BMP-2/CPC scaffold with dexamethasone-loaded blood clot embedment accelerates clinical bone regeneration.

Delayed repair caused by prolonged inflammatory response might lead to clinical nonunion and failed bone regeneration. The design of desirable biomaterials requires precise regulation of the initial osteoimmune responses and efficient osteoinductive capacity to facilitate later bone regeneration. Herein, a Dex-loaded blood clot-embedded BMP-2/CPC scaffold (Dex/blood/BMP-2/CPC) was fabricated for clinical bone regeneration with the sequential release of dexamethasone (Dex), a clinical immunosuppression drug, and BMP-2, a potent osteogenic growth factor. The introduction of Dex at a BMP-2/Dex ratio of 1/6 effectively facilitated M2 polarization of macrophages and exerted a synergetic effect on BMP-2-mediated osteogenic differentiation. The highest in vivo bone regenerative efficacy was achieved by Dex/blood/BMP-2/CPC scaffold with a 1/6 BMP-2/Dex dose, exhibiting significantly enhanced endochondral ossification and attenuated bone resorption in an ectopic model, as well as reduced fibrosis at the orthotopic defect site. Blood clot embedment further provides nutrition and cytokines for the endochondral ossification process. On these bases, a pilot clinical trial was carried out and the Dex/blood/BMP-2/CPC scaffold was demonstrated to accelerate fracture healing, improve therapeutic quality, and eliminate local inflammation compared to current bone regenerative treatment. Taken together, this work designed an immunoregulatory and osteoinductive Dex/blood/BMP-2/CPC scaffold, which might provide new insights for future biomaterial development (Trial registration: ChiCTR2100047693).

The role of biomechanical forces and MALAT1/miR-329-5p/PRIP signalling on glucocorticoid-induced osteonecrosis of the femoral head.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common orthopaedic disease. GIONFH primarily manifests clinically as hip pain in the early stages, followed by the collapse of the femoral head, narrowing of the hip joint space and damage to the acetabulum, resulting in severely impaired mobility. However, the pathogenesis of GIONFH is not clearly understood. Recently, biomechanical forces and non-coding RNAs have been suggested to play important roles in the pathogenesis of GIONFH. This study aimed to evaluate the role of biomechanical forced and non-coding RNAs in GIONFH. We utilized an in vivo, rat model of GIONFH and used MRI, µCT, GIONFH-TST (tail suspension test), GIONFH-treadmill, haematoxylin and eosin staining, qRT-PCR and Western blot analysis to analyse the roles of biomechanical forces and non-coding RNAs in GIONFH. We used RAW264.7 cells and MC3T3E1 cells to verify the role of MALAT1/miR-329-5p/PRIP signalling using a dual luciferase reporter assay, qRT-PCR and Western blot analysis. The results demonstrated that MALAT1 and PRIP were up-regulated in the femoral head tissues of GIONFH rats, RAW264.7 cells, and MC3T3E1 cells exposed to dexamethasone (Dex). Knockdown of MALAT1 decreased PRIP expression in rats and cultured cells and rescued glucocorticoid-induced osteonecrosis of femoral head in rats. The dual luciferase reporter gene assay revealed a targeting relationship for MALAT1/miR-329-5p and miR-329-5p/PRIP in MC3T3E1 and RAW264.7 cells. In conclusion, MALAT1 played a vital role in the pathogenesis of GIONFH by binding to ('sponging') miR-329-5p to up-regulate PRIP. Also, biomechanical forces aggravated the pathogenesis of GIONFH through MALAT1/miR-329-5p/PRIP signalling.

Comparison of the modified Smith-Petersen (S-P) and ilioinguinal (I-I) approaches for periacetabular osteotomy in adult developmental dysplasia of the hip: a retrospective study.

BACKGROUND: Adult developmental dysplasia of the hip is an untreated congenital hip dysplasia that results in adult hip pain. One of the usual and effective methods for the treatment of this condition is periacetabular osteotomy. However, which approach is better between the modified S-P and the I-I approaches is still unclear and controversial. METHOD AND MATERIALS: We retrospectively assessed our experience with the modified S-P and the I-I approaches by inquiring and evaluating intraoperative blood loss, postoperative radiographic material, postoperative function of the hip, and related complications from July 2014 to January 2019. RESULTS: A total of 61 patients with adult developmental dysplasia of the hip were enrolled, and 33 patients were divided into a modified S-P group and 28 patients were divided into I-I group. The operation time and blood loss of group I-I were higher than that of group modified S-P. Other clinical and radiographic indexes showed no statistical significance between group the modified S-P and I-I groups. CONCLUSION: There is no significant difference in the improvement of the function of the hip at the post-operation stage, but group I-I may require more operation time and blood loss at the intra-operation stage.

Individualized Drug Repositioning For Rheumatoid Arthritis Using Weighted Kolmogorov-Smirnov Algorithm.

BACKGROUND: Existing drugs are far from enough for investigators and patients to administrate the therapy of rheumatoid arthritis. Drug repositioning has drawn broad attention by reusing marketed drugs and clinical candidates for new uses. PURPOSE: This study attempted to predict candidate drugs for rheumatoid arthritis treatment by mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. METHODS: We firstly measured the individualized pathway aberrance induced by rheumatoid arthritis based on the microarray data and various drugs from CMap database, respectively. Then, the similarities of pathway aberrances between RA and various drugs were calculated using a Kolmogorov-Smirnov weighted enrichment score algorithm. RESULTS: Using this method, we identified 4 crucial pathways involved in rheumatoid arthritis development and predicted 9 underlying candidate drugs for rheumatoid arthritis treatment. Some candidates with current indications to treat other diseases might be repurposed to treat rheumatoid arthritis and complement the drug group for rheumatoid arthritis. CONCLUSION: This study predicts candidate drugs for rheumatoid arthritis treatment through mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. Our framework will provide novel insights in personalized drug discovery for rheumatoid arthritis and contribute to the future application of custom therapeutic decisions.

Bone Defects in Revision Total Knee Arthroplasty and Management.

This article reviews the recent updates in revision of total knee arthroplasty (RTKA). We reviewed the recent articles on RTKA in databases including PubMed, Google Scholar, and SCOPUS. Total knee arthroplasty (TKA) involves the replacement of all three compartments of the knee in surgery of the knee joint to restore capacity and function. TKA is one of the most common and reliable surgical treatment options for the treatment of knee diseases. However, some patients require revision of TKA (RTKA) after primary TKA for various reasons, including mechanical wear, implant loosening or breakage, malalignment, infection, instability, periprosthetic fracture, and persistent stiffness. Unfortunately, the overall outcome of RTKA is not as satisfactory as for primary TKA due to the uncertainty regarding the actual success rate and the risk factors for failure. Cementation, modular metal augmentation, bone grafting, autologous bone grafting, allogenic bone grafting, impactation bone grafting, structural bone allografting, metaphyseal fixation, using porous titanium coated press fit metaphyseal sleeves and porous tantalum structural cones, and megaprostheses or customized prostheses are the currently available management options for RTKA. However, most of the management systems possess specific complications. Novel approaches should be developed to improve functional capacity, implant survival rates, and quality of life in a cost-efficient manner.

A CARE-compliant article: Biomechanics of treating early-stage femoral-head osteonecrosis by using a ß-tricalcium phosphate bioceramic rod system: a 3-dimensional finite-element analysis.

The effect of implanting a ß-TCP bioceramic rod system (BRS) can be observed with using the 3-dimensional (3D) finite-element method on the biomechanics of early-stage osteonecrosis of the femoral head (ONFH), to provide a theoretical basis for the biomechanics of applying the ß-TCP BRS in the treatment of ONFH.A healthy 172 cm tall male adult volunteer (age: 40 years, weight: 70 kg, and femoral diameter: 50 mm) was selected for this study. The volunteer had no history of diseases in the hip, lower back, and lower limbs. He also had no history of trauma and surgery and had no lesions in the femoral head.A finite-element model of the normal proximal femur was constructed, and on this basis, 4 ONFH finite-element models were constructed, which had 15% and 30% necrotic areas in the superolateral area and 2 and 4 mm collapse in the weight-bearing area of the femoral head, respectively.This process was followed by simulated implantation of the ß-TCP BRS in the finite-element models of the femoral head. Changes in the stress and displacement of the femoral head were observed before and after treatment with the ß-TCP BRS, and the risk of femoral-head collapse was assessed.Under an applied walking load, the stress concentration on the femoral head was alleviated after treatment. Moreover, the stress and collapse values of the weight-bearing area decreased compared with those before treatment, and the differences were statistically significant (P < .05); the risk of collapse was also lower than that before treatment. As the area of the necrosis increased, the collapse value also increased, and the risk of collapse increased. More severe preoperative collapse implied that a greater risk of postoperative recollapse exists.This case report was written for 4 purposes: Implantation of the ß-TCP BRS could effectively improve the internal mechanical properties of ONFH, enhance the support capacity of bones in the weight-bearing area in ONFH, reduce the compressive stress on the necrotic bone, and lower the risk of collapse in ONFH.

Efficacy and safety of low-molecular-weight heparin after knee arthroscopy: A meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear. METHODS: Seven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software. RESULTS: The meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39-2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28-2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37-4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12-3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group. CONCLUSION: Compared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746.

Clinical value of 3D printing guide plate in core decompression plus porous bioceramics rod placement for the treatment of early osteonecrosis of the femoral head.

BACKGROUND: The conventional method of core decompression combined with porous bioceramics rod is usually performed under C-arm fluoroscopy for the treatment of early osteonecrosis of the femoral head (ONFH). This study was to evaluate the clinical value and efficacy of three-dimensional (3D) printing guide plate in the process of core decompression plus porous bioceramics rod for the treatment of early ONFH. METHODS: Forty patients were enrolled, including 20 patients undergoing the surgery with 3D printing guide plate in the experiment group and 20 controls with C-arm fluoroscopy. The following parameters such as surgery time, blood loss, fluoroscopy times, and the accuracy of core decompression for necrosis area, function outcome according to Harris Hip Score (HHS), and any possible complications were recorded and compared between the two groups. All the patients were followed up at 6, 12, and 18 months postoperatively. RESULTS: The surgery time, fluoroscopy time, and intraoperative blood loss in the experiment group was significantly less (P < 0.05) than those in the control group. There was no statistical significance in the accuracy of core decompression and porous bioceramics rod placement between the two groups (P > 0.05). All patients were followed up for 18 months. There was a significant difference between the preoperative and final follow-up HSS scores in both groups (P < 0.05). In addition, there was also a significant difference between the groups in the last follow-up HSS scores (P < 0.05). CONCLUSIONS: Compared with the traditional method, 3D printing guide plate could shorten the surgery time and fluoroscopy times and decrease intraoperative blood loss. It seems to be an effective method in the combined core decompression with porous bioceramics rod placement for early ONFH.

Real-time computerised tomography assisted porous tantalum implant in ARCO stage I-II non-traumatic osteonecrosis of the femoral head: minimum five-year follow up.

PURPOSES: This study was established to investigate the medium-term clinical effect of real-time CT assisted porous tantalum implant for the treatment of ARCO stage I-II non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: This study comprised 24 ONFH patients (29 hips) who were treated with intra-operative real-time CT accurate rapid positioning assisted drilling decompression, lesion removal and porous tantalum implant. Harris score, VAS score and imaging in pre-operation and follow-up period were recorded. RESULTS: The average operative time and intra-operative blood loss were 72.6 min and 158.8 ml, respectively. The mean follow-up was 5.4 years. No femoral head penetrating, wound infection, and death occurred. Harris and VAS score improved significantly (73.78 vs. 88.11; 7.13 vs. 2.66) at last follow-up (P < 0.05). The functional improvement and pain relief rate was 100% at six months after operation. The effective rate was 86.21% at 12 months after operation and last follow-up. Five pre-operative ARCO stage I hips had no radiographic progress. Meanwhile, four among the 24 ARCO stage II hips progressed into stage III between eight and 12 months after surgery, among which two progressed into stage IV and two remained in stage III at the last follow-up. The average value of Kerboul combined necrotic angle was 263.24°. There was no progress in Kerboul combined necrotic angle among the grades 2 and 3 patients. However, among the six cases at grade 4, four cases with post-operative progress, two patients converted to THA. CONCLUSIONS: Our technique is safety and effective in the treatment of ARCO stage I-II non-traumatic ONFH.

Potential role of andrographolide in the proliferation of osteoblasts mediated by the ERK signaling pathway.

The aim of the present study was to explore the effects of andrographolide (AG) and the ERK signaling pathway on the proliferation of osteoblasts (OBs) in vitro. The calvarial OBs from Sprague Dawley (SD) rats were collected and treated at different concentrations of AG and U0126. The concentrations of AG were measured by colorimetry. Based on different treatment methods, the cells were separated into four groups: control group, U0126 group, AG group, and AG+U0126 group. The cells were cultured for 24h, 48h and 72h. An inverted phase contrast microscope was used to observe the morphologies of treated OBs. The MTT assay was performed to plot OB proliferation curves, and to measure the changes in alkaline phosphatase and hydroxyproline contents after U0126 treatments. The expressions of proliferating cell nuclear antigen (PCNA), Ki67, core binding factor alpha-1 (Cbfa1), type I collagen (Col I), osterix (OSX), p38, extracellular signal regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) were measured by fluorescent quantitative polymerase chain reaction (PCR) and Western blotting. In different cell groups, the in vitro proliferation rates of OBs reached the highest at an AG concentration of 20µmol/L, and the amounts of alkaline phosphatase, hydroxyproline, PCNA, Ki67, Cbfa1, Col I, OSX, and ERK were significantly higher than at other concentrations (all P<0.05). U0126 intervention significantly decreased the expressions of these factors (all P<0.05). At the meantime, p38 and JNK were not affected by AG and were only inhibited by U0126. In conclusion, ERK played an important role in mediating the functions of AG in the proliferation of OBs, indicating that the ERK signaling pathway may be the main pathway through which AG exerts its effects.

Establishing a Customized Guide Plate for Osteotomy in Total Knee Arthroplasty Using Lower-extremity X-ray and Knee Computed Tomography Images.

BACKGROUND: The conventional method cannot guarantee the precise osteotomies required for a perfect realignment and a better prognosis after total knee arthroplasty (TKA). This study investigated a customized guide plate for osteotomy placement in TKAs with the aid of the statistical shape model technique using weight-bearing lower-extremity X-rays and computed tomography (CT) images of the knee. METHODS: From October 2014 to June 2015, 42 patients who underwent a TKA in Guizhou Provincial People's Hospital were divided into a guide plate group (GPG, 21 cases) and a traditional surgery group (TSG, 21 cases) using a random number table method. In the GPG group, a guide plate was designed and printed using preoperative three-dimensional measurements to plan and digitally simulate the operation. TSG cases were treated with the conventional method. Outcomes were obtained from the postoperative image examination and short-term follow-up. RESULTS: Operative time was 49.0 ± 10.5 min for GPG, and 62.0 ± 9.7 min in TSG. The coronal femoral angle, coronal tibial angle, posterior tibial slope, and the angle between the posterior condylar osteotomy surface and the surgical transepicondylar axis were 89.2 ± 1.7°, 89.0 ± 1.1°, 6.6 ± 1.4°, and 0.9 ± 0.3° in GPG, and 86.7 ± 2.9°, 87.6 ± 2.1°, 8.9 ± 2.8°, and 1.7 ± 0.8° in TSG, respectively. The Hospital for Special Surgery scores 3 months after surgery were 83.7 ± 18.4 in GPG and 71.5 ± 15.2 in TSG. Statistically significant differences were found between GPG and TSG in all measurements. CONCLUSIONS: A customized guide plate to create an accurate osteotomy in TKAs may be created using lower-extremity X-ray and knee CT images. This allows for shorter operative times and better postoperative alignment than the traditional surgery. Application of the digital guide plate may also result in better short-term outcomes.

Cementless total hip arthroplasty with structural allograft for massive acetabular defect in hip revision.

OBJECTIVE: To study retrospectively 20 hip revison patients treated by cementless total hip arthroplasty with structural allograft. METHODS: Twenty patients suffering from aseptic loosening of an uncemented cup complicated by a large defect underwent cementless total hip arthroplasty with structural allograft and were followed up for at least 5 years. Clinical results were evaluated by Harris score and leg length measurements. Radiographic analysis included implants migration, graft absorbance, osteolysis and liner wear. RESULTS: No cup loosening or graft reabsorption was found at final follow-up. Clinical improvements in pain and functional status were demonstrated during the follow-up period. The mean Harris hip scores improved from 29 preoperatively (range 20-41) to 81 postoperatively (range 73-89). CONCLUSION: Our study shows that cementless total hip arthroplasty with allograft is a good way for massive defect in acetabular bone stock.

Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty.

BACKGROUND: Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2 (hBMP2) gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putty on repairing bone defects. METHODS: Twenty four Kunming mice were randomly divided into two groups. The nanobone putty + hBMP2 plasmid was injected into the right thigh muscle pouches of the mice (experiment side). The nanobone putty + blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1 (control side 1) or group 2 (control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty + hBMP2 plasmid; Group B, putty + blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. RESULTS: The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level. The new bone formation rate and antibending strength of group A was significantly higher than those of group B and C. The defects in blank control were not healed. CONCLUSIONS: The hBMP2 gene activated nanobone putty exhibited osteoinductive ability, and had a better bone defect repair capability than that of nanobone putty only.