Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well-known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mM lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3b (GSK-3b) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK-3b activity, b-catenin accumulation and Wnt pathway activation. Utilizing a specific GSK-3b inhibitor SB216763 or siRNA-mediated inhibition of GSK-3b produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the b-catenin/TCF pathway, or siRNA-mediated knockdown of b-catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK-3b-dependent b-catenin/ Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from b-catenin/ Wnt pathway suppression.

While it has been proved that centrifugal conditions for pure platelet-rich plasma (P-PRP) preparation influence the cellular composition of P-PRP obtained, the optimal centrifugal conditions to prepare P-PRP have not yet been identified. In the present study, platelet-containing plasma (PCP) was prepared with the first-spin of different double-spin methods and P-PRP was prepared with different double-spin methods. Whole-blood analysis was performed to evaluate the cellular composition of PCP and P-PRP. The basal and ADP-induced CD62P expression rates of platelets were assessed by flow cytometry to evaluate the function of platelets in PCP and P-PRP. Enzyme-linked immune sorbent assay was performed to quantify interleukin-1β, tumor necrosis factor-α, platelet-derived growth factor AB and transforming growth factor β1 concentrations of PCP and P-PRP. Correlations between the cellular characteristics and cytokine concentrations of P-PRP were analyzed by Pearson correlation analysis. Effects of P-PRP on the proliferation, survival and migration of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes were evaluated by a Cell Counting Kit-8 assay, live/dead staining and Transwell assay, respectively. The results showed that centrifugation at 160 × g for 10 min and 250 × g for 15 min successively captured and concentrated platelets and growth factors significantly more efficiently with preservation of platelet function compared with other conditions (P<0.05). The correlation analysis showed that the similar leukocyte concentrations and leukocyte-reducing efficiencies resulted in similar pro-inflammatory cytokine concentrations in P-PRP (P>0.05) and the maximization of platelet concentration, platelet enrichment factor, platelet capture efficiency and platelet function resulted in the maximization of growth factor concentrations in P-PRP obtained using the optimal conditions (P<0.05). Compared with P-PRP obtained under other conditions, P-PRP obtained under the optimal conditions significantly promoted the proliferation and migration of cells (P<0.05) and did not alter cell survival (P>0.05). Therefore, centrifugation at 160 × g for 10 min and 250 × g for 15 min successively with removal of the buffy coat as a crucial step may provide an optimal preparation system of P-PRP for clinical application.

Free vascularised fibular grafting has been reported to be successful for adult patients with osteonecrosis of the femoral head (ONFH). However, its benefit in teenage patients with post-traumatic ONFH has not been determined. We evaluated the effectiveness of free vascularised fibular grafting in the treatment of this condition in children and adolescents. We retrospectively analysed 28 hips in 28 patients in whom an osteonecrotic femoral head had been treated with free vascularised fibular grafting between 2002 and 2008. Their mean age was 16.3 years (13 to 19). The stage of the disease at time of surgery, and results of treatment including pre- and post-operative Harris hip scores, were studied. We defined clinical failure as conversion to total hip replacement. All patients were followed up for a mean of four years (2 to 7). The mean Harris hip score improved from 60.4 (37 to 84) pre-operatively to 94.2 (87 to 100) at final follow-up. At the latest follow-up we found improved or unchanged radiographs in all four initially stage II hips and in 23 of 24 stage III or IV hips. Only one hip (stage V) deteriorated. No patient underwent total hip replacement. Free vascularised fibular grafting is indicated for the treatment of post-traumatic ONFH in teenage patients.

Treatment of skeletal defects secondary to osteomyelitis is a challenging problem. The purpose of this study was to present our experience of the use of free vascularised fibular grafts to treat such defects. Ten patients with a mean age of 31 years (range 16-50 years) and a skeletal defect with a mean length of 9.5 cm (range 6-17 cm) were managed with a protocol which included radical debridement of the lesion and a vascularised fibular graft. The mean follow-up time was 26 months. Union of the graft occurred in all patients, at a mean of 4.5 months. No recurrence of osteomyelitis was observed. The mean time to full weight bearing was ten months, and all patients were pain-free and able to walk without supportive devices. A free vascularised fibular graft is a viable option for the management of large skeletal defects resulting from osteomyelitis.

The goal for treatment of osteonecrosis of the femoral head (ONFH) is to relieve pain, preserve the contour of the femoral head, and delay the need for total hip arthroplasty. The free vascularized fibular grafting (FVFG) has been shown to support the subchondral architecture as well as restore local circulation for the necrotic femoral head in treatment of ONFH. This report aimed to present the clinical results of the use of a modified surgical technique of FVFG for treatment of ONFH. Four hundred and seven patients with 578 hips of ONFH were included. The patients' average age was 36.7 years old (ranging 19-55 years old). The disease was staged from II to V based on the Steinberg classification system. By the modified procedure, the vascularized fibular graft was harvested via a lateral incision with fibular osteotomy prior to the exposure of the vascular pedicle, and the removal of necrotic tissue and inset of graft were performed through an anterior approach. The operative time averaged 90 min for unilateral ONFH (ranging 75-110 min) and 190 min for simultaneous treatment of bilateral ONFH (ranging 160-230 min). The average length of follow-up was 5.0 years (ranging 3-10 years). The complications included one infection in one case, temporary loss of sensation of the thigh in eleven cases, and restricted motion of the great toe in nine cases. The Harris hip score of patients improved from 65.0 to 86.9 on average. Radiographic evaluation showed no changes in 331 hips (57.3%), improvement in 195 hips (33.7%) and necrosis progression in 52 hips (9.0%). Twenty-three hips (4.0%) in 20 patients had total hip arthroplasty during the period. These results show that the modified technique of the use of FVFG for treatment of ONFH yields similar postoperative results in comparison to the traditional method.

Background:There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients.Methods:We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm2) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping.Results:All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up.Conclusions:ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The cytotoxicity of silver-containing borate bioactive glass was evaluated in vitro from the response of osteoblastic and fibroblastic cells in media containing the dissolution products of the glass. Glass frits containing 0-2 weight percent (wt %) Ag were prepared by a conventional melting and quenching process. The amount of Ag dissolved from the glass into a simulated body fluid (SBF), measured using atomic emission spectroscopy, increased rapidly within the first 48 h, but slowed considerably at longer times. Structural and microchemical analysis showed that the formation of a hydroxyapatite-like layer on the glass surface within 14 days of immersion in the SBF. The response of MC3T3-E1 and L929 cells to the dissolution products of the glass was evaluated using SEM observation of cell morphology, and assays of MTT hydrolysis, lactate dehydrogenase release, and alkaline phosphatase activity after incubation for up to 48 h. Cytotoxic effects were found for the borate glass containing 2 wt % Ag, but not for 0.75 and 1 wt % Ag. This borate glass containing up to ∼1 wt % Ag could provide a coating material for bacterial inhibition and enhanced bioactivity of orthopaedic implant materials such as titanium.

Failed treatment of intertrochanteric (IT) femoral fractures leads to remarkable disability and pain, and revision surgery is frequently accompanied by higher complication and reoperation rates than primary internal fixation or primary hip arthroplasty. There is an urgent need to establish a profound strategy for the effective surgical management of these fragile patients. Salvage options are determined according to patient physiological age, functional level, life expectancy, nonunion anatomical site, fracture pattern, remaining bone quality, bone stock, and hip joint competency. In physiologically young patients, care should be taken to preserve the vitality of the femoral head with salvage internal fixation; however, for the elderly population, conversion arthroplasty can result in early weight bearing and ambulation and eliminates the risks of delayed fracture healing. Technical challenges include a difficult surgical exposure, removal of broken implants, deformity correction, critical bone defects, poor bone quality, high perioperative fracture risk, and prolonged immobilization. Overall, the salvage of failed internal fixations of IT fractures with properly selected implants and profound techniques can lead to the formulation of valuable surgical strategies and provide patients with satisfactory clinical outcomes.