Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. METHODS AND RESULTS: Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. CONCLUSION: The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Subtrochanteric shortening osteotomy during cementless total hip arthroplasty in young patients with severe developmental dysplasia of the hip.

BACKGROUND: This retrospective study was designed to determine complications, functional and radiographic results of transverse subtrochanteric osteotomy during cementless, modular total hip arthroplasty (THA) in a series of active patients younger than 45 years with Crowe Type-III or IV developmental dysplasia of the hip (DDH). METHODS: We followed 49 patients (56 hips) with DDH who were treated with cementless THA, where the acetabular cup was positioned in the anatomic hip center and where a simultaneous transverse femoral osteotomy was performed. Complication rate evaluation and clinical outcomes were measured by validated clinical scores and radiographic evaluation were performed at a mean follow up of 10 years (range, 4.8-14.3 years). RESULTS: The mean limb-length discrepancy was reduced from 4.2 cm to 1.1 cm (P < 0.01). The mean Harris hip score (HSS) significantly improved from 40.6 points to 87.4 points (P < 0.01). Similarly, severity of low back pain, modified MAP, HOOS, and SF-12 also showed significant improvement (P < 0.01). There were 3 cases of postoperative dislocation, 3 cases of transient nerve palsy, 2 cases of nonunion, and 4 cases of intraoperative fracture. At 10 years follow-up, the estimated survival rate with any component revision as end points was 92%. CONCLUSION: The cementless THA combined with transverse subtrochanteric osteotomy is a reliable technique with restoration of a more normal limb, satisfactory clinical outcomes, and mid-term survival of components.

Near-Infrared Light-Controllable Multifunction Mesoporous Polydopamine Nanocomposites for Promoting Infected Wound Healing.

The successful treatment of infected wounds requires strategies with effective antimicrobial, anti-inflammatory, and healing-promoting properties. Accordingly, the use of Cu2+ and tetracycline (TC), which can promote angiogenesis, re-epithelialization, and collagen deposition, also antibacterial activity, at the wound site, has shown application prospects in promoting infected wound repair. However, realizing controllable release to prolong action time and avoid potential toxicities is critical. Moreover, near-infrared light (NIR)-activated mesoporous polydopamine nanoparticles (MPDA NPs) reportedly exert anti-inflammatory effects by eliminating the reactive oxygen species generated during inflammatory responses. In this study, we assess whether Cu2+ and TC loaded in MPDA NPs can accelerate infected wound healing in mice. In particular, Cu2+ is chelated and immobilized on the surface of MPDA NPs, while a thermosensitive phase-change material (PCM; melting point: 39-40 °C), combined with antibiotics, was loaded into the MPDA NPs as a gatekeeper (PPMD@Cu/TC). Results show that PPMD@Cu/TC exhibits significant great photothermal properties with NIR irradiation, which induces the release of Cu2+, while inducing PCM melting and, subsequent, TC release. In combination with anti-inflammatory therapy, NIR-triggered Cu2+ and TC release enables the nanocomposite to eradicate bacterial wound infections and accelerate healing. Importantly, negligible damage to primary organs and satisfactory biocompatibility were observed in the murine model. Collectively, these findings highlight the therapeutic potential of this MPDA-based platform for controlling bacterial infection and accelerating wound healing.

[Cortical windowing of the femoral diaphysis for cement/plug removal in hip revision surgery].

OBJECTIVE: To analyze the results of cortical windowing of the femoral diaphysis for well-fixed cement/plug removal during hip revision surgery. METHODS: From May 2005 to June 2009, 14 patients (14 hips) were undergone revision total hip arthroplasty (THA), window was cut into the cortex of the femur, and the well-fixed cement/plug distal to the window was removed under the direct vision. After reimplanted the cementless revision stem, the cortical lids were replanted and fixed with 2 to 3 cerclage wires. Six patients who had suffered from osteoporosis were undergone morselized bone graft to the osteotomy site. Postoperatively, the patients were maintained at partial weight-bearing (touchdown) for 6 weeks and then advanced as they were able. RESULTS: The length of the cortical windows varied from 2.5 to 6.0 cm (mean, 3.4 cm), the width ranged from 0.8 to 1.4 cm (mean, 1.2 cm). In one patient the window was enlarged during the procedure to facilitate the cement/plug removal. The mean radiologically healing time for the windows was 19 weeks. There was no intraoperative femoral perforation during cement/plug removal. One femoral fracture during the revision stem was implanted. No postoperative periprosthetic fracture and other complications such as infection, implant subsidence occurred during the fellow-up. There was no femoral thigh pain or implant loosening with femoral window. CONCLUSION: The cortical windowing technique is very helpful to facilitate the well-fixed cement/plug distal to the prosthesis tip removal and the windows heal rapidly and decrease the femoral complications associated with revision THA.

Extensively coated non-modular stem used in two-stage revision for infected total hip arthroplasty: mid-term to long-term follow-up.

OBJECTIVE: To determine the rate of curing the infection and mid- to long-term outcomes of using extensively coated non-modular stems in two-stage revision for infected total hip arthroplasty (THA). METHODS: The clinical data of 33 patients (33 hips) in whom extensively coated non-modular stems had been used in two-stage revision THA for deep infection were retrospectively analyzed. All operations received two-stage reimplantation, which included resection arthroplasty, thorough debridement, insertion of a hand-molded antibiotic-impregnated cement spacer with stainless steel reinforcement, a course of intravenous antibiotics, and delayed reimplantation. Microorganism-specific antibiotics had been chosen according to the results of microbiological studies performed postoperatively. All patients received i.v. antimicrobial therapy for 4 weeks and oral antibiotics to which their organisms were sensitive for a further 6 weeks. Harris hip score (HHS) and plain X-ray films were used to perform clinical and radiological evaluations. RESULTS: During follow-up for a minimum of 5 years, no reinfection or loosening were found. Cultures of samples taken during the second stage were all negative for infection. The mean HHS improved from 42 preoperative to 89 at the final follow-up. All granular bones had fused well with the host bones by 12 months after the surgery. CONCLUSION: Using extensively coated non-modular stems combined with intramedullary allografts in two-stage revision for treating infected THAs can achieve satisfactory outcomes.