Biphasic electric current stimulates proliferation and induces VEGF production in osteoblasts

The repair of diseased or damaged cartilage remains one of the most challenging problems of musculoskeletal medicine. Tissue engineering advances in cartilage repair have utilized autologous and allogenic chondrocyte and cartilage grafts, biomaterial scaffolds, growth factors, stem cells, and genetic engineering. The mesenchymal stem cell has specifically attracted much attention because of its accessibility, potential for differentiation, and manipulability to modern molecular, tissue and genetic engineering techniques. Mesenchymal stem cells provide invaluable tools for the study of tissue repair when combined with a carrier vehicle/matrix scaffold, and/or bioactive growth factors. However, an underappreciated source of knowledge lies in the relationship between fetal development and adult tissue repair. The multitude of events that take place during fetal development which lead from stem cell to functional tissue are poorly understood. A more thorough understanding of the events of development as they pertain to cartilage organogenesis may help elucidate some of the unknowns of adult tissue repair.

Mesenchymal Stem Cells in Tissue Engineering

Background: It has been assumed that outcome after open reduction and internal fixation of displaced intra-articular calcaneal fractures may be affected by the presence of institutional trauma care and the institution's fracture volume. The purpose of this systematic review was to investigate whether a relationship exists between institutional fracture load and the rates of serious infection and subtalar arthrodesis following the treatment of these fractures.

Methods: With use of a systematic method, all studies published between 2000 and 2006 describing adult patients undergoing open reduction and internal fixation of a displaced intra-articular fracture of the calcaneus were included. Patients with open fractures and patients undergoing percutaneous procedures were excluded. Institutional fracture load was calculated by dividing the number of calcaneal fractures that were treated operatively by the number of months that were included in the reported studies. A serious deep infection was defined as an infection requiring surgical debridement and hardware removal, reconstruction with a flap, and/or the presence of osteomyelitis. Traumatic subtalar arthritis was considered to be severe when subtalar arthrodesis was required. Numerous confounding factors were also analyzed, and a systematic methodological quality assessment was performed.

Results: Of a total of 236 studies, twenty-one were included in the analysis. The total number of fractures included was 1656. The median institutional fracture load was 0.8 fracture per month (95% confidence interval, 0.2 to 4.6 fractures per month). The median infection rate in the studies combined was 5.1% (95% confidence interval, 0.0% to 19.9%). The infection rate increased exponentially with a decreasing fracture load (r2 = −0.5; p = 0.03). The median rate of subtalar arthrodesis was 2.5% (95% confidence interval, 0.0% to 15.4%). A significant inverse correlation was present between the fracture volume and the subtalar arthrodesis rate (r2 = −0.7; p = 0.008). These factors were unrelated to the methodological quality. Multivariate analysis identified fracture volume as an independent determinant of the infection rate.

Conclusions: A significant relationship between the deep infection rate, traumatic subtalar arthritis, and the fracture load may indicate a need for specialized institutional trauma care to improve outcomes associated with the operative treatment of calcaneal fractures.

Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

The relationship between the outcome of operatively treated calcaneal fractures and institutional fracture load. A systematic review of the literature.

Typically patients with multiple sclerosis (MS) experience acute episodes of neurological dysfunction, which recover followed, at a later stage, by slow and insidious accumulation of disability (disease progression). Disease progression reflects axon damage and loss within the central nervous system. However, the precise mechanism of axon injury in MS is not clear. Inflammation occurring during acute relapses undoubtedly causes some degree of acute axon damage, but epidemiological data and treatment studies have suggested that inflammation alone is not the sole cause of axonopathy. Indeed, there appears to be dissociation between inflammation and disease progression once a certain level of clinical disability has been reached because immune suppression in patients who have established disease progression does not halt the slow decrease of function. The slow and insidious loss of neurological function that occurs during the progressive phase of the disease implies a degenerative process. Whether axon drop-...

Protecting axons in multiple sclerosis.

Intrapleural Injection of Transforming Growth Factor-β Antibody Inhibits Pleural Fibrosis in Empyema

The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor (TGF)-beta 1 genes in bone marrow-derived mesenchymal stem cells (MSCs) in vitro. The full-length rat TGF-beta 1 cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418, a synthetic neomycin analog. The transient and stable expression of TGF-beta 1 by MSCs was detected by using immunohistochemical staining. The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-beta 1 gene causing a marked up-regulation in TGF-beta 1 expression as compared with the vector-transfected control groups, and the increased expression persisted for at least 4 weeks after selected with G418. It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-beta 1 gene transfer and that transgene expression persisted for at least 4 weeks. Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology, an innovative concept, i.e. molecular tissue engineering, are put forward for the first time. As a new branch of tissue engineering, it represents both a new area and an important trend in research. Using this technique, we have a new powerful tool with which: (1) to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and (2) to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.

Expression of transforming growth factor beta 1 in mesenchymal stem cells: potential utility in molecular tissue engineering for osteochondral repair.

Objective: To elucidate the effects of exogenous basic fibroblast growth factor ( bFGF ) on biological characteristics of rat osteoblasts cultured in vitro.
Methods: The osteoblasts isolated from a Sprague-Dawley rat and cultured in vitro were treated with different concentrations of bFGF (5-50 ng/ml) respectively. At 24 hours after treatment, the proliferating cell nuclear antigen was measured with immunocytochemistry, alkaline phosphatase ( ALP) activity was determined and the expression of transforming growth factor beta 1 (TGF-β1) was detected to observe the effects of bFGF on growth and differentiation of osteoblasts. Results: bFGF ( 5-50 ng/ml ) could obviously promote the growth of osteoblasts. The intracellular expression of TGF-β, mRNA increased significantly, but the intracellular ALP content decreased.
Conclusions: bFGF can obviously stimulate the proliferation of osteoblasts and promote the synthesis of TGF-β1, but cannot promote the differentiation of osteoblasts.

Effects of basic fibroblast growth factor on biological characteristics of osteoblasts.

To evaluate the biocompatibility of poly(lactic acid/glycolic acid/ asparagic acid-co-polyethylene glycol)(PLGA-[ASP-PEG]) tri-block copolymer in vitro, L929 fibroblast was co-cultured with the copolymer for cytotoxicity, hemolysis and pyrogen tests. And, compared with PLGA, the adhesiveness rate of the copolymer was calculated. The experimental results show that the toxicity gradation of the material was 0–1; L929 fibroblasts had a good cell morphology and proliferated rapidly on the surface of the material; hemolysis ratio was 3.08%; there was no pyrogen reaction. The adhesiveness of PLGA-[ASP-PEG] was better than that of the PLGA’s(P<0.05). The results confirm that the PLGA-[ASP-PEG] has a good biocompatibility.

Biocompatibility of tri-block bone-matrix material in vitro

To discuss and evaluate the method and effect of using calcaneal anatomic plate in treatment of intra-articular fractures of the calcaneus with assistant of arthroscope, 86 intra-articular fractures of the calcaneus in 78 patients were reduced by open reduction, and rigid fixation was made with calcaneal anatomic plate under assistant of arthroscope. The average follow-up duration was 18 months (range 12–30 months). The effect of treatment was evaluated according to AOFAS and X-ray before and after operation. The results showed that 86 patients have obtained satisfactory reduction according to X-ray, and there was significant difference before and after operation (P<0.01), the total excellent and fine rate was 91.86%. Treating intra-articular fractures of the calcaneus with calcaneal anatomic plate under arthroscope may provide more chance to achieve anatomical reconstruction, which can lead to satisfied recovery of function and few complication.

Deyu Duan

Papers

Expression of transforming growth factor beta 1 in mesenchymal stem cells: potential utility in molecular tissue engineering for osteochondral repair.

Effects of basic fibroblast growth factor on biological characteristics of osteoblasts.

Biocompatibility of tri-block bone-matrix material in vitro

The use of calcaneal anatomic plate in arthroscopically-assisted open reduction and internal fixation of intra-articular calcaneal fractures.