Fracture healing is a complex process, which is more complicated if the bone is osteoporotic. One of the vitamin E isomers, α-tocopherol, has been found to prevent osteoporosis and improve bone fracture healing but its role in the healing of osteoporotic fractures is still unclear. We carried out a study on the effects of α-tocopherol supplementation on osteoporotic fracture healing using an ovariectomized rat model, whereby we focused on the early phase of fracture healing, that is, the phase with excessive production of free radicals. Twenty-four female Sprague-Dawley rats were divided into three groups: sham-operated (SO), ovariectomized-control (OVC), and ovariectomized + α-tocopherol supplementation (ATF) groups. The right femora of all the rats were fractured at mid-diaphysis and K-wires were inserted for internal fixation. After 2 weeks of treatment, the rats were euthanized and the femora were dissected out for measurement of callous volume by CT-scan and radiological staging of callous formation and fracture healing. The oxidative parameters of the fractured femora were also measured. The results showed that the callous volume and callous staging were not different between the groups. However, the fracture healing stage of the OVC group was lower than the SO group, while α-tocopherol supplementation in the ATF group had improved the healing until it was comparable to the SO group. The activities of the anti-oxidatant enzymes, superoxide dismutase, and glutathione peroxidase in the ATF group were found to be significantly higher than in the OVC group. In conclusion, α-tocopherol improved fracture healing but had no effect on the callous volume and staging. The improvement in fracture healing may be due to the increased activities of the anti-oxidatant enzymes in the bone during the early phase of fracture healing of osteoporotic bone.
Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p 0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes.
Fracture healing is a complex process, which is further complicated if the bone is osteoporotic. Calcium is one of the important minerals in bone and has been found to prevent osteoporosis but its role in fracture healing of osteoporotic bone is still unclear. We carried out a study on the effects of calcium supplementation on the late phase healing of fractured osteoporotic bone using an ovariectomized rat model. Twenty-four female Sprague-Dawley rats were divided into three groups: sham-operated (SO), ovariectomized-control (OVXC), and ovariectomized + calcium supplements (Ca). The right femurs of all the rats were fractured at mid-epiphysis and a K-wire was inserted for internal fixation. After 2 months of treatment, the rats were sacrificed and the femora were dissected out for radiological and biomechanical assessment. As expected, osteoporosis resulted in impaired healing as shown by the poor radiological and biomechanical properties of the OVXC group. CT scans showed significantly lower callus volumes in the SO and Ca groups compared to the OVXC group. Radiological scoring of fracture healing and callus staging of the SO and Ca groups were better than the OVXC group. However, the biomechanical parameters of the Ca group were significantly lower than the SO group and similar to the OVXC group. Therefore, calcium supplements may appear to improve fracture healing of osteoporotic bone but failed to improve strength.
This study investigated the effect of loading the iliotibial band (ITB) on the stability of the patellofemoral joint. We measured the restraining force required to displace the patella 10 mm medially and laterally (defined as medial and lateral stability, respectively) in 14 fresh-frozen knees from 0 to 90 degrees knee flexion. The testing rig allowed the patella to rotate and translate freely during this displacement. The quadriceps was separated into five components and loaded with 175 N total tension. Testing was performed at 0 to 90 N ITB tension. With no ITB tension, the lateral restraining force ranged from 82 to 101 N across 0 to 90 degrees flexion. Increasing ITB tension caused progressive reduction of the lateral restraining force. The maximum reduction was 25% at 60 degrees flexion and 90 N ITB tension. Medial restraining force increased progressively with increasing knee flexion and increasing ITB loads; it ranged from 74 N at 0 degrees knee flexion and 0 N ITB tension to 211 N at 90 degrees knee flexion and 90 N ITB tension. The maximum effect was an increase of medial restraining force of 50% at 90 degrees flexion and 90 N ITB tension.
Posterior instrumentation is a common fixation method used to treat thoracolumbar burst fractures. However, the role of different cross-link configurations in improving fixation stability in these fractures has not been established. A 3D finite element model of T11-L3 was used to investigate the biomechanical behavior of short (2 level) and long (4 level) segmental spine pedicle screw fixation with various cross-links to treat a hypothetical L1 vertebra burst fracture. Three types of cross-link configurations with an applied moment of 7.5 Nm and 200 N axial force were evaluated. The long construct was stiffer than the short construct irrespective of whether the cross-links were used (p < 0.05). The short constructs showed no significant differences between the cross-link configurations. The XL cross-link provided the highest stiffness and was 14.9% stiffer than the one without a cross-link. The long construct resulted in reduced stress to the adjacent vertebral bodies and screw necks, with 66.7% reduction in bending stress on L2 when the XL cross-link was used. Thus, the stability for L1 burst fracture fixation was best achieved by using long segmental posterior instrumentation constructs and an XL cross-link configuration. Cross-links did not improved stability when a short structure was used.
Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves.
The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.
Degeneration of articular cartilage is often triggered by a small tissue crack. As cartilage structure and composition change with age, the mechanics of cracked cartilage may depend on the tissue age, but this relationship is poorly understood. Here, we investigated cartilage mechanics and crack deformation in immature and mature cartilage exposed to a full-thickness tissue crack using indentation testing and histology, respectively. When a cut was introduced, tissue cracks opened wider in the mature cartilage compared to the immature cartilage. However, the opposite occurred upon mechanical indentation over the cracked region. Functionally, the immature-cracked cartilages stress-relaxed faster, experienced increased tissue strain, and had reduced instantaneous stiffness, compared to the mature-cracked cartilages. Taken together, mature cartilage appears to withstand surface cracks and maintains its mechanical properties better than immature cartilage and these superior properties can be explained by the structure of their collagen fibrous network.
Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild-to-moderate OA pain, while engaging in a shared decision-making process with patients for optimal clinical outcomes.