Nacre-mimetic cerium-doped nano-hydroxyapatite/chitosan layered composite scaffolds regulate bone regeneration via OPG/RANKL signaling pathway.

Autogenous bone grafting has long been considered the gold standard for treating critical bone defects. However, its use is plagued by numerous drawbacks, such as limited supply, donor site morbidity, and restricted use for giant-sized defects. For this reason, there is an increasing need for effective bone substitutes to treat these defects. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable "brick-and-mortar" architecture. Inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). Hydroxyapatite can provide a certain strength to the material like a brick. And as a polymer material, chitosan can slow down the force when the material is impacted, like an adhesive. As seen in natural nacre, the combination of these inorganic and organic components results in remarkable tensile strength and fracture toughness. Cerium ions have been demonstrated exceptional anti-osteoclastogenesis capabilities. Our scaffold featured a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 µm, which provided a conducive environment for human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, allowing for in situ growth of newly formed bone tissue. In vitro, Western-blot and qPCR analyses showed that the CeHA/CS layered composite scaffolds significantly promoted the osteogenic process by upregulating the expressions of osteogenic-related genes such as RUNX2, OCN, and COL1, while inhibiting osteoclast differentiation, as indicated by reduced TRAP-positive osteoclasts and decreased bone resorption. In vivo, calvarial defects in rats demonstrated that the layered CeHA/CS scaffolds significantly accelerated bone regeneration at the defect site, and immunofluorescence indicated a lowered RANKL/OPG ratio. Overall, our results demonstrate that CeHA/CS scaffolds offer a promising platform for bone regeneration in critical defect management, as they promote osteogenesis and inhibit osteoclast activation.

Open Reduction and Internal Fixation by Volar Locking Plates and the "Poking Reduction" Technique in Distal Radius Fractures with Displaced Dorsal Ulnar Fragments: A Retrospective Study.

OBJECTIVE: To investigate the clinical and radiological outcomes of distal radius fractures (DRFs) with displaced dorsal ulnar fragments treated with volar locking plate (VLP) and the "poking reduction" technique. METHODS: Between January 2014 and January 2019, 78 unilateral DRFs with displaced dorsal ulnar fragment (AO type C3) treated with VLP were conducted. According to the reduction technique of the dorsal ulnar fragment, the patients were divided into the conventional reduction (CRG) group (33 patients, 14 males and 19 females, mean age 57.2 ± 12.1 years old) and the "poking reduction" (PRG) group (45 patients, 11 males and 34 females, mean age 60.1 ± 12.4 years old). According to the AO classification, there were 21 cases of C3.1 and 12 of C3.2 in the CPG group, 27 cases of C3.1 and 18 of C3.2 in the PRG group. Clinical and radiographic data were extracted from the electronic medical record system. These data were reviewed for clinical outcomes (range of motion, grip strength), radiological outcomes (volar tilt, radial inclination, radial height, step of articular surface), and postoperative complications. The final functional recovery was evaluated by the disabilities of the arm, shoulder, and hand (DASH) score. RESULTS: The mean duration of follow-up was 27 months (range from 12 to 56). The average operation time and intraoperative blood loss did not significantly differ between groups (p > 0.05). Postoperative CT examination showed that the step of articular surface in CPG group (0.8 ± 0.3 mm) was larger than that in PRG group (0.5 ± 0.2 mm) (p < 0.001). The DASH score did not significantly differ between groups (26.1 ± 4.6 in CRG and 24.7 ± 4.0 in PRG, p > 0.05) at 3 months postoperatively. At 6 months and 12 months postoperatively, the DASH score was better in PRG group (11.8 ± 2.5 and 10.4 ± 2.0) than in CRG group (13.6 ± 2.7 and 12.2 ± 2.5) (p = 0.004, p = 0.001, respectively). At 12 months postoperatively, wrist range of motion did not significantly differ between groups (p > 0.05). There was no significant difference in radiological parameters between the two groups (p > 0.05). The incidence of complications was higher in the CRG group (7/33) than in the PRG group (2/45) (p = 0.009). CONCLUSION: The "poking reduction" technique is a wise option for reduction of dorsal ulnar fragment in DRFs. This innovative technique could restore smoothness of the radiocarpal joint effectively, and the dorsal ulnar fragment could be fixed effectively combined with the volar plate.

Post-Marketing Surveillance of Qishe Pill () Use for Management of Neck Pain in a Chinese Patient Cohort to Determine its Safety, Tolerability and Effectiveness.

OBJECTIVE: To evaluate the safety and effectiveness of Qishe Pill () on neck pain in real-world clinical practice. METHODS: A multi-center, prospective, observational surveillance in 8 hospitals across Shanghai was conducted. During patients receiving 4-week Qishe Pill medication, Visual Analogue Scale (VAS) and Neck Disability Index (NDI) assessments have been used to assess their pain and function, while safety monitoring have been observed after 2 and 4 weeks. RESULTS: Results from 2,023 patients (mean age 54.5 years) suggest that the drug exposure per unit of body mass was estimated at 3.41 ± 0.62 g/kg. About 8.5% (172/2,023) of all participants experienced adverse events (AEs), while 3.8% (78/2,023) of all participants experienced adverse reaction. The most common AEs were gastrointestinal events and respiratory events. The VAS score (pain) and NDI score (function) significantly decreased after 4-week treatment. An effect-quantitative analysis was also conducted to show that the normal clinical dosage may be consider as 3-4 g/kg, at which dosage the satisfactory pain-relief effect may achieve by 40-mm reduction in VAS. CONCLUSION: These findings showed that patients with cervical radiculopathy who received Qishe Pill experienced significant improvement on pain and function. (Registration No. NCT01875562).

[Comparison of surgical effects between extension and flexion type of distal radius fracture].

OBJECTIVE: To compare therapeutic effects of internal fixation with volar locking plate in treating extension and flexion type of distal radius fracture (DRF). METHODS: From January 2015 to June 2018, 103 patients with DRF were retrospectively analyzed. According to original fracture displacement direction, patients were divided into extension fracture(Colles) group and flexion fracture (Smith) group. In Colles fracture group, there were 24 males and 44 females aged from 20 to 79 years old with an average of (59.0±13.4) years old;according to AO classification, 9 patients of type A2, 13 patients of type A3, 16 patientsof type C1, 17 patients of type C2 and 13 patients of type C3;the time from injury to operation ranged from 2 to 9 days with an average of (3.9±0.8) days. In Smith fracture group, there were 15 males and 20 females, aged from 27 to 87 years old with an average of (60.1±15.3) years old;according to AO classification, 4 patienst of A2, 7 patients of A3, 14 patients of C1, 5 patients of C2 and 5 patients of C3;the time from injury to operation ranged from 2 to 6 days with an average of (4.1±0.9) days. Operation time, fracture healing time and postoperative complications were recorded between two groups. Disabilities of arm, shoulder and hand (DASH) score at 6 and 8 weeks, 6 and 8 months were used to evaluate functional recovery of affected limbs during each follow up. Volar tilt, radial inclination and radius height were measured at 8 months after operation. Mayo score was measured at 8 months after operation to evaluate recovery of limb function. RESULTS: All patients were followed up for 8 to 30 months with an average of (14.8±4.3) months, and no difference in follow up between two groups (P> 0.05). There were no statistical differences in operation time, fracture healing time and postoperative complications between two groups(P>0.05). DASH score at 6 and 12 weeks in Colles fracture group were (37.24±5.08) and (19.68±4.55), while in Smith fracture group were (39.05±4.79) and (23.44±4.21);Colles fracture group was better than that of Smith fracture group (P<0.001);while there were no differences in DASH score at 6 and 8 months between two groups (P>0.05). Volar tilt of Smith fracture group (11.1±3.1)° was better than that of Colles fracture group (8.6±4.1) °, and there were no significant difference in radial inclination and radius height between two groups(P>0.05). Also there was no significant difference in Mayo score between two group(P>0.05). CONCLUSION: Patients with Colles fracture and Smith fracture could receive good reduction and fixation through volar locking plate. The radiographic parameters of both groups recovered satisfactorily after operation. Recovery of volar tilt of Smith fracture group is better than that of Colles fracture group, and early recovery function of Colles fracture group is better than that of Smith group, but there is no significant difference in long-term wrist joint function and incidence of postoperative complications between two groups.

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability.

BACKGROUND: Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. METHODS: Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. RESULTS: Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. CONCLUSION: The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Quercetin inhibits macrophage polarization through the p-38α/ß signalling pathway and regulates OPG/RANKL balance in a mouse skull model.

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/ß signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p-38α/ß 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/ß signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.

Changes in Alignment of Ipsilateral Knee on Computed Tomography after Total Hip Arthroplasty for Developmental Dysplasia of the Hip.

OBJECTIVE: To assess the changes in alignment of ipsilateral knee joint after total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). METHODS: Thirty-four patients with DDH (38 hips) who underwent THA between February and December 2008 were included in the study: 4 men and 30 women with a mean age of 56.2 years. According to Crowe classification, 11 patients were grade I, 12 were grade II, 9 were grade III, and 6 were grade IV. Computed tomography scans were performed from the anterior superior iliac spine to the tibial tubercle before surgery and at last follow-up. Femoral anteversion angle, leg lengthening, and knee alignment, including patellar tilt angle, lateral patellar displacement, and tibiofemoral rotation angle, were measured on computed tomography scans, and their relationships were analyzed. RESULTS: The mean follow-up period was 51.5 months (range, 39-70 months). There were no intraoperative fractures, and no infections occurred during the follow-up period. One patient developed deep venous thrombosis and another suffered from femoral nerve palsy. The mean preoperative Harris Hip Score was 48.9 ± 7.5 and improved to 91.2 ± 8.3 by the last follow-up (P < 0.001). There was no sign of prosthetic loosening in all hips. Postoperatively, mean leg lengthening was 26.08 ± 21.81 mm (P < 0.001), femoral anteversion decreased 9.03° ± 12.80° (P < 0.001), and patellar tilt, lateral patellar displacement, and tibiofemoral rotation increased by 3.58° ± 4.96° (P < 0.001), 1.78 ± 3.36 mm (P = 0.002), and 2.56° ± 3.37° (P < 0.001), respectively. Postoperative increase in patellar tilt and lateral patellar displacement had significant linear relationships with the decrease in femoral anteversion (r = 0.621, P < 0.001 and r = 0.437, P = 0.0037, respectively). These results revealed that patellofemoral alignment would change more with the decrease in femoral anteversion. Postoperative increase in external rotation of the tibia had significant positive linear relationships with leg lengthening (r = 0.34, P = 0.037) and the decrease in femoral anteversion (r = 0.693, P < 0.001). These results revealed that the external rotation of the proximal tibia would increase with the leg lengthening or the decrease of femoral anteversion. Postoperative changes in patellar tilt and lateral patellar displacement had no significant linear relationships with leg lengthening (P = 0.795 and P = 0.082, respectively). CONCLUSIONS: Total hip arthroplasty for DDH could induce changes in alignment of ipsilateral patellofemoral and tibiofemoral joints, with increases in patellar tilt and displacement, and increases in external rotation of the tibia. These secondary alterations still existed at medium-term follow-up after surgery, which should be considered during THA for patients with DDH. Extended follow-up is necessary to evaluate long-term changes in the knee joint.

Ursolic acid loaded-mesoporous bioglass/chitosan porous scaffolds as drug delivery system for bone regeneration.

Bioglass scaffolds have great application potentials in orthopedics, and Ursolic acid (UA) can effectively promote in vivo new bone formation. Herein, we for the first time developed the mesoporous bioglass/chitosan porous scaffolds loaded with UA (MBG/CS/UA) for enhanced bone regeneration. The MBG microspheres with particle sizes of ~300 nm and pore sizes of ~3.9 nm were uniformly dispersed on the CS films. The mesoporous structure within the MBG microspheres and the hydrogen bonding between the scaffolds and UA drugs made the MBG/CS/UA scaffolds have controlled drug release performances. The as-released UA drugs from the scaffolds increased remarkably the alkaline phosphatase activity, osteogenic differentiation related gene type I collagen, runt-related transcription factor 2 expression, and osteoblast-associated protein expression. Moreover, the results of micro-CT images, histomorphological observations demonstrated that the MBG/CS/UA scaffolds improved new bone formation ability. Therefore, the MBG/CS/UA porous scaffolds can be used as novel bone tissue engineering materials.

Titanium particle­mediated osteoclastogenesis may be attenuated via bidirectional ephrin­B2/eph­B4 signaling in vitro.

The present study investigated the role of bidirectional ephrin­B2/erythropoietin­producing human hepatocellular receptor 4 (ephB4) signaling in the regulation of wear particle­mediated osteoclastogenesis in vitro. Mouse bone marrow macrophages (BMMs) were induced into osteoclasts by receptor activator of nuclear factor­κB ligand (RANKL, 50 ng/ml). EphB4­Fc, an osteoblast membrane surface receptor (4 µg/ml), was used to stimulate the ephrin­B2 ligand of osteoclasts in the presence and absence of titanium (Ti). Tartrate­resistant acid phosphatase (TRAP) staining was used to detect the number of osteoclasts, and phalloidin staining was used to examine the cytoskeletons of the osteoclasts. A bone pit absorption experiment was used to measure osteoclast function. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine osteoclastogenesis. ELISAs were used to detect the production of inflammatory factors. The data demonstrated that Ti significantly promoted the differentiation of BMMs into mature osteoclasts in the presence of RANKL and significantly promoted expression of the ephrin­B2, nuclear factor of activated T­cells 1 (NFATc1), TRAP, Fos proto­oncogene, AP­1 transcription factor subunit (C­FOS), and matrix metalloproteinase 9 (MMP9) genes. Phalloidin and TRAP staining revealed that following the addition of ephB4­Fc, the number, size and cytoskeletal elements of osteoclasts were significantly decreased compared with those in the titanium particle group without ephB4­Fc. Compared with the titanium particle group, the bone pit absorption experiment revealed significantly decreased absorption pit areas in the titanium particle+ephB4­Fc group. The expression of the NFATc1, TRAP, C­FOS and MMP9 genes was markedly decreased in the ephB4­Fc group; however, the expression of the ephrin­B2 gene was increased compared with the Ti particle group without ephB4­Fc after 5 days. Production of inflammatory cytokines was inhibited by Ti particles through bidirectional signals. Addition of ephB4­Fc inhibited the osteoclast­mediated formation of Ti particles via bidirectional ephrin­B2/ephB4 signaling. Activation of this bidirectional signaling pathway may be a potential clinical treatment for osteolysis surrounding prostheses.

Hydroxyapatite coatings with oriented nanoplate and nanorod arrays: Fabrication, morphology, cytocompatibility and osteogenic differentiation.

Hydroxyapatite (HA) crystals exhibit rod-like shape with c-axis orientation and plate-like shape with a(b)-axis orientation in vertebrate bones and tooth enamel surfaces, respectively. Herein, we report the synthesis of HA coatings with the oriented nanorod arrays (RHACs) and HA coatings with oriented nanoplate arrays (PHACs) by using bioglass coatings as sacrificial templates. After soaking in simulated body fluid (SBF) at 120°C, the bioglass coatings are hydrothermally converted into the HA coatings via a dissolution-precipitation reaction. If the Ca/P ratios in SBF are 2.50 and 1.25, the HA crystals on the coatings are oriented nanorod arrays and oriented nanoplate arrays, respectively. Moreover, the bioglass coatings are treated with SBF at 37°C, plate-like HA coatings with a low crystallinity (SHACs) are prepared. As compared with the Ti6Al4V and SHACs, the human bone marrow stromal cells (hBMSCs) on the RHACs and PHACs have better cell adhesion, spreading, proliferation and osteogenic differentiation because of their moderately hydrophilic surfaces and similar chemical composition, morphology and crystal orientation to human hard tissues. Notably, the morphologies of HA crystals have no obvious effects on cytocompatibility and osteogenic differentiation. Hence, the HA coatings with oriented nanoplate arrays or oriented nanorod arrays have a great potential for orthopedic applications.

[VASCULARITY STUDY ON PERIPROSTHETIC TISSUES AROUND ASEPTIC LOOSENING AFTER TOTAL HIP ARTHROPLASTY].

OBJECTIVE: To observe the vascularity in periprosthetic tissues of aseptic loosening after total hip arthroplasty (THA) and to explore the relationship between expression of vascularity and osteolysis. METHODS: Between October 2009 and June 2012, interface tissues were obtained from 22 patients (22 hips) who underwent revision of THA because of prosthetic aseptic loosening, including 12 males and 10 females with the age range of 53-81 years and prosthesis survival range of 6-14 years. The interface tissues were divided into osteolysis group and non-osteolysis group based on preoperative X-ray findings and intraoperative observation. The synovial tissues were harvested from another 8 patients (3 males and 5 females, aged 58-72 years) with osteoarthritis undergoing THA as control group. HE stainging was used to observe the histological character, and low-wear or high-wear was identified according to metal or polyethylene particles amount in osteolysis group. The CD34 immunohistochemical staining was used to mark the blood vessels. Microvessel density and microvessel index were calculated with the use of image analysis software. RESULTS :Histological observation showed that wear particles and numerous macrophages/multinucleated giant cells accumulated in the membrane of osteolysis group, while many fibroblasts and synovial cells existed in non-osteolysis group. The microvessels density and microvessel index were significantly lower in non-osteolysis group than those in osteolysis group and control group (P < 0.05), and there was no significant difference in microvessel density and microvessel index between osteolysis group and control group (P > 0.05). There were less microvessel density and microvessel index in heavy-loaded metal or polyethylene wear particles areas than those in low-loaded metal or polyethylene wear particles areas (P < 0.05), and there for either polyethylene or metal particles (P > 0.05). CONCLUSION: The phagocytosis of macrophage in periprosthetic tissues need vicinal microvessels formation and blood supply to some extent. Vascular injury and decreased blood supply at the implant-bone interface seem to be one of the reasons for insufficient implant osseointegration and aseptic loosening.

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis.

BACKGROUND: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. METHODS: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. CONCLUSION: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed.

Hydroxyapatite coatings with oriented nanoplate arrays: synthesis, formation mechanism and cytocompatibility.

Hydroxyapatite (HA) is the main inorganic constituent of natural bones and teeth with c-axis orientation and a(b)-axis orientation, respectively. Designing HA coatings (HACs) with specific orientation and morphology is an important strategy to improve their biological properties. Herein, we report, for the first time, the hydrothermal synthesis of HACs with oriented nanoplate arrays according to the following steps: (i) deposition of brushite/chitosan coatings (BCCs) on Ti6Al4V substrates; and (ii) transformation of HACs with oriented nanoplate arrays from BCCs after hydrothermal treatment with alkaline solutions. After soaking the BCCs in a NaOH solution under hydrothermal conditions, the Ca2+ and PO4 3- ions are released from the coatings because of the dissolution reaction of brushite, and they react with OH- ions to form HA nanoplates. Interestingly, these HA nanoplates with a preferential c-plane orientation are perpendicular to the coating surfaces. Hydrothermal reaction time and Ca/P ratio of BCCs have great effects on the morphologies of HA nanoplates. On increasing the reaction time from 3 h to 3 days or decreasing the Ca/P ratio from 2.0 to 1.0, the widths (or lengths) of HA nanoplates increase gradually. Simulated body fluid immersion (SBF) tests reveal that the HACs with oriented nanoplate arrays can promote the formation of apatite on the surfaces, suggesting their good in vitro bioactivity. Moreover, human bone marrow stromal cells (hBMSCs) have been used as cell models to investigate cytocompatibility of the HACs. The hBMSCs on the HACs have better cell adhesion, spreading, proliferation and osteogenic differentiation than those on Ti6Al4V substrates because the HACs are similar to the minerals of human hard tissues in chemical composition, morphology and crystallographic orientation. Therefore, HACs with oriented nanoplate arrays have great potential for use as implants of human hard tissues.

Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.

An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 µm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application.

Bactericidal properties and biocompatibility of a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating.

Postoperative implant-associated infection remains a serious complication in total joint arthroplasty (TJA) surgery. The addition of antibiotics to bone cement is used as an antimicrobial prophylaxis in cemented joint arthroplasty; however, in cementless arthroplasty, there are no comparable measures for the local delivery of antibiotics. In this study, a gentamicin-loaded Fe3O4/carbonated hydroxyapatite coating (Gent-MCHC) was fabricated according to the following steps: (i) deposition of Fe3O4/CaCO3 particles on Ti6Al4V substrates by electrophoretic deposition; (ii) conversions of MCHC from Fe3O4/CaCO3 coatings by chemical treatment; and (iii) formation of Gent-MCHC by loading gentamicin into MCHC. MCHC possessed mesoporous structure with a pore size of about 3.8 nm and magnetic property with the saturation magnetization strength of about 4.03 emu/g. Gent-MCHC had higher drug loading efficiency and drug release capacity, and superior biocompatibility and mitogenic activity than Ti6Al4V. Moreover, Gent-MCHC deterred bacterial adhesion and prevented biofilm formation. These results demonstrate that Gent-MCHC can be used as a local drug delivery system to prevent implant-associated infection in TJA surgery.

A genetic pedigree analysis to identify gene mutations involved in femoral head necrosis.

The present study presents results from a linkage and mutation screening analysis aiming to identify the causative gene of femoral head necrosis, also known as osteonecrosis of femoral head (ONFH), in a Chinese pedigree. We collected clinical data on the osteonecrosis pedigree, and extracted blood and genomic DNA from the family members. Polymerase chain reaction (PCR) and direct sequencing allowed to identify a mutation in the COL2A1 gene of the proband; the clinical manifestations of the proband meet the criteria for osteonecrosis. The exons of COL2A1 were amplified by polymerase chain reaction and mutation screening was conducted by direct sequencing in all the family members. The locus was also sequenced in 50 unrelated healthy controls. The c.3665G>A heterozygous mutation was detected in patients of the pedigree, but not in healthy individuals. We conclude that a mutation in the COL2A1 gene is the causative agent of ONFH in this family. Therefore, this mutation may be associated with osteonecrosis in Chinese populations.

Nitric oxide show its survival role by NO-PKC pathway through cGMP-dependent or independent on the culture of cerebella granular neurons.

The role of nitric oxide in the development of neurons is conflicting. In the present work, cerebellar granule neurons (CGNs) were used as a model to assess the survival role of nitric oxide and to find novel signal transduction pathways related to this role. It is reported that sustained inhibition of nitric oxide production induces apoptosis in differentiated cerebellar granule neurons. The antagonist (MK-801, or ODQ)-induced decrease of cell viability, caspase-3 activated, the expression of P-PKC decreased, which were normalized by the provision of the sodium nitroprusside, an NO donor. The data show that blockade of NO production induces apoptotic death in differentiating CGC through activation of caspase-3. This study provides direct evidence that NO plays an active role in sustaining the survival of developing CGNs and that NO-PKC pathway is important for the survival of CGNs in vitro. The endogenous NO exerts its effects in cGMP-dependent manner while the exogenous NO in cGMP-independent manner.

Drug delivery property, bactericidal property and cytocompatibility of magnetic mesoporous bioactive glass.

A multifunctional magnetic mesoporous bioactive glass (MMBG) has been widely used for a drug delivery system, but its biological properties have been rarely reported. Herein, the effects of mesopores and Fe3O4 nanoparticles on drug loading-release property, bactericidal property and biocompatibility have been investigated by using mesoporous bioactive glass (MBG) and non-mesoporous bioactive glass (NBG) as control samples. Both MMBG and MBG have better drug loading efficiency than NBG because they possess ordered mesoporous channels, big specific surface areas and high pore volumes. As compared with MBG, the Fe3O4 nanoparticles in MMBG not only provide magnetic property, but also improve sustained drug release property. For gentamicin-loaded MMBG (Gent-MMBG), the sustained release of gentamicin and the Fe3O4 nanoparticles minimize bacterial adhesion significantly and prevent biofilm formation against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Moreover, the magnetic Fe3O4 nanoparticles in MMBG can promote crucial cell functions such as cell adhesion, spreading and proliferation. The excellent biocompatibility and drug delivery property of MMBG suggest that Gent-MMBG has great potentials for treatment of implant-associated infections.