Bismuth-coated 80S15C bioactive glass scaffolds for photothermal antitumor therapy and bone regeneration.

Background: Malignant bone tumors usually occur in young people and have a high mortality and disability rate. Surgical excision commonly results in residual bone tumor cells and large bone defects, and conventional radiotherapy and chemotherapy may cause significant side effects. In this study, a bifunctional Bi-BG scaffold for near-infrared (NIR)-activated photothermal ablation of bone tumors and enhanced bone defect regeneration is fabricated. Methods: In this study, we prepared the Bi-BG scaffold by in-situ generation of NIR-absorbing Bi coating on the surface of a 3D-printing bioactive glass (BG) scaffold. SEM was used to analyze the morphological changes of the scaffolds. In addition, the temperature variation was imaged and recorded under 808 nm NIR laser irradiation in real time by an infrared thermal imaging system. Then, the proliferation of rat bone mesenchymal stem cells (rBMSCs) and Saos-2 on the scaffolds was examined by CCK-8 assay. ALP activity assay and RT-PCR were performed to test the osteogenic capacity. For in vivo experiments, the nude rat tumor-forming and rat calvarial defect models were established. At 8 weeks after surgery, micro-CT, and histological staining were performed on harvested calvarial samples. Results: The Bi-BG scaffolds have outstanding photothermal performance under the irradiation of 808 nm NIR at different power densities, while no photothermal effects are observed for pure BG scaffolds. The photothermal temperature of the Bi-BG scaffold can be effectively regulated in the range 26-100°C by controlling the NIR power density and irradiation duration. Bi-BG scaffolds not only significantly induces more than 95% of osteosarcoma cell death (Saos-2) in vitro, but also effectively inhibit the growth of bone tumors in vivo. Furthermore, they exhibit excellent capability in promoting osteogenic differentiation of rBMSCs and finally enhance new bone formation in the calvarial defects of rats. Conclusion: The Bi-BG scaffolds have bifunctional properties of photothermal antitumor therapy and bone regeneration, which offers an effective method to ablate malignant bone tumors based on photothermal effect.

Polydopamine Coating-Mediated Immobilization of BMP-2 on Polyethylene Terephthalate-Based Artificial Ligaments for Enhanced Bioactivity.

Background/objectives: Polyethylene terephthalate (PET)-based artificial ligaments are one of the most commonly used grafts in anterior cruciate ligament (ACL) reconstruction surgery. However, the lack of favorable hydrophilicity and cell attachment for PET highly impeded its widespread application in clinical practice. Studies found that surface modification on PET materials could enhance the biocompatibility and bioactivity of PET ligaments. In this study, we immobilized bone morphogenetic protein-2 (BMP-2) on the surface of PET ligaments mediated by polydopamine (PDA) coating and investigated the bioactivation and graft-to-bone healing effect of the modified grafts in vivo and in vitro. Methods: In this study, we prepared the PDA coating and subsequent BMP-2-immobilized PET artificial ligaments. Scanning electron microscopy (SEM) was used to analyze the morphological changes of the modified grafts. In addition, the surface wettability properties of the modified ligaments, amount of immobilized BMP 2, and the release of BMP-2 during a dynamic period up to 28 days were tested. Then, the attachment and proliferation of rat bone mesenchymal stem cells (rBMSCs) on grafts were examined by SEM and Cell Counting Kit-8 (CCK-8) assay, respectively. Alkaline phosphatase (ALP) assay, RT-PCR, and Alizarin Red S staining were performed to test the osteoinduction property. For in vivo experiments, an extra-articular graft-to-bone healing model in rabbits was established. At 8 weeks after surgery, biomechanical tests, micro-CT, and histological staining were performed on harvested samples. Results: A surface morphological analysis verified the success of the PDA coating. The wettability of the PET artificial ligaments was improved, and more than 80% of BMP-2 stably remained on the graft surface for 28 days. The modified grafts could significantly enhance the proliferation, attachment, as well as expression of ALP and osteogenic-related genes, which demonstrated the favorable bioactivity of the grafts immobilized with BMP-2 in vitro. Moreover, the grafts immobilized with BMP-2 at a concentration of 138.4 ± 10.6 ng/cm2 could highly improve the biomechanical properties, bone regeneration, and healing between grafts and host bone after the implantation into the rabbits compared with the PDA-PET group or the PET group. Conclusion: The immobilization of BMP-2 mediated by polydopamine coating on PET artificial ligament surface could enhance the compatibility and bioactivity of the scaffolds and the graft-to-bone healing in vivo.

3D printing of pearl/CaSO4 composite scaffolds for bone regeneration.

The development of biomaterials with high osteogenic ability for fast osteointegration with a host bone is of great interest. In this study, pearl/CaSO4 composite scaffolds were fabricated using three-dimensional (3D) printing, followed by a hydration process. The pearl/CaSO4 scaffolds showed uniform interconnected macropores (∼400 µm), high porosity (∼60%), and enhanced compressive strength. With CaSO4 scaffolds as a control, the biological properties of the pearl/CaSO4 scaffolds were evaluated in vitro and in vivo. The results showed that the pearl/CaSO4 scaffolds possessed a good apatite-forming ability and stimulated the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), as well as giving a better expression of related osteogenic genes. Importantly, micro-computed tomography and histology of the critical-sized rabbit femoral condyle defects implanted with the scaffolds illustrated the osteogenic capacity of the pearl/CaSO4 scaffolds. New bone was observed within 8 weeks. The bone-implant contact index was significantly higher for the pearl/CaSO4 scaffolds implant than for the CaSO4 scaffolds implant, indicating that the pearl/CaSO4 scaffolds would be promising implants for bone regeneration.

The use of morselized allografts without impaction and cemented cage support in acetabular revision surgery: a 4- to 9-year follow-up.

BACKGROUND: Acetabular revision arthroplasty with major bone loss is one of the most difficult operations in orthopedic surgery. The goal of the study was to evaluate midterm clinical results of the use of morselized allografts with cemented cage support in revision total hip replacement. METHODS: We identified 28 patients (29 hips) at an average follow-up of 73 months. Harris Hip Scores (HHS) were assessed before and after surgery. Pre- and postoperative radiographs were evaluated for restoration of the center of rotation, component migration, and graft incorporation. RESULTS AND DISCUSSION: At follow-up, the mean HHS improved from 34 (range, 20-45) to 80 (range, 71-98) points. None of the components had been re-revised. On average, the revised hip center of rotation was improved significantly. Incorporation of the graft was complete in 23 hips. The midterm result of cage reconstruction with morselized bone allograft is relatively better than other studies using a similar cage construction. We believe we have three special modifications of this reconstruction technique that are beneficial for bone incorporation. CONCLUSIONS: These data confirm that acetabular reconstruction using morselized allografts and cemented acetabular cages is effective in the midterm as a treatment for acetabular loosening with massive bone deficiency.

The use of combined anteversion in total hip arthroplasty for patients with developmental dysplasia of the hip.

The combined anteversion technique has been proposed recently and proved to be an applicable technique in general THA. The corresponding author routinely applied this approach to DDH patients in clinical practice. The current study aimed to provide clinical evidence for this approach. We studied 35 DDH patients (47 hips). Every patient underwent pelvic CT scans before and after surgery and the HHs was recorded. The data indicate a high accuracy of controlling components orientation and satisfactory clinical outcomes. Using this approach, we reduced dislocation risk and got better impingement free range of motion. Therefore, we conclude that combined anteversion is effective for DDH patients who receive a THA. This approach could guarantee stable and functioning joints for DDH patients receiving THA.

Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.

AIM: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). METHODS: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. CONCLUSION: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model.

AIM: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. METHODS: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 µg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. RESULTS: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. CONCLUSION: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

Comparison of the cytotoxic and inflammatory responses of titanium particles with different methods for endotoxin removal in RAW264.7 macrophages.

It is generally accepted that periprosthetic bone resorption is initiated through aseptic inflammation aggravated by wear particles that are generated from artificial joint. However, some studies have demonstrated that "endotoxin-free" wear particles are almost completely unable to stimulate the macrophage-mediated production of proinflammatory cytokines. Here, we compare the titanium particles with different methods of endotoxin removal. The results indicated that different titanium particle preparation dosages did not significantly change particle size, morphology, and chemical composition. But it could cause variations in the endotoxin concentration of titanium particles and inflammatory responses in RAW264.7 macrophages. The particles with higher endotoxin levels correlated with more extensive inflammatory responses. When testing endotoxins using the supernatant of particle suspensions, it would lead to false negative results compared with testing the particle themselves. And when using the particles themselves, all the particles should be removed by centrifugation to avoid particle interference before the absorbance value was determined. Therefore, we suggest that research concerning wear particles should completely describe the endotoxin testing process, including endotoxin removal from particles and the details of endotoxin testing. Moreover, future research should focus on the surface of wear particles (the potential role of adherent endotoxin) rather than the particles themselves.

[Micro-particles of bioceramics could cause cell and tissue damage].

We conducted studies to confirm the hypothesis that the cellular damage occurring around implanted biphasic bioceramics could be related to a micro-particles release because of an insufficient sintering. An in vitro cytotoxicity study was performed on four biphasic ceramic (BCP) samples. Without the treatment of extraction medium, a cytotoxicity was observed, although after centrifugation this cytotoxicity disappeared in all samples. (2) Micro-particles of HA, beta-TCP and 40%beta-TCP/60%HA mixture were used for a cell inhibition study. A decrease of cell viability was observed with the increase in particles concentration. At 10000 particles/ cell, the viability and proliferation were completely inhibited. (3) HA, beta-TCP and BCP ceramic granules were implanted in rabbit femoral cavities for 12 weeks. No degradation of HA granules was observed. The degradation was higher for beta-TCP (40%) than for BCP (5%). On the other hand, new bone formation was significantly higher for beta-TCP (21%) and HA (18%) than for BCP (12%). Much more micro-particles were formed around BCP granules than around beta-TCP, and were phagocytosed by macrophages. The release of ceramic micro-particles could be related to the sintering process. BCP ceramics have to be sintered at only 1160 degrees C. Consequently, HA microparticles of BCP ceramic are incompletely sintered and easily released after immersion or implantation. The microparticles could be at the origin of local inflammation and cell damage and could perhaps modify osteogenesis. Particular attention must be paid to this problem with regard to BCP ceramics because of the sintering difficulties of this bioceramic.