Matthew W. Squire

Unicompartmental knee replacement. A minimum 15 year followup study.

One hundred forty Marmor cemented unicompartmental knee replacements were inserted in 103 patients between 1975 and 1982. Fifty-two patients were women and 51 were men. One hundred twenty-five were medial compartment knee replacements and 15 were lateral knee replacements. At minimum 15 year followup 34 patients with 48 knee replacements were living; only four patients with four knee replacements were lost to followup. Average preoperative and final followup Hospital for Special Surgery knee scores were 57 and 82 points, respectively for the knees of living patients. Average preoperative and final followup Knee Society clinical and Knee Society functional scores were 31 and 42, and 85 and 71 points, respectively. For all knees, 10.2% (14 knees) were revised [4.4% (six knees) for tibial loosening, 5.1% (seven knees) for disease progression, and .7% (one knee) for pain]. For patients living 15 years, 12.5% (six knees) were revised [2.1% (one knee) for tibial loosening, and 10.4% (five knees) for disease progression]. Revision for failure of fixation of these unicompartmental replacements was comparable with that reported for fixed bearing total knee replacement. Disease progression (46%; 62 of 136 knees) and tibial subsidence with wear (10.4%; 15 of 136 knees, five of which required revision) were the major long term problems in this group of patients.

Mechanical, material, and antimicrobial properties of acrylic bone cement impregnated with silver nanoparticles.

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 cements 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.

Modification of acrylic bone cement with mesoporous silica nanoparticles: Effects on mechanical, fatigue and absorption properties

Polymethyl methacrylate bone cement is the most common and successful method used to anchor orthopedic implants to bone, as evidenced by data from long-term national joint registries. Despite these successes, mechanical failure of the cement mantle can result in premature failure of an implant which has lead to the development of a variety of techniques aimed at enhancing the mechanical properties of the cement, such as the addition of particulate or fiber reinforcements. This technique however has not transitioned into clinical practice, likely due to problems relating to interfacial particle/matrix adhesion and high cement stiffness. Mesoporous silica nanoparticles (MSNs) are a class of materials that have received little attention as polymer reinforcements despite their potential ability to overcome these challenges. Therefore, the objective of the present study was to investigate the use of mesoporous silica nanoparticles (MSNs) as a reinforcement material within acrylic bone cement. Three different MSN loading ratios (0.5%, 2% and 5% (wt/wt)) were incorporated into a commercially available bone cement and the resulting impact on the cements static mechanical properties, fatigue life and absorption/elution properties were quantified. The flexural modulus and compressive strength and modulus tended to increase with higher MSN concentration. Conversely, the flexural strength, fracture toughness and work to fracture all significantly decreased with increasing MSN content. The fatigue properties were found to be highly influenced by MSNs, with substantial detrimental effects seen with high MSN loadings. The incorporation of 5% MSNs significantly increased cements hydration degree and elution percentage. The obtained results suggest that the interfacial adhesion strength between the nanoparticles and the polymer matrix was poor, leading to a decrease in the flexural and fatigue properties, or that adequate dispersion of the MSNs was not achieved. These findings could potentially be mitigated in future work by chemically modifying the mesoporous silica with functional groups.

Preoperative Diagnosis of Periprosthetic Joint Infection: Role of Aspiration

OBJECTIVE The purpose of this article is to illustrate how total knee arthroplasty (TKA) and total hip arthroplasty (THA) aspiration by the radiologist can assist the health care team in determining the presence or absence of periprosthetic joint infection. CONCLUSION The increasing incidence of periprosthetic TKA and THA infection, as well as the changing role of aspiration for diagnosing periprosthetic joint infection, will likely increase demand for this important procedure in the future.

Premixed Antibiotic Bone Cement: An In Vitro Comparison of Antimicrobial Efficacy☆

After Food and Drug Administration (FDA) approval of premixed antibiotic bone cements (polymethylmethacrylate [PMMA]), these products are being used with increasing frequency during revision and primary hip and knee arthroplasties. To date, no studies have compared the antimicrobial efficacy of more than 2 products directly. Using a 7-day modified Kirby-Bauer assay, we assessed the in vitro antibacterial properties of 5 FDA-approved, commercially available antibiotic PMMAs. Significant differences in antimicrobial activity were noted among the antibiotic PMMA products included in this investigation. Antibacterial activity of all products tested was greatest on day 1 and rapidly diminished thereafter. Results of this investigation suggest that the antibacterial efficacies of premixed antibiotic PMMA products are not equivalent.

Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow

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 (TGFβ1)-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 TGFβ1, H1-MSCs can be effectively induced as BM-MSCs for chondrogenesis.

Endothelial cells direct human mesenchymal stem cells for osteo- and chondro-lineage differentiation through endothelin-1 and AKT signaling

IntroductionHuman 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.MethodsWe 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.ResultsCo-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.ConclusionOur 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.

Multiscale characterization of acrylic bone cement modified with functionalized mesoporous silica nanoparticles.

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.

Preoperative “NPO” as an opportunity for diabetes screening

BACKGROUND Novel preventive care opportunities, such as in hospitalized patients, may merit further investigation in an Accountable Care Organization (ACO) model. As 40% of patients with diabetes are undiagnosed, diabetes screening is an urgent public health need. Screening fasting preoperative patients may present an effective means to identify patients who might otherwise remain undiagnosed. OBJECTIVE To pilot an inpatient preventive care strategy for diabetes screening that would ascertain prevalence of unrecognized inpatient diabetes (DM) and impaired fasting glucose (IFG), determine reproducibility of preoperative fasting blood glucose (FBG), and establish feasibility of inpatient preventive screening. DESIGN Prospective observational study. SETTING Large Midwestern academic medical center. PATIENTS Two hundred seventy-five elective orthopedic patients with a preoperative visit between December 1, 2007 and November 30, 2008. Most patients (96.6%) had seen their primary care provider (PCP) within 12 months, and 100% were insured. MEASUREMENTS Medical history was recorded, and hemoglobin A(1C) (Hgb A(1C) ) and FBG were drawn immediately prior to surgery. Patients with preoperative FBG ≥100 mg/dL had FBG drawn 6-8 weeks postoperatively. RESULTS Twenty-four percent (67/275) of patients had previously unrecognized DM or IFG by virtue of 2 abnormal values. Sixty-four percent of patients with FBG ≥100 mg/dL preoperatively remained elevated at ambulatory follow-up. No patients with new DM or IFG had point-of-care glucose checks ordered or had dysglycemia mentioned on discharge summary. CONCLUSIONS Inpatient undiagnosed DM and IFG is common, even in insured, elective surgery patients with recent primary care visits. Preoperative FBG can be used to screen, but results need to be conveyed to PCPs.

Metabolic activity of osteoarthritic knees correlates with BMI

Osteoarthritis of the knee has consistently been linked to obesity, defined as a body mass index (BMI) >30kg/m(2). It has been hypothesized that obesity may lead to osteoarthritis through increased joint pressure, accumulated microtrauma, and disruption of normal chondrocyte metabolism. These changes in chondrocyte metabolism have not been thoroughly investigated, and it is the purpose of this study to identify a relationship between BMI and altered chondrocyte metabolism in osteoarthritic tissue. Articular cartilage was harvested from the femoral condyles of patients after total knee arthroplasty, and analyzed in explant and alginate models. Glycosaminoglycan (GAG) content was measured using a dimethylmethylene blue assay and normalized to DNA content using a PicoGreen(R) assay. Studies have reported GAGs to be a reliable measurement of chondrocyte metabolism and osteoarthritis progression. Our results show a significant linear relationship of increasing BMI and increasing GAG content in both alginate and explant models (p<0.001 and p=0.001). Obese (BMI>/=30kg/m(2)) and non-obese (BMI<30kg/m(2)) comparisons also demonstrated significant differences with higher GAG/DNA content in obese individuals compared to non-obese (p=0.001 and p=0.015). The study results reveal significant relationships between GAG content and BMI in this population of osteoarthritic patients. The significant difference in GAG content between the obese and non-obese patients supports the connection between osteoarthritis and obesity previously reported. Higher patient BMI (>30kg/m(2)) may be similar to dynamic compression injuries which cause increased GAG synthesis in response to cartilage damage.