Carpal bone replacement using personalized 3D printed tantalum prosthesis.

Objective: Scaphoid and lunate fractures have a relatively high incidence rate. Traditional carpectomy and carpal arthrodesis in the treatment of carpal osteonecrosis will lead to many complications. Three-dimensional (3D) printed tantalum has good biocompatibility and can be designed to match the patient's personalized anatomical carpal structure. This study aims to investigate carpal function and prosthesis-related conditions after carpal bone replacement using 3D printed tantalum prostheses. Methods: From July 2020 to January 2022 at our center, seven patients with osteonecrosis of the carpus received carpal bone replacement using 3D printed tantalum prosthesis. The Disability of the Arm, Shoulder and Hand (DASH) score and patient satisfaction, as well as the Mayo Wrist Scores (Cooney method, modified Green, and O'Brien wrist score), were used to evaluate the preoperative and postoperative wrist function of patients. The Visual Analog Scale (VAS) pain scores were also recorded before and after surgery. The angles of flexion, dorsiflexion, ulnar deviation, and radial deviation were measured using an arthrometer. The grip strength and pinch strength of the operated hand after carpal bone replacement and the contralateral healthy carpus were measured using a dynamometer. Radiographs were taken to confirm the condition and complications of the tantalum prosthesis. Results: All seven patients were followed for 19.6 ± 2.7 months. At the last follow-up, the grip strength of the operated wrist joint after carpal bone replacement was 33.4 ± 2.3 kg, the pinch strength was 8.9 ± 0.7 kg, the flexion was 54.6° ± 0.8°, the dorsiflexion was 54.7° ± 1.7°, the ulnar deviation was 34.6° ± 1.9°, and the radial deviation was 25.9° ± 0.8°, all of which showed no statistically significant difference with the contralateral healthy carpus (p > 0.05). There were significant differences in the VAS, DASH, and MAYO scores between the preoperative and the last follow-up (p < 0.01). Patients had reduced postoperative pain and improved wrist function and range of motion (ROM), and the tantalum prostheses were stable. Conclusion: The 3D printed tantalum brings us new hope, not only for hip or knee replacement, but also for joint replacement of other complex anatomical structures, and patients with other irregular bone defects such as bone tumors and deformity, which could realize personalized treatment and precise medicine.

Turning anecdotal irradiation-induced anti-cancer immune responses into reproducible in situ cancer vaccines via disulfiram/copper-mediated enhanced immunogenic cell death of breast cancer cells.

Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE). However, combining IR with immune checkpoint inhibitors has shown anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug disulfiram (DSF) and copper complex (DSF/Cu) via induction of tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anti-cancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs, i.e., spontaneous lung metastasis. Additionally, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anti-cancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral injection of DSF/Cu and IR demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8 + and CD4 + cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, DC, and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8 + and CD4 + cells abolished the vaccine's anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anti-cancer immune response, resulting in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., the absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Repeated intra-articular injections of umbilical cord-derived mesenchymal stem cells for knee osteoarthritis: a phase I, single-arm study.

INTRODUCTION: Stem cell therapy has emerged as an effective treatment for multiple diseases, and some studies also demonstrate that it may be a promising treatment for osteoarthritis (OA). However, few studies have clarified the safety of repeated intra-articular injection of human umbilical cord-derived mesenchymal stem cells (UC-MSCs). To promote its application in treating OA, we conducted an open-label trial to investigate the safety of repeated intra-articular injections of UC-MSCs. METHODS: Fourteen patients with OA (Kellgrene-Lawrence grade 2 or 3) who received repeated intra-articular injections of UC-MSCs were evaluated in three months of follow-up. The primary outcomes were the adverse events, and the second outcomes included visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores and SF-12 quality of life score. RESULTS: A total of 5 of 14 patients (35.7%) experienced transient adverse reactions, which resolved spontaneously. All patients showed some improvement in knee function limitation and pain after receiving stem cell therapy. VAS score 6.0 to 3.5, WOMAC score 26.0 to 8.5, MOCART score 42.0 to 58.0, SF-12 score 39.0 to 46.0. CONCLUSION: Repeated intra-articular injection of UC-MSCs demonstrates safety in treating OA and does not induce serious adverse events. This treatment may transiently improve symptoms in patients with knee OA and may be a potential therapeutic option for OA.

Design and biomechanical analysis of patientspecific porous tantalum prostheses for knee joint revision surgery.

Artificial joint revision surgery, as an increasingly common surgery in orthopedics, often requires patient-specific prostheses to repair the bone defect. Porous tantalum is a good candidate due to its excellent abrasion and corrosion resistance and good osteointegration. Combination of 3D printing technology and numerical simulation is a promising strategy to design and prepare patient-specific porous prostheses. However, clinical design cases have rarely been reported, especially from the viewpoint of biomechanical matching with the patient's weight and motion and specific bone tissue. This work reports a clinical case on the design and mechanical analysis of 3D-printed porous tantalum prostheses for the knee revision of an 84-year-old male patient. Particularly, standard cylinders of 3D-printed porous tantalum with different pore size and wire diameters were first fabricated and their compressive mechanical properties were measured for following numerical simulation. Subsequently, patientspecific finite element models for the knee prosthesis and the tibia were constructed from the patient's computed tomography data. The maximum von Mises stress and displacement of the prostheses and tibia and the maximum compressive strain of the tibia were numerically simulated under two loading conditions by using finite element analysis software ABAQUS. Finally, by comparing the simulated data to the biomechanical requirements for the prosthesis and the tibia, a patient-specific porous tantalum knee joint prosthesis with a pore diameter of 600 µm and a wire diameter of 900 µm was determined. The Young's modulus (5719.32 ± 100.61 MPa) and yield strength (172.71 ± 1.67 MPa) of the prosthesis can produce both sufficient mechanical support and biomechanical stimulation to the tibia. This work provides a useful guidance for designing and evaluating a patient-specific porous tantalum prosthesis.

Application of three-dimensional-printed porous tantalum cones in total knee arthroplasty revision to reconstruct bone defects.

Purpose: Three-dimensional (3D) printing technology has emerged as a new treatment method due to its precision and personalization. This study aims to explore the application of a 3D-printed personalized porous tantalum cone for reconstructing the bone defect in total knee arthroplasty (TKA) revision. Methods: Between November 2017 and October 2020, six patients underwent bone reconstruction using 3D-printed porous tantalum cones in TKA revision. The knee function was assessed using the Hospital for Special Surgery (HSS) score pre- and postoperatively. The pain was measured by the visual analog scale (VAS) pre- and postoperatively. The quality of life was measured using the 36-Item Short Form Health Survey (SF-36) to pre- and postoperatively evaluate the relief of pain. Operation time, intraoperative blood loss, postoperative drainage volume, and complications were also recorded. At the last follow-up, all patients received X-ray and computed tomography (CT) to confirm the effect of bone reconstruction. Results: After an average follow-up duration of 26.3 months, no patients developed any operation-related complications. The average intraoperative blood loss and postoperative drainage volumes were 250.1 ± 76.4 ml and 506.7 ± 300.8 ml, respectively. At the last follow-up, the HSS score was significantly higher than that before operation, indicating that the knee function was significantly improved (p < 0.001). During the follow-up, the mean VAS score decreased and the mean SF-36 score increased, both of which were significantly improved compared with preoperative conditions (p < 0.001). Radiological examination at the final follow-up showed that cones implanted into the joint were stable and bone defects were effectively reconstructed. Conclusion: This study demonstrated that 3D-printed porous tantalum cones could effectively reconstruct bone defects and offer anatomical support in TKA revision. Further studies are still needed to confirm the long-term effect of 3D-printed tantalum cones for reconstructing bone defects.

Personalized three-dimensional printed polyether-ether-ketone prosthesis for reconstruction after subtotal removal of chronic clavicle osteomyelitis: A case report.

RATIONALE: Three-dimensional (3D) printing has attracted wide attention for its potential and abilities in the assistance of surgical planning and the development of personalized prostheses. We herewith report a unique case of chronic clavicle osteomyelitis treated with a two-stage subtotal clavicle reconstruction using a 3D printed polyether-ether-ketone (PEEK) prosthesis. PATIENT CONCERNS: A 23-year-old Chinese female presented to our clinic complaining about a progressive pain of her right clavicle for about 1 year. DIAGNOSES: Chronic clavicle osteomyelitis confirmed by percutaneous biopsy and lesion biopsy. INTERVENTIONS: This patient accepted a long-term conservative treatment, which did not gain satisfactory outcomes. Thus, a subtotal removal and two-stage reconstruction of the right clavicle with a 3D-printed polyether-ether-ketone prosthesis stabilized by screw fixation system was performed. OUTCOMES: At 2-year follow-up, complete pain relief and satisfactory functional recovery of her right shoulder were observed. LESSONS: Personalized 3D printed prosthesis is an effective and feasible method for reconstruction of complex bone defects.

Treatment of massive iliac chondrosarcoma with personalized three-dimensional printed tantalum implant: a case report and literature review.

Although customized three-dimensional tantalum implants have been used to treat a large variety of diseases, few reports have described the application of such implants to reconstruct large pelvic bone defects after the removal of massive tumors. We herein describe a 30-year-old woman with a 9-year history of a massive low-grade chondrosarcoma in the pelvic bone. After removal of a solid 12- × 8- × 6-cm tumor with clear margins, we used a customized three-dimensional printed tantalum implant to fill the large pelvic bone defect and performed hip arthroplasty in a one-step surgery. The patient's postoperative recovery was uneventful. She started walking 1 month after surgery, and she developed no tumor recurrence, instrumentation failure, or implant loosening during the 12-month follow-up period. This report describes the successful application of a customized three-dimensional printed implant to reconstruct a massive pelvic bone defect. Satisfactory functional recovery was achieved with no apparent complications. The methodology of the current case may benefit orthopedic and oncologic surgeons in designing treatment strategies for similar cases.

A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma.

BACKGROUND: Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice. METHODS: We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10-20 mm in diameter, we performed survival surgery on each mouse to harvest 90-95% of subcutaneous PDX (incomplete resection), allowing the remaining 5-10% of PDX to continue growing in the same mouse. RESULTS: We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors. CONCLUSIONS: Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.

Three-dimensional printed porous tantalum prosthesis for treating inflammation after total knee arthroplasty in one-stage surgery - a case report.

Chronic inflammation and bone defects after total knee arthroplasty are a challenge for the orthopedic surgeon. There have been few reports on application of a three-dimensional (3D) printed porous tantalum prosthesis in such situations. We report an 83-year-old female patient who presented to our clinic with consistent pain of the left knee for 10 years and a severe decline in mobility for 2 years. Chronic inflammation, loosening of a tibial prosthesis with a bone defect, and severe osteoporosis were diagnosed. The patient was treated with computer designed and manufactured, personalized, 3D printed porous pure tantalum pad-assisted left total knee arthroplasty. The surgery went smoothly and the patient achieved a satisfactory recovery after surgery. A 3D printed porous tantalum prosthesis can be used to reconstruct tibial bone defects in patients with chronic inflammation after joint replacement surgeries.

LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis.

BACKGROUND: Many studies have reported that long noncoding RNAs (lncRNAs) could act as sponges for microRNAs (miRNAs) and play important roles in the regulation of osteoarthritis (OA). Yet, the underlying mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OA are still unclear. Therefore, we aimed to explore the regulation mechanisms of MALAT1 in OA procession. METHODS: IL-1ß treatment in chondrocyte was used to mimic OA in vitro. MALAT1, miR-150-5p and AKT3 expression levels were detected via qRT-PCR. The protein levels of AKT3, MMP-13, ADAMTS-5, Bax, Bcl-2, cleaved-PARP, collagen II and aggracan were measured by western blot. MTT assay was performed to detect cell proliferation ability. The apoptosis of chondrocytes was determined using flow cytometry and western blot. Luciferase assay and RNA immunoprecipitation (RIP) assays were used to confirm the relationship among MALAT1, miR-150-5p and AKT3. RESULTS: In our study, MALAT1 and AKT3 were upregulated while miR-150-5p was downregulated in OA in vitro and vivo. The level of miR-150-5p was negatively correlated with that of MALAT1 or AKT3. More importantly, overexpression of MALAT1 promoted the expression of AKT3 by negatively regulating miR-150-5p. MALAT1 knockdown inhibited cell proliferation, promoted apoptosis, increased MMP-13, ADAMTS-5 expression and decreased collagen II, aggracan expression in IL-1ß treated chondrocytes. MALAT1 upregulation or AKT3 overexpression enhanced proliferation, inhibited apoptosis and extracellular matrix (ECM) degradation, which was undermined by overexpression of miR-150-5p. By contrast, miR-150-5p depletion rescued the effect of MALAT1 downregulation or loss of AKT3 on IL-1ß-stimulated chondrocytes. CONCLUSION: MALAT1 was responsible for cell proliferation, apoptosis, and ECM degradation via miR-150-5p/AKT3 axis.

Application of 3D-printed Customized Guides in Subtalar Joint Arthrodesis.

OBJECTIVE: To explore the feasibility of 3D printed customized guides assisting the precise drilling of Kirschner wires in subtalar joint arthrodesis. METHODS: We retrospectively reviewed the data of 29 patients (30 subtalar joints) who underwent subtalar joint arthrodesis between 1 July 2013 and 31 December 2017. The customized guides were designed on a full-scale 3D polylactic acid model made from computed tomography (CT) data of patients by Model Intestinal Microflora in Computer Simulation (MIMICS) software, which were manufactured by 3D printing technology. A total of 14 joints used customized guides (experimental group); the remained 16 joints used the traditional method (control group). The time of drilling the Kirschner wires to the correct position, the time of subtalar fusion, American Orthopaedic Foot & Ankle Society (AOFAS) scores, and complications were evaluated in both groups. RESULTS: All customized guides were successfully manufactured. In the experimental group, it took 2.1 ± 0.7 min to drill the Kirschner wire to the satisfactory position, and 2 cases needed to be re-drilled; in the control group, it took 4.6 ± 1.9 min to drill the Kirschner wire to the satisfactory position (P < 0.05), and 8 cases needed to be re-drilled. No serious complications occurred in both groups during and after the surgery. Postoperative radiographic fusion was confirmed in all cases. No significant difference was observed in the fusion time and AOFAS scores 1 year postoperatively between the two groups (P > 0.05). CONCLUSION: It is safe to apply 3D-printed customized guides for subtalar joint arthrodesis, which can assist the accurate drilling of Kirschner wires into the appropriate position according to the preoperative plan, and reduce the operation time as well as intraoperative radiation.

One-step strategy for chondral defect repair.

One-step clinical therapies of articular cartilage defects remains a challenge. In this study, a strategy was proposed to utilize type II collagen (Col-II) gels with autologous bone marrow-derived cells (BMDCs) embedded to repair full-thickness chondral defects. Its feasibility and efficacy were further assessed in a minipig model. An 8-mm full-thickness chondral defect was created on the femoral trochlea of two knees in Guizhou minipigs. One knee received Col-II gels with BMDCs implantation versus the untreated one as control. After 1, 3, and 6 months operation, the animals were sacrificed, and the repair outcomes of chondral defects were evaluated using Magnetic Resonance Imaging (MRI), macro- and microscopic observation, and histological analysis. The treatment group showed significantly better repair outcomes of chondral defects than that in the control group at each time point (P < 0.01). Furthermore, the image showed that the repaired tissue in the treatment group was more similar to the surrounding healthy cartilage tissue. Based on the hyaline-like tissue regenerated ability, this one-step strategy provides a promising therapeutic potential for clinical application.

Application of 3D-Printed Personalized Guide in Arthroscopic Ankle Arthrodesis.

OBJECTIVE: To accurately drill the Kirschner wire with the help of the 3D-printed personalized guide and to evaluate the feasibility of the 3D technology as well as the outcome of the surgery. METHODS: Patients' DICM data of ankle via CT examinations were introduced into the MIMICS software to design the personalized guides. Two 2mm Kirschner wires were drilled with the help of the guides; the C-arm fluoroscopy was used to confirm the position of the wires before applying the cannulated screws. The patients who underwent ankle arthrodesis were divided into two groups. The experimental group adopted the 3D-printed personalized guides, while the control group received traditional method, i.e., drilling the Kirschner wires according to the surgeon's previous experience. The times of completing drilling the Kirschner wires to correct position were compared between the two groups. Regular follow-ups were conducted to statistically analyze the differences in the ankle fusion time and AOFAS scores between the two groups. RESULTS: 3D-printed personalized guides were successfully prepared. A total of 29 patients were enrolled, 15 in the experimental group and 14 in the control group. It took 2.2 ± 0.8 minutes to drill the Kirschner wires to correct position in the experimental group and 4.5 ± 1.6 minutes in the control group (p=0.001). No obvious complications occurred in the two groups during and after surgery. Postoperative radiographs confirmed bony fusion in all cases. There were no significant differences in the fusion time (p=0.82) and AOFAS scores at 1 year postoperatively between the two groups (p=0.55). CONCLUSIONS: The application of 3D-printed personalized guide in assisting the accurate drilling of Kirschner wire in ankle arthrodesis can shorten the operation time and reduce the intraoperative radiation. This technique does not affect the surgical outcome. TRIAL REGISTRATION NUMBER: This study is registered on www.clinicaltrials.gov with NCT03626935.

Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

BACKGROUND: The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone. METHODS: This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score. RESULTS: The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p < 0.05) compared with Group TP at 420.5 ± 188.4 mL on postoperative day 1 and 531.1 ± 231.4 mL on postoperative day 3 and Group CT at 520.4 ± 228.4 mL on postoperative day 1 and 633.7 ± 237.3 mL on postoperative day 3. Intravenous low-dose epinephrine exhibited a net anti-inflammatory activity in total knee arthroplasty and did not induce an obvious hypercoagulable status. Transfusion values were significantly reduced (p < 0.05) in Group IV, but no significant differences were observed in the incidence of thromboembolic complications, wound score, range of motion, and HSS score among the 3 groups (p > 0.05). CONCLUSIONS: The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Magnetic-targeting of polyethylenimine-wrapped iron oxide nanoparticle labeled chondrocytes in a rabbit articular cartilage defect model.

Osteoarthritis (OA) is the most prevalent form of joint disease and lacks effective treatment. Cell-based therapy through intra-articular injection holds great potential for effective intervention at its early stage. Despite the promising outcomes, major barriers for successful clinical application such as lack of specific targeting of transplanted cells still remain. Here, novel polyethylenimine-wrapped iron oxide nanoparticles (PEI/IONs) were utilized as a magnetic agent, and the in vitro efficiency of PEI/ION labeling, and the influence on the chondrogenic properties of chondrocytes were evaluated; the in vivo feasibility of magnetic-targeting intra-articular injection with PEI/ION labeled autologous chondrocytes was investigated using a rabbit articular cartilage defect model. Our data showed that chondrocytes were conveniently labeled with PEI/IONs in a time- and dose-dependent manner, while the viability was unaffected. No significant decrease in collagen type-II synthesis of labeled chondrocytes was observed at low concentration. Macrographic and histology evaluation at 1 week post intra-articular injection revealed efficient cell delivery at chondral defect sites in the magnetic-targeting group. In addition, chondrocytes in the defect area presented a normal morphology, and the origin of cells within was confirmed by immunohistochemistry staining against BrdU and Prussian blue staining. The present study shows proof of concept experiments in magnetic-targeting of PEI/ION labeled chondrocytes for articular cartilage repair, which might provide new insight to improve current cartilage repair strategies.

How Do Axial Scan Orientation Deviations Affect the Measurements of Knee Anatomical Parameters Associated with Patellofemoral Instability? A Simulated Computed Tomography Study.

The purpose of this study was to detect the correlation between axial scan orientation discrepancy and the knee anatomical parameters associated with patellofemoral instability during computed tomography (CT) scanning. CT scan data of 16 knees from 16 healthy subjects were retrieved. The reslicing processes were performed to simulate different axial scan orientations generated due to leg adduction/abduction during CT scanning. Eight parameters (tibial tubercle to trochlear groove [TT-TG], tibial tubercle to posterior cruciate ligament [TT-PCL], patellar tilt, lateral trochlear inclination, sulcus angle, trochlear depth, trochlear facet asymmetry, and trochlear condyle asymmetry) of five angles (neutral zero, 4/8 degrees of adduction and 4/8 degrees abduction) were quantified. All eight parameters showed varying degrees of deviations to the different axial scan orientations. TT-TG, patellar tilt, lateral trochlear inclination, and trochlear condyle asymmetry were relatively sensitive to axial scan orientation changes, whereas TT-PCL, sulcus angle, trochlear depth, and trochlear facet asymmetry were relatively insensitive. Although the sensitivities are various, surgeons should be aware of this situation and make necessary corrections.

Altered spontaneous calcium signaling of in situ chondrocytes in human osteoarthritic cartilage.

Intracellular calcium ([Ca2+]i) signaling is an essential universal secondary messenger in articular chondrocytes. However, little is known about its spatiotemporal features in the context of osteoarthritis (OA). Herein, by examining the cartilage samples collected from patients undergoing knee arthroscopic surgery, we investigated the spatiotemporal features of spontaneous [Ca2+]i signaling in in situ chondrocytes at different OA stages. Our data showed zonal dependent spontaneous [Ca2+]i signaling in healthy cartilage samples under 4 mM calcium environment. This signal was significantly attenuated in healthy cartilage samples but increased in early-degenerated cartilage when cultured in 0 mM calcium environment. No significant difference was found in [Ca2+]i intensity oscillation in chondrocytes located in middle zones among ICRS 1-3 samples under both 4 and 0 mM calcium environments. However, the correlation was found in deep zone chondrocytes incubated in 4 mM calcium environment. In addition, increased protein abundance of Cav3.3 T-type voltage dependent calcium channel and Nfatc2 activity were observed in early-degenerated cartilage samples. The present study exhibited OA severity dependent spatiotemporal features of spontaneous [Ca2+]i oscillations of in situ chondrocytes, which might reflect the zonal specific role of chondrocytes during OA progression and provide new insight in articular cartilage degradation during OA progression.

Chondromodulin­I expression and correlation with angiogenesis in human osteoarthritic cartilage.

The present study aimed to evaluate the expression and localization of chondromodulin­I (ChM­I) in human osteoarthritic cartilage and its correlation with vascular invasion during osteoarthritis (OA) progression. Osteochondral specimens were collected from patients with OA, as well as from young and aged donors without joint diseases. The grade and the number of vascular channels terminating in non­calcified cartilage of these collected specimens were assessed by Safranin­O/Fast green staining. ChM­I expression in articular cartilage was examined by immunohistochemistry, western blotting and reverse transcription­quantitative polymerase chain reaction analyses. ChM­I protein and mRNA levels in articular cartilage appeared to be consistent between the normal young and aged groups (P>0.05). In mildly degene-rated cartilage, ChM­I expression decreased in the extracellular matrix (ECM) of the superficial zone and in the cytoplasm of the superficial and middle zone compared with normal cartilage (P<0.05). In moderately degenerated cartilage, ChM­I protein expression was reduced in the ECM of all zones of articular cartilage, but the immunostaining intensity in the cytoplasm was increased. In severely degenerated cartilage, ChM­I expression was detected primarily in the cytoplasm of the cluster­forming chondrocytes. The density of vascular channels was correlated with the ChM­I expression levels in cartilage ECM. ChM­I expression was reduced in OA cartilage matrix, compared with normal cartilage (both young and aged), and correlated with angiogenesis, indicating that loss of ChM­I may promote angiogenesis in OA cartilage. Expression of ChM­I protein in the cytoplasm was decreased in mildly degenerated cartilage, whereas ChM­I expression increased in moderately degenerated cartilage accompanied by chondrocyte proliferation. These findings suggested that attenuation of ChM­I in the cartilage ECM may be due to decreased expression of ChM­I in cytoplasm of early stage OA and increased depletion of ChM­I in the ECM of advanced stage OA.