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Interlocked DNA nanostructures perform programmable movements in nanoscales such as sliding, contraction, and expansion. However, utilizing nanoscaled interlocked movements to regulate the functions of larger length scaled matrix and developing their applications has not yet been reported. Herein we describe the assembly of DNA-based daisy chain rotaxane nanostructure (DNA-DCR) composed of two hollow DNA nanostructures as macrocycles, two interlocked axles and two triangular prism-shaped DNA structures as stoppers, in which three mechanical states─fixed extended state (FES), sliding state (SS), and fixed contracted state (FCS)─are characterized by using toehold-mediated strand displacement reaction (SDR). The DNA-DCRs are further used as nanocomposites and introduced into hydrogel matrix to produce interlocked hydrogels, which shows modulable stiffness by elongating the interlocked axles to regulate the hydrogel swelling with hybridization chain reaction (HCR) treatment. Then the DCR-hydrogels are employed as dynamic biointerfaces for human mesenchymal stem cells (hMSCs) adhesion studies. First, hMSCs showed lower cell density on bare DCR-hydrogel treated with HCR-initiated swelling for stiffness decreasing. Second, the cell adhesion ligand (RGD) modified DNA-DCRs are constructed for hydrogel functionalization. DCR

Surface modification of titanium has been a hot topic to promote bone integration between implants and bone tissue. Titanium dioxide nanotubes fabricated on the surface of titanium by anodic oxidation have been a mature scheme that has shown to promote osteogenesis

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle‐mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p‐38α/β signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p‐38α/β RNA. We used enzyme‐linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro‐inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ‐CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro‐inflammatory factors were released. Titanium particle‐mediated M1 macrophage polarization, which caused the release of pro‐inflammatory factors through the p‐38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.

Previous studies demonstrated cycle mechanical strain induced osteogenic differentiation of MSCs. But in general, MSCs are typically seeded on a flexible membrane or within a soft matrix. TiO2 nanotubes substrate topography plays a critical role in promoting the MSCs response and affects MSCs fate. Titanium implants surface modified by TiO2 nanotubes topography provides the opportunity to improve osseointegration by additionally regulating the MSCs fate. Titanium is one of most commonly used materials in the orthopedics and can undergo elastic deformation under certain mechanical stress. Therefore, for clinic trails, it is necessary to investigate the effect of mechanical strain on osteogenesis of MSCs on TiO2 nanotubes modified titanium substrate. But until now, there has been no research focused on the relationship between mechanical strain and osteogenesis of MSCs on the TiO2 nanotubes topography substrate. Here, we firstly applied the mechanical stress to the TiO2 nanotubes modified titanium specimen to investigate the effects of mechanical strain on the biological behaviors of MSCs. Our present study showed that mechanical strain promoted cell proliferation, spreading and increased vinculin expression of MSCs on the TiO2 nanotubes substrate. Additionally, mechanical strain enhanced the ALP activity and osteogenesis genes expression such as Runx2, BSP, ALP, OPN and OCN. Our results preliminarily demonstrated that mechanical strain enhanced the osteogenic differentiation of MSCs through the FAK-Erk1/2-Runx2 pathway on the TiO2 nanotubes substrate.

Background The closure of high-tension incisions without any assistance can be difficult and challenging for surgeons. A common practice is to fix the first knot with a clamp and then tie a reverse locking knot; however, this practice has certain disadvantages. The aim of this study was to introduce a novel and efficient surgical knotting technique with various advantages. Methods The two knotting methods used in this study were the absorbable braided suture where the first suture was fixed with a clamp (with assistance) and the SH-9Hospital knotting technique (without assistance) applied on the smooth surface of a cylinder. Mechanical testing was performed using a universal material testing machine. The load-elongation curve and ultimate tensile load (UTL) were recorded. Results The mean knotting time was 36.40±1.50 s (range, 32-41 s) and 24.80±1.16 s (range, 21-28 s) in the clamp and SH-9Hosptial groups, respectively. The mean UTL was 120.8±10.14 N (range, 81.11-136.55 N)and 126.5±6.29 N (range, 104.88-139.56 N) in the clamp and SH-9Hospital groups, respectively. The knot strength of the SH-9Hospital technique was not inferior to traditional clinical practice. Conclusions The SH-9Hospital knotting technique was a secure, convenient, and efficient method for high-tension closure.

Background: The occurrence of oscillating saw malfunction, power shortage, or contamination occurs frequently when implementing femoral neck osteotomy during total hip arthroplasty (THA). This study aimed to introduce the fretsaw as a novel substitute osteotomy tool with various advantages.Methods: Twenty patients (20 hips) who underwent primary THA were included. Ten patients underwent femoral neck osteotomy using a fretsaw, while the other 10 patients underwent the procedure using an oscillating saw. Intraoperative evaluation and radiographic data were obtained for all patients during and after surgery.Results: The mean osteotomy time was 20.60 ± 1.08s (range 16–27) and 22.10 ± 1.49s (range 16–31) in the oscillating saw and fretsaw groups, respectively. The mean osteotomy height was 1.21 ± 0.16 (range 1.01–1.43) cm and 1.14 ± 0.08 (range 1.02–1.28) cm in the oscillating saw and fretsaw groups, respectively. The use of fretsaw did not result in bone notch or blood splashes.Conclusion: The fretsaw can be a substitute femoral neck osteotomy tool with various advantages in THA while oscillating saw malfunction.

BACKGROUND: The removal of permanent internal fixation devices by secondary surgery could be avoided if these devices were made of degradable magnesium and magnesium alloys. Before such implants can be used clinically, however, the biological effect of magnesium exposure on surrounding bone must be evaluated. Previous studies have focused on bone formation; few have examined the effects of magnesium on the bone quality that affect many biomechanical properties. METHODS: Using bone quality parameters, we analyzed in vivo changes in bone properties and biomechanics after exposure to locally high levels of magnesium. RESULTS: Local bone mineralization was significantly disrupted following exposure to a porous rod of pure magnesium. Normal crystal formation and crystallinity were inhibited and the mineral-to-matrix ratio decreased. These results were consistent with those of in vitro experiments, in which high levels of magnesium inhibited mineral deposition by mesenchymal stem cells (MSCs) but increased alkaline phosphatase (ALP) expression. The same mineralization inhibition was observed around magnesium implants via micro-computerized tomography (micro-CT) and von Kossa staining. Such reduced bone quality around degrading magnesium rods could negatively impact bone biomechanics. CONCLUSIONS: This study showed that exposure to the local high magnesium levels that arise from rapidly degrading magnesium devices may significantly disrupt bone mineralization and negatively impact bone biomechanics.

Background: Repairing complex anatomical load-bearing bone defects is difficult because it requires restoration of load-bearing function, reconstruction of anatomical shape and repair by regenerated bone. We previously developed a Screen–Enrich–Combine(-biomaterials) Circulating System (SECCS) for rapid intraoperative enrichment of autologous bone marrow mesenchymal stem cells (MSCs) to enhance the osteogenic ability of porous bone substitutes. In this study, we prepared a 3D-printed Ti6A14V macroporous frame matching the defect shape to provide early load-bearing support and evaluated the efficacy of filling the frame with SECCS-processed MSCs/beta tricalcium phosphate (β-TCP) for long-term bone growth. Method: Mechanical testing of the cylindrical Ti6Al4V frame identified optimal 3D printing parameters. The lateral part of a goat distal femur was used as the defect model, and a matching electron beam melting technology-prepared (EBM) Ti6Al4V frame was fitted. Three frames filled with nothing, pure porous β-TCP or SECCS-processed MSCs/β-TCP were fixed onto the defect site. Repair efficacy was evaluated by X-ray radiography, computed tomography, histology and histomorphology. Results: In the basic regular hexagon printing unit, the combined side width (w) and inscribed circle diameter (d) determines the printing frame’s mechanical strength. The compressive load was significantly higher for w = 1.9 mm, d = 4.4 mm than for w = 1.7 mm, d = 4.0 mm or w = 2.0 mm, d = 5.0 mm (P < 0.05). The EBM-prepared Ti6Al4V defect-matched frame was well maintained 9 months after implantation. The MSCs successfully adhered to the wall of the porous β-TCP in the SECCS-processed group and had spread fully in the test samples. Each goat in the MSCs/β-TCP–filling group had approximately 31,321.7 ± 22,554.7 MSCs and a larger area of new bone growth inside the frame than the areas in the control and blank groups.Conclusion: Filling the 3D-printed Ti6Al4V large-aperture frame with osteogenic materials achieved biological reconstruction over a larger area of regenerated bone for repair of complex anatomical weight-bearing bone defects under the condition of early frame-supported load bearing. MSCs/β-TCP prepared by SECCS can be used as a filling material for this type of bone defect to obtain more efficacious bone repair.

BACKGROUND: Total hip arthroplasty (THA) is frequently performed in patients with end-stage hip disease. Periacetabular osteophytes are common during THA; however, these osteophytes should be removed intraoperatively to avoid potential impingement between osteophytes and femoral prostheses and decrease dislocation risk. There are no current standard procedures or surgical technique criteria to remove these osteophytes. Osteophytes around the acetabulum are usually removed with an osteotome, yet this presents certain disadvantages. Hence, this study aimed to introduce a novel and more efficient technique than the aforementioned one, the SH-9Hospital acetabular edge file. METHODS: Fifty-four patients (54 hips) who underwent primary THA using osteotome and the SH-9Hospital acetabular edge file to remove periacetabular osteophytes intraoperatively were retrospectively studied. Clinical and radiographic data were obtained for all patients intra- and postoperatively. RESULTS: The mean osteophyte removal time was 274.6±102.7 s and 51.3±21.1 s in the osteotome and SH-9Hospital acetabular edge file groups, respectively. Intraoperative images and postoperative radiographs showed that acetabular osteophytes were removed thoroughly and precisely by the acetabular edge file and that there was no iatrogenic injury and prostheses malposition in both groups. CONCLUSIONS: The SH-9Hospital acetabular edge file was a novel, efficient, highly precise, and repeatable method for removing periacetabular osteophytes in patients undergoing total hip arthroplasty.

Background The removal of permanent internal fixation devices by secondary surgery could be avoided if these devices were made of degradable magnesium and magnesium alloys. Before such implants can be used clinically, however, the biological effect of magnesium exposure on surrounding bone must be evaluated. Previous studies have focused on bone formation; few have examined the effects of magnesium on the bone quality that affect many biomechanical properties. Methods Using bone quality parameters, we analyzed in vivo changes in bone properties and biomechanics after exposure to locally high levels of magnesium. Results Local bone mineralization was significantly disrupted following exposure to a porous rod of pure magnesium. Normal crystal formation and crystallinity were inhibited and the mineral-to-matrix ratio decreased. These results were consistent with those of in vitro experiments, in which high levels of magnesium inhibited mineral deposition by mesenchymal stem cells (MSCs) but increased alkaline phosphatase (ALP) expression. The same mineralization inhibition was observed around magnesium implants via micro-computerized tomography (micro-CT) and von Kossa staining. Such reduced bone quality around degrading magnesium rods could negatively impact bone biomechanics. Conclusions This study showed that exposure to the local high magnesium levels that arise from rapidly degrading magnesium devices may significantly disrupt bone mineralization and negatively impact bone biomechanics.

Previous studies demonstrated cycle mechanical strain induced osteogenic differentiation of MSCs. But in general, MSCs are typically seeded on a flexible membrane or within a soft matrix. TiO

Background: Aseptic loosening caused by wear particles is one of the common complications after total hip arthroplasty. We investigated the effect of the quercetin on wear particle-mediated macrophage polarization, inflammatory response and osteolysis. Methods: In vitro, we verified whether quercetin can inhibit the polarization of macrophages and reduce the release of pro-inflammatory factors, ultimately improving osteolysis by regulating the balance of OPG/RANKL ratio. In vivo, we further simulated osteolysis around the prosthesis by establishing a Ti particle osteolysis mouse model. Finding: Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p-38α/β signaling pathway, and M1 macrophages release large amounts of pro-inflammatory factors. These pro-inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, they could be suppressed, and the protein expression of the M2 macrophages expression was increased in the presence of the quercetin. In vivo, we further revealed similar results in the mouse skull by μ-CT, H&E staining, immunohistochemistry and immunofluorescence. Most importantly, we took the sample from patients with osteolytic tissue. And it was also confirmed that most of the macrophages surrounding the wear particles were M1 macrophages by immunofluorescence and pro-inflammatory factors were released by immunohistochemistry. Interpretation: Titanium particle-mediated M1 macrophage polarization through the p-38α/β signaling pathway, which caused pro-inflammatory factors released, regulated OPG/RANKL balance. However, they could be suppressed by the quercetin. The macrophage polarization is expected to become a new clinical drug therapeutic target. Funding Statement: The present study was supported by grants from the National Natural Science Foundation of China (grant nos., 81572158, 81772361 and 81572116). Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the local Ethics Committee. All animal procedures were approved by the Animal's Hospital affiliated to Shanghai Jiao Tong University.

Three‐dimensional (3D) printing is a digital rapid prototyping technology based on a discrete and heap‐forming principle. We identified 53 articles from PubMed by searching “Hip” and “Printing, Three‐Dimensional”; 52 of the articles were published from 2015 onwards and were, therefore, initially considered and discussed. Clinical application of the 3D printing technique in the hip joint mainly includes three aspects: a 3D‐printed bony 1:1 scale model, a custom prosthesis, and patient‐specific instruments (PSI). Compared with 2‐dimensional image, the shape of bone can be obtained more directly from a 1:1 scale model, which may be beneficial for preoperative evaluation and surgical planning. Custom prostheses can be devised on the basis of radiological images, to not only eliminate the fissure between the prosthesis and the patient's bone but also potentially resulting in the 3D‐printed prosthesis functioning better. As an alternative support to intraoperative computer navigation, PSI can anchor to a specially appointed position on the patient's bone to make accurate bone cuts during surgery following a precise design preoperatively. The 3D printing technique could improve the surgeon's efficiency in the operating room, shorten operative times, and reduce exposure to radiation. Well known for its customization, 3D printing technology presents new potential for treating complex hip joint disease.

Bone is a rigid and dynamic organ that continuously undergoes remodeling and repair. The balance between osteoblastic bone formation and osteoclastic bone resorption is essential for normal bone homeostasis. Osteoclasts are giant multinucleated cells derived from the monocyte/macrophage hematopoietic lineage and are regulated by various cytokines. Long non-coding (lnc) RNAs are known to regulate many biological processes in the skeletal system in both normal and diseased states; however, the lncRNA-mediated regulation of osteoclastogenesis has not been extensively studied. Hence, in the present study, we performed microarray analysis of lncRNAs expressed during different stages of osteoclast differentiation and fusion. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the biological functions of target genes of lncRNAs that were specifically up- or downregulated at the different stages. Microarray and bioinformatic prediction results were used to generate co-expression networks of lncRNAs-mRNAs and lncRNAs-transcription factors. Based on the analysis, we identified one lncRNA, NONMMUT037835.2, which plays an important role during osteoclastogenesis. Upregulation of lncRNA-NONMMUT037835.2 inhibited osteoclastic differentiation, whereas downregulation of lncRNA-NONMMUT037835.2 promoted osteoclast formation and fusion. Our study also indicated that lncRNA-NOMMUT037835.2 might regulated osteoclastogenesis through negatively regulating RANK expression and inhibiting NF-κB/MAPK signaling pathway. Our results lead to a better understanding of the molecular mechanisms and provided a theoretical basis for developing therapeutic agents for diseases related to dysregulation of bone homeostasis.