Treatment Of Post-traumatic Osteoarthritis Research Articles

Mechanism study of BMSC-exosomes combined with hyaluronic acid gel in the treatment of posttraumatic osteoarthritis

ObjectiveTo explore the mechanism and efficacy of gel in the treatment of posttraumatic osteoarthritis (PTOA), combined with hyaluronic acid (HA) and bone marrow mesenchymal stem cell exosomes (BMSC-EXOs), and to explain its role in alleviating oxidative stress damage induced by mitochondrial reactive oxygen species (ROS). MethodsHow is the therapeutic potential of toa influenced by bone marrow mesenchymal stem cells-EXO to be evaluated both in vitro and in vivo. In vitro, BMSC-EXOs were extracted and characterized from rat specimens and labeled with Dil. Rat primary chondrocytes were then isolated to create a cellular PTOA model. BMSC-EXOs + HA group, BMSC-EXOs + HA + 740Y–P group, model group, BMSC-EXOs group, HA group, and control group were included in the cell group, and the function of cartilage matrix and the level of oxidative stress could be evaluated. Cartilage matrix integrity and oxidative stress can be assessed by grouping rats. At the same time, a rat model of ptosis can be established by excision of the anterior cruciate ligament, and joint rehabilitation, with pro-inflammatory and Enzyme-linked immunosorbent assay (ELISA) can be used to determine anti-inflammatory markers. ResultsThe combined use of BMSC-EXOs and HA gel was found to significantly reduce oxidative stress in chondrocytes and PTOA rat models, improving cartilage mechanical properties more effectively than BMSC-EXOs alone. ConclusionBMSC-EXOs combined with HA gel offer a promising treatment for PTOA by modulating damage caused by mitochondrial ROS-induced oxidative stress.

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice

Background: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. Purpose: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. Study Design: Controlled laboratory study. Methods: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro−computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. Results: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. Conclusion: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. Clinical Relevance: TXA might be beneficial in patients with posttraumatic OA of the knee.

Can the Contralateral Ankle be used for Preoperative Planning in Total Ankle Arthroplasty in the Posttraumatic Patient? A Prospective Study

Category: Ankle Arthritis; Ankle Introduction/Purpose: Total ankle arthroplasty (TAA) for posttraumatic osteoarthritis (OA) is becoming an increasingly popular treatment option. Clinical results and prosthesis longevity correlate directly with the hind foot and components' postoperative alignment. Therefore, a preoperative plan (PROP) that can accurately predict postoperative alignment of TAA could be valuable. Most PROPs use the diseased ankle as a reference despite the arthritic deformation. PROPs of the contralateral, unaffected limb have been tested in other fields, but not in TAA. In most cases of posttraumatic OA, the contralateral ankle is relatively preserved and therefore could serve as a valuable tool for preoperative planning. This prospective study aims to assess the accuracy of preoperative planning using a WBCT of the contralateral healthy ankle for TAA in the treatment of posttraumatic OA. Methods: A total of 44 patients were included. For each case, a preoperative WBCT scan of the contralateral foot was acquired. Individual PROPs consisted of virtual realignment and osteotomies prior to each surgery. After surgery, postoperative WBCT scan of the affected foot was performed. Six angles were used to assess the accuracy of the coronal and sagittal alignment of the prosthesis. Results: Forty-four ankles across 44 patients were operated on. Three angles had a statistically significant difference between the pre and postoperative measurements: (1) α angle was -3±4 degrees (p-value < 0.0001), (2) TTS 2.884±4 degrees (p-value < 0.00001), (3) TTR -7±14 mm (p-value < 0.001). Only 49% and 34% of the coronal and sagittal angles could be found within 3 degrees from the PROPs. Conclusion: In conclusion, the contralateral ankle cannot be used accurately as a preoperative planning tool for TAA. It should be used only in cases where the diseased ankle cannot be a referenced in the setting of deformation.

Comparisons of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis

BackgroundThe aim of this study was to explore the clinical efficacy of ankle arthrodesis with different internal fixation methods in the treatment of post-traumatic osteoarthritis. MethodsWe collected 85 patients with post-traumatic osteoarthritis who underwent different ankle arthrodesis between December 2015 and December 2020. The operation performance, complication rate, hindfoot alignment, talus tilt angle, visual analogue scale (VAS), and American Orthopedic Foot and Ankle Society (AOFAS) score were preoperatively and postoperatively evaluated. ResultsIn an anterior approach, the locking plate-fixation exhibited a similarity in operation time, incision length, postoperative drainage, bone fusion, hindfoot alignment, and talus tilt angle with fibula support compression screw-fixation, but it was better in increasing postoperative AOFAS. The locking plate-fixation in the anterior approach had lower operation time, incision length, and postoperative drainage than that in the lateral approach. In addition, the lateral locking plate combined with posterolateral compression screw fixation (LLPPCSF) presented shorter bone fusion time, higher AOFAS score, and lower complication rate than either plate- or screw-fixation alone. ConclusionLateral locking plate fixation was better than fibula support compression screw fixation in relieving postoperative pain. Anterior locking plate fixation was more time-saving and less invasiveness than lateral locking plate fixation, but its application was limited in low degree of ankle deformation. LLPPCSF was the most effective in improving bone fusion and postoperative pain, considering an optimal option for the treatment of post-traumatic osteoarthritis.

Coculture with interleukin-10 overexpressed chondrocytes: a cell therapy model to ameliorate the post-traumatic osteoarthritis development.

Autologous chondrocyte (CH) transplantation is a novel strategy to treat post-traumatic osteoarthritis (PTOA). In this study, an in vitro coculture model was used to explore the effects of interleukin (IL)-10 overexpressed CHs on degenerated CHs. The original CHs were isolated from the patients' knee joint cartilage and pretreated with IL-1β to get degenerated CHs. Moreoer, CHs were transfected with a lentivirus vector to overexpress IL-10. After coculture with the degenerated CHs, the apoptosis, collagen X, IL-6, and TNF-α of original CHs were increased, and the collagen II and IL-10 were decreased compared to the separated culture condition. Coculture with original CHs did not alleviate the degeneration of the IL-1β-pretreated CHs. However, coculture with the IL-10-overexpressed CHs rescued the proliferation, collagen II, aggrecan, SOX9, and IL-10 expression, and suppressed the apoptosis, collagen X, RUnx2, IL-6, and TNF-α levels in the IL-1β pretreated CHs. Additionally, the IL-10-overexpressed CHs also maintained a healthy state when cocultured with the degenerated CHs. Therefore, transplanting the IL-10-overexpressed CHs in the treatment of PTOA would obtain a more durable and visible effect in alleviating the CH degeneration.

Immunosuppressive regulatory T cells are unable to suppress T helper 17 cells in post-traumatic osteoarthritis

Immunosuppressive regulatory T cells are unable to suppress T helper 17 cells in post-traumatic osteoarthritis

A Translational Porcine Model for Human Cell–Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury

Background: There is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies. Purpose: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell–based interventions. Study Design: Descriptive laboratory study. Methods: Nine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1β) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 107 human bone marrow–derived mesenchymal stem cells (hBM-MSCs) combined with a fibrin carrier. These cells were labeled with the luciferase reporter gene (hBM-MSCs-Luc) as well as fluorescent markers and intracellular iron nanoparticles. These animals were euthanized on day 0 (n = 1) or day 14 (n = 2) after injection. hBM-MSC-Luc viability and localization were assessed using ex vivo bioluminescence imaging, fluorescence imaging, and MRI. Results: PTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1β shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging. Conclusion: This study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks. Clinical Relevance: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury–associated PTOA in the future (see Appendix Figure A1, available online).

Early Results of Cementless versus Hybrid Total Hip Arthroplasty in Patients with Posttraumatic Osteoarthritis

Abstract Background: Various types of THA were used in treatment of different forms of osteoarthritis. In this study, we aimed to compare the early results of cementless versus hybrid Total Hip Arthroplasty (THA) in treatment of Posttraumatic Oste-oarthritis (PTOA). Aim of Study: Prospective comparative study. Patients and Methods: Twenty two cases were included in the study and they were divided into two equal groups; group A that performed cementless THA, group B that under-went hybrid THA. Perioperative circumstances of perioperative complications, operating room time, blood transfusion require-ments and length of hospital stay were reported. Post-operative evaluation was done using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Hip Score (OHS) and Harris Hip Score (HHS). Results: Demographic data did not differ between the three study groups (p>0.05). Group B showed a significantly longer operative time (p=0.001). However, complications rate, blood transfusion requirements and length of hospital stay did not differ between the study groups (p>0.05). Addi-tionally, no statistically significant difference (p>0.05) was detected between groups as regard as Patient Reported Out-come Measures (PROMs). Conclusion: Intrathecal dexmedetomidine is superior to both dexamethasone and bupivacaine alone regarding duration of analgesia and pain severity. Moreover, it has more rapid onset and longer duration of sensory blockade. No significant side effects were noted when compared to the remaining groups.

Local Tensile Stress in the Development of Posttraumatic Osteoarthritis.

The pathogenesis of posttraumatic osteoarthritis (PTOA) remains unrevealed. We speculate that cartilage crack caused by joint trauma will induce local abnormal tensile stress, leading to change in extracellular matrix (ECM) expression of chondrocytes, cartilage degeneration, and initiation of osteoarthritis. Finite element model was used to examine whether the local tensile stress could be produced around the crack. Cell experiments were conducted to test the effect of tensile strain on chondrocyte ECM expression. Animal tests in rabbits were carried out to examine the change around the cartilage crack. The results indicated that the local tensile stress was generated around the crack and varied with the crack angles. The maximum principal tensile stress was 0.59 MPa around the 45° crack, and no tensile stress was found at 90°. 10% tensile strain could significantly promote type I collagen mRNA expression and inhibit type II collagen and aggrecan (the proteoglycan core protein) mRNA expression. Type I collagen was detected around the 45° crack region in the cartilage with no change in type II collagen and proteoglycan. We conclude that the local tensile stress produced around the cartilage crack can cause the change in cartilage matrix expression which might lead to cartilage degeneration and initiation of osteoarthritis. This study provides biomechanical-based insight into the pathogenesis of PTOA and potentially new intervention in prevention and treatment of PTOA.

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis.

Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers. Therapeutic effects of a single intra-articular injection of low dose avidin-Dex (0.5mg Dex) were evaluated in rabbits 3 weeks after anterior cruciate ligament transection (ACLT). Immunostaining confirmed that avidin penetrated the full cartilage thickness and was retained for at least 3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene expression to a greater extent than free Dex. It also significantly improved the histological score of cell infiltration and morphogenesis within the periarticular synovium. Micro-computed tomography confirmed the reduced incidence and volume of osteophytes following avidin-Dex treatment. However, neither treatment restored the loss of cartilage stiffness following ACLT, suggesting the need for a combinational therapy with a pro-anabolic factor for enhancing matrix biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG) loss, suggesting the use of higher Dex : avidin ratios in future formulations, such that the delivered avidin dose could be much less than that shown to affect GAGs. This charge-based delivery system converted cartilage into a drug depot that could also be employed for delivery to nearby synovium, menisci and ligaments, enabling clinical translation of a variety of DMOADs.

Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.

Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development. This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.

Total Knee Arthroplasty for Osteoarthritis Secondary to Fracture of the Tibial Plateau. A Prospective Matched Cohort Study

A prospective matched cohort study was performed to compare outcomes of total knee arthroplasties (TKA) between 29 patients with posttraumatic osteoarthritis (POA) after a fracture of tibial plateau and 58 patients underwent routine TKA. Mean follow-up was 6.7years. There were no significant differences in KSS, WOMAC, SF12 scores or range of motion. In the control group there were no complications. In the posttraumatic group, complications occurred in 4 patients (13.7%) (P=0.010) including partial patellar tendon detachment, superficial infection, skin necrosis, and knee stiffness. Only this last patient required revision for manipulation under anesthesia. Also, there was a revision for tibial aseptic loosening in each group. TKA is an effective treatment for POA after tibial plateau fracture. We recommend the prior removal of hardware, as well as tibial tubercle osteotomy when necessary.

Intra-Articular Injection of Hyaluronic Acid Is Not Effective for the Treatment of Post-traumatic Osteoarthritis of the Elbow

Intra-Articular Injection of Hyaluronic Acid Is Not Effective for the Treatment of Post-traumatic Osteoarthritis of the Elbow