The purpose of this study was to investigate the survival and differentiation status of MSCs transplanted to ONFH. Traumatic ONFH was surgically produced in skeletally mature mongrel dogs. Osteonecrosis was treated with either saline (control) or autologous mesenchymal stem cells (MSCs) transplantation after decompression. Green fluorescent protein (GFP) was used to track the transplanted MSCs, the differentiation of MSCs were evaluated by fluorescent double‐labeling with GFP between osteocalcin or von Willebrand factor (vWF) at 2nd, 8th, and 12th week after the transplantation. It was demonstrated that GFP‐positive cells were present in the necrotic area up to 12 weeks after the transplantation, their number increased from 15% at 2nd week to 38% at 12th week (p < 0.05). Neither osteocalcin nor vWF was detected by immunocytochemistry in GFP‐labeled MSCs in vitro, but osteocalcin was immunohistochemically positive in 90% of the GFP‐labeled MSCs in vivo, while vWF was still negative. The vWF expression was of no significant difference between the control group and MSCs‐transplanted group. The percentages of trabeculae bone volume were 9.36% and 8.42% at 2nd week (p > 0.05), 22.82% and 14.72% at 8th week, and 31.08% and 20.66% at 12th week (p < 0.05) in MSCs‐transplanted group and control group, respectively; new trabeculae bone in MSCs‐transplanted group was significantly increased as compared to that of control group at 8th and 12th week. The results demonstrated that the transplanted MSCs could survive, proliferate, and differentiate into osteoblasts directly, which contributed to the accelerated repair process. The possible mechanism is site‐dependant differentiation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 442–446, 2009

Omized controlled study, in terms of improved vascularity of the femoral head, progression of disease, or hip scores. Question/purposes (1) What is the effect of core decompression and fibular grafting on vascularity of the femoral head as measured by single-photon emission CT (SPECT)/CT? (2) Does one of these two methods lead to greater progression of Association Research Circulation Osseous (ARCO) stage as determined by serial MRI? (3) What is the relationship between the change in vascularity of the femoral head and hip function as measured by the Harris hip score (HHS) and progression to THA as an endpoint? Methods A randomized controlled trial was performed between June 2010 and October 2012 at Zhongshan Hospital, Fudan University. During the study period, 51 patients who presented with ARCO Stages I to IIIB bilateral osteonecrosis were potentially eligible for inclusion, and 33 patients were identified as meeting the inclusion criteria and offered enrollment and randomization. Six patients declined to participate at the time of randomization, leaving a final sample of 27 participants (54 hips). Bilateral hips of each patient were randomly assigned to surgical options: one side was treated with core decompression and the contralateral side was concurrently treated with fibular grafting. SPECT/CT examinations were performed to quantify radionuclide uptake to evaluate vascularity of the femoral head before treatment and at 6 and 36 months after surgery. With the numbers available, we found no differences between the groups regarding vascularity at baseline (64% ± 8% core decompression-treated hips versus 64% ± 7% in the fibular-grafted hips; 95% CI, −5% to 5%; p = 0.90). MR images of the hips were obtained before surgery and at 6, 12, 24, and 36 months postoperatively and staged based on the ARCO classification. All patients were assessed clinically before treatment and followed up at 6, 12, 18, 24, 30, and 36 months after treatment using the HHS. We considered a difference in the HHS of 10 as the minimal clinically important difference (MCID). Patient progression to THA was defined as the endpoint for followup. Six patients (22%) were lost to followup. Results By SPECT/CT analysis, decompression-treated hips had lower vascularity than fibular-grafted hips at 6 months (68 % ± 6% versus 95% ± 5%; mean difference, −27%; 95% CI, −32% to −23%; p < 0.001) and 36 months (57% ± 4% versus 91% ± 3%; mean difference, −34%; 95% CI, −37% to −32%; p < 0.001). MRI analysis showed no differences between decompression-treated hips and fibular-grafted hips regarding ARCO stage at 12 months (p = 0.306) and 24 months (p = 0.06). Progression of ARCO staging was more severe in the decompression group than the fibular grafting group at 36 months (p = 0.027). The mean HHS was lower in the decompression group than in the fibular grafting group throughout the followup period, although these differences were at or below the MCID of 10 points early on. However, by 18 months, the scores favored fibular grafting (72 ± 4 versus 84 ± 4; mean difference, −13; 95% CI, −15 to −7; p < 0.001), a finding that was maintained at 24, 30, and 36 months. We found no differences between decompression-treated hips and fibular-grafted hips regarding progression to THA at 36 months (two of 21; p = 0.893). Conclusions Hips that underwent a vascularized fibular grafting procedure fared better than hips receiving core decompression as measured by improved vascularity and less progression of osteonecrosis as measured by ARCO staging. The mean HHS of the fibular-grafted hips was better than that of the decompression-treated hips during the entire postoperative period, but the differences were modest early on, and for the early postoperative period the differences were unlikely to have been clinically important; by 18 months after surgery, the differences probably were clinically important. The mid-term outcomes associated with vascularized fibular grafting seen in our patients are associated with improvements in femoral head vascularity and the potential for bone revitalization. Level of Evidence Level I, therapeutic study....

Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability, there is an urgent need to attenuate the progression of OA. Intra-articular (IA) injection is an effective treatment for joints diseases, however, the therapeutic effects mostly depend on the efficacy of drug duration in joints. Drug delivery system can provide drug-controlled release and reduce the number of IA injection. In this study, amphiphilic polyurethanes with pendant amino group were synthesized and amide bonds were formed between the amine group of polyurethane and the carboxyl group of kartogenin (KGN), a small molecular reported to show both regenerative and protective effects on cartilage. Our results showed that KGN-conjugated polyurethane nanoparticles (PN-KGN) were spherical and regular in shape with an average size of 25 nm and could sustained and controlled release of KGN in vitro. PN-KGN showed no cytotoxicity and pro-inflammatory effects on chondrocytes. The therapeutic effects in OA model showed that IA injection of KGN could attenuate the progress of OA, however, the cartilage degeneration became obviously at 12 weeks with matrix loss and vertical fissures. By contrast, IA injection of PN-KGN showed less cartilage degeneration with significant lower OARSI scores even at 12 weeks, indicating PN-KGN could further arrest the development of OA. Immunohistochemistry also validated that IA injection of PN-KGN retained the normal compositions of cartilage matrix, with much stronger Col II staining and less Col I staining. In conclusion, IA injection of PN-KGN is a better potential strategy to treat OA, with long-time cartilage protection and less IA injections.