Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 mu g) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 mu g NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA

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

Double-bundle anterior cruciate ligament reconstruction using autologous hamstring tendon hybrid grafts in a patient with hypermobile Ehlers-Danlos Syndrome : A case report

Background: Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue friability. Hypermobile type Ehlers-Danlos syndrome (hEDS) is considered one of the EDS subtypes characterized by generalized joint hypermobility. Although there have been a few case reports which described surgical considerations for anterior cruciate ligament (ACL) reconstructions in patients with other types of EDS, no reports have described those in patients with hEDS. Case presentation: We report a case of ACL injury in an 18-year-old male patient with hEDS. The patient was successfully treated with an anatomic double-bundle ACL reconstruction using autologous hamstring tendon hybrid grafts which consist of hamstring tendons connected in a series with commercially available polyester tape. The autogenous tendon portion of the anteromedial and posterolateral bundles were composed of 4 and 2 strands of hamstring tendons, respectively. After 2 weeks of knee joint immobilization, continuous passive motion exercise of the knee joint and partial weight-bearing was allowed. A hinged knee brace was used for a period of 5 months postoperatively. Second-look arthroscopy at 30 months showed that the ACL graft had no laceration and an excellent coverage of the synovium. At 36 months after surgery, the side-to-side differences in the anterior laxity was remarkably improved. The operated knee showed negative Lachman test and had a full range of motion. Conclusions: To the best of our knowledge, this represents the first report of anatomic double-bundle ACL reconstruction in patients with hEDS and demonstrates excellent clinical and functional outcomes. (C) 2022 Elsevier B.V. All rights reserved

Occurrence Rate of Cyclops Lesion After Anatomic Double-Bundle ACL Reconstruction : Comparison Between Remnant Tissue Preservation and Resection Methods

Background: The occurrence rate of cyclops lesion after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with remnant tissue preservation remains unclear. Hypothesis: The study hypotheses were as follows: (1) the occurrence rate of cyclops lesion will be comparable between the remnant-preserving and remnant-resecting ACL reconstruction methods, and (2) there will be no significant differences in clinical outcomes between the remnant-preserving and remnant-resecting procedures. Methods: This retrospective comparative study involved 177 patients who underwent unilateral anatomic double-bundle ACL reconstruction using hamstring tendon autografts from 2014 to 2018 at our hospital. According to the Crain classification of ACL remnant tissue, 98 patients with remnant types I, II, or III underwent the remnant-preserving procedure (group A), and the remaining 79 patients with remnant type IV underwent the remnant-resecting procedure (group B). All patients underwent second-look arthroscopy. Patients were evaluated according to arthroscopic and clinical results at postoperative 15.2 +/- 8.4 months (mean +/- SD). Statistical comparisons between groups were made using the paired Student t test, chi-square test, and Fisher exact test. Study Design: Cohort study; Level of evidence, 3. Results: At second-look arthroscopy, the incidence of cyclops lesions was significantly higher in group B than in group A (29.1% vs 13.3%; P = .0139). Cyclops lesions were divided into 4 locations: femoral side (type 1), midsubstance (type 2), tibial side (type 3), and anterior (type 4) of the ACL graft. The ratio of the tibial-side cyclops lesion (type 3) was significantly higher in group B than in group A (P = .0354). There were no significant differences in the clinical evaluation scores between the procedures. Side-to-side anterior laxity was significantly less in group A than in group B (0.7 vs 1.6 mm; P = .0035). Concerning postoperative laceration and synovium coverage of the grafts, group A was significantly better than group B (P < .0001). Conclusion: In this cohort of patients undergoing double-bundle ACL reconstruction, resection of the ACL remnant was associated with a significantly higher rate of cyclops lesion formation when compared with preservation of the remnant

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

Chondrogenic differentiation of mouse induced pluripotent stem cells (iPSCs) using the 3 three-dimensional culture with ultra-purified alginate gel (UPAL 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. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019