Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass. Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR. Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment. Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons.
Aim. Prosthetic joint infections pose a major clinical challenge. Developing novel material surface technologies for orthopedic implants that prevent bacterial adhesion and biofilm formation is essential. Antimicrobial coatings applicable to articulating implant surfaces are limited, due to the articulation mechanics inducing wear, coating degradation, and toxic particle release. Noble metals are known for their antimicrobial activity and high
Anterior cruciate ligament (ACL) reconstruction is the current standard of care for ACL tears. However, the results are not consistently successful, autografts or allografts have certain disadvantages, and synthetic grafts have had poor clinical results. The aim of this study was to determine the efficacy of tissue engineering decellularized tibialis tendons by recellularization and culture in a dynamic tissue bioreactor. To determine if recellularization of decellularized tendons combined with mechanical stimulation in a bioreactor could replicate the mechanical properties of the native ACL and be successfully used for ACL reconstruction in vivo. Porcine tibialis tendons were decellularized and then recellularized with human adult bone marrow-derived stem cells. Tendons were cultured in a tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To reproduce mechanical stresses similar to hose experienced by the ACL within the knee joint, the tendons were subjected to simultaneous tension and torsion in the bioreactor. Expression of tendon-specific genes, and newly synthesized collagen and glycosaminoglycan (GAG) were used to quantify the efficacy of recellularization and dynamic bioreactor culture. The
Background. Tigecycline, the first member of glycylcycline family, has effective antimicrobial activity against resistant and implant associated infectious organisms. The objectives of this study are to assess the compressive and tensile
Background. Antibiotic-loaded cement has been used over decades as a local antibiotic delivery for the treatment of bone and joint infections. However, there were some disadvantages such as unpredictable elution, insufficient local concentration and reduced
Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and
Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient
Introduction. Total Elbow Arthroplasty (TEA) is recognized as an effective treatment solution for patients with rheumatoid arthritis or for traumatic conditions. Current total elbow devices can be divided into linked or unlinked design. The first design usually presents a linking element (i.e. an axle) to link together the ulnar and humeral components to stabilize the joint; the second one does not present any linkage and the stability is provided by both intrinsic design constraints and the soft tissues. Convertible modular solutions allow for an intraoperative decision to link or unlink the prosthesis; the modular connections introduce however additional risks in terms of both
INTRODUCTION. Electron beam melting is a promising technique to produce surface structures for cementless implants. Biomimetic apatite coatings can be used to enhance bone ingrowth. The goal of this study was to evaluate bone ingrowth of an E-beam produced structure with biomimetic coating and compare this to an uncoated structure and a conventionally made implant surface. METHODS. Implants. The implants (10×4×4mm) were produced with E-beam technology. (Eurocoating). All E-beam implants had a cubic surface structure (porosity 77%). Two structures were coated (Eurocoating), one with hydroxyapatite (cubicHA) and one with brushite (cubicBR). One was left uncoated. A control specimen with a titanium plasma spray coating (TiPS) was also tested. (Figure 1). Experimental design. Surgery was performed on 12 goats. A double set of specimens was implanted in the iliac crest. 4 goats were sacrificed 3 weeks after surgery and 8 goats after 15 weeks. Push out test. The specimens were pushed out the surrounding bone by a Material Testing System (MTS) to define the
Purpose. The Birmingham Mid-Head Resection (BMHR) is a bone-conserving, short-stem alternative to hip resurfacing for patients with compromised femoral head anatomy. It is unclear, however, if an uncemented, metaphyseal fixed stem confers a mechanical advantage to that of a traditional hip resurfacing in which the femoral prosthesis is cemented to the prepared femoral head. Thus, we aimed to determine if a metaphyseal fixed, bone preserving femoral component provided superior
Purpose. Failure resulting from a recurrent infection in total knee arthroplasty (TKA) is a challenging problem. Knee arthrodesis is one treatment option, however fusion is not always successful, as there is huge bone defect. The authors reports a new arthrodesis technique that uses a bundle of flexible intramedullary rods and an antibiotic-loaded cement spacer. Methods. There were 13 cases of arthrodesis due to recurrent periprosthetic joint infection, which were performed by the first author (WS Cho) at Asan Medical Center in Seoul from 2005 to 2014. All previous prosthetic components were removed and cement was thoroughly excised using a small osteotome. Two stage operation was done in most of cases. After thorough debridement, antibiotics loaded cement was inserted in first stage, flexible intramedullary rods were inserted retrogradely in the femoral side with the knee in flexion under fluoroscopy guidance. After filling the femoral intramedullary canal, the rods were then driven back securely into the tibial medullary canal. We aimed for as much rod length as possible to maximize stability. After 6 weeks of first stage operation, the rods of the femoral and tibial sides were arranged such that they overlapped and interdigitated to maximize
Patella fracture after total knee arthroplasty has a variety of etiologies and has been reported to occur with an incidence ranging from 3% to 21%. Heavy patients with full flexion are at greatest risk for sustaining patella fracture. Overstuffing the patellofemoral joint with an oversized femoral component, an anteriorised femoral component or a femoral component placed in excessive extension can also overload the underlying patella. A similar phenomenon may be seen with underrsection of the patella or use of a thick button. Excessive patellar resection can predispose to patellar fracture as well. It has been demonstrated that a residual patella thickness of less than 15 mm can substantially increase anterior patellar strain. Asymmetric patellar resection can also critically alter the
Introduction. In vitro studies showed that the anti-oxidative properties of vitamin E stabilize free radicals while retaining the
Porous surfaces on orthopaedic implants have been shown to promote tissue ingrowth. This study evaluated biological fixation of novel additively manufactured porous implants with and without hydroxyapatite coatings in a canine transcortical model. Laser rapid manufacturing (LRM) Ti6Al4V cylindrical implants were built with a random interconnected architecture mimicking cancellous bone (5.2 mm diameter, 10mm length, 50–60% porous, mean pore size 450μm). Three groups were investigated in this study: as-built with no coating (LRM), as-built coated with solution precipitated hydroxyapatite (LRM-PA), and as-built coated with a plasma sprayed hydroxyapatite (LRM-PSHA). Implants were press-fit into a 5mm unicortical, perpendicular drill hole in the femoral diaphysis of the left and right femurs in 12 canines. Right femora were harvested for histology (SEM, bone ingrowth into implant within cortical region) and left femora for mechanical push-out testing (shear strength of bone-implant interface) at 4 and 12 weeks (N=6, un-paired Student's t-test, p=0.05). For mean bone ingrowth, there was no significant difference between groups at 4 weeks (LRM, LRM-PA, LRM-PSHA: 41.5+8.6%, 51+5.5% and 53.2+11%, respectively) or 12 weeks (LRM, LRM-PA, LRM-PSHA: 64.4+2.8%, 59.9+7.6%, 64.9+6.4%, respectively). LRM and LRM-PA implants had more bone ingrowth at 12 weeks than 4 weeks (p < 0 .05). Mean shear strength of all implants at 12 weeks (LRM, LRM-PA, LRM-PSHA: 39.9+3.6MPa, 33.7+4.6MPa, 36+4.1MPa respectively) were greater than at 4 weeks (LRM, LRM-PA, LRM-PSHA: 21.6+2.8MPa, 20.7+1.1MPa, 20.2+2.5MPa respectively) (p < 0 .05). No significant difference was observed between all groups at 4 or 12 weeks. Overall, this canine study confirmed the suitability of this novel additive manufacturing porous material for biological fixation by bone ingrowth. All implants exhibited high bone ingrowth and
Aim. Cementless prosthesis is one of the major bone-implant interface fixation methods in total joint replacement. Grit blasted surface, hydroxyapatite coated surface and plasma sprayed metallic porous coating have been popularly used. The latter has demonstrated higher bone implant mechanical stability in previous laboratory study in early and middle stages. However, question remains what the mechanism is to make it performing better and how to improve them further. This study is designed to examine the mode of failure in bone-implant interface in a sheep model. Method. Plasma sprayed porous coated (TiPL); hydroxyapatite (HA) coated and and grit blasted (TiGB) titanium implants were examined in the study. Each type has 36 specimens. Implants were inserted into cortical bones in a press-fit fashion in a total of 22 sheep bilateral hind limbs. Specimens were retrieved at 4 weeks and 12 weeks. Push- out testing was performed to just reach ultimate failure. Failed bone-implant interface were investigated by histology and BSEM. The percentage of failure at bone-coating interface, bone itself fracture, coating itself failure, and coating-substrate dissociation were measured by BSEM. Results. In TiPL group, failure occurred mainly at new bone itself on ingrowing new bone and adjacent bone, with 74% at 4 weeks, and 82% at 12 weeks. The percentages were significantly higher than that of the failure at bone-porous coating dissociation. Furthermore, the percentage of failure occurred at bone was also higher in TiPS group than in the other groups at both time points. In HA group, the main proportion of failure, 69%, occurred at bone-HA dissociation at 4 weeks, higher than the 25% at bone itself fracture. 57% of failure occurred at HA-substrate dissociation at 12 weeks, which was followed by HA coating itself breakage (Figure 1). Bone itself fracture has the lowest proportion of only 4% breakage at 12 weeks. HA coating revealed micro cracks at some area although not all of them were failed. In TiGB group, failure mainly occurred at bone-implant surface dissociation at both time points. Conclusion. The failure mode at the HA and TiGB groups demonstrate that new bone was less likely to break, or stronger, than bone-implant surface interface at early stage, and new bone at middle stage was stronger than the other interfaces. The bone ingrowth to metallic porous coating results in that major proportion failure has to occur at bone anchorage, either at the entry level or at adjacent bone. The anchorage is the reason why TiPS has higher
Self-locking button-like fixation devices for ACL reconstruction are attracting knee surgeons' attention due to promising technical advantages: complete filling of the tunnel with graft, anatomic reconstruction (AM portal), fixation achievement even when a short tunnel is reamed, opportunity of graft re-tensioning after tibial fixation and/or cyclic load. We compared two similar devices (TightRope vs ToggleLocZL). 20 fresh-frozen porcine femurs (mean age 2.1 years) were assigned to the two groups by randomization. Hamstrings with 9 mm of diameter were obtained using bovine tendons that show the same biomechanic behaviour of human hamstrings. Femoral tunnel was created by AM portal technique (anatomic position). Zwick-Roell z010 tension/compression device with bone and tendon clamps, was used for the study:. Cyclic test (1000 cycles, 0.5 Hz, 50–250 N/cycle, 50 cycles of preload at 10–80 N/cycle). Final pull-out test (1 mm/s). Failure analysis. CT scan and densitometry. Any implant didn't fail during cyclic test. The elongation average was 2.85±1.63 for ToggleLoc and 2.71±.85 for TightRope (P>0.05). Pull-out test showed different values in terms of Ultimate Strength Failure (USF), Stiffness at USF, and Stiffness:. The failure mode was:. The mean method of failure was the fracture of the cortical bone of the femoral condyle, for both groups. But if we extrapolate the USF the difference was favourable(P<0.05) for TightRope (707.83 N) than ToggleLoc (580.16). The mean bone density of porcine femora was comparable to young human femora (1.12±0.31 BMD). The reproducibility of surgical technique, the
Introduction. Recently, the combination of press-fit acetabular cup with ceramic articulation is a widely used for implanting cementless acetabular components and has been shown to provide good initial stability. However, these methods may lead to elevating stresses, changing in the bearing geometries, and increasing wear due to deformation of the cup and insert. In addition, there is a potential for failure of ceramic inserts when a large ball head was used because it should be assembled with shallow thickness of the acetabular cup. For risk reduction of it, we applied direct metal tooling (DMT) based on 3D printing for porous coating on the cup. Due to its capability of
Predictable fracture healing fails to occur in 5–10% of cases. This is particularly concerning among individuals with osteoporosis. With an increasing aging population, one in three women and one in five men above the age of 50 experience fragility fractures. As such, there is a critical need for an effective treatment option that could enhance fracture healing in osteoporotic bone. Lithium, the standard treatment for bipolar disorder, has been previously shown to improve fracture healing through modulation of the Wnt/beta-catenin pathway. We optimised the precise oral lithium administration parameters to improve
There is no question that excellent long-term results have been demonstrated with all-polyethylene tibial components. Moreover, improvements in polyethylene to increase wear resistance, maintain
Background. In young patients with femoral neck non-union it is desirable to preserve the femoral head. The objective of this study was to assess the outcome results of revision internal fixation and nonvascular fibular bone grafting. Patients and Methods:. Ten patients with non united fracture neck femur were included in this prospective study. Fixation was done with two cancellous screws leaving behind a space between two screws for fibular strut graft. Assessment of union was done by both clinical and radiological criteria. Results:. union was achieved in 8 cases in an average time of 16 weeks (range 12–20 weeks). There was no infection, thromboembolic complications, donor site morbidity or implant failure in our series. Conclusion:. Nonvascularized fibular strut graft along with cancellous screws provides a biological and mechanically sound method of treatment. Fibula being cortical provides