Medial Open-wedge Osteotomy with Double-plate Fixation for Varus Malunion of the Distal Femur.

OBJECTIVE: To present our clinical experience of treating varus malunion of the distal femur through a medial open-wedge osteotomy with double-plate fixation. METHODS: A prospective cohort study was performed. From January 2005 to February 2015, 15 consecutive patients with varus malunion following distal femur fractures were surgically treated at a single level I trauma center. The coronal and sagittal deformity were corrected by a medial open-wedge osteotomy of the distal femur. A medial buttress plate was used to maintain the realignment. A lateral locking plate was additionally used as a protection plate. The mean age of patients at the time of the surgery was 35.5 years (range, 22-58 years). The radiographical evaluation included the mechanical femorotibial angle, the mechanical lateral distal femoral angle, the anatomic posterior distal femoral angle, and the leg length discrepancy. Clinical outcome evaluation consisted of the range of motion (ROM) and Hospital for Special Surgery (HSS) score. RESULTS: Mean follow-up was 7.4 years (range, 4-11.5 years). Varus and flexion malalignment and limb discrepancy were adequately corrected in all patients. The mechanical femorotibial angle, the mechanical lateral distal femoral angle, and the anatomic posterior distal femoral angle were restored from 17.5° (range, 13°-25°) to 2.3° (range, - 2°-7°), 102.3° (range, 95°-112°) to 85.2° (range, 81°-92°), and 77.1° (range, 65°-87°) to 82.7° (range, 76°-88°), respectively. The leg length discrepancy was diminished from 3.4 cm (range, 2.4-4.5 cm) to 0.8 cm (range, 0-1.7 cm). The average bone healing time was 4.1 months (range, 2.5-6 months). The average ROM of the affected knees at 24-month follow-up was 3.4°-112.55°. The score of HSS at 4-years follow-up was 76.1 (range, 64-88). No internal fixation failure or secondary operation was noted until the last follow-up. CONCLUSION: Medial open-wedge osteotomy can adequately correct the posttraumatic varus malunion of the distal femur. With fixation of the double plate, non-displaced bone healing and good functional outcome are expected.

pH-responsive mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with doxorubicin against osteosarcoma.

Oral or intravenous chemotherapy is an important strategy to treat metastatic cancer, but it may cause systemic toxicity for healthy tissue. Herein, we for the first time fabricated mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with doxorubicin (ZSM-5/CS/DOX) as drug delivery systems against osteosarcoma. The mesoporous ZSM-5 zeolites exhibited disk-like shapes with thicknesses of 100nm and diameters of 300nm, and the mesopores with pore sizes of 3.75nm were originated from desilication treatment. The pH-responsive ZSM-5/CS/DOX nanodisks possessed a great drug loading efficiency of 97.7%, and their controlled release trends of DOX were fitted well with the Korsmeyer-Peppas model. The DOX could be efficiently released the ZSM-5/CS/DOX nanodisks after cellular endocytosis and induced cancer cells apoptosis. Moreover, the pH-responsive drug carriers led to efficient tumor inhibition with low side effects, especially cardiac toxicity, as confirmed by pharmacokinetic study, serological examination and H&E staining assays. Therefore, the ZSM-5/CS/DOX nanodisks are a promising pH-responsive drug carrier for targeted cancer therapy.

Magnetic nanoparticles modified-porous scaffolds for bone regeneration and photothermal therapy against tumors.

For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe12O19 nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the SrFe12O19 nanoparticles in MBCS improved the photothermal conversion property. Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the multifunctional MBCS with excellent bone regeneration and photothermal therapy functions has a great application for treating the tumor-related bone defects.

Hollow mesoporous ZSM-5 zeolite/chitosan ellipsoids loaded with doxorubicin as pH-responsive drug delivery systems against osteosarcoma.

The toxic risks and adverse effects of anticancer drugs on healthy tissues limit their wide clinical application. Herein, we for the first time fabricated hollow mesoporous ZSM-5/chitosan ellipsoids loaded with doxorubicin (HM-ZSM-5/CS/DOX) as pH-responsive drug delivery systems against osteosarcoma. The HM-ZSM-5 ellipsoids including a hollow core and a mesoporous shell could efficiently load DOX drugs with a loading efficiency of 95.8%. The CS layer was uniformly distributed on the HM-ZSM-5 ellipsoids that contributed to the pH-responsive release of DOX drugs. The controlled DOX release kinetics from the HM-ZSM-5/CS/DOX ellipsoids was fitted well with the Korsmeyer-Peppas model. The HM-ZSM-5/CS/DOX ellipsoids exhibited good biocompatibility due to the low DOX release rate in the neutral media that simulated healthy tissues or blood. Moreover, the cellular uptake of the HM-ZSM-5/CS/DOX ellipsoids took place in tumor cells, and the quick release of DOX significantly promoted the apoptosis of MG63 cells. The levels of MDA, LDH and CK markers for the HM-ZSM-5/CS/DOX group were lower than those for the free DOX group, suggesting no systemic toxicity to the heart. Therefore, the HM-ZSM-5/CS/DOX ellipsoids as novel pH-responsive drug delivery systems can effectively treat osteosarcoma without systemic toxicity.

Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis.

BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. MATERIAL AND METHODS Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1ß (IL-1ß) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. RESULTS Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1ß and PGE2 concentrations. CAPE injections reversed the increased IL-1ß and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. CONCLUSIONS Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis.

Continuous hypoxia regulates the osteogenic potential of mesenchymal stem cells in a time-dependent manner.

The effects of hypoxia on the osteogenic potential of mesenchymal stem cells (MSCs) have been previously reported. From these studies, possible factors affecting the association between hypoxia and the osteogenic differentiation of MSCs have been suggested, including hypoxia severity, cell origin and methods of induction. The effect of the duration of hypoxia, however, remains poorly understood. The aim of the present study was to investigate the effect of continuous hypoxia on the induced osteogenesis of MSCs. Rat MSCs were isolated and cultured in vitro. Once the cells had been cultured to passage three, they were switched to 1% oxygen and cultured either with or without osteogenic medium, while cells in the control groups were cultured under normoxia in corresponding conditions. Four osteogenic differentiation biomarkers, runt-related transcription factor 2, osteopontin, osteocalcin and alkaline phosphatase, were analyzed by quantitative polymerase chain reaction and western blotting at defined intervals throughout the culture period. In addition, Alizarin Red staining was used to assess changes in mineralization. The results showed that 1% hypoxia was able to enhance and accelerate the osteogenic ability of the MSCs during the initial phases of differentiation, and the protein expression of certain associated biomarkers was upregulated. However, continuous hypoxia was shown to impair osteogenesis in the latter stages of differentiation. These findings suggest that hypoxia can regulate the osteogenesis of MSCs in a time-dependent manner.

Osteogenic induction protects rat bone marrow-derived mesenchymal stem cells against hypoxia-induced apoptosis in vitro.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) undergo hypoxia-induced apoptosis when cells are transplanted from a normoxic to a hypoxic microenvironment in vivo. The effect of the osteogenic microenvironment on BMSCs under hypoxic conditions has not yet been revealed. MATERIALS AND METHODS: In the current study, we investigated the effects on BMSCs of hypoxia and osteogenic induction (OI) individually and in combination. We isolated BMSCs from rat bone marrow and confirmed them by recognition of surface antigens using cytometry. After passaging the BMSCs to the third generation, we treated them with the following conditions: 1% oxygen and OI, normoxia and OI, and 1% oxygen without OI; normoxia without OI was the control condition. On days 3, 7, 14, and 21, we detected the expression levels of hypoxia inducible factor-1α and alkaline phosphate via Western blotting. Cellular apoptosis was detected by Hoechst staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine, 5'-triphosphate nick end labeling; caspase activity was also detected. RESULTS: The expression of hypoxia inducible factor-1α was induced and up-regulated when BMSCs were grown under 1% oxygen. The incidence of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine, 5'-triphosphatenick end labeling-positive cells in the hypoxia plus OI group was much lower than that in the hypoxia group without OI. Caspase activity increased on days 3, 7, 14, and 21. The absolute value of caspase was statistically higher in the BMSC hypoxia group than in the other three groups, whose values were similar to each other. CONCLUSIONS: Osteogenic induction could protect BMSCs against hypoxia-induced apoptosis. Bone marrow-derived mesenchymal stem cells may be appropriate candidate cells for cytotherapy for skeletal diseases.

Retrospective comparison of titanium elastic nail (TEN) and reconstruction plate repair of displaced midshaft clavicular fractures.

BACKGROUND: Titanium elastic nails (TENs) are commonly used to repair displaced midshaft clavicular fractures. Although several clinical studies have shown that the use of TENs is more effective and less invasive than traditional plate fixation, high rates of complications associated with TENs have been reported. This retrospective study compared the use of TENs with reconstruction plates in the treatment of displaced midshaft clavicular fractures. MATERIALS AND METHODS: From January 2005 to July 2007, 141 patients with displaced midshaft clavicular fractures were treated with TEN or plate fixation. At 6 and 24 months postoperatively, we evaluated the patients' general health, operative complications, and functional recovery. RESULTS: The mean bone union time of TEN patients was 12.4 ± 3.4 weeks, whereas that in the plate group was 14.4 ± 3.7 weeks. The time of union was significantly shorter in the TEN group than that in the plate group. There was no significant difference between these 2 groups' rates of complications such as nonunion or malunion. Shoulder function scores were significantly better in the TEN group than in the plate group at 6 months postoperatively. There was no significant difference at 24 months postoperatively. Patients were more satisfied with the cosmetic appearance and overall outcome after TEN repair than after plate fixation. CONCLUSIONS: TEN fixation of displaced midshaft clavicular fractures allows for a faster functional recovery, higher patient satisfaction, and a more cosmetically satisfactory appearance than plate fixation. The complication rates of both TENs and reconstruction plates were similar.

Medial sural artery perforator flap.

In the last decade, the medial sural artery perforator flap (MSAP) has emerged as one of the most popular reconstructive options for multiple body sites. The versatility of the flap hinges on the ability to harvest multiple tissue components in various combinations but from the same wound. The flap can be used as a pedicled, free, or chimeric design, or even may be used in sequential order. Anatomic anomalies of these perforators are rare compared with other perforator flaps, but well-prepared preoperative planning and the identification of perforators remain the cornerstone of successful flap harvest. So far, the MSAP has been proved to be an excellent alternative for skin resurfacing and functional reconstruction in head and neck as well as in the extremities. In this review, the anatomy, preoperative planning and flap design, harvest technique, and its clinical application in multiple body sites are summarized. Both the advantages and disadvantages are also included.

Salvage of a femoral nonunion after primary non-Hodgkin's lymphoma of bone: a case report and literature review.

BACKGROUND: With the advent of superb microsurgery techniques and advanced stabilization instruments, recent decades have seen great progress in treating nonunions secondary to traumatic fractures. However, those nonunions that are secondary to primary non-Hodgkin's lymphoma of bone and often related to irradiation still remain a challenging problem. The condition could be more perplexing when bone healing abilities are greatly compromised and reliable stabilization is difficult. CASE REPORT: We performed an operation using free vascularized fibular graft in combination with a locking plate on a 47-year-old female patient who had suffered from a three-year femoral nonunion after courses of radiochemotherapy for the treatment of primary non-Hodgkin's lymphoma of bone, a spontaneous femoral shaft fracture, an intramedullary nailing, and some nonoperative interventions in sequence. Primary union of the graft was obtained at 9 months without wound infection. No recurrence of lymphoma occurred in the 61-month follow-up, nor did a stress fracture or failure of fixation. Limb salvage was achieved and the range of motion of the adjacent joints was acceptable. CONCLUSIONS: Free vascularized fibular graft in combination with a locking plate can effectively enhance bone union in compromised bone and soft tissue milieu. More cases have yet to be further investigated.

Clinical outcomes of midclavicular fractures treated with titanium elastic nails.

BACKGROUND: Midclavicular fractures are common clinically, accounting for about 76% of all clavicular fractures. Recent studies have revealed a previously unrecognized incidence of nonunion and malunion after conservative treatment of more severe midclavicular fractures. Our aim was to evaluate the clinical outcomes of midclavicular fractures treated with titanium elastic nails. METHODS: From February 2005 to February 2007, 41 patients with displaced midclavicular fractures received open reduction and internal fixation with a titanium elastic nail inserted through the sternal end of the clavicle. We evaluated the visual analogue scale (VAS), the Constant score and the Disabilities of the Arm, Shoulder and Hand (DASH) scale to determine outcomes. RESULTS: A mean follow-up of 14.5 months (range 7-24 mo) revealed radiographic fracture union in all patients with an average clinical healing time of 2.2 months. Mean subjective pain 3 days after surgery was significantly lower than the day before surgery (p < 0.001). The mean range of motion 3 days after surgery was significantly improved compared with the day before surgery (p < 0.001). The nails were removed in all patients a mean of 7.2 months (range 5.4-9.5 mo) after surgery, and no fractures recurred. The mean postoperative DASH score was 2.5 (range 0.5-8.0) and the mean postoperative Constant score was 95.2 (range 86.5-97.0). CONCLUSION: Limited open reduction and internal fixation with titanium elastic nails is a safe and minimally invasive surgical procedure for the treatment of displaced midclavicular fractures in adults and achieves good functional results and high patient satisfaction.

Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro.

No satisfactory method currently exists for repairing long peripheral nerve defects. Efforts have been made to fabricate bioactive artificial nerve conduits, comprised of a biomaterial pre-seeded with Schwann cells (SCs), which creating a favorable micro-environment for axonal regeneration, to be an alternative to autografting by means of tissue engineering. Small intestinal submucosa (SIS) possesses special biological characteristics and is comprehensively researched for tissue repairing at varied tissues and organs. This study investigated the biocompatibility of SIS with SCs in vitro. Cultured rat SCs were seeded on SIS. Cell morphology was observed by light microscopy, scanning electron microscopy and transmission electron microscope. The viability of SCs was measured by MTT assay. Secretion of NGF-beta and BDNF was quantitatively assessed by ELISA, and NGF-beta mRNA and BDNF mRNA were semi-quantitatively assessed by RT-PCR. The results indicated that SCs could adhere, migrate and proliferate on the surface of SIS in good condition with productive function of secreting growth factors. SIS has a good biocompatibility with SCs and SIS pre-seeded with SCs has potential to be an alternate candidate of autografting for repairing long peripheral nerve defects.

Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles.

Anticancer drug resistance results from selective pressure of chemotherapy, together with mutations or epigenetic changes that make cells refractory to treatment. In cancer cells, we report that gene expression associated with vesicle shedding correlates with chemosensitivity profiles. Experiments with doxorubicin and other small molecules confirm drug accumulation and expulsion in shed vesicles. Relative differences in the rate of vesicle shedding correspond with doxorubicin resistance across various cell lines. Moreover, accumulation of drug in membrane domains in which vesicles originate accounts for drug expulsion in shed vesicles. These observations implicate vesicle shedding as a drug efflux mechanism potentially involved in drug resistance.