Mechanical property and biological behaviour of additive manufactured TiNi functionally graded lattice structure

Bio-inspired porous metallic scaffolds have tremendous potential to be used as artificial bone substitutes.In this work,a radially graded lattice structure (RGLS),which mimics the structures of natural human bones,was designed and processed by laser powder bed fusion of martensitic Ti-rich TiNi powder.The asymmetric tension-compression behaviour,where the compressive strength is significantly higher than the tensile strength,is observed in this Ti-rich TiNi material,which echoes the mechanical behaviour of bones.The morphologies,mechanical properties,deformation behaviour,and biological compatibility of RGLS samples were characterised and compared with those in the uniform lattice structure.Both the uniform and RGLS samples achieve a relative density higher than 99%.The graded porosities and pore sizes in the RGLS range from 40%-80% and 330-805 µm,respectively,from the centre to the edge.The chemical etching has significantly removed the harmful partially-melted residual powder particles on the lattice struts.The compressive yield strength of RGLS is 71.5 MPa,much higher than that of the uniform sample (46.5 MPa),despite having a similar relative density of about 46%.The calculated Gibson-Ashby equation and the deformation behaviour simulation by finite element suggest that the dense outer regions with high load-bearing capability could sustain high applied stress,improving the overall strength of RGLS significantly.The cell proliferation study suggests better biological compatibility of the RGLS than the uniform structures.The findings highlight a novel strategy to improve the performance of additively manufactured artificial implants by bio-inspiration.

The Construction of Heparin Sulfate-collagen Protein Based Scaffolds and Its Effects on the Neural Stem Cells

The objective of this study was to construct the heparin sulfate-collagen pro-tein-based scaffolds and to explore its effects on the proliferation and differentiation abilities of neural stem cells(NSCs).The heparin sulfate-collagen protein-based scaffolds were produced by injection molding/freezing/cross-linking technique.The proliferation ability was detected by MTT and the dif-ferentiation ability was detected by immunofluorescence technique.The results indicate that the heparin sulfate-collagen protein-based scaffolds with porous and longitudinal parallel structures are successfully constructed.The NSCs grow well in the pores of scaffold and still maintain the prolif-eration and differentiation abilities.It is concluded that the scaffolds possess stable porous and longi-tudinal parallel structures and great biocompatibility to NSCs.The combination of scaffold and NSCs may suggest a possible treatment strategy for spinal cord injury

Immune mediated support of metastasis:Implication for bone invasion

Bone is a common organ affected by metastasis in various advanced cancers,including lung,breast,prostate,colorectal,and melanoma.Once a patient is diagnosed with bone metastasis,the patient’s quality of life and overall survival are significantly reduced owing to a wide range ofmorbidities and the increasing difficulty of treatment.Many studies have shown that bone metastasis is closely related to bone microenvironment,especially bone immune microenvironment.However,the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear.Here,we described the changes in various immune cells during bone metastasis and discussed their related mechanisms.Osteoblasts,adipocytes,and other non-immune cells closely related to bone metastasis were also included.This review also summarized the existing treatment methods and potential therapeutic targets,and provided insights for future studies of cancer bone metastasis.

NG2 expression in rats with acute T_(10) spinal cord injury

Rat models of T10 spinal cord injury were established with a clamp method. NG2 expression was detected with immunohistochemical staining and western blot. Ten days after spinal cord injury, the number of NG2-positive cells in the damaged areas and NG2 absorbance were both significantly increased. The findings indicate that acute T10 spinal cord injury in rats can lead to upregulation of NG2 protein expression in damaged areas.

Value of knee skin temperature measured by infrared thermography and soluble intercellular adhesion molecule-1 in the diagnosis of peri-prosthetic knee infection in Chinese individuals following total knee arthroplasty

Background Total knee arthroplasty （TKA） is a successful and frequently performed procedure in orthopedic surgery.The diagnosis of peri-prosthetic joint infection following TKA remains challenging.The present study estimated the usefulness of knee skin temperature （measured by infrared thermography） and serum soluble intercellular adhesion molecule-1 （slCAM-1） in the diagnosis of post-operative knee peri-prosthetic infection.Methods Patients were divided into three groups：21 patients undergoing uncomplicated TKAs,seven with prosthesis infection,and three undergoing TKA revisions.The serum levels of interleukin-6 （IL-6）,C-reactive protein （CRP）,erythrocyte sedimentation rate （ESR）,and slCAM-1 as well as the local knee skin temperature were measured preoperatively and on Days 1 and 7 and at 1,3,and 6 months post-operatively in Groups 1 and 3.The same parameters were measured in Group 2 at the time of prosthesis infection diagnosis.Results In Group 1,the levels of IL-6,CRP,ESR,and knee skin temperature were significantly elevated post-operatively,but returned to baseline levels within 6 months.The slCAM-1 levels were not significantly different.The mean differential temperature （MDT） and levels of siCAM-1,IL-6,CRP,and ESR differed significantly between Groups 1 and 2.The MDT had returned to normal in Group 3 by 6 months post-operatively.Conclusions Elevations in IL-6,CRP,ESR,and MDT in patients undergoing TKA could be a normal response to surgical trauma,but sustained elevations may be indicative of complications.The knee skin temperature and slCAM-1 may be used as indicators in the diagnosis of knee prosthesis infection following TKA.

Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes

A composite construct comprising of a bone mesenchymal stem cell (BMSC) sheet, plasmid DNA, encoding human bone morphogenic protein-2 (hBMP-2), and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) sponge was designed and employed in the restoration of rat calvarial defects. To improve gene transfection efficiency, a cationic chitosan derivative, N,N,N,-trimethyl chitosan chloride (TMC), was employed as the vector. The TMC/DNA complexes had a transfection efficiency of 13% in rat BMSCs, resulting in heterogeneous hBMP-2 expression in a 10-d culture period in vitro. In vivo culture of the composite constructs was performed by implantation into rat full-thickness calvarial defects, using constructs lacking pDNA-hBMP-2 or BMSC sheets as controls. Significantly higher heterogeneous expression of hBMP-2 was detected in vivo at 2 weeks for the cell sheet/DNA complex/scaffold constructs, compared with the constructs lacking pDNA-hBMP-2 or BMSC sheets. New bone formation was evident as early as 4 weeks in the experimental constructs. At 8 weeks, partial bridging of calvarial defects was observed in the experimental constructs, which was significantly better than the constructs lacking pDNA-hBMP-2 or BMSC sheets. Therefore, the combination of the PLGA/HA scaffold with BMSC sheets and gene therapy vectors is effective at enhancing bone formation.

Thoracic cord compression caused by contiguous multilevel ossification of ligamentum flavum in Chinese patients

Objective： To explore the epidemiology, clinical presentation, radiology and surgical treatment outcome in Chinese patients with myelopathy caused by contiguous multilevel ossification of ligamentum flavum. Methods. Medical notes and imaging data of 18 Chinese patients （14 males and 4 females, aged 43-72 years, mean： 57 years ） with myelopathy caused by contiguous multilevel ossification of ligamentum flavum were studied retrospectively in this article. The diagnosis was based on clinical examination, X-ray films, computerized tomography （CT） and magnetic resonance imaging （MRI） scanning results and pathological results. Sixteen patients were treated by laminectomy and two by laminoplasty, The average follow-up duration was 34 months （range, 28-49 months ）. The outcome was evaluated by Japanese Orthopaedics Association （JOA） Score. Results： The average time for occurring clinical symptoms was 7.5 months （range, 2 days-16 months）. All the 18 cases presented with clinical evidences of chronic and progressive thoracic spinal cord compression, which included bilateral leg weakness, spastic gait, numbness in lower limbs, paresthesia in terminal and perineum, and urinary incontinence. Neurological examination revealed severe spastic paraparesis, absence of abdominal reflexes, and reduction of the sensory function below the compression level. The mean JOA score before operation was 3. 6 （range, 0-6 ）. MRI and CT scans of the thoracic spine confirmed the presence of contiguous multilevel ossification of the ligamentum flavum. The mean recovery rate after surgery in terms of JOA score was 66.3 % （ range, 33.3 %- 100% ）, with a mean final JOA score of 8. 3. Thoracic decompression laminectomy or laminoplasty could result in a good postoperative outcome. Conclusions ： Contiguous multilevel ossification of the ligamentum flavum is not a common cause of myelopathy in Chinese population and should be treated as early as possible. MRI and CT scan examinations may diagnose the presence of thoracic ossification of ligamentum flavum （OLF）. Posterior decompression, especially with en bloc dissection of the laminae, can obtain satisfactory results.

Treatment of irreducible femoral intertrochanteric fractures using a wire-guided device

Purpose:Treatment of irreducible femoral intertrochanteric fractures often requires open reduction.However,the technique unavoidably causes patients to suffer greater trauma.As such,minimally invasive techniques should be employed to reduce the surgical-related trauma on these patients and maintain a stable reduction of the fractures.Herein,a minimally invasive wire introducer was designed and used for the treatment of femoral intertrochanteric fractures.The effectiveness of using a wireguided device to treat irreducible femoral intertrochanteric fractures was evaluated.Methods:Between 2013 and 2018,patients with femoral intertrochanteric fractures who were initially treated by intramedullary nail fixation but had difficult reduction using the traction beds were retrospectively reviewed.Decision for an additional surgery was based on the displacement of the fracture.The patients were then divided into two groups:those in the control group received an open reduction surgery while those in the observation group received a closed reduction surgery using a minimally invasive wire introducer to guide the wire that could assist in fracture reduction.The operation time,blood loss,visual analogue scale scores,angulation,reduction,neck-shaft angle,re-displacement,limb length discrepancy,and union time were then recorded and analyzed to determine the efficiency of the wire introducer technique.Categorical variables were analyzed by using Chi-square test,while continuous variables by independent t-test and the Mann-Whitney test accordingly.Results:There were 92 patients included in this study:61 in the control group and 31 in the observation group.There were no significant differences in baseline demographic factors between the two groups.All surgeries were successful with no deaths within the perioperative period.The average follow-up time for the patients was 23.8 months.However,the observation group had a significantly shorter operation time,lower visual analogue scale score,less intraoperative bleeding,and shorter fracture healing time.There were no significant differences in the angulation,reduction,neck-shaft angle,and limb length discrepancy between the two groups.Conclusion:The minimally invasive wire guide achieved a similar effect to that of open reduction in the treatment of intertrochanteric fractures with difficult reduction.Moreover,the minimally invasive wire introducer is a good technology that accurately guides the wire during reduction.Indeed,it is an effective technique and achieves good clinical outcomes in restoration of irreducible femoral intertrochanteric fractures.

Implanting hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 and hyaluronic acid into distal femoral metaphysis of rabbits

Objective： To assess the osseointegration capability of hydroxyapatite-coated porous titanium with bone morphogenetic protein-2 （BMP-2） and hyaluronic acid to repair defects in the distal femur metaphysis in rabbits. Methods： Porous titanium implants were made by sintering titanium powder at high temperature, which were coated with hydroxyapatite by alkali and heat treatment and with BMP-2 combined with bone regeneration materials. And hyaluronic acid was further used as delivery system to prolong the effect of BMP-2. The implants were inserted into the metaphysis of the distal femur of rabbits. The animals were killed at 6, 12 and 24 weeks to accomplish histological and biomechanical analyses. Results： According to the result of histological analysis, the osseointegration in BMP-2 group was better than that of the HA-coated porous titanium group. In push-out test, all the samples had bigger shear stress as time passed by. There was statistical difference between the two groups in 6 and 12 weeks but not in 24 weeks. Conclusion： Hydroxyapatite-coated porous titanium with BMP-2 and hyaluronic acid has a good effect in repairing defects of distal fumur in rabbits, which is a fine biotechnology for future clinical application.

Radiation-induced tumor immune microenvironments and potential targets for combination therapy

As one of the four major means of cancer treatment including surgery,radiotherapy(RT),chemotherapy,immunotherapy,RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery.Although RT is an important modality for cancer treatment,the consequential changes caused by RT in the tumor microenvironment(TME)have not yet been fully elucidated.RT-induced damage to cancer cells leads to different outcomes,such as survival,senescence,or death.During RT,alterations in signaling pathways result in changes in the local immune microenvironment.However,some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions,leading to the development of radioresistance.Patients who are radioresistant respond poorly to RT and may experience cancer progression.Given that the emergence of radioresistance is inevitable,new radiosensitization treatments are urgently needed.In this review,we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT.Overall,this review highlights the possibilities of synergistic therapy by building on existing research.

Icariin associated with exercise therapy is an effective treatment for postmenopausal osteoporosis

Background There are no conclusive studies evaluating the interaction between icariin and exercise for treatment of osteoporosis; the efficacy and safety of this treatment combination remains to be evaluated. The purpose of this study was to investigate the effects of icariin treatment combined with exercise therapy on bone parameters and body weight of ovariectomized rats. Methods Ovariectomized rats were used as a model of postmenopausaJ osteoporosis and were exposed to either icariin treatment, exercise, hormone replacement therapy, or a combination of the above. Untreated, ovariectomized rats and sham operated rats were used as controls. After 3 months of experimental interventions the effects of the treatments on the body and uterine weights, the physical and biomechanical properties of bones, and the expression of the osteoblast-specific gene Osterix （Osx）, were assessed. Results The weight gain of the ovariectomized rats was greater than that of the treated experimental groups. Uterine weight and serum estradiol levels were significantly greater in sham operated and estrogen-treated ovariectomized rats than in the other groups. Biomechanical parameters were improved significantly in ovariectomized rats treated with exercise alone or treated with exercise and icariin. Osx expression was increased in ovariectomized rats treated with exercise and icariin or treated with just icariin. Conclusions Exercise combined with icariin had a synergistic effect in the early prevention of osteoporosis in ovariectomized rats. The effects of icariin and exercise on osteoporosis are worth further exploration.

Multiple Arthroplasty in a Patient with Alkaptonuric Arthritis

Alkaptonuria （AKU） is an extremely rare autosomal recessive metabolic disorder characterized by a triad of homogentisic aciduria, arthritis, and ochronosis, affecting only 2 5 in a million individuals. The management of AKU is usually symptomatic. However, surgical intervention necessitates in cases of signiticant arthritis, Here, we presented a 64-year-old female who underwent bilateral total hip and right total knee arthroplasties achieving a successful clinical outcome throughout the 3 years of follow-up.