Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs.

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.

3D Printing-Assisted Supramalleolar Osteotomy for Ankle Osteoarthritis.

Ankle osteoarthritis (OA) is an important factor that causes pain and dysfunction after ankle joint movement. In early and mid-term ankle OA, supramalleolar osteotomy can delay the progression of disease and maximize the preservation of ankle joint function. Three-dimensional printing (3DP) technology has brought us new hope, which can improve the accuracy of osteotomy, reduce the number of fluoroscopy, reduce the amount of blood loss, and achieve personalized and accurate treatment. The data of 16 patients with ankle OA in our center from January 2003 to July 2020 were retrospectively analyzed and divided into the 3DP group and the traditional group according to different treatment methods. Seven patients in the 3DP group used the 3DP personalized osteotomy guide; nine patients were treated by traditional osteotomy. All patients were followed up for 13.9 ± 3.1 months after the operation. The operation time in the 3DP group was 126.4 ± 11.1 min, its intraoperative blood loss was 85.7 ± 24.1 mL, and its intraoperative fluoroscopy time was 2.4 ± 0.2, which were all significantly less than 167.3 ± 12.2 min, 158.3 ± 22.8 mL, and 5.8 ± 0.2 times in the traditional group (P < 0.05), respectively. In the 3DP group, its postoperative tibial anterior surface (TAS) angle was 90.6 ± 0.3° and the talar tilt (TT) angle was 2.2 ± 0.6°, which were all significantly different compared with its preoperative data of 83.4 ± 1.7 and 8.0 ± 1.5°, respectively (P < 0.05). Compared with traditional osteotomy, 3DP-assisted supramalleolar osteotomy for varus and valgus ankle OA can significantly shorten the operation time and reduce intraoperative bleeding and the frequency of intraoperative fluoroscopy; personalized 3DP osteotomy guides and models can assist in the accurate correction of varus deformity during operation, restore the lower limb alignment, and improve the biomechanical status of the lower limbs. In addition, the 3DP of porous tantalum has good histocompatibility, and its interface structure and porosity are more conducive to bone ingrowth. For complex bone defects and revision prostheses, matching implants can be printed individually, which could realize the personalized precise treatment.

Quantitative MRI evaluation of articular cartilage in patients with meniscus tear.

Purpose: The aim of this study was to assess quantitatively articular cartilage volume, thickness, and T2 value alterations in meniscus tear patients. Materials and methods: The study included 32 patients with meniscus tears (17 females, 15 males; mean age: 40.16 ± 11.85 years) and 24 healthy controls (12 females; 12 males; mean age: 36 ± 9.14 years). All subjects were examined by 3 T magnetic resonance imaging (MRI) with 3D dual-echo steady-state (DESS) and T2 mapping images. All patients underwent diagnostic arthroscopy and treatment. Cartilage thickness, cartilage volume and T2 values of 21 subregions of knee cartilage were measured using the prototype KneeCaP software (version 2.1; Siemens Healthcare, Erlangen, Germany). Mann-Whitney-U tests were utilized to determine if there were any significant differences among subregional articular cartilage volume, thickness and T2 value between patients with meniscus tear and the control group. Results: The articular cartilage T2 values in all subregions of the femur and tibia in the meniscus tear group were significantly higher (p< 0.05) than in the healthy control group. The cartilage thickness of the femoral condyle medial, femur trochlea, femur condyle lateral central, tibia plateau medial anterior and patella facet medial inferior in the meniscus tear group were slightly higher than in the control group (p< 0.05). In the femur trochlea medial, patella facet medial inferior, tibia plateau lateral posterior and tibia plateau lateral central, there were significant differences in relative cartilage volume percentage between the meniscus tear group and the healthy control group (p< 0.05). Nineteen patients had no cartilage abnormalities (Grade 0) in the meniscus tear group, as confirmed by arthroscopic surgery, and their T2 values in most subregions were significantly higher (p< 0.05) than those of the healthy control group. Conclusion: The difference in articular cartilage indexes between patients with meniscus tears and healthy people without such tears can be detected by using quantitative MRI. Quantitative T2 values enable early and sensitive detection of early cartilage lesions.

Postoperative management of spontaneous pneumothorax in arthroscopic shoulder superior capsular reconstruction: A case report and review of literature.

Arthroscopic superior capsular reconstruction is an innovative technique for the irreparable rotator cuff tears, but spontaneous pneumothorax after surgery is very rare. The present case was a 66-year-old female with irreparable rotator cuff tears of the right shoulder, treated with the arthroscopic shoulder superior capsular reconstruction. The general anesthesia and operation went smoothly, but the patient experienced stuffiness in the chest and shortness of breath after recovery from anesthesia. Thoracic CT scans showed spontaneous pneumothorax in the right side, which was successfully treated by the conservative treatments (oxygen therapy) according to multidisciplinary team. Prompt and accurate early-stage diagnosis is necessary in controlling postoperative complications and standardized treatment is the key to relieve the suffering. Spontaneous pneumothorax after arthroscopic shoulder surgery has been rarely reported in previous literatures.

Mixed bacterial-fungal infection following total hip arthroplasty: A case report.

Prosthetic infection is one of the severe postoperative complications of arthroplasty. Mixed bacterial-fungal prosthetic infection is rare but can be disastrous. This case was a 76-year-old female suffered from prosthetic infection following total hip replacement due to femoral neck fracture and underwent multiple debridements. The culture of periprosthetic tissue was bacteriologically sterile following the first debridement, while the Staphylococcus hominis was identified in the second debridement in the previous hospitalization where fungal infection had not been considered. Thus the pathogen spectrum of anti-infection therapy failed to contain fungus. Ultimately, the culture result of our sampled periprosthetic tissue during the third debridement was Candida albicans without bacterium in our hospital. The fungal prosthetic infection was successfully treated by a two-stage revision with antifungal drugs. Accurate diagnosis and standardized treatment is the key to the therapy of infection after hip arthroplasty, especially for mixed bacterial-fungal prosthetic infection.

Triple Hemisection Percutaneous Achilles Tendon Lengthening for Severe Ankle Joint Deformity.

OBJECTIVE: To investigate the efficacy of modified percutaneous Achilles tendon lengthening for severe ankle joint deformity. METHODS: This retrospective case series study included 33 patients with an average age of 25.2 years who underwent surgery in our hospital from April 1, 2010 to March 1, 2018. Triple hemisection percutaneous Achilles tendon lengthening was performed. One stage surgery, other soft tissue surgery or bone correction surgery could be performed. After surgery, a plaster cast was used to fix the functional position, and rehabilitation training was carried out as planned. Complications during the perioperative period were recorded. Statistical analysis of the patients' visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) score before and at the last follow-up was performed. The recurrence rate of Achilles tendon contracture at the last follow-up and the patients' satisfaction rate were investigated. RESULTS: All patients were followed up, with an average follow-up period of 56.31 months (8-104 months). All achieved good ankle joint function and appearance improvement And there were no infection or skin necrosis complications. In two cases, the incision was poorly healed at non-Achilles tendon site and was cured by change of dressing. The average VAS score at the last follow-up was reduced from (2 ± 1.48) points before surgery to (0.26 ± 0.51) points (P = 0.001), and the average AOFAS score was increased from (64.97 ± 13.56) points before surgery to (90.06 ± 10.06) points (P = 0.001). During the follow-up period, there was no chronic rupture of Achilles tendon. There were two cases of recurrence of foot drop (5.7%), and the patients' satisfaction rate was 93.9%. CONCLUSION: In the surgical treatment of severe ankle joint deformity, the application of triple hemisection percutaneous Achilles tendon lengthening for Achilles tendon contracture has the advantages of less trauma, beautiful incision, and reliable efficacy. The satisfaction rate of patients with this treatment is high, and it is worth promoting in the clinic.

Arthroscopic Ankle Arthrodesis for End-Stage Tuberculosis of the Ankle: A 2-Year Follow-Up.

Surgical treatment for end-stage ankle joint tuberculosis (TB) has rarely been reported. This study followed cases treated by arthroscopic arthrodesis for ankle joint TB to evaluate its efficacy and safety in the clinic. Patients who underwent arthroscopic ankle arthrodesis for ankle joint TB between April 11, 2010, and December 31, 2016, were followed. Their diagnoses were confirmed by bacterial culture or pathological examination. During arthroscopy, tissue samples were first obtained to further confirm the diagnosis. Then the necrotic tissue, hyperplasia of synovial tissue, and exfoliated cartilage were removed. Ankle joint arthrodesis was performed if the area of articular cartilage damage was >2 cm2. Continued nutritional support and standardized anti-TB drug treatment were given after surgery. Follow-up measurements included visual analogue scale score, American Orthopaedic Foot and Ankle Society score, erythrocyte sedimentation rate, and radiographic imaging. All 9 patients in this study, with an average age of 54 (range 37 to 68) years, were followed. The mean follow-up duration was 55.44 ± 31.15 (range 24 to 96) months. There were significant differences in the visual analogue scale scores, American Orthopaedic Foot and Ankle Society scores, and erythrocyte sedimentation rate between before treatment and 18 months postoperatively (p < .05). All patients (100%) showed union at 18 ± 4 weeks. Arthroscopic treatment for ankle joint TB has the advantages of minor trauma and low complications. It can be used to accurately obtain samples from specific areas of TB for further diagnosis. According to the degree of articular cartilage damage, the surgeon can determine whether to perform arthrodesis. Thorough debridement of necrotic tissue and residual articular cartilage on the fusion surface can improve the rate of ankle fusion.

Modified Percutaneous Achilles Tendon Lengthening by Triple Hemisection for Achilles Tendon Contracture.

BACKGROUND: Both percutaneous Achilles tendon lengthening by triple hemisection and the traditional open Z-lengthening are effective methods for Achilles tendon contracture. This study aims to evaluate the efficacy and safety of this new therapeutic method, which is based on the percutaneous sliding technique with three hemi-cuts in the tendon, as compared with the traditional open Z-lengthening. METHODS: Retrospective analysis of the Achilles tendon contracture cases in our hospital between January 2010 and September 2016 was conducted. Twenty-five cases received percutaneous Achilles tendon lengthening (group A), and 30 patients who underwent open Z-lengthening during the same period were in the control group (group B). Operative time and hospital stay were statistically analyzed. Incision complication, equinus recurrence rate and Achilles tendon rupture morbidity were recorded. The function was assessed by American Orthopaedic Foot & Ankle Society (AOFAS) score. All cases in group A received Magnetic Resonance Imaging (MRI) of ankle preoperatively and in the follow-ups. RESULTS: The mean follow-up period was 42.04 months in group A and 61.7 months in group B. The entire operative time and the mean hospitalization days were lower in group A than in group B. No incision and infection complication occurred in group A. The infection rate in group B was 3.3%. Equinus recurrence rate was 4% in group A and the equinus recurrence rate in group B was 21.4%. In group A, the mean AOFAS score increased from 64 ± 10.16 points preoperatively to 96.08 ± 3.17 at final follow-up, while the score in group B increased from 63.48 ± 6.2 points to 85.4 ± 10.3. MRI showed continuity of the Achilles tendon and homogeneous signal in group A. CONCLUSION: Modified surgery can significantly reduce the risk of Achilles tendon rupture, provide better balance in soft tissue strength between ankle dorsiflexion and ankle plantarflexion, helping to avoid recurrence of the deformity.

MOF Capacitates Cyclodextrin to Mega-Load Mode for High-Efficient Delivery of Valsartan.

PURPOSE: To investigate the mechanism of enhancing solubility and bioavailability of water-insoluble drug, valsartan (VAL), with being mega-loaded by cyclodextrin metal organic framework (CD-MOF). METHODS: VAL was successfully mega-loaded into CD-MOF by magnetic agitation of VAL in ethanolic solution. Characterizations including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), synchrotron radiation-based Fourier transform-infrared spectroscopy (SR-FTIR) 13C solid-state nuclear magnetic resonance spectroscopy ( 13C SS-NMR), nitrogen gas adsorption, and small-angle X-ray scattering (SAXS) were carried out to confirm the mechanism and incorporation behavior of VAL in CD-MOF. Ball milling process combined with molecular modeling was also used to confirm the mechanism. Improvement of bioavailability in vivo was confirmed by pharmacokinetic experiment in beagles. RESULTS: As a carrier with payload 150% higher than conventional CD complexation, CD-MOF included molecules of VAL as complexations in the chambers of (γ-CD)2, and nanoclusters in the confined spherical cages of (γ-CD)6 confirmed by SAXS and 13C SS-NMR. Ball milling combined with molecular modeling inferred that the reduced release rate of the milled CD-MOF with ultrahigh drug payload was mainly due to the partial aggregation of the VAL nanoclusters. The molecules of VAL as nanoclusters in the cages of (γ-CD)6 are critical in dramatically improving the apparent solubility (39.5-fold) and oral bioavailability (1.9-fold) of VAL in contrast to γ-CD inclusion. CONCLUSIONS: The new understanding of drug nanoclusters in CD-MOF will help to design more efficient drug delivery systems using CD-MOF carrier with nanocavities.

V-Y Tendon Plasty for Reconstruction of Chronic Achilles Tendon Rupture: A Medium-term and Long-term Follow-up.

OBJECTIVE: To evaluate the surgical results of V-Y tendon plasty in the treatment of chronic Achilles tendon rupture during medium and long-term follow-up. METHODS: Between June 2005 and September 2017, 20 patients with chronic Achilles tendon rupture underwent V-Y tendon plasty in our hospital. The mean injury-to-surgery time was 20.4 weeks (range, 4-96 weeks). The Matles test and an improved Thompson test was used to examine Achilles tendon rupture. These patients were not able to stand on the tiptoes of the injured lower extremity. X-ray tests ruled out the chance of fracture and were used to examine the Kager triangle. MRI was used to confirm the final diagnosis. The function of the ankle and the foot was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the Achilles Tendon Total Rupture Score (ATRS). V-Y tendon plasty for Achilles tendon reconstruction was performed. A below-knee cast was used to keep the ankle in plantar flexion (up to 20°) for 4 weeks. Non-weight-bearing exercise was allowed with crutches. After 4 weeks, partial weight-bearing was allowed. Physical exercises were performed under rehabilitation guidelines. At 10-12 weeks postoperation, patients began to return to daily life activity levels without restrictions. Preoperative and postoperative MRI was obtained. RESULTS: The mean follow-up period was 32.8 months. The mean operative gap of the Achilles tendon after debridement was 5 cm (range, 4-9 cm), with 85% of the gap less than or equal to 6 cm. The mean AOFAS score increased from 59.25 ± 12.28 preoperatively to 96.55 ± 3.75 at final follow-up (P < 0.05). The mean ATRS score increased from 39.55 ± 14.21 preoperatively to 94.05 ± 4.89 at final follow-up (P < 0.05). All patients had no recurrent Achilles tendon rupture during the follow up. No patient had developed serious complications, such as sural nerve injury or deep vein thrombosis. Patients were able to return to daily life activity levels without restrictions. At the latest follow-up, all patients were able to perform repetitive single heel rise on the involved limb, and to walk without a visible limp. All of the postoperative MRI showed the continuity of the Achilles tendon with no signs of cysts or inflammation, indicating perfect healing at the final follow-up. CONCLUSIONS: V-Y tendon plasty can be used in most cases of chronic Achilles tendon rupture. It yields satisfactory functional results and low complication rates. The advantage of this procedure is that it is an easy and economic method without the need for expensive synthetic implants. V-Y tendon plasty should be considered an acceptable first-choice treatment.

Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling.

The prevascularization of tissue-engineered bone grafts (TEBGs) has been shown to accelerate capillary vessel ingrowth in bone defect remodeling and to enhance new bone formation. However, the exact mechanisms behind this positive effect remain unknown. Here, we report that basic fibroblast growth factor (FGF2)-Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) signaling functions as a molecular switch to regulate the lineage fate of bone mesenchymal stem cells (BMSCs) and that prevascularization promotes the cell fate switch, which contributes to increased bone regeneration with the use of prevascularized TEBGs compared with control TEBGs. Prevascularized TEBGs enhanced the in vivo endothelial differentiation of BMSCs by inhibiting RhoA/ROCK signaling. In vitro data more clearly showed that BMSCs differentiated into von Willebrand factor (vWF)-positive endothelial cells, and FGF2-induced inhibition of RhoA/ROCK signaling played a key role. Our novel findings uncovered a new mechanism that stimulates the increased vascularization of engineered bone and enhanced regeneration by promoting the endothelial differentiation of BMSCs implanted in TEBGs. These results offer a new molecular target to regulate TEBG-induced bone regeneration.

Intramembranous ossification and endochondral ossification are impaired differently between glucocorticoid-induced osteoporosis and estrogen deficiency-induced osteoporosis.

A fracture is the most dangerous complication of osteoporosis in patients because the associated disability and mortality rates are high. Osteoporosis impairs fracture healing and prognosis, but how intramembranous ossification (IO) or endochondral ossification (EO) during fracture healing are affected and whether these two kinds of ossification are different between glucocorticoid-induced osteoporosis (GIOP) and estrogen deficiency-induced osteoporosis (EDOP) are poorly understood. In this study, we established two bone repair models that exhibited repair via IO or EO and compared the pathological progress of each under GIOP and EDOP. In the cortical drill-hole model, which is repaired through IO, osteogenic differentiation was more seriously impaired in EDOP at the early stage than in GIOP. In the periosteum scratch model, in which EO is replicated, chondrocyte hypertrophy progression was delayed in both GIOP and EDOP. The in vitro results were consistent with the in vivo results. Our study is the first to establish bone repair models in which IO and EO occur separately, and the results strongly describe the differences in bone repair between GIOP and EDOP.

Surgical Strategy for the Chronic Achilles Tendon Rupture.

Background. Chronic Achilles tendon rupture is usually misdiagnosed and treated improperly. This study aims to better understand the treatment of chronic Achilles tendon rupture. Methods. Patients who were not able to perform a single-limb heel rise were chosen. Pre- and postoperative magnetic resonance imaging (MRI) were conducted. By evaluating the presence or absence of Achilles tendon stumps and the gap length of rupture, V-Y advancement, gastrocnemius fascial turndown flap, or flexor halluces longus tendon transfer were selected for tendon repair. The function of ankle and foot was assessed by American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores and Achilles Tendon Total Rupture Score (ATRS). Results. Twenty-nine patients were followed up. One patient had superficial incision infection, which was healed after debridement and oral antibiotics. Three months postoperatively, MRI showed some signs of inflammation, which disappeared at one or two years postoperatively. All patients were able to perform a single-limb heel rise. Mean AOFAS scores and ATRS scores were increased at the latest follow-up. Conclusion. Surgical options can be determined by evaluating the presence of the Achilles tendon stumps and the gap length, which can avoid using the nearby tendon and yield satisfactory functional results.

Disturbed MEK/ERK signaling increases osteoclast activity via the Hedgehog-Gli pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis is a worldwide health problem and is characterized by increased and activated osteoclasts. However, the mechanism by which osteoclasts are dysregulated in postmenopausal osteoporosis is not fully understood. In this study, we found that the Hedgehog-Gli pathway was upregulated in postmenopausal osteoporotic osteoclasts and that 17ß-estradiol both inhibited osteoclastogenesis and induced osteoclast apoptosis by downregulating Hedgehog-Gli signaling. Furthermore, we demonstrated that the Hedgehog-Gli pathway was negatively regulated by MEK/ERK signaling and that this effect was Sonic Hedgehog (SHH)-dependent and was partially blocked by an anti-SHH antibody. Moreover, we found that the stimulatory effect of Hedgehog signaling on osteoclastogenesis and the inhibitory effect on osteoclast apoptosis were dependent on the Gli family of transcription factors. The pathways and molecules that contribute to the regulation of osteoclastogenesis and apoptosis represent potential new strategies for designing molecular drugs for the treatment of postmenopausal osteoporosis.