Elimination of bacteria on different implant surfaces through photosensitization and soft laser. An in vitro study.

Microbiologic examinations of implants have shown that certain micro‐organisms described as periodontal pathogens may have an influence on the development and the progression of peri‐implant disease. This experimental study aimed to examine the bactericidal effect of irradiation with a soft laser on bacteria associated with peri‐implantitis following exposure to a photo‐sensitizing substance. Platelets made of commercially pure titanium, either with a machined surface or with a hydroxyapatite or plasma‐flame‐sprayed surface or with a corundum‐blasted and etched surface, were incubated with a pure suspension of Actinobacillus actinomyetemcomitans or Porphyromonas gingivalis or Prevotella intermedia. The surfaces were then treated with a toluidine blue solution and irradiated with a diode soft laser with a wave length of 905 nm for 1 min. None of the smears obtained from the thus treated surfaces showed bacterial growth, whereas the smears obtained from surfaces that had been subjected to only one type of treatment showed unchanged growth of every target organism tested ( P <0.0006). Electron microscopic inspection of the thus treated platelets revealed that combined dye/laser treatment resulted in the destruction of bacterial cells. The present in vitro results indicate that lethal photosensitization may be of use for treatment of peri‐implantitis.     

Longitudinal Model of Periprosthetic Joint Infection in the Rat

The majority of periprosthetic joint infections occur shortly after primary joint replacement (<3 months) and require the removal of all implant components for the treatment period (~4 months). A clinically relevant animal model of periprosthetic infection should, therefore, establish an infection with implant components in place. Here, we describe a joint replacement model in the rat with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components inoculated at the time of surgery by methicillin-sensitive Staphylococcus aureus (S. aureus), which is one of the main causative microorganisms of periprosthetic joint infections. We monitored the animals for 4 weeks by measuring gait, weight-bearing symmetry, von Frey testing, and micro-CT as our primary endpoint analyses. We also assessed the infection ex vivo using colony counts on the implant surfaces and histology of the surrounding tissues. The results confirmed the presence of a local infection for 4 weeks with osteolysis, loosening of the implants, and clinical infection indicators such as redness, swelling, and increased temperature. The utility of specific gait analysis parameters, especially temporal symmetry, hindlimb duty factor imbalance, and phase dispersion was identified in this model for assessing the longitudinal progression of the infection, and these metrics correlated with weight-bearing asymmetry. We propose to use this model to study the efficacy of using different local delivery regimens of antimicrobials on addressing periprosthetic joint infections. Statement of clinical significance: We have established a preclinical joint surgery model, in which postoperative recovery can be monitored over a multi-week course by assessing gait, weight-bearing, and allodynia. This model can be used to study the efficacy of different combinations of implant materials and medication regimens. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1101-1112, 2020     

Advances in the processing, sterilization, and crosslinking of ultra-high molecular weight polyethylene for total joint arthroplasty.

Despite the recognized success and worldwide acceptance of total joint arthroplasty, wear is a major obstacle limiting the longevity of implanted UHMWPE components. Efforts to solve the wear problem in UHMWPE have spurred numerous detailed studies into the structure, morphology, and mechanical properties of the polymer at every stage of its production from original resin into stock material and final fabricated form. Scientific developments in this field are occurring at an accelerating rate, and periodic review of UHMWPE technology is therefore increasingly necessary. The present article provides a four-part comprehensive review of technological advancements in the processing, manufacture, sterilization, and crosslinking of UHMWPE for total joint replacements. The first part of this article describes the recently updated nomenclature of UHMWPE, including the process of resin production and conversion to stock material. The second part outlines the methods of manufacturing UHMWPE into joint replacement components and provides overviews of alternate forms of UHMWPE, namely carbon-fiber reinforced UHMWPE (Poly II) and UHMWPE recrystallized under high temperature and pressure (Hylamer). The third part summarizes the sterilization and degradation of UHMWPE. Newly developed methods for accelerating the oxidation of UHMWPE after sterilization (for preconditioning of test specimens), as well as methods for quantifying the oxidation of UHMWPE, are also discussed. Finally, the fourth part reviews the development and properties of crosslinked UHMWPE, a promising alternate biomaterial for total joint replacements.     

Identifying disease modifying genes in multiple sclerosis

Evidence is mounting that genetic variation influences not only susceptibility to multiple sclerosis (MS), but also its course and severity. Identification of disease modifying genes, however, poses unique challenges, especially on how to classify the course and outcome of the disease in ways that may be relevant to analysis of biological factors that might be influenced by genes. The power of the statistical approaches to detect small effects of individual genes in complex disorders such as MS is problematic, and approaches to estimate power must be appropriate for the data. Nonetheless, using contemporary schemes of classification, genetic variants that influence disease course have been found; in fact, a small number have been confirmed to influence disease course in two or more independent studies. This review addresses strategies relevant to identification of disease modifying genes in MS, and summarizes and critically evaluates the current state of knowledge in this area.     

Third-body wear testing of a highly cross-linked acetabular liner: the effect of large femoral head size in the presence of particulate poly(methyl-methacrylate) debris

The hip simulator wear performance of an electron beam cross-linked and subsequently melted ultrahigh molecular weight polyethylene against femoral heads of 28-, 38-, and 46-mm diameter in the presence of poly(methyl-methacrylate) particulate debris was contrasted with that of conventional polyethylene against a 46-mm diameter head. Over 5 million cycles of testing, the average wear rate of the conventional polyethylene liners was 29.3 +/- 3.0 mg per million cycles. All highly cross-linked components exhibited marked reduction in wear, with the highest wear measuring 0.74 +/- 0.85 mg per million cycles. This study, using a clinically relevant third-body material, showed the electron beam cross-linked material to be far more resistant to this third-body wear than conventional ultrahigh molecular weight polyethylene, even when very large diameter femoral heads were used.     

The measurement of creep in ultrahigh molecular weight polyethylene: a comparison of conventional versus highly cross-linked polyethylene

Quantification of creep of highly cross-linked polyethylene would enable separation of creep from wear when evaluating femoral head penetration into polyethylene. We compared creep magnitude of a highly cross-linked versus conventional polyethylene in the laboratory. Twelve acetabular liners of each material were tested, 6 of which had a 32-mm inner diameter (ID) and 6 had 28-mm ID. Creep was measured using coordinate measuring machines during loading at 2 Hz without motion to 4 million cycles. Penetration into 32-mm ID conventional liners reached 97 microm versus 107 microm for highly cross-linked material, not significant. Penetration into 28-mm conventional liners was 132 microm versus 155 microm for highly cross-linked material (P = .017). Ninety percent of the creep had occurred by 2.5 million cycles.     

CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis

Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS.     

CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS

CD95/CD95L interaction results in activation-induced apoptosis thereby regulating clonal expansion of T cells outside the thymus. Genetic defects in this system result in autoimmune lymphoproliferation in mice and men. CD95-induced cell death may be defective in MS. We studied the association of CD95 and CD95L polymorphisms with MS in 221 unique patients representing 79% ascertainment in Olmsted County, MN, and 442 gender-, age- and ethnicity-matched controls. Being a homozygote for the G allele of CD95 5'(-670)*A-->G SNP (p=0.034; OR: 1.59, 95% CI: 1.06-2.38) and for the C allele of CD95 E7(74)*C-->T SNP (p=0.007; OR: 1.73, 95% CI: 1.17-2.56) increased susceptibility to MS exclusively in women. There was strong but incomplete linkage disequilibrium between the two markers (p<0.001; D'=0.546). Homozygosity for 5'(-670)*A or E7(74)*C explained 28% of risk of MS in women but 0% of the risk in men in Olmsted County, MN. Our results agree with the previously published studies and highlight that the association of the polymorphisms is restricted to women with MS. We did not find an association between CD95L and susceptibility to MS nor CD95 or CD95L and age of onset, disease course and disease severity.