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Mathijssen N.M.C.,Netherlands Bone Bank Foundation | Petit P.L.C.,Vlietland Hospital | Pilot P.,Reinier de Graaf Gasthuis | Schreurs B.W.,UMC St. Radboud | And 2 more authors.
BMC Musculoskeletal Disorders | Year: 2010

Background. Allograft bone used in joint replacement surgery can additionally serve as a carrier for antibiotics and serve as a prophylaxis against infections. However, in vitro dose-response curves for bone chips impregnated with different kinds of antibiotics are not available. In addition, while it would be desirable to add the antibiotics to allograft bone chips before these are stored in a bone bank, the effects of different storage temperatures on antibiotics are unknown. Methods. Five different antibiotics (cefazolin, clindamycin, linezolid, oxacillin, vancomycin) were stored, both as pills and as solutions, at -80°C, -20°C, 4°C, 20°C and 37°C; in addition, bone chips impregnated with cefazolin and vancomycin were stored at -80°C and -20°C. After 1 month, 6 months and 1 year, the activity of the antibiotics against Staphylococcus epidermidis was measured using an inoculated agar. The diameter of the S. epidermidis-free zone was taken as a measure of antibiotic activity. In a separate experiment, in vitro dose-response curves were established for bone chips impregnated with cefazolin and vancomycin solutions at five different concentrations. Finally, the maximum absorbed amounts of cefazolin and vancomycin were established by impregnating 1 g of bone chips with 5 ml of antibiotic solution. Results. A decrease of the S. epidermidis-free zone was seen with oxacillin and cefazolin solutions stored at 37°C for 1 month, with vancomycin stored at 37°C for 6 months and with cefazolin and oxacillin solutions stored at 20°C for 6 months. The activity of the other antibiotic solutions, pills and impregnated bone chips was not affected by storage. The in vitro dose-response curves show that the free-zone diameter increases logarithmically with antibiotic concentration. The absorbed antibiotic amount of one gram bone chips was determined. Conclusions. Storage of antibiotics in frozen form or storage of antibiotic pills at temperatures up to 37°C for 12 months does not affect their activity. However, storage of antibiotic solutions at temperatures above 20°C does affect the activity of some of the antibiotics investigated. The in vitro dose-response curve can be used to determine the optimal concentration(s) for local application. It provides the opportunity to determine the antibiotic content of bone chips, and thus the amount of antibiotics available locally after application. © 2010 Mathijssen et al; licensee BioMed Central Ltd.


PubMed | Wayne State University, Beaumont Health System and Orthopaedic Research Laboratory
Type: Comparative Study | Journal: Osteoarthritis and cartilage | Year: 2016

Animal models are frequently used to study post-traumatic osteoarthritis (PTOA). A common anterior cruciate ligament (ACL) injury model is surgical transection, which may introduce confounding factors from surgery. Noninvasive models could model human injury more closely. The purpose of this study was to compare subchondral and epiphyseal trabecular bone remodeling after surgical transection and noninvasive rupture of the ACL.Thirty-six rats were randomized to an uninjured control, surgical transection (Transection), or noninvasive rupture (Rupture). Animals were randomized to 4 or 10 week time points (n=6 per group). Micro computed tomography (CT) imaging was performed with an isotropic voxel size of 12m. Subchondral and epiphyseal bone was segmented semi-automatically, and morphometric analysis was performed.Transection caused a greater decrease in subchondral bone volume fraction (BV/TV) than Rupture in the femur and tibia. Rupture had greater subchondral bone tissue mineral density (TMD) at 4 and 10 weeks in the femur and tibia. Subchondral bone thickness (SCB.Th) was decreased in the femur in Transection only. Epiphyseal BV/TV was decreased in Transection only, and Rupture exhibited increased femoral epiphyseal TMD compared to both Control and Transection. Rupture exhibited greater femoral epiphyseal trabecular thickness (Tb.Th.) compared to Control and Transection at 4 weeks, and both Rupture and Transection had increased femoral epiphyseal Tb.Th. at 10 weeks. Epiphyseal trabecular number (Tb.N) was decreased in both injury groups at both time points. Femoral and tibial epiphyseal structure model index (SMI) increased in both groups.The two injury models cause differences in post-injury bone morphometry, and surgical transection may be introducing confounding factors that affect downstream bony remodeling.


News Article | November 7, 2016
Site: www.sciencedaily.com

Some potentially good news for aging Baby Boomers: researchers believe that they have developed a hip replacement that will last longer and create fewer problems for the people who receive them than those currently in use. The secret? An implant that "tricks" the host bone into remaining alive by mimicking the varying porosity of real bones. Interestingly, the key factor that distinguishes the new implant is that is LESS rather than more solid than those in current use, while still being just as strong. Damiano Pasini, the man behind the design of the new hip replacement, points at the pyramid-like shapes visible on its surface. The implant is known as a femoral stem and connects the living femur with the artificial hip joint. "What we've done throughout the femoral stem is to replicate the gradations of density found in a real femur by using hollowed-out tetrahedra," he explains. "Despite the fact that there are spaces within the tetrahedra, these forms are incredibly strong and rigid so they're a very efficient way of carrying a load. Just think of the lattice-work in the legs of the Tour Eiffel." Pasini teaches mechanical engineering at McGill University and first started working on the concept for the implant more than 6 years ago. He smiles ruefully as he pulls earlier versions of the implant down from the shelves in his office to show how far he has come since then. He elaborates: "So because the implant loosely mimics the cellular structure of the porous part of the surrounding femur, it can "trick" the living bone into keeping on working and staying alive. This means that our implant avoids many of the problems associated with those in current use." Indeed, the main problem with most implants is that because they are solid, or only porous on the surface, they are much harder and more rigid than natural bone. As a result, the implants absorb much of the stress along with the weight-bearing role that is normally borne by the living femur. Without sufficient stress to stimulate cell formation, the bone material in the living femur then becomes reabsorbed by the body and the bone itself begins to deteriorate and become less dense. This is one of the reasons that many implants become painful and need to be replaced after a time. It also explains why people often have difficulty if they have to have the same hip replaced a second time, because there simply isn't enough normal, healthy bone to hold the implant in place. It is a problem that orthopaedic surgeons are seeing more and more frequently. Implants not so easy the second-time around Dr. Michael Tanzer from the Jo Miller Orthopaedic Research Laboratory at McGill has been collaborating with Damiano Pasini for several years. "Because people engage in various sports where they may be injured more than they did in the past, we see younger people needing hip replacements more frequently," says Dr. Tanzer. "And because people are also living longer, they often need to have the same hip replaced a second time. Unfortunately, I've seen many cases where people simply don't have enough living bone for that to work easily. We are optimistic that this implant will reduce these kinds of problems." After successfully performing various tests on their implant, the researchers are so convinced that their femoral stem will work that they have already filed patents on it. They believe that because their current design is fully compatible with existing surgical technology for hip replacements it should be easier for the FDA to approve and surgeons to adopt. In the meantime, Burnett Johnston, who started working with Damiano Pasini on developing the implants when he was a Masters student has now enrolled at McGill's medical school. His goal? To be the first person to actually implant one of these replacement hips once he qualifies as a surgeon and the new femoral stems have been fully tested, adjusted and accepted -- something that Damiano Pasini estimates may happen in about three-five years' time.


News Article | November 2, 2016
Site: www.eurekalert.org

Some potentially good news for aging Baby Boomers: researchers believe that they have developed a hip replacement that will last longer and create fewer problems for the people who receive them than those currently in use. The secret? An implant that "tricks" the host bone into remaining alive by mimicking the varying porosity of real bones. Interestingly, the key factor that distinguishes the new implant is that is LESS rather than more solid than those in current use, while still being just as strong. Damiano Pasini, the man behind the design of the new hip replacement, points at the pyramid-like shapes visible on its surface. The implant is known as a femoral stem and connects the living femur with the artificial hip joint. "What we've done throughout the femoral stem is to replicate the gradations of density found in a real femur by using hollowed-out tetrahedra," he explains. "Despite the fact that there are spaces within the tetrahedra, these forms are incredibly strong and rigid so they're a very efficient way of carrying a load. Just think of the lattice-work in the legs of the Tour Eiffel." Pasini teaches mechanical engineering at McGill University and first started working on the concept for the implant more than 6 years ago. He smiles ruefully as he pulls earlier versions of the implant down from the shelves in his office to show how far he has come since then. He elaborates: "So because the implant loosely mimics the cellular structure of the porous part of the surrounding femur, it can "trick" the living bone into keeping on working and staying alive. This means that our implant avoids many of the problems associated with those in current use." Indeed, the main problem with most implants is that because they are solid, or only porous on the surface, they are much harder and more rigid than natural bone. As a result, the implants absorb much of the stress along with the weight-bearing role that is normally borne by the living femur. Without sufficient stress to stimulate cell formation, the bone material in the living femur then becomes reabsorbed by the body and the bone itself begins to deteriorate and become less dense. This is one of the reasons that many implants become painful and need to be replaced after a time. It also explains why people often have difficulty if they have to have the same hip replaced a second time, because there simply isn't enough normal, healthy bone to hold the implant in place. It is a problem that orthopaedic surgeons are seeing more and more frequently. Dr. Michael Tanzer from the Jo Miller Orthopaedic Research Laboratory at McGill has been collaborating with Damiano Pasini for several years. "Because people engage in various sports where they may be injured more than they did in the past, we see younger people needing hip replacements more frequently," says Dr. Tanzer. "And because people are also living longer, they often need to have the same hip replaced a second time. Unfortunately, I've seen many cases where people simply don't have enough living bone for that to work easily. We are optimistic that this implant will reduce these kinds of problems." After successfully performing various tests on their implant, the researchers are so convinced that their femoral stem will work that they have already filed patents on it. They believe that because their current design is fully compatible with existing surgical technology for hip replacements it should be easier for the FDA to approve and surgeons to adopt. In the meantime, Burnett Johnston, who started working with Damiano Pasini on developing the implants when he was a Masters student has now enrolled at McGill's medical school. His goal? To be the first person to actually implant one of these replacement hips once he qualifies as a surgeon and the new femoral stems have been fully tested, adjusted and accepted - something that Damiano Pasini estimates may happen in about three-five years' time.


Mathijssen N.M.C.,Reinier de Graaf Groep | Hannink G.,Orthopaedic Research Laboratory | Pilot P.,Reinier de Graaf Groep | Schreurs B.W.,UMC St. Radboud | And 2 more authors.
BMC Musculoskeletal Disorders | Year: 2012

Background: Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods. 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 g/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results: Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions: A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. © 2012 Mathijssen et al; licensee BioMed Central Ltd.


Shimmin A.,Melbourne Orthopaedic Group | Martinez-Martos S.,Melbourne Orthopaedic Group | Owens J.,Entrance | Iorgulescu A.D.,Orthopaedic Research Laboratory | Banks S.,Orthopaedic Research Laboratory
Knee | Year: 2015

Background: The ideal total knee arthroplasty should provide maximum range of motion and functional stability for all desired daily activities. The SAIPH™ (MatOrtho; UK) knee has a medial pivot knee kinematic pattern designed to achieve medial stability and an asymmetric posterior translation of the lateral femoral condyle during knee flexion and in this way attempts to mimic the natural knee motion. This study aims to analyze knee kinematics of the SAIPH™ total knee arthroplasty (TKA) by videofluoroscopy during four different weightbearing activities. Methods: Fourteen consecutive patients operated on by a single surgeon, with a minimum follow-up of 24. months were included in this IRB-approved study. There were no exclusions based on patient's functional level. A medially conforming knee was implanted in all cases. Participants in the study were asked to perform the clinically relevant functional activities of pivoting, kneeling, lungeing and step-up/down activities while their knee motion was recorded by videofluoroscopy. Results: Maximum knee flexion during the kneeling activity mean 127° (100°-155°). An asymmetric posterior translation of the lateral femoral condyle (LFC) was observed during pivoting, kneeling, lungeing and stepping. No paradoxical anterior translation of the femoral condyles was observed in any activity. Conclusion: The kinematics observed in this implant are similar in pattern, although smaller in magnitude, to normal functional knees, showing a posterior translation of the lateral femoral condyle during knee flexion, with internal rotation of the tibia, and no paradoxical anterior motion in any of the four weight bearing activities. © 2014 Elsevier B.V.


Maiti A.,Orthopaedic Research Laboratory | Jiranek W.A.,Virginia Commonwealth University
BMC Cell Biology | Year: 2014

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant cause of bone infection. Toll like receptors (TLRs) are an important segments of host response to infection and are expressed by a variety of cells including human mesenchymal stem cells (hMSCs). The active form of Vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunoregulatory properties, but the mechanism remains poorly understood. The genomic action of 1,25(OH)2D3 is mediated by vitamin D receptor (VDR), hormone-regulated transcription factor. VDR interacts with co-activators and co-repressors are associated with chromatin histone modifications and transcriptional regulation. The aim of our study is to explore MRSA-induced TLRs-mediated pro-inflammatory cytokines expression in hMSCs. Further, we hypothesized that 1,25(OH)2D3 inhibits MRSA-induced cytokines synthesis in hMSCs via inhibition of NF-k{cyrillic}B transcription factor. Finally, we explored the regulatory role of 1,25(OH)2D3 in MRSA-mediated global epigenetic histone H3 mark, such as, trimethylated histone H3 lysine 9 (H3K9me3), which is linked to gene silencing.Results: Quantitative PCR data revealed that MRSA-infection predominantly induced expression of TLRs 1, 2, 6, NR4A2, and inflammatory cytokines IL-8, IL-6, TNFα in hMSCs. MRSA-mediated TLR ligands reduced osteoblast differentiation and increased hMSCs proliferation, indicating the disrupted multipotency function of hMSCs. Pretreatment of 1,25(OH)2D3 followed by MRSA co-culture inhibited nuclear translocation of NF-k{cyrillic}B-p65, reduced expression of NR4A2 and pro-inflammatory cytokines IL-8, IL-6, and TNFα in hMSCs. Further, NF-κB-p65, VDR, and NR4A2 were present in the same nuclear protein complex, indicating that VDR is an active part of the nuclear protein complexes for transcriptional regulation. Finally, 1,25(OH)2D3 activated VDR, restores the global level of H3K9me3, to repress MRSA-stimulated inflammatory cytokine IL-8 expression. Pretreatment of 5-dAZA, DNA methylatransferases (Dnmts) inhibitor, dramatically re-expresses 1,25(OH)2D3-MRSA-mediated silenced IL-8 gene.Conclusions: This data indicates that TLR 1, 2, and 6 can be used as markers for localized S. aureus bone infection. 1,25(OH)2D3-VDR may exhibits its anti-inflammatory properties in MRSA-stimulated infection by inhibiting nuclear translocation of NF-kB-p65 and transcripts of IL-8, IL-6, TNFα, and NR4A2 in hMSCs. Finally, 1,25(OH)2D3-activated VDR, acting as an epigenetic regulator, inhibits synthesis of cytokines in MRSA-stimulated infection by restoring the global level of H3K9me3, a histone H3 mark for gene silencing. © 2014 Maiti and Jiranek; licensee BioMed Central Ltd.


De Mulder E.L.W.,Orthopaedic Research Laboratory | Hannink G.,Orthopaedic Research Laboratory | Hannink G.,Radboud University Nijmegen | Koens M.J.W.,Radboud University Nijmegen | And 4 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2013

Polyurethane scaffolds (PUs) have a good biocompatibility but lack cell recognition sites. In this study, we functionalized the surface of a PU, P(D/L)LA and PCL (50:50) containing urethane segments, with heparin. The first step in this functionalization, aminolysis, lead to free amine groups on the surface of the PU. Free amine content was determined to be 6.4 nmol/mL/mg scaffold, a significant increase of 230%. Subsequently, heparin was crosslinked. Immunohisto-chemistry demonstrated the presence of heparin homogeneous throughout the 3D porous scaffold. Young's modulus decreased significantly till 50% of the native stiffness after aminolysis and did not change after heparin crosslinking. Contact angle on PU films significantly decreased from 82.7° to 64.3° after heparin crosslinking, indicating a more hydrophilic surface. This functionalization beholds great potential for tissue engineering purposes. When used in a load-bearing environment, caution is necessary due to reduction in mechanical stiffness. © 2012 Wiley Periodicals, Inc.


Weinans H.,Orthopaedic Research Laboratory | Siebelt M.,Orthopaedic Research Laboratory | Agricola R.,Orthopaedic Research Laboratory | Botter S.M.,Erasmus MC | And 2 more authors.
Bone | Year: 2012

Osteoarthritis (OA) is a disease that involves the entire joint, but its pathophysiology is not well described. Alterations in peri-articular bone are an integral part of the OA disease process and different aspects of bone changes have been described in different patient (sub)groups and animal models. In this review we will discuss the osteoarthritis pathophysiology from the perspective of periarticular bone changes, which can be considered at three hierarchical levels: the bone (or joint) shape, the subchondral bone architecture and its cellular and molecular phenotype. In this review we try to provide an overview of the current knowledge of peri-articular bone changes in OA and what it could possibly imply for the initiation of OA and its progression.This article is part of a Special Issue entitled "Osteoarthritis". © 2012 Elsevier Inc.


PubMed | Orthopaedic Research Laboratory and Lawrence Technological University
Type: | Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society | Year: 2016

The objective of this study was to quantify and compare the contrast-enhancing properties of the anionic contrast agent ioxaglate/Hexabrix, and cationic contrast agent CA

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