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.

Impact of Surgical Timing on Clinical Outcomes in Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autografts.

BACKGROUND: To date, no studies have analyzed the influence on clinical outcomes of the interval between an anterior cruciate ligament (ACL) injury and double-bundle (DB) reconstruction with hamstring tendon autografts. HYPOTHESES: (1) Performing ACL reconstruction sooner after an injury will reduce postoperative anterior and rotatory knee instability, (2) postoperative range of knee motion or functional results will not be affected by different intervals between injury and surgery, and (3) preoperative isokinetic peak torque of the quadriceps and hamstring muscles will be lower in patients undergoing surgery earlier, while postoperative muscle strength will not be affected by surgery timing. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was conducted on a total of 171 patients who had undergone anatomic DB ACL reconstruction with hamstring tendon autografts. The patients were divided into 3 groups based on the time to surgery: (1) ≤1 month after the injury (group E; n = 25), (2) between 1 and 3 months after the injury (group M; n = 72), and (3) >3 months after the injury (group D; n = 74). Patients were assessed for a minimum of 2 years after surgery. RESULTS: Concerning postoperative anterior laxity, 1-way analysis of variance demonstrated a significant difference (P = .0274) among the 3 groups. Anterior laxity was significantly less in group E than in group D (P = .0206). Spearman rank correlation analysis showed a significant correlation (ρ = 0.200; P = .0327) between anterior knee laxity and time to surgery. Also, a significant correlation (P = .0461) was found between the degree of the pivot-shift phenomenon and time to surgery. There were no significant differences in loss of knee extension or flexion among the 3 groups, nor were there any differences in the Lysholm knee score or International Knee Documentation Committee grade. Postoperatively, there were no significant differences in peak torque of the quadriceps or hamstring muscles among the 3 groups. CONCLUSION: Early DB reconstruction led to significantly less anterior laxity compared with delayed reconstruction. There were no significant differences in postoperative range of knee motion or functional results among the 3 time intervals between injury and surgery in this study.

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.

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.

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.

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.