Yong-Quan Zhang

Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion.

Interbody fusion cages made of poly-ether-ether-ketone (PEEK) have been widely used in clinics for spinal disorders treatment; however, they do not integrate well with surrounding bone tissue. Ti-6Al-4V (Ti) has demonstrated greater osteoconductivity than PEEK, but the traditional Ti cage is generally limited by its much greater elastic modulus (110 GPa) than natural bone (0.05-30 GPa). In this study, we developed a porous Ti cage using electron beam melting (EBM) technique to reduce its elastic modulus and compared its spinal fusion efficacy with a PEEK cage in a preclinical sheep anterior cervical fusion model. A porous Ti cage possesses a fully interconnected porous structure (porosity: 68 ± 5.3%; pore size: 710 ± 42 μm) and a similar Youngs modulus as natural bone (2.5 ± 0.2 GPa). When implanted in vivo, the porous Ti cage promoted fast bone ingrowth, achieving similar bone volume fraction at 6 months as the PEEK cage without autograft transplantation. Moreover, it promoted better osteointegration with higher degree (2-10x) of bone-material binding, demonstrated by histomorphometrical analysis, and significantly higher mechanical stability (P < 0.01), shown by biomechanical testing. The porous Ti cage fabricated by EBM could achieve fast bone ingrowth. In addition, it had better osseointegration and superior mechanical stability than the conventional PEEK cage, demonstrating great potential for clinical application.

Elevated Serum Concentrations of Inflammatory Cytokines and Chemokines in Patients with Haemorrhagic Fever with Renal Syndrome

OBJECTIVE: Prospective case—control study, undertaken to investigate serum cytokine and chemokine concentrations during all clinical phases and in different clinical types of haemorrhagic fever with renal syndrome (HFRS). METHODS: Serum was collected at various disease phases from patients with HFRS (n = 35) and healthy control subjects (n = 10). Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-4, interferon (IFN)-γ, IL-8, interferon inducible protein-10 (IP-10) and chemokine (C—C motif) ligand 5 (also known as ‘regulated upon activation, normal T-cell expressed and secreted’ [RANTES]) were quantified using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum concentrations of TNF-α, IL-6, IFN-γ, IL-8, IP-10 and RANTES (but not IL-4) were significantly higher in patients compared with controls. Highest concentrations were generally found during the febrile, hypotensive and oliguric disease phases, as well as in clinically severe and critical cases. CONCLUSION: Serum concentrations of proinflammatory cytokines and chemokines increased in line with disease severity in HFRS patients.

A canine model of femoral head osteonecrosis induced by an ethanol injection navigated by a novel template.

There is no consensus on how to establish models of osteonecrosis of the femoral head (ONFH) in large mammals. The aim of this study was to investigate the effectiveness of a novel canine model of ONFH, induced by a navigated injection of absolute ethanol. Using three-dimensional reconstruction and rapid prototyping manufacturing techniques, a new template was designed and processed to navigate the ethanol injection. The femoral heads of 18 adult dogs were injected with ethanol. Macroscopic, X-ray and histological examinations were performed at 3, 6, and 9 weeks after the operation. Further, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide scans were performed 6 weeks postoperatively. Three weeks after the operation, the femoral heads showed evidence of osteonecrosis including increasing numbers of empty lacunae, decreased hematopoietic cells, and destroyed adipose tissue in the medullary cavity, which increased in severity at the subsequent follow-up evaluations at 6 and 9 weeks. Fractured trabeculae and fibrous tissue were noted 9 weeks postoperatively. Image analysis also revealed evidence of osteonecrosis, such as several osteopenic areas with sclerotic rims on the X-ray, several areas of low bone mineral density with sclerosis on the CT scan, increased uptake of the nuclide species in MRI, and an inhomogeneous long T2 signal on the radioisotopic images. Ethanol injection navigated by our novel template was successful in establishing a canine model of ONFH. This model can be used to test new treatment modalities for human ONFH.

The Treatment Effect of Porous Titanium Alloy Rod on the Early Stage Talar Osteonecrosis of Sheep

Osteonecrosis of the talus (ONT) may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group). The curative effect of the rods was compared to treatment by core decompression (DC group). No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT.

Extracellular matrix metalloproteinase inducer is associated with severity of brain oedema following experimental subarachnoid haemorrhage in rats.

OBJECTIVE: Brain oedema is a major cause of clinical deterioration and death following brain trauma; cellular mechanisms involved in its development remain elusive. This study investigated the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in brain oedema. METHODS: The monofilament puncture model was used to induce subarachnoid haemorrhage. Adult male Sprague—Dawley rats were divided into five groups (n = 20 per group): sham-operated, sacrificed immediately after surgery (sham group); sacrificed 12, 24 or 72 h after subarachnoid haemorrhage induction (SAH-12, SAH-24 and SAH-72 groups, respectively); treated with EMMPRIN inhibitor immediately after subarachnoid haemorrhage, sacrificed at 24 h (SAH-inhibition group). Mean brain water content, and EMMPRIN mRNA and protein levels, were determined. RESULTS: Compared with the sham group, mean brain water content, EMMPRIN mRNA and protein levels in the SAH-12, SAH-24 and SAH-72 groups increased rapidly and significantly (maximal at 24 h). EMMPRIN inhibition significantly reduced mean brain water content and EMMPRIN mRNA and protein levels in the SAH-inhibition group, compared with the SAH-24 group. CONCLUSIONS: EMMPRIN upregulation may be important in the formation of brain oedema; inhibition of EMMPRIN activity may provide a potential approach to reduce oedema after subarachnoid haemorrhage.

Low elastic modulus contributes to the osteointegration of titanium alloy plug.

Resurfacing of cartilage defect with mini titanium plug is considered a promising alternative for the treatment of focal chondral defects. Elastic modulus of the metal implant plays a significant role in force transmission which influences the stability of plug. This study assessed the effects of two kinds of titanium alloy plug with different elastic modulus, that is, titanium 2448 (Ti2448) plug and titanium-6 aluminum-4 vanadium (TAV) plug on osteointegration. The full-thickness chondral defects were created in bilateral knees of dogs and then TAV and Ti2448 plugs were implanted, respectively. After 12 weeks, radiographic evaluation did not reveal any signs of disassembly, subsidence, or periprosthetic radiolucency in both groups. Microcomputed tomography analysis revealed that bone histomorphometric parameters in Ti2448 group were all significantly better than those of TAV group. Furthermore, the value of pullout force in Ti2448 group was also significantly higher. Histology showed that the screw threads of Ti2448 plug were well integrated into the newly formed bone. In contrast, the trabecular bone was sparsely distributed around TAV plug. In conclusion, Ti2448 plug with low elastic modulus showed more favorable characteristics in osteointegration. Ti2448 may be a promising biomaterial for fabricating mini plug applied for cartilage resurfacing.

Development of a clinically relevant animal model for the talar osteonecrosis in sheep.

There are a lot of reports and reviews about osteonecrosis of the talus (ONT), yet reports about the animal model of ONT to evaluate proper therapeutic approaches are rarely heard. In our study, a novel animal model was established. Pure ethanol was injected into the cancellous bone of sheeps talus. Macroscopic observation, X-ray, CT and histology were performed at two, four, 12 and 24 weeks postoperatively. It was revealed that the trabeculae of talar head began to change their structure after two weeks postoperatively compared to the normal talus. The ONT was obvious at the end of the fourth week, and their outstanding feature was the damage of trabeculae bone and formation of cavities. CT scans and pathological changes of the subjects all showed characteristics of the early stage of osteonecrosis, also the sections of the specimens confirmed necrosis of tali. By 12 weeks, the phenomenon of necrosis still existed but fibrous tissue proliferated prominently and bone reconstruction appeared in certain area. Most specimens (3/4) got late stage necrosis which presented as synarthrosis in X-ray and mass proliferation of fibrous tissue in histology at the end of 24 weeks. The novel animal model of ONT was successful, and it is inclined to deteriorate without any intervention. The study provides us a new way to evaluate various treatments on ONT in laboratory, which may eventually pave way to clinical applications.