The alterations in nerve growth factor concentration in plasma and synovial fluid before and after total knee arthroplasty.

Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.

Bone Density Distribution Pattern in the Lateral Wall of the Femoral Intercondylar Notch: Implications for the Direct Insertion of the Femoral ACL Attachment.

Background: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. Purpose/Hypothesis: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. Study Design: Descriptive epidemiology study. Methods: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. Results: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope (r = -0.38, P = .02). Conclusion: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.

Three-stage total knee arthroplasty combined with deformity correction and leg lengthening using Taylor spatial frames and conversion to internal fixation for severe intra- and extra-articular deformities and hypoplasia in a patient with hemophilic knee arthropathy: A case report.

BACKGROUND: Hemophilic arthropathy is a cause of severe knee deformity, because chronic synovitis due to repeated hemarthrosis affects the area of the epiphyseal plates in juvenile cases. Total knee arthroplasty (TKA) is the standard treatment for end-stage knee arthropathy. However, it is difficult to perform one-stage TKA in patients with severe intra- and extra-articular deformities. CASE PRESENTATION: We reported a case of hemophilic arthropathy in a 55-year-old male with leg length discrepancy of 4 cm, limited range of knee motion (-40° extension and 85° flexion), intra-articular deformity (medial proximal tibial angle: 69°; mechanical lateral distal femoral angle: 79°), extra-articular deformity at the distal femoral metaphyseal (30° valgus and 45° flexion deformity), and varus malalignment (% mechanical axis: 33%). We planned a three-stage TKA. Firstly, we performed gradual correction and lengthening of the distal femur using Taylor spatial flame. Six months after surgery, we performed conversion surgery from external fixation to internal fixation. Finally, we performed TKA with rotating hinged type implant. Two years after surgery, physical examination showed a normal gait, leg length discrepancy of 2 cm (the right leg was shorter), improvement in the range of knee motion (0° extension and 100° flexion). CONCLUSION: To the best of our knowledge, this presents the first combination of three-stage TKA with correction of femoral deformity and leg lengthening using a Taylor spatial frame and conversion to internal fixation in a patient with hemophilic knee arthropathy and severe intra- and extra-articular deformities.

Effect of the Inverted V-Shaped Osteotomy on Patellofemoral Joint and Tibial Morphometry as Compared With the Medial Opening Wedge High Tibial Osteotomy.

BACKGROUND: Recent studies have reported that medial opening wedge (OW) high tibial osteotomy (HTO) induces patella baja, resulting in degenerative changes in the patellofemoral joint. We have developed an inverted V-shaped (iV) HTO, which is classified as a neutral wedge osteotomy. HYPOTHESES: The study hypotheses were as follows: (1) patellar height, posterior tibial slope, and tibial length will not change between pre- and postoperative evaluations after iV-HTO; (2) the lateral shift ratio of the patella and the distance between the tibial tubercle and the trochlear groove may be significantly decreased after iV-HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 191 patients (220 knees) who underwent HTO for medial osteoarthritis were enrolled retrospectively in this study: 107 knees underwent OW-HTO and 113 knees underwent iV-HTO. Clinical and radiological evaluations were performed before and at least 3 years after surgery. RESULTS: Postoperatively, the mean Caton-Deschamps ratio was significantly decreased (P < .0001) from 0.95 to 0.79 in the OW group, while there were no significant changes in the iV group. The mean posterior tibial slope was significantly increased (P < .0001) from 8.5° to 10.5° in the OW group, while there were no significant differences in the iV group. Although the entire leg length was significantly increased (P < .0003) in both groups after HTO, there were no significant differences in tibial length between the pre- and postoperative periods in the iV group. Regarding the congruity of the patellofemoral joint, the mean lateral shift ratio did not significantly change in the OW group, whereas it was significantly decreased (P = .0012) from 11.5% to 8.8% in the iV group. The mean tibial tubercle-trochlear groove distance was significantly decreased (P < .0001) from 12.8 to 9.7 mm in the iV group, while it was significantly increased in the OW group (P < .0001). Concerning the clinical outcome, the Japanese Orthopaedic Association (JOA) and Lysholm knee scores at final follow-up (OW vs iV: JOA, 91.2 vs 90.1; Lysholm, 92.5 vs 89.0) were significantly increased (P < .0001) as compared with the preoperative values (OW vs iV: JOA, 68.3 vs 66.8; Lysholm, 67.9 vs 61.0). CONCLUSION: Patellar height, posterior tibial slope, and tibial length did not change after the iV-HTO, while they were significantly changed after the OW-HTO. Although the preoperative degrees of varus knee and patellofemoral osteoarthritis were more severe in the iV group than the OW group, the iV-HTO led to altered patellofemoral joint congruity.

The effect of local injection of tranexamic acid into peri-articular tissue versus drain clamping in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is used as a synthetic anti-fibrinolytic agent for total knee arthroplasty (TKA) to reduce postoperative bleeding. Though the effects on bleeding reduction of several methods of administering TXA have been demonstrated, the optimal method remains controversial. Recently, the hemostatic effect of periarticular local injection of TXA during TKA was reported. Although this method can be expected to suppress postoperative bleeding without placing a drain, its hemostatic effect has not yet been assessed in comparison with local injection and other methods of administering TXA. The aim of this randomized, prospective study was to assess the efficacy of local injection of TXA during TKA. METHODS: To confirm the effect of the local injection of TXA, drain clamping was set as the control. The subjects included a prospective series of 109 patients randomly divided into 2 groups: the local injection (group L) and the drain clamping (group D). The main outcome measure was postoperative bleeding. Secondary outcomes included pain, physical measurements, and laboratory findings. RESULTS: The calculated total blood loss (CTBL) in groups L and D was nearly equal and did not show the non-inferiority of group L to group D (883 ± 248 vs. 841 ± 257 ml, P = .564). Drained blood loss was significantly higher in group L than in group D (395 ± 130 vs 276 ± 78.8 ml, P < .0001). There was no significant difference in hidden blood loss between the groups (488 ± 269 vs 565 ± 261 ml, P = .131). The other laboratory findings and physical measurements were identical between the groups. CONCLUSIONS: Although CTBL in group L did not show non-inferiority to group D, the local injection of TXA was considered to be superior for suppressing bleeding considering the risk of the adverse effects of using a drain. TRIAL REGISTRATION: This was a randomized, prospective study registered with UMIN Clinical Trials Registry (Registration number: UMIN000036146, date of disclosure: 10/3/2019).

Stress on the posteromedial region of the proximal tibia increased over time after anterior cruciate ligament injury.

PURPOSE: Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. METHODS: Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. RESULTS: HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). CONCLUSIONS: Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.

Discrepancy in the Distribution Patterns of Subchondral Bone Density Across the Ankle Joint After Medial Opening-Wedge and Lateral Closing-Wedge High Tibial Osteotomy.

BACKGROUND: High tibial osteotomy (HTO) changes the alignment and dynamics of the ankle joint; however, differences in the stress distribution of the ankle joint after opening-wedge HTO (OWHTO) and closing-wedge HTO (CWHTO) are not understood. It is believed that subchondral bone density of the articular surface reflects the pattern of cumulative stress distribution across the joint surface. PURPOSE: To clarify the effects of OWHTO and CWHTO on the distribution patterns of subchondral bone density across the ankle joint using computed tomography (CT)-osteoabsorptiometry. STUDY DESIGN: Cohort study; Level of evidence, 4. METHODS: Radiographic and CT data of 18 cases who underwent OWHTO (OW group), 12 cases who underwent CWHTO (CW group), and 11 cases with unilateral anterior cruciate ligament injury serving as controls were retrospectively reviewed. The subchondral bone density of the distal tibia was assessed in the 3 groups using CT-osteoabsorptiometry. The distal tibial surface of the ankle joint was divided into 4 parts in the coronal direction, and the percentage of the high-density area (%HDA) to each subregion was compared before and after HTO. RESULTS: Preoperatively, comparing %HDA among the 3 groups, there were no significant differences in any regions. In the OW group, postoperative %HDA in the most medial region was significantly increased compared with preoperative %HDA (49.3% to 53.0%; P = .011), and postoperative %HDA in the most lateral region was significantly decreased (21.4% to 17.2%; P = .003). On the other hand, in the CW group, postoperative %HDA in the most medial region was significantly decreased (55.7% to 35.7%; P = .001), and %HDA in the second lateral region was significantly increased (23.6% to 29.2%; P = .002). CONCLUSION: The ankle distribution pattern of subchondral bone density shifted significantly medially after OWHTO without fibular osteotomy, whereas the distribution pattern shifted laterally after CWHTO with fibular osteotomy. When the OWHTO is performed for patients with medial ankle osteoarthritis, surgeons should pay attention to potential postoperative progression of ankle osteoarthritis due to medial shift of the stress distribution in the ankle joint.

Brain Metastasis in Soft Tissue Sarcoma at Initial Presentation.

BACKGROUND/AIM: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis. PATIENTS AND METHODS: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined. RESULTS: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis. CONCLUSION: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes.

Delayed Onset of Infectious Foreign Body Granuloma for Nonabsorbable Sutures After Open Achilles Tendon Repair: A Case Report.

Foreign body granulomas from sutures are more common among non-absorbable sutures compared to absorbable sutures and have been reported as a postoperative complication in a variety of medical fields. However, only a few cases of delayed foreign body reaction have been reported and addressed with orthopedics. We present a patient with systemic lupus erythematosus who developed an infectious suture granuloma that extended to the entire Achilles tendon and was induced by nonabsorbable sutures that were used for open Achilles tendon repair 20 years before. This granuloma was resistant to antibiotic treatment and drainage and required surgical intervention. The tumor was marginally resected, and the continuity of the Achilles tendon was preserved. Histopathological examination detected many suture materials surrounded by xanthochromic necrotic lesions and the lesion was diagnosed as a foreign body granuloma. At 1 year after the operation, the patient did not exhibit exacerbation of infection or recurrence of the tumor, and she became able to walk by herself. To the best of our knowledge, this represents the first report of an infectious delayed foreign body granuloma in autoimmune disorder patient after open Achilles tendon repair. Surgical intervention should be considered, as treatment with conservative therapy such as antibiotics may be difficult.

Hallux Valgus With Second Brachymetatarsia Discovered Accidentally: A Case Report.

Hallux valgus deformity is one of the most common foot and ankle diseases, while brachymetatarsia is a rare foot anomaly with pathological shortening of a metatarsal bone. We present a case of hallux valgus deformity possibly due to second brachymetatarsia. As the hallux valgus was associated with dorsal dislocation of the second toe that made it difficult to evaluate the length of the second toe, the patient was unaware of the second metatarsal shortening until the lengths of the toes compared by manual reposition of the second MTP joint. In this case, proximal osteotomy of the first metatarsal on the hallux valgus and single-stage bone lengthening of the second metatarsal with iliac bone grafting on the second brachymetatarsia were performed. One year after the operation, the callosity of the third toe resolved and the clinical scores were improved. In the case of a hallux valgus deformity with second dorsal dislocation of the toes, surgeons should consider that there are rare cases with second metatarsal shortening. When hallux valgus associated with second brachymetatarsia is diagnosed, second metatarsal lengthening should be considered in addition to hallux valgus surgery.

Effect of High Tibial Osteotomy on the Distribution of Subchondral Bone Density Across the Proximal Tibial Articular Surface of the Knee With Medial Compartment Osteoarthritis.

BACKGROUND: The effect of high tibial osteotomy (HTO) on the stress distribution across the knee joint is not completely understood. Subchondral bone density is considered to reflect the pattern of stress distribution across a joint surface. PURPOSE: To assess the distribution of subchondral bone density across the proximal tibia in nonarthritic knees and in the knees of patients with osteoarthritis (OA) before and after HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively collected radiological and computed tomography data from 16 patients without OA (control group) and 17 patients with OA. Data from the OA group were collected before and 1.5 years after HTO. Subchondral bone density of the proximal tibia was assessed with computed tomography-osteoabsorptiometry. The locations and percentages represented by high-density areas (HDAs) on the articular surface were quantitatively analyzed. RESULTS: The ratio of the HDA of the medial compartment to the total HDA (medial ratio) was significantly higher in the preoperative OA group (mean, 80.1%) than in the control group (61.3%) (P < .001). After HTO, the medial ratio decreased significantly to 75.1% (P = .035 in comparison with preoperative values) and was significantly correlated with the hip-knee-ankle angle in both groups: control (r = -0.551; P = .033) and OA (r = -0.528; P = .043). The change in medial ratio after HTO was significantly correlated with the change in hip-knee-ankle angle (r = 0.587; P = .035). In the medial compartment, the HDA in the most lateral region of 4 subregions increased after HTO, but that in 3 medial subregions decreased. CONCLUSION: In this exploratory study, HTO shifted the HDA of the medial compartment of the proximal tibial articular surface toward the lateral compartment. In contrast, the HDA of the most lateral region of the medial compartment increased after HTO. This change in subchondral bone density may result from the change in stress distribution.

Depletion of glycosphingolipids induces excessive response of chondrocytes under mechanical stress.

Glycosphingolipids (GSLs) are ubiquitous membrane components that play an indispensable role in maintaining chondrocyte homeostasis. To gain better insight into roles of GSLs, we studied the effects of GSL-deletion on the physiological responses of chondrocytes to mechanical stress. Mice lacking Ugcg gene (Ugcg-/-) were genetically generated to obtain GSL-deficient mice, and their chondrocytes from the joints were used for functional analyses in vitro culture experiments. The cells were seeded in a three-dimensional collagen gel and subjected to 5%, 10% or 16% cyclic tensile strain for either 3 or 24 h. The gene expressions of chondrocyte anabolic and catabolic factors, and the induction of Ca2+ signaling were analyzed. Our results revealed that chondrocytes derived from GSL-deficient mice exhibited an elevation in the expression of catabolic factors (ADAMTS-5, MMP-13) following the exposure to strain with amplitudes of 10%. Likewise, applying cyclic tensile strain with these amplitudes resulted in an increased Ca2+ oscillation ratio in chondrocytes from GSL-deficient as compared to the ratio from control mice. These results demonstrated that deletion of GSL stimulated the catabolic responses of chondrocytes to mechanical stress via the augmentation of the sensitivity to mechanical stress that may lead to the cartilage deterioration. These findings suggest that the regulation of the physiological responses of chondrocytes by GSLs could be a potential target in a therapeutic intervention in osteoarthritis.

CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults.

Juvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21 in vivo can improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.

Effects of Ultra-Purified Alginate Gel Implantation on Meniscal Defects in Rabbits.

BACKGROUND: Many tissue-engineered methods for meniscal repair have been studied, but their utility remains unclear. HYPOTHESIS: Implantation of low-endotoxin, ultra-purified alginate (UPAL) gel without cells could induce fibrocartilage regeneration on meniscal defects in rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two mature Japanese White rabbits were divided into 2 groups of 21 animals each. In each animal, a cylindrical defect measuring 2 mm in diameter was created with a biopsy punch on the anterior horn of the medial meniscus. In the control group, no treatment was applied on the left medial meniscal defect. In the UPAL gel group, the right medial meniscal defect was injected with the UPAL gel and gelated by a CaCl2 solution. Samples were evaluated at 3, 6, and 12 weeks postoperatively. For biomechanical evaluation, 6 additional samples from intact animals were used for comparison. RESULTS: The macroscopic score was significantly greater in the UPAL gel group than in the control group at 3 weeks (mean ± SE: 5.6 ± 0.82 vs 3.4 ± 0.83, P = .010), 6 weeks (5.9 ± 0.72 vs 2.5 ± 0.75, P = .026), and 12 weeks (5.2 ± 1.21 vs 1.0 ± 0.63, P = .020). The histological score was significantly greater in the UPAL group than in the control group at 3 weeks (2.1 ± 0.31 vs 1.2 ± 0.25, P = .029) and 12 weeks (2.2 ± 0.55 vs 0.3 ± 0.21, P = .016). The mean stiffness of the reparative tissue in the UPAL gel group was significantly greater than that in the control group at 6 weeks (24.325 ± 3.920 N/mm vs 8.723 ± 1.190 N/mm, P = .006) and at 12 weeks (27.804 ± 6.169 N/mm vs not applicable [because of rupture]). CONCLUSION: The UPAL gel enhanced the spontaneous repair of fibrocartilage tissues in a cylindrical meniscal defect in rabbits. CLINICAL RELEVANCE: These results imply that the acellular UPAL gel may improve the repair of traumatic meniscal injuries.

Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model.

BACKGROUND: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. HYPOTHESIS: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. RESULTS: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. CONCLUSION: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. CLINICAL RELEVANCE: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.

Chondrogenic differentiation of mouse induced pluripotent stem cells using the three-dimensional culture with ultra-purified alginate gel.

As articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019.

Bone Marrow Stimulation Technique Augmented by an Ultrapurified Alginate Gel Enhances Cartilage Repair in a Canine Model.

BACKGROUND: The optimal treatment for a medium- or large-sized cartilage lesion is still controversial. Since an ultrapurified alginate (UPAL) gel enhances cartilage repair in animal models, this material is expected to improve the efficacy of the current treatment strategies for cartilage lesions. HYPOTHESIS: The bone marrow stimulation technique (BMST) augmented by UPAL gel can induce hyaline-like cartilage repair. STUDY DESIGN: Controlled laboratory study. METHODS: Two cylindrical osteochondral defects were created in the patellar groove of 27 beagle dogs. A total of 108 defects were divided into 3 groups: defects without intervention (control group), defects with the BMST (microfracture group), and defects with the BMST augmented by implantation of UPAL gel (combined group). At 27 weeks postoperatively, macroscopic and histological evaluations, micro-computed tomography assessment, and mechanical testing were performed for each reparative tissue. RESULTS: The defects in the combined group were almost fully covered with translucent reparative tissues, which consisted of hyaline-like cartilage with well-organized collagen structures. The macroscopic score was significantly better in the combined group than in the control group ( P < .05). The histological scores in the combined group were significantly better than those in the control group ( P < .01) and microfracture group ( P < .05). Although the repaired subchondral bone volumes were not influenced by UPAL gel augmentation, the mechanical properties of the combined group were significantly better than those of the microfracture group ( P < .05). CONCLUSION: The BMST augmented by UPAL gel elicited hyaline-like cartilage repair that had characteristics of rich glycosaminoglycan and matrix immunostained by type II collagen antibody in a canine osteochondral defect model. The present results suggest that the current technique has the potential to be one of the autologous matrix-induced chondrogenesis techniques of the future and to expand the operative indications for the BMST without loss of its technical simplicity. CLINICAL RELEVANCE: The data support the clinical reality of 1-step minimally invasive cartilage-reparative medicine with UPAL gel without harvesting donor cells.

Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice.

Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair.

Extensor tendon dislocation after end-to-side transfer in a rheumatoid patient.

We report a case of extensor tendon dislocation at the metacarpophalangeal joint of the middle finger in which it appeared that an ulnar translation force created by an end-to-side transfer contributed to the dislocation. We recommend alterations in technique or alternative method of extensor tendon reconstruction to avoid this complication if unfavorable factors for end-to-side transfer exist.

Spinal cord compression by hematoma in the cervical ligamentum flavum: a case report.

BACKGROUND CONTEXT: There have been some reports describing hematoma in the thoracic and lumbar ligamentum flavum, but there have been only three reports of hematoma in the cervical ligamentum flavum. PURPOSE: We describe another case of the ligamentum flavum hematoma in the cervical spine with a different feature of occurrence that required surgical treatment. STUDY DESIGN: Case report. PATIENT SAMPLE: Patient with ligamentum flavum hematoma in the cervical spine. OUTCOME MEASURES: Preoperative magnetic resonance imaging and pathologic finding from operative specimen confirmed the diagnosis. METHODS: A 69-year-old man insidiously presented with pain in his left upper arm and difficulty in left shoulder abduction. Neurologic examination demonstrated a cervical myelopathy with diffuse muscle weakness of left upper extremity and sensory disturbance. Imaging studies revealed a mass of high intense on T1-weighted images and isointense on T2-weighted images posterior to the dura at C4 lower end level. The patient underwent C4-C5 hemilaminectomy and the removal of the mass. The mass existed within the ligamentum flavum and was connected toward the pedicle like the beads of a rosary. RESULTS: Histopathologic examination of the surgical specimen showed that the hematoma was present within the ligamentum flavum and contained macrophages that had phagocytosed red blood cells and hemosiderin. After surgery, the patients' symptoms immediately improved, and no recurrence was observed at 2 years postoperatively. CONCLUSIONS: We reported a very rare case of hematoma in the ligamentum flavum of the cervical spine that required surgery. Because the patient was without the history of trauma, it was suggested that the use of antiplatelet drugs was responsible for the occurrence of the disease.