English | MEDLINE | ID: mdl-32090917

ABSTRACT

Prosthetic joint infection (PJI) is one of the most devastating failures in total joint replacement (TJR). Infections are becoming difficult to treat due to the emergence of multi-drug resistant bacteria. These bacteria produce biofilm on the implant surface, rendering many antibiotics ineffective by compromising drug diffusion and penetration into the infected area. With the introduction of new antibiotics there is a need to create benchmark data from the traditional antibiotic loaded bone cements. Vancomycin, one of the commonly used antibiotics, shows activity against Methicillin-resistant Staphylococcus aureus (MRSA) and S.epidermidis. In our study, vancomycin added to bone cement was evaluated for elution properties, antimicrobial properties, and mechanical properties of the bone cement. Vancomycin at five different loading masses (0.125, 0.25, 0.5, 1.0 and 2.0 g) was added to 40 g of Simplex™ P cement. Addition of vancomycin affected the mechanical properties and antimicrobial activity with significant differences from controls. Flexural and compression mechanical properties were compromised with added vancomycin. The flexural strength of samples with added vancomycin of 0.5 g and greater were not greater than ISO 5833 minimum requirements. 2.0 g of vancomycin added to bone cement was able to eliminate completely the four bacterial strains tested. 2.0 g of vancomycin also showed the highest mass elution from the cement over a 60-day period. Given the reduced flexural strength in samples with 0.5 g and greater of added vancomycin and the inability of vancomycin in amounts less than 2.0 g to eliminate bacteria, this study did not find an ideal amount of vancomycin added to Simplex™ P that meets both strength and antibacterial requirements.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Vancomycin , Anti-Bacterial Agents/pharmacology , Bone Cements , Polymethyl Methacrylate , Vancomycin/pharmacology
4.
J Arthroplasty ; 34(10): 2347-2350, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31227302

ABSTRACT

BACKGROUND: Peri-prosthetic fractures after total knee arthroplasty (TKA) are associated with poorer outcomes and high costs. We hypothesize that osteoporosis is under-recognized in the TKA population. The purpose of this study is to report osteoporosis prevalence in a healthy cohort of patients with well-functioning TKA and to compare prevalence between males and females. METHODS: This study is a cross-sectional study of 30 adults (15 males/15 females) aged 59-80 years without known bone health issues who volunteered to undergo routine dual-energy X-ray absorptiometry 2-5 years (average 3.2 ± 0.8) after primary unilateral TKA. These data plus clinical risk factors were used to estimate fracture risk via the Fracture Risk Assessment Tool and skeletal status (normal, osteopenic, osteoporotic) was determined based on the World Health Organization definition. The National Osteoporosis Foundation criteria for treatment were applied to all patients. RESULTS: Six of 30 (20%) patients had T-score ≤ -2.5. Eighteen of 30 (60%) patients had T-score between -1 and -2.5 and 6 (20%) patients had T-score ≥ -1. Five patients with normal or osteopenic bone mineral density (BMD) had occult vertebral fractures. Eleven of 30 (36.7%) patients met National Osteoporosis Foundation criteria for pharmacologic treatment. CONCLUSION: The prevalence of occult osteoporosis meeting treatment guidelines after TKA is substantial in this sample (36.7%). BMD and osteoporosis prevalence are similar between men and women. This underappreciated prevalence of osteoporosis may contribute to peri-prosthetic fracture risk. Arthroplasty surgeons and bone health specialists must be aware of post-operative changes in bone density. These data support the further study of post-operative osteoporosis and consideration of routine BMD screening after TKA. LEVEL OF EVIDENCE: III.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Osteoporosis/complications , Osteoporosis/surgery , Absorptiometry, Photon , Adult , Aged , Aged, 80 and over , Bone Density , Cross-Sectional Studies , Female , Hip/pathology , Humans , Male , Middle Aged , Prevalence , Reoperation , Risk Factors , Spine , Young Adult
5.
J Arthroplasty ; 34(7): 1347-1353, 2019 07.
Article in English | MEDLINE | ID: mdl-30992237

ABSTRACT

BACKGROUND: Osteoporosis is common in total joint arthroplasty (TJA) patients and likely contributes to the increasing incidence of periprosthetic fracture. Despite this, the prevalence of osteoporosis in patients undergoing elective TJA is inadequately studied. We hypothesize that preoperative osteoporosis is underrecognized and undertreated in the TJA population. The purpose of this study is to report preoperative osteoporosis screening rates and prevalence prior to TJA and rates of pharmacologic osteoporosis treatment in the TJA population. METHODS: This is a retrospective case series of 200 consecutive adults (106F, 94M) aged 48-92 years who underwent elective TJA (100 total hip, 100 total knee) at a single tertiary-care center. Charts were retrospectively reviewed to determine preoperative osteoporosis risk factors, prior dual-energy X-ray absorptiometry (DXA) testing, and prior osteoporosis pharmacotherapy. Fracture risk was estimated using the Fracture Risk Assessment Tool and the National Osteoporosis Foundation criteria for screening and treatment were applied to all patients. RESULTS: One hundred nineteen of 200 patients (59.5%) met criteria for DXA testing. Of these 119, 21 (17.6%) had DXA testing in the 2 years prior to surgery, and 33% had osteoporosis by T-score. Forty-nine patients (24.5%) met National Osteoporosis Foundation criteria for pharmacologic osteoporosis treatment, and 11 of these 49 received a prescription for pharmacotherapy within 6 months before or after surgery. CONCLUSION: One quarter of TJA patients meet criteria to receive osteoporosis medications, but only 5% receive therapy preoperatively or postoperatively. This lack of preoperative osteoporosis screening and treatment may contribute to periprosthetic fracture risk.


Subject(s)
Arthritis/complications , Arthroplasty, Replacement, Knee , Osteoporosis/epidemiology , Periprosthetic Fractures/etiology , Postoperative Complications/etiology , Absorptiometry, Photon/statistics & numerical data , Adult , Aged , Aged, 80 and over , Arthritis/surgery , Arthroplasty, Replacement, Hip , Bone Density Conservation Agents/therapeutic use , Elective Surgical Procedures , Female , Humans , Knee Joint , Male , Middle Aged , Osteoporosis/complications , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Prevalence , Retrospective Studies , Tertiary Care Centers/statistics & numerical data , Wisconsin/epidemiology
6.
Stem Cells Transl Med ; 8(6): 522-534, 2019 06.
Article in English | MEDLINE | ID: mdl-30784225

ABSTRACT

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non-T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin-induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM-assocaited bone loss. Stem Cells Translational Medicine 2019;8:522-534.


Subject(s)
Bone Diseases, Metabolic/etiology , Bone Morphogenetic Protein 6/metabolism , Diabetes Mellitus, Type 1/pathology , Animals , Bone Density , Bone Morphogenetic Protein 6/genetics , Bone Morphogenetic Protein Receptors, Type II/metabolism , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Cell Differentiation/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 1/complications , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL , Osteogenesis/drug effects , Receptor, Transforming Growth Factor-beta Type II/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , X-Ray Microtomography
9.
FASEB J ; 33(1): 996-1007, 2019 01.
Article in English | MEDLINE | ID: mdl-30096039

ABSTRACT

Blood vessels composed of endothelial cells (ECs) contact with mesenchymal stem cells (MSCs) in different tissues, suggesting possible interaction between these 2 types of cells. We hypothesized that endothelin-1 (ET1), a secreted paracrine factor of ECs, can differentially direct the lineages of adipose-derived stem cells (ASCs) and bone marrow-derived MSCs (BMSCs). Predifferentiated ASCs and BMSCs were treated with ET1 for 2 cell passages and then induced for multilineage differentiation. Our results showed that adipogenesis of ET1-pretreated ASCs and osteogenesis of ET1-pretreated BMSCs were increased compared to those of control cells. The effect of ET1 on enhancing adipogenesis of ASCs and osteogenesis of BMSCs was attenuated by blocking endothelin receptor type A (ETAR) and/or endothelin receptor type B (ETBR). Western blot analysis indicated that regulation by ET1 was mediated through activation of the protein kinase B and ERK1/2 signaling pathways. We analyzed subpopulations of ASCs and BMSCs with or without ETAR and/or ETBR, and we found that ETAR+/ETBR- and ETAR-/ETBR+ subpopulations of ASCs and those of BMSCs pretreated with ET1 were prone to turning into adipocytes and osteoblasts, respectively, after differentiation induction. Our findings provide insight into the differential regulation of MSC specification by ET1, which may help develop viable approaches for tissue regeneration.-Lee, M.-S., Wang, J., Yuan, H., Jiao, H., Tsai, T.-L., Squire, M. W., Li, W.-J. Endothelin-1 differentially directs lineage specification of adipose- and bone marrow-derived mesenchymal stem cells.


Subject(s)
Adipose Tissue/cytology , Bone Marrow Cells/cytology , Endothelin-1/metabolism , Stem Cells/cytology , Adult , Cell Differentiation , Cell Lineage , Cell Proliferation , Cells, Cultured , Female , Humans , Male , Osteogenesis , Receptors, Endothelin/metabolism
10.
Data Brief ; 20: 14-19, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30101160

ABSTRACT

In this article, we report data on the antibiotic elution and efficacy, and mechanical properties of Palacos bone cement with different amounts of added vancomycin (0.0, 0.125, 0.25, 0.5, 1.0, 2.0 g), see "Vancomycin elution, activity and impact on mechanical properties when added to orthopedic bone cement" (Bishop et al., 2018) [1]. Mechanical testing was performed for four-point bending, compression, and fracture toughness. The release characteristics of vancomycin was recorded for up to 60 days to estimate the elution profile. The eluted vancomycin efficacy at eliminating the four most common causative orthopedic implant pathogens is also reported.

11.
J Mech Behav Biomed Mater ; 87: 80-86, 2018 11.
Article in English | MEDLINE | ID: mdl-30048880

ABSTRACT

Infection incidence for total hip and knee arthroplasty (THA and TKA, respectively) is between 0.2% and 5% and results in approximately 100,000 device failures per year in the United States. Treatment requires prolonged systemic antibiotic therapy with additional surgical revisions. As a prophylactic measure against infection, antibiotics can be incorporated into bone cement during THA and TKA to provide drug administration at the implant site. Antibiotics in bone cement are only effective if they can elute out of the cement at a concentration that is active against common organisms. There is evidence that added antibiotics may affect the cement's mechanical properties, especially at higher dosages. The purposes of this investigation were to (i) determine the mechanical properties of a commercially available bone cement with the addition of vancomycin, (ii) determine the release characteristics of vancomycin added to bone cement, and (iii) evaluate eluted vancomycin efficacy at eliminating some of the most common causative orthopedic implant pathogens. Palacos bone cement was impregnated with incrementally larger clinically relevant weight percentages of vancomycin. Vancomycin is a treatment standard for invasive gram-positive infections, and Palacos cement is one of the most commonly used bone cements. After 21 days of curing in PBS, added masses of vancomycin greater than 0.5 g per 40.0 g cement packet decreased the cement's compressive yield strength to below ISO standard. The addition of vancomycin reduced the bone cement's mechanical properties in compression more than in bending. Vancomycin eluted from Palacos with a steady rise in eluted volume up to 8 days, after which non-therapeutic elution concentrations were observed up to a 60-day end point. The eluted concentration from samples with greater than 0.25 g vancomycin per Palacos packet was sufficient to eliminate a 103 colony forming unit per mL (CFU/mL) initial inoculum of S. aureus, including methicillin-resistant S. aureus (MRSA). However, none of the tested dosages were able to fully clear a 103 CFU/mL initial inoculum of a known high biofilm producing strain of S. epidermidis. When used for infection prophylaxis at the time of THA and TKA, the findings of this study do not support the addition of more than 0.5 g vancomycin to a 40 g packet of Palacos cement due to a reduction in compression yield strength below ISO standards. Vancomycin doses up to 0.5 g were shown to elute from the bone cement matrix and are effective at treating bacterial infections of 103 CFU/mL in bacterial strains of S. aureus, but may have limited effect against high-biofilm producing strains including S. epidermidis.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bone Cements/chemistry , Mechanical Phenomena , Vancomycin/chemistry , Vancomycin/pharmacology , Orthopedics , Prosthesis-Related Infections/prevention & control , Staphylococcus/drug effects , Staphylococcus/physiology
12.
Am J Sports Med ; 46(3): 623-631, 2018 03.
Article in English | MEDLINE | ID: mdl-29328886

ABSTRACT

BACKGROUND: Insertion force has been shown to significantly reduce chondrocyte viability during osteochondral allograft transplantation. How graft size influences the required insertion force and chondrocyte viability has yet to be determined. Hypothesis/Purpose: The purpose was to characterize how graft size influences insertion force requirements and chondrocyte viability during osteochondral transplantation. The hypothesis was that larger grafts would require greater force and reduce chondrocyte viability. STUDY DESIGN: Controlled laboratory study. METHODS: Four graft sizes-15 × 5 mm, 15 × 10 mm, 25 × 5 mm, and 25 × 10 mm (diameter × depth)-were harvested from 13 thawed fresh-frozen human cadaveric distal femurs. Average, maximum, and cumulative force and number of impacts were recorded for 44 grafts by a surgical mallet embedded with a calibrated force sensor. In a separate experiment, fresh osteochondral tissues were subjected to mechanical loading. To capture a range of clinically important forces, categories were selected to correspond to impaction force data. Chondrocyte viability was assessed with confocal laser microscopy and live/dead staining. RESULTS: Total force for all grafts averaged 4576 N. Median number of impacts for all grafts was 20 (range, 7-116). The mean number of impacts for 5-mm-deep grafts was 14.2 (95% CI, 10.8-18.6), as compared with 26.3 (95% CI, 19.9-34.4) for 10-mm-deep grafts ( P < .001). The mean cumulative force for 5-mm-deep grafts was 2128 N (95% CI, 1467-3087), as opposed to 4689 N (95% CI, 3232-6803) for 10-mm-deep grafts ( P = .001). For every 1 mm in graft depth, an average of 13.1% (95% CI, 6.2%-20.3%) more impacts are required when controlling for diameter and density ( P < .001). For every 1 mm in graft depth, the force required increases on average by 17.1% (95% CI, 7.7%-27.4%) when controlling for diameter and density ( P = .001). There was a significant reduction in chondrocyte viability for the forces required for graft thickness values >10 mm. Only forces associated with graft thickness <10 mm had chondrocyte viabilities consistently >70%. CONCLUSION: Insertion force increases significantly with increasing graft depth. Controlling for diameter and bone density, a 1-mm increase in graft depth is associated with 13.1% more impacts and 17.1% more force. Chondrocyte viability was significantly reduced to <70% at average forces associated with grafts thicker than 10 mm. CLINICAL RELEVANCE: Based on the current data, graft depth is an important consideration for surgeons when sizing osteochondral allograft transplant for chondral lesions of the knee.


Subject(s)
Bone Transplantation , Chondrocytes/transplantation , Knee Joint/surgery , Cadaver , Cartilage/cytology , Cell Survival , Femur/transplantation , Humans , Staining and Labeling , Transplantation, Homologous , Transplants
13.
J Orthop Res ; 36(4): 1078-1085, 2018 04.
Article in English | MEDLINE | ID: mdl-28876459

ABSTRACT

Two-stage revision treatment of prosthetic joint infection (PJI) frequently employs the use of a temporary bone cement spacer loaded with multiple antibiotic types. Tobramycin and vancomycin are commonly used antibiotics in cement spacers, however, there is no consensus on the relative concentrations and combinations that should be used. Therefore, the purpose of this study was to investigate the influence of dual antibiotic loading on the total antibiotic elution and compressive mechanical properties of acrylic bone cement. Varying concentrations of tobramycin (0-3 g) and vancomycin (0-3 g) were added either alone or in combination to acrylic cement (Palacos R), resulting in 12 experimental groups. Samples were submerged in 37°C saline for 28 d and sampled at specific time points. The collected eluent was analyzed to determine the cumulative antibiotic release. In addition, the cement's compressive mechanical properties and porosity were characterized. Interestingly, the cement with the highest concentration of antibiotics did not possess the best elution properties. Cement samples containing both 3 g of tobramycin and 2 g vancomycin demonstrated the highest cumulative antibiotic release after 28 d, which was coupled with a significant decrease in the mechanical properties and an increased porosity. The collected data also suggests that tobramycin elutes more effectively than vancomycin from cement. In conclusion, this study demonstrates that high antibiotic loading in cement does not necessarily lead to enhanced antibiotic elution. Clinically this information may be used to optimize cement spacer antibiotic loading so that both duration and amount of antibiotics eluted are optimized. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1078-1085, 2018.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bone Cements , Compressive Strength , Polymethyl Methacrylate , Arthritis, Infectious/drug therapy , Humans , Porosity , Prosthesis-Related Infections/drug therapy , Tobramycin/administration & dosage , Vancomycin/administration & dosage
14.
J Biomed Mater Res B Appl Biomater ; 105(6): 1461-1468, 2017 08.
Article in English | MEDLINE | ID: mdl-27087200

ABSTRACT

Acrylic bone cement is often used in total joint replacement procedures to anchor an orthopaedic implant to bone. Bone cement is a viscoelastic material that exhibits creep and stress relaxation properties, which have been previously characterized using a variety of techniques such as flexural testing. Nanoindentation has become a popular method to characterize polymer mechanical properties at the nanoscale due to the technique's high sensitivity and the small sample volume required for testing. The purpose of the present work therefore was to determine the mechanical properties of bone cement using traditional macroscale techniques and compare the results to those obtained from nanoindentation. To this end, the quasi-static and viscoelastic properties of two commercially available cements, Palacos and Simplex, were assessed using a combination of three-point bending and nanoindentation. Quasi-static properties obtained from nanoindentation tended to be higher relative to three-point bending. The general displacement and creep compliance trends were similar for the two methods. These findings suggest that nanoindentation is an attractive characterization technique for bone cement, due to the small sample volumes required for testing. This may prove particularly useful in testing failed/retrieved cement samples from patients where material availability is typically limited. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1461-1468, 2017.


Subject(s)
Bone Cements/chemistry , Materials Testing , Elasticity , Stress, Mechanical , Viscosity
15.
Stem Cell Res Ther ; 6: 88, 2015 May 01.
Article in English | MEDLINE | ID: mdl-25998005

ABSTRACT

INTRODUCTION: Human mesenchymal stem cells (hMSCs) reside in a perivascular niche of the body, suggesting that they interact closely with vascular endothelial cells (ECs) through cell-cell interaction or paracrine signaling to maintain cell functions. Endothelin-1 (ET1) is a paracrine factor mainly secreted by ECs. We thus hypothesize that ECs can regulate cellular activities of hMSCs and direct their stem cell fate. METHODS: We investigated whether co-cultured human aortic endothelial cells (HAECs) were able to regulate expression of potency- and lineage-related markers in bone marrow-derived hMSCs. We further explored the regulatory effects of ET1 on cell proliferation, expression of surface antigens and pluripotency-related markers, and multilineage differentiation in hMSCs. Activation of the AKT signaling pathway in hMSCs was also analyzed to identify its mechanistic role in the ET1-induced regulation. RESULTS: Co-cultured HAECs enhanced expression of mesenchymal lineage-related markers in hMSCs. Treatment of ET receptor antagonist downregulated the increased expression of CBFA1 in hMSCs cultured with HAEC-conditioned medium. hMSCs treated with ET1 showed cell proliferation and expression of surface antigens, CD73, CD90, and CD105, comparable with those without ET1 treatment. ET1-treated hMSCs also expressed upregulated mRNA transcript levels of OCT3/4, NANOG, CBFA1 and SOX9. When induced for lineage-specific differentiation, hMSCs pre-treated with ET1 showed enhanced osteogenesis and chondrogenesis. However, adipogenic differentiation of hMSCs was not affected by ET1 pretreatment. We further showed that the ET1-induced regulation was mediated by activation of AKT signaling. CONCLUSION: Our results demonstrate that ET1 secreted by HAECs can direct bone marrow-derived hMSCs for osteo- and chondro-lineage differentiation through activation of the AKT signaling pathway, suggesting that ET1 plays a crucial role in regulation of hMSC activity. Our findings may help understand how hMSCs interact with ECs in a perivascular niche.


Subject(s)
Endothelial Cells/cytology , Endothelin-1/metabolism , Mesenchymal Stem Cells/cytology , Proto-Oncogene Proteins c-akt/metabolism , Antigens, CD/metabolism , Aorta/cytology , Bone Marrow Cells/cytology , Cell Differentiation/drug effects , Cell Lineage , Cell Proliferation/drug effects , Cells, Cultured , Chondrogenesis/drug effects , Coculture Techniques , Core Binding Factor Alpha 1 Subunit/metabolism , Culture Media, Conditioned/pharmacology , Down-Regulation/drug effects , Endothelial Cells/metabolism , Endothelin-1/analysis , Endothelin-1/pharmacology , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism
16.
Mater Sci Eng C Mater Biol Appl ; 48: 188-96, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25579913

ABSTRACT

Prosthetic joint infection is one of the most serious complications that can lead to failure of a total joint replacement. Recently, the rise of multidrug resistant bacteria has substantially reduced the efficacy of antibiotics that are typically incorporated into acrylic bone cement. Silver nanoparticles (AgNPs) are an attractive alternative to traditional antibiotics resulting from their broad-spectrum antimicrobial activity and low bacterial resistance. The purpose of this study, therefore, was to incorporate metallic silver nanoparticles into acrylic bone cement and quantify the effects on the cement's mechanical, material and antimicrobial properties. AgNPs at three loading ratios (0.25, 0.5, and 1.0% wt/wt) were incorporated into a commercial bone cement using a probe sonication technique. The resulting cements demonstrated mechanical and material properties that were not substantially different from the standard cement. Testing against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer and time-kill assays demonstrated no antimicrobial activity against planktonic bacteria. In contrast, cements modified with AgNPs significantly reduced biofilm formation on the surface of the cement. These results indicate that AgNP-loaded cement is of high potential for use in primary arthroplasty where prevention of bacterial surface colonization is vital.


Subject(s)
Anti-Infective Agents/pharmacology , Bone Cements/chemistry , Metal Nanoparticles/chemistry , Polymethyl Methacrylate/chemistry , Silver/pharmacology , Animals , Anti-Infective Agents/chemistry , Biofilms/drug effects , Biomechanical Phenomena , Bone Cements/pharmacology , Cell Line/drug effects , Materials Testing/methods , Mice, Transgenic , Osteoblasts/drug effects , Polymethyl Methacrylate/pharmacology , Silver/chemistry , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/physiology
17.
Mater Sci Eng C Mater Biol Appl ; 42: 168-76, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25063107

ABSTRACT

Soluble particulate fillers can be incorporated into antibiotic-loaded acrylic bone cement in an effort to enhance antibiotic elution. Xylitol is a material that shows potential for use as a filler due to its high solubility and potential to inhibit biofilm formation. The objective of this work, therefore, was to investigate the usage of low concentrations of xylitol in a gentamicin-loaded cement. Five different cements were prepared with various xylitol loadings (0, 1, 2.5, 5 or 10 g) per cement unit, and the resulting impact on the mechanical properties, cumulative antibiotic release, biofilm inhibition, and thermal characteristics were quantified. Xylitol significantly increased cement porosity and a sustained increase in gentamicin elution was observed in all samples containing xylitol with a maximum cumulative release of 41.3%. Xylitol had no significant inhibitory effect on biofilm formation. All measured mechanical properties tended to decrease with increasing xylitol concentration; however, these effects were not always significant. Polymerization characteristics were consistent among all groups with no significant differences found. The results from this study indicate that xylitol-modified bone cement may not be appropriate for implant fixation but could be used in instances where sustained, increased antibiotic elution is warranted, such as in cement spacers or beads.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Bone Cements/chemistry , Gentamicins/pharmacology , Xylitol/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Bone Cements/pharmacokinetics , Bone Cements/pharmacology , Gentamicins/chemistry , Gentamicins/pharmacokinetics , Materials Testing , Mechanical Phenomena , Polymethyl Methacrylate/chemistry , Solubility , Staphylococcus aureus/drug effects , Xylitol/pharmacology
18.
J Mech Behav Biomed Mater ; 37: 141-52, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24911668

ABSTRACT

Acrylic bone cement is widely used to anchor orthopedic implants to bone and mechanical failure of the cement mantle surrounding an implant can contribute to aseptic loosening. In an effort to enhance the mechanical properties of bone cement, a variety of nanoparticles and fibers can be incorporated into the cement matrix. Mesoporous silica nanoparticles (MSNs) are a class of particles that display high potential for use as reinforcement within bone cement. Therefore, the purpose of this study was to quantify the impact of modifying an acrylic cement with various low-loadings of mesoporous silica. Three types of MSNs (one plain variety and two modified with functional groups) at two loading ratios (0.1 and 0.2wt/wt) were incorporated into a commercially available bone cement. The mechanical properties were characterized using four-point bending, microindentation and nanoindentation (static, stress relaxation, and creep) while material properties were assessed through dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, FTIR spectroscopy, and scanning electron microscopy. Four-point flexural testing and nanoindentation revealed minimal impact on the properties of the cements, except for several changes in the nano-level static mechanical properties. Conversely, microindentation testing demonstrated that the addition of MSNs significantly increased the microhardness. The stress relaxation and creep properties of the cements measured with nanoindentation displayed no effect resulting from the addition of MSNs. The measured material properties were consistent among all cements. Analysis of scanning electron micrographs images revealed that surface functionalization enhanced particle dispersion within the cement matrix and resulted in fewer particle agglomerates. These results suggest that the loading ratios of mesoporous silica used in this study were not an effective reinforcement material. Future work should be conducted to determine the impact of higher MSN loading ratios and alternative functional groups.


Subject(s)
Materials Testing , Nanoparticles/chemistry , Polymethyl Methacrylate/chemistry , Silicon Dioxide/chemistry , Mechanical Phenomena , Microtechnology , Nanotechnology , Porosity , Surface Properties , Temperature
19.
Cell Tissue Res ; 358(1): 149-64, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24927918

ABSTRACT

Embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have been studied for years as primary cell sources for regenerative biology and medicine. MSCs have been derived from cell and tissue sources, such as bone marrow (BM), and more recently from ESCs. This study investigated MSCs derived from BM, H1- and H9-ESC lines in terms of morphology, surface marker and growth factor receptor expression, proliferative capability, modulation of immune cell growth and multipotency, in order to evaluate ESC-MSCs as a cell source for potential regenerative applications. The results showed that ESC-MSCs exhibited spindle-shaped morphology similar to BM-MSCs but of various sizes, and flow cytometric immunophenotyping revealed expression of characteristic MSC surface markers on all tested cell lines except H9-derived MSCs. Differences in growth factor receptor expression were also shown between cell lines. In addition, ESC-MSCs showed greater capabilities for cell proliferation, and suppression of leukocyte growth compared to BM-MSCs. Using standard protocols, induction of ESC-MSC differentiation along the adipogenic, osteogenic, or chondrogenic lineages was less effective compared to that of BM-MSCs. By adding bone morphogenetic protein 7 (BMP7) into transforming growth factor beta 1 (TGFß1)-supplemented induction medium, chondrogenesis of ESC-MSCs was significantly enhanced. Our findings suggest that ESC-MSCs and BM-MSCs show differences in their surface marker profiles and the capacities of proliferation, immunomodulation, and most importantly multi-lineage differentiation. Using modified chondrogenic medium with BMP7 and TGFß1, H1-MSCs can be effectively induced as BM-MSCs for chondrogenesis.


Subject(s)
Bone Marrow Cells/metabolism , Cell Differentiation/physiology , Cell Proliferation/physiology , Embryonic Stem Cells/metabolism , Mesenchymal Stem Cells/metabolism , Bone Marrow Cells/cytology , Bone Morphogenetic Protein 7/pharmacology , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Cell Shape/drug effects , Cell Shape/physiology , Embryonic Stem Cells/cytology , Humans , Mesenchymal Stem Cells/cytology , Transforming Growth Factor beta1/pharmacology
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