Three-dimensional porous titanium alloys printed via electron beam melting have low stiffness similar to that of cortical bone and are promising scaffolds for orthopedic applications. However, the bio-inert nature of titanium alloy is poorly compatible with bone ingrowth. We previously observed that simvastatin/poloxamer 407 thermosensitive hydrogel induces endogenous angiogenic/osteogenic growth factors and promotes angiogenesis and osteogenesis, but the mechanical properties of this hydrogel are poor. The purpose of this study was to construct 3D-printed porous titanium scaffolds (pTi scaffolds) filled with simvastatin/hydrogel and evaluate the effects of this composite on osseointegration, bone ingrowth and neovascularization using a tibial defect rabbit model. Four and eight weeks after implantation, the bone volume, bone mineral density, mineral apposition rate, and push-in maximum force of the pTi scaffolds filled with simvastatin/hydrogel were significantly higher than those without simvastatin (p < 0.05). Moreover, filling with simvastatin/hydrogel significantly enhanced vascularization in and around the pTi scaffolds, and a significant correlation was observed between the volume of new bone and neovascularization (p < 0.01). In conclusion, incorporating simvastatin/poloxamer 407 hydrogel into pTi scaffolds significantly improves neovascularization, osseointegration and bone ingrowth.

In vivo assessment of a novel artificial vertebral body fabricated by electron beam melting (EBM) for cervical vertebral body replacement in a sheep model. To investigate the feasibility of a novel artificial vertebral body: a "self-stabilizing artificial vertebral body" (SSAVB) fabricated by EBM in a sheep model. Artificial vertebral body is widely used for vertebral body replacement and spinal fusion, but research on an artificial vertebral body fabricated by EBM has not been reported. An SSAVB made of porous Ti6Al4V was implanted into a sheep cervical spine to replace the C4 vertebral body for 6 and 12 weeks. Bone ingrowth and implant stability were radiologically evaluated, and histological and biomechanical tests were performed. No screw loosening, implant dislocation, or bone fractures occurred during the experimental period. A significant difference (P = 0.001) in bone ingrowth between the 6- and 12-week groups was noted. Comparison of the range of motion of C3-C5 segments between the in vivo group and the control groups (intact C2-C6 segment and fresh sheep cervical spines from C2 to C6 segments that underwent C4 subtotal corpectomy with the posterior vertebral wall retention by SSAVB implantation) suggests that the implant can stably replace this area of the cervical spine. The open porous structure of Ti6Al4V fabricated by EBM facilitated bone ingrowth and the SSAVB can maintain cervical spine stability of the sheep. A porous metal implant can be used for load-bearing applications in a sheep model. It is hoped that these results will stimulate further study in human. 4.

Study Design. Retrospective review. Objective. To perform a single-institution analysis of incidence, treatment, and clinical outcome in patients with thoracic ossification of the ligamentum flavum (OLF) who experienced dural tears and cerebrospinal fluid (CSF) leakage. Summary of Background Data. There is a paucity of clinical reports focusing on dural tears and CSF leakage after thoracic OLF surgery. Because dural adhesion and dural ossification are common features of thoracic OLF, the incidence of CSF leakage in OLF patients is high and represents a significant clinical challenge. Methods. A total of 266 patients with thoracic OLF were admitted to our hospital from 1995 to 2011. Each patient's medical records were reviewed to identify cases of dural tears and CSF leakage. Information on therapeutic strategy used to repair the dural tears and complications related to CSF leakage was extracted. Results. The incidence of dural tears and CSF leakage in OLF patients was 32% (85/266). The incidence of dural ossification was 25.2%. The dural tears were repaired with a range of materials, including gelatin sponge, muscle/fascia, artificial dura, silk suture, and fibrin glue. The intraoperative repair procedure did not resolve CSF leakage in 65 cases, and 16 of those cases experienced complications related to the continued CSF leakage, including CSF pseudocyst, wound dehiscence, and meningitis. Fifty-eight patients with CSF leakage were eventually cured by a series of comprehensive treatments, which included prone position, continuous pressure by sandbag, ultrasound-guided puncture, and aspiration. Only 7 patients required reoperation. Conclusion. Dural ossification was the main reason for dural tears. In all, 78 of the 85 patients with CSF leakage or dural tear were successfully cured. The success rate was 91.8%, which indicated that a series of comprehensive treatments was an effective strategy to treat these patients.

Angiogenesis and osteogenesis are tightly coupled during bone development. We studied the effect of inhibition of Hif1α and Runt-related protein 2 (Runx2) on the formation of heterotopic ossification (HO). We constructed lentivirus vectors expressing Hif1α small interfering RNA (siRNA) and Runx2 siRNA. The inhibition of Hif1α function impaired osteoblast proliferation while osteoblasts differentiated normally. Osteoblasts lacking Runx2 proliferated normally while the differentiation was impaired. The osteoblast differentiation was significantly inhibited by co-Runx2 and Hif1α siRNA treatment. The formation of HO by inhibiting Runx2 and Hif1α in an animal model induced by Achilles tenotomy was investigated. The results showed that lacking of Runx2 and Hif1α could inhibit HO formation. Inhibition of Hif1α prevented HO formation only at the initial step and inhibition of Runx2 worked both at the initial step and after chondrogenesis. Angiogenesis and the expressions of osteogenic genes were downregulated in the Hif1α siRNA group. We found synergistic inhibition of endochondral bone formation by silencing Hif1α and Runx2. Our study provided new insight into the roles of Hif1α and Runx2 during the processes of endochondral bone formation, and had important implications for the new therapeutic methods to inhibit HO or to enhance bone formation.