Tranexamic acid (TXA) use has become the gold standard in total joint arthroplasty to limit intraoperative blood loss and transfusion rates. More recently, the indications for TXA have expanded to knee and shoulder arthroscopy with promising early results. However, the effectiveness of TXA during arthroscopic rotator cuff repair (RCR) is unclear. Therefore, the purpose of this study was to investigate perioperative outcomes following the use of TXA during RCR.

A systematic review was performed via the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed, MEDLINE, Embase, and Cochrane databases in November 2024. Studies were assessed for quality of visual clarity, operative time, mean arterial pressure (MAP), volume of arthroscopy irrigation used, arthroscopic pump pressure, and clinical outcomes.

A total of 12 clinical trials involving 999 patients were included. 9 studies reported on visual clarity and 6 of these reported improvements in visual clarity with TXA administration. Four studies reported improvements in postoperative pain, however outcomes varied greatly depending on when follow-up assessment occurred. A majority of studies did not report differences in operative time, irrigation volume, or postoperative swelling. There were no venous thromboembolism events reported in the included studies.

TXA dosing during RCR surgery may improve visual clarity, however its effect on other perioperative outcomes remains unclear.

Level I.

This study compared the hemostatic effects and complications of oxidized regenerated cellulose (ORC) and topical TXA in total knee arthroplasty (TKA), thus providing a reference for the use of ORC as an alternative hemostatic agent to TXA in TKA.

A total of 105 patients were included in this study and randomized into blank control, ORC, and TXA groups. The primary outcomes were total blood loss, hemoglobin drop (Hb drop), transfusion rates, and incidence of thrombosis. The secondary outcomes included operation time, tourniquet duration, coagulation parameters, inflammation markers, and complication rates.

Total blood loss was 1,002.47 ± 308.58 ml and 964.68 ± 273.00 ml in the ORC and TXA groups, respectively, both significantly lower than that in the blank control group (1,168.94 ± 405.04 ml) (P 1 = 0.043 and P 2 = 0.014, respectively). Hb Drop was statistically insignificantly different between the ORC (36.03 ± 12.17 g/L) and TXA (34.32 ± 10.19 g/L) groups (P = 0.555). There was no statistically significant difference in transfusion rate, operation time, tourniquet duration, coagulation parameters, inflammation markers, and complication rates among the three groups.

In conclusion, our prospective randomized controlled trial (RCT) highlights that, oxidized regenerated cellulose (ORC) can reduce postoperative invisible blood loss in total knee arthroplasty and achieve a hemostatic effect similar to topical tranexamic acid (TXA). This provides a safe and effective hemostatic option for patients with severe underlying diseases or contraindications to tranexamic acid.

https://www.chictr.org.cn/bin/project/edit?pid=186370, identifier (ChiCTR2200066633).

Background: The aim of our study was to examine the combined effects of tranexamic acid (TXA) and vancomycin powder (VP) on chondrocytes in vitro. Despite the use of TXA and VP being linked to a reduced risk of extensive postoperative blood loss and periprosthetic joint infections (PJIs) in TKA, the possible cytotoxic side effects on periarticular cell types remain unclear. Methods: Human chondrocytes were harvested from hyaline cartilage and expanded in monolayer culture before being simultaneously exposed to different concentrations of TXA and VP for varying exposure times. Cell viability and proliferation were assessed using an ATP assay and an Annexin 5 assay, respectively, while changes in the relative expression of chondrogenic marker genes were examined using semiquantitative RT-PCR. Results: The simultaneous exposure of chondrocytes to TXA and VP for more than 48 h led to a reduction in both cell viability and proliferation rates. When exposing chondrocytes to the lowest examined concentrations of both TXA (10 mg/mL) and VP (3 mg/mL), the observed effects were delayed until 96 h. However, our study found no dependencies of the observed effects on the concentrations tested. Further, we found no effects on the expression of chondrogenic marker genes. Conclusions: Consequently, limiting the exposure time of chondrocytes to TXA and VP in an in vitro setting to 24 h may be considered safe and could help to further improve the understanding of the safe use of substances in vivo. However, further in vitro research is required to develop a comprehensive understanding of the effects of both VP and TXA on important periarticular cell types in TKA, including chondrocytes, osteocytes, and tenocytes.

Tranexamic acid (TXA) is commonly used to reduce perioperative bleeding in various surgeries, including acetabular and pelvic fractures treated with open reduction and internal fixation (ORIF). However, research on TXA's effectiveness and safety in this context is conflicting. To address this, we conducted a systematic review and meta-analysis on TXA's efficacy and safety in patients with acetabular and pelvic fractures undergoing ORIF.

We systematically searched Cochrane, PubMed, and EMBASE databases until August 30, 2023. Our evaluation of TXA focused on 6 domains: estimated blood loss (EBL), blood transfusion units, transfusion rates, thromboembolic events, other complications, and surgery duration. Data from these studies were analyzed using RevMan Manager 5.4.

This study included 4 randomized controlled trials with 179 patients with acetabular and pelvic fractures treated with TXA. The analysis showed that TXA did not significantly reduce EBL, packed red blood cell transfusion units, blood transfusion rates, or surgery duration. There was no significant difference in thromboembolic events or other postoperative complications, like surgical wound issues, pneumonia, heterotopic ossification, and sciatic nerve injuries, between the TXA and control groups.

TXA did not demonstrate a significant benefit in reducing perioperative bleeding or complications in patients treated with ORIF for acetabular and pelvic fractures. The utilization of TXA in such clinical scenarios remains a topic necessitating further rigorous investigation to delineate its role in this clinical setting.

Many different regimes of intravenous and local tranexamic acid (TXA) reduce total blood loss (TBL) in patients undergoing total knee arthroplasty (TKA). However, the most effective TXA regime in reducing blood loss might not be most beneficial for the patient. The aim of the present study was to investigate the effect of commonly used TXA regimes on blood loss and on early clinical outcomes.

We performed this monocentric retrospective study in patients undergoing primary TKA. Primary outcome was the estimated TBL. Secondary outcomes were the rates of adverse events (AE) as well as the range of motion (ROM), mobility and pain intensity during the first three physiotherapy sessions (PTS).

We analysed the data of 1250 TKAs. 5 different TXA regimes were applied. TBL (mean ± SE) was 953 ± 64 ml (2xiv), 999 ± 19 ml (2xiv + 1xlocal), 1075 ± 19 ml (1xiv + 1xlocal), 1191 ± 39 ml (1xlocal) and 1241 ± 48 ml (1xiv) (p < 0.01). In the linear regression model for TBL a lower number of TXA applications was a predictor for increased blood loss (p < 0.01). AE rates were lowest under 2xiv (0%) and 2xiv + 1xlocal (4.8%). Highest mobility and lowest pain intensity were observed under 1x iv and 2x iv. The largest portions of fully mobile patients on day three were observed under 1xiv (100%), 2xiv (100%) and 2xiv + 1local TXA (86.9%).

Our results suggest that multiple applications of TXA are more effective in decreasing blood loss than excessive dosing of TXA. Interestingly, local use of TXA might be associated with higher pain intensity and decreased mobility on the first days after surgery.

Several studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model.

We tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM).

When TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin.

We confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.

The aim of this study was to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) for reducing blood loss in patients undergoing total knee replacement.

A retrospective study of 530 individuals with a mean age of 71.44 years was performed after posterior stabilized total knee arthroplasty. Patients were divided into three groups according to the method of bleeding control: I - patients without an additional bleeding protocol (control group); II - patients receiving IV TXA (TXA group); and III - patients receiving the exact TXA protocol plus intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured according to the maximal decrease in Hb compared to the preoperative Hb level.

The mean hospitalization duration was 7.02 (SD 1.34) days in the control group, 6.08 (SD 1.06) days in the TXA group, and 5.56 (SD 0.79) in the TXA + LIA group. The most significant decrease in haemoglobin was found in the control group, which was an average of 30.08%. The average decrease in haemoglobin was 25.17% (p < 0.001) in the TXA group and 23.67% (p < 0.001) in the TXA + LIA group. A decrease in the rate of allogeneic blood transfusions was observed: 24.4% in the control group, 9.9% in the TXA group, and 8% in the TXA + LIA group (p < 0.01).

Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia significantly reduced blood loss in patients after total knee replacement.

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.

To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice.

Controlled laboratory study.

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.

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.

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.

TXA might be beneficial in patients with posttraumatic OA of the knee.

Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection.

To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point).

The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively).

Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration.

It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus.

To show the effects of tranexamic acid, which is a drug frequently used to control bleeding, on the hip joint and sciatic nerve in animal experiments. There were 15 rats in each of the 3 groups, with a total of 45 rats. Topical saline injections were applied to the first group, topical TXA injections to the second group, and intravenous (IV) TXA injections to the third group. In the samples taken from the hip joint 3 weeks later, femoral head cartilage, sciatic nerve, and joint capsule thicknesses were analyzed histologically. Statistically significantly more cartilage degradation was detected in the femoral head cartilage in both the IV and intraarticular TXA group when compared to the control group. The groups were also compared in terms of acetabular cartilage; however, no histological difference was found between the groups. It was seen that when the femoral head cartilage thickness (the average of the measurements made from 3 different points were used) was examined, the cartilage thickness in the topical TXA group was less when compared to the other 2 groups. However, this difference was determined to not be statistically significant. The data of the hip joint capsule thickness measurement, it was found that the capsule thickness in the topical TXA applied group was less when compared to the other 2 groups. However, this difference was not statistically significant. When the sciatic nerves in all 3 groups were compared, no different staining characteristics were found in the immunofluorescence examination. TXA, which is frequently used in orthopedic practice, shows negative effects on hip joint cartilage in both topical and intravenous application.

In this study, the effects of tranexamic acid (TXA) on the knee's articular cartilage, anterior cruciate ligament (ACL), and joint capsule were assessed histologically. There were 15 rats in each of the 3 groups, totaling 45 rats. Intraarticular (IA) saline injections were applied for the first group, IA TXA injections for the second group, and intravenous (IV) TXA injections for the third group. Using samples taken from the knee joint 3 weeks later, the medial/lateral femoral condyle and medial/lateral tibial plateau articular cartilages were evaluated with Osteoarthritis Research Society International (OARSI) scoring, while ACL diameter and joint capsule thickness were analyzed histologically. In comparisons of OARSI scores for the medial/lateral femoral condyle and medial/lateral tibial plateau cartilage regions, the scores obtained for the IV TXA group were significantly higher than those of the IA saline group (P < 0.001, P = 0.001, P = 0.003, P = 0.011). In comparisons of medial/lateral femoral condyle and medial/lateral tibial plateau OARSI scores, the scores obtained for the IV TXA group were again significantly higher than those of the IA TXA group (P < 0.001, P < 0.001, P < 0.001, P = 0.002). When ACL diameters were compared, a significant decrease was observed in the ACL diameters of the IV TXA group compared to the IA saline and IA TXA groups (P < 0.001, P = 0.039). Histologically, IV TXA damages the articular cartilage and ACL more than IA TXA. IA administration of TXA is more protective when the articular cartilage and ACL are preserved.

The use of periarticular (PA) tranexamic acid (TXA) and its efficacy in comparison with intra-articular (IA) TXA have not been well explored in the literature. This retrospective cohort study aimed to compare the effects of IA and PA TXA with analgesic components in reducing blood loss and improving immediate postoperative pain relief and functional outcomes in patients after unilateral primary total knee arthroplasty (TKA).

A total of 63 patients underwent TKA, and they were divided into the IA TXA delivery group ( n = 42) and PA TXA delivery group ( n = 21). All patients were administered 1 g of TXA. They also received pericapsular infiltration consisting of 0.5 mL of adrenaline, 0.4 mL of morphine, 1 g of vancomycin, 1 mL of ketorolac and 15 mL of ropivacaine. Outcomes for blood loss and surrogate markers for immediate functional recovery were measured.

Of the 63 patients, 54% were female and 46% male. The mean drop in postoperative haemoglobin levels in the PA and IA groups was 2.0 g/dL and 1.6 g/dL, respectively, and this was not statistically significant ( P = 0.10). The mean haematocrit drop in the PA and IA groups was 6.1% and 5.3%, respectively, and this was also not statistically significant ( P = 0.58). The postoperative day (POD) 1 and discharge day flexion angles, POD 1 and POD 2 visual analogue scale (VAS) scores, gait distance on discharge and length of hospitalisation stay were largely similar in the two groups.

Our study showed that both IA and PA TXA with analgesic components were equally efficient in reducing blood loss and improving immediate postoperative pain relief and functional outcomes.

Tranexamic acid (TXA) has been studied extensively during the last 5-8 years. It inhibits clot dissolution during surgery and can therefore reduce blood loss. However, there has been concern that this could result in more frequent complications, specifically in terms of thromboembolic events. The indications for TXA are widespread, and this review covers the literature on orthopaedic indications such as joint replacement, fracture surgery, and arthroscopic procedures. In general, TXA is safe and can be used in a wide variety of orthopaedic procedures, lowering blood loss without increasing the risk of complications.

Knee arthroscopic arthrolysis serves as an effective treatment for knee arthrofibrosis. However, hemarthrosis is the most common complication in arthroscopic surgery, which has potential adverse effects on postoperative rehabilitation. The purpose of this study was to evaluate the effects of topical tranexamic acid (TXA) in knee arthroscopic arthrolysis.

A total of 87 patients with knee arthrofibrosis who underwent arthroscopic arthrolysis from September 2019 to June 2021 were eligible for this retrospective review. Patients in the TXA group (n = 47) received topical administration of TXA (50 mL, 10 mg/mL) at the end of the surgery, and patients in the control group (n = 40) received no TXA. The postoperative drainage volumes, hematologic levels, inflammatory marker levels, knee range of motion (ROM), visual analog scale (VAS) pain scores, Lysholm knee scores and complications were compared between the two groups. The curative effect of each group was calculated according to Judet's criteria.

The mean drainage volumes on postoperative day (POD) 1 and POD 2, and total drainage volume were significantly lower in the TXA group than in the control group (P < 0.001 for all). The TXA group had significantly lower postoperative CRP and IL-6 levels on POD 1 and POD 2, and at postoperative week (POW) 1 and POW 2 than the control group. The VAS pain scores in the TXA group were significantly lower on POD 1 and POD 2, and at POW 1 and POW 2 than those in the control group (P < 0.001 for all). Patients in the TXA group showed better postoperative ROM and Lysholm knee scores at POW 1 and POW 2. No patient had any complications such as deep venous thrombosis (DVT) or infection. The excellent and good rates of knee arthroscopic arthrolysis were comparable between the two groups at the sixth postoperative month (P = 0.536).

Topical administration of TXA in knee arthroscopic arthrolysis can reduce postoperative blood loss and inflammatory response, alleviate early postoperative pain, increase early postoperative knee ROM, and improve early postoperative knee function without increased risks.

Tranexamic acid (TXA) has been used surgically to decrease blood loss. The ability of TXA to improve arthroscopic visualization and allow for reduction in pump pressure is unknown. The purpose of this study was to determine the effect of intravenous (IV) TXA on change in pump pressure and visualization during arthroscopic rotator cuff repair.

This was a single-center, prospective, randomized, double-anonymized controlled trial. Patients with full-thickness rotator cuff tears undergoing operative repair were enrolled. Patients were randomized to receive 1 g of IV TXA preoperatively or no TXA (control group). All patients underwent arthroscopy using saline irrigation fluid with 3 mL epinephrine injected into the first 1000-mL saline bag. Total operative time, final pump pressure, number of increases in pump pressure, total amount of irrigation fluid used, blood pressure and anesthesia medical interventions for blood pressure were recorded. Visualization was measured by a visual analog scale (VAS) completed by the surgeon at the end of the case. Postoperative VAS pain scores were obtained 24 hours after surgery. The primary aim of this study was to investigate the effect that IV TXA has on change in pump pressure (ΔP) during shoulder arthroscopy, with a ΔP of 15 mm Hg set as a threshold for clinical significance.

There were 50 patients randomized to the TXA group and 50 patients in the no TXA group. No significant differences were found between the TXA group and the control group regarding any measure of pump pressure, including the final arthroscopic fluid pump pressure (44.5 ± 8.1 mm Hg vs. 42.0 ± 8.08 mm Hg, P = .127), the mean ΔP (20.9 ± 10.5 mm Hg vs. 21.8 ± 8.5 mm Hg, P = .845), or the number of times a change in pump pressure was required (1.7 ± 0.9 vs. 1.7 ± 0.8, P = .915). Overall arthroscopic visualization was not significantly different between the TXA group and the control group (7.2 ± 1.8 vs. 7.4 ± 1.6, P = .464). No significant difference existed between the TXA and control groups regarding postoperative pain scores assessed by VAS pain scale (4.1 ± 2.0 vs. 4.3 ± 1.9, P = .519) at 24 hours after surgery.

The use of IV TXA demonstrated no measurable improvement in surgeon ability to maintain a lower pump pressure during arthroscopic rotator cuff repair. Additionally, there was no measurable improvement in arthroscopic visualization or early pain scores.

Tranexamic acid (TXA) is an antifibrinolytic agent applied in orthopedic surgery and has been proven to reduce post-surgery infection rates. We previously showed that TXA also had an additional direct antimicrobial effect against planktonic bacteria. Therefore, we aimed to evaluate whether it has a synergistic effect if in combination with antibiotics.

Three ATCC and seven clinical strains of staphylococci were tested against serial dilutions of vancomycin and gentamicin alone and in combination with TXA at 10 and 50 mg/ml. The standardized microtiter plate method was used. Minimal inhibitory concentrations (MICs) were calculated by standard visualization of well turbidity (the lowest concentration at which complete absence of well bacterial growth was observed by the researcher) and using the automated method (the lowest concentration at which ≥80% reduction in well bacterial growth was measured using a spectrophotometer).

Tranexamic acid-10 mg/ml reduced the MIC of vancomycin and gentamicin with both the standard method (V: 1-fold dilution, G: 4-fold dilutions) and the automated turbidity method (vancomycin: 8-fold dilutions, gentamicin: 8-fold dilutions). TXA-50 mg/ml reduced the MIC of gentamicin with both the standard turbidity method (6-fold dilutions) and the automated turbidity method (1-fold dilutions). In contrast, for vancomycin, the MIC remained the same using the standard method, and only a 1-fold dilution was reduced using the automated method.

Ours was a proof-of-concept study in which we suggest that TXA may have a synergistic effect when combined with both vancomycin and gentamicin, especially at 10 mg/ml, which is the concentration generally used in clinical practice.

Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery.

Male Sprague-Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery.

Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28.

Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.

Osteoarthritis (OA) is the most common degenerative joint disease. Rapamycin is a potential candidate for OA treatment by increasing the autophagy process implicated in its physiopathology. To optimize Rapamycin profit and avoid systemic side effects, intra-articular (i.a.) administration appeared helpful. However, Rapamycin's highly hydrophobic nature and low bioavailability made it challenging to develop purpose-made drug delivery systems to overcome these limitations. We developed Rapamycin-loaded nanoparticles (NPs) using poly (lactic-co-glycolic acid) by emulsion/evaporation method. We evaluated these NPs' cytocompatibility towards cartilage (chondrocytes) and synovial membrane cells (synoviocytes) for a potential i.a. administration. The in vitro characterization of Rapamycin-loaded NPs had shown a suitable profile for an i.a. administration. In vitro biocompatibility of NPs was highlighted to 10 µM of Rapamycin for both synoviocytes and chondrocytes, but significant toxicity was observed with higher concentrations. Besides, synoviocytes are more sensitive to Rapamycin-loaded NPs than chondrocytes. Finally, we observed in vitro that an adapted formulated Rapamycin-loaded NPs could be safe at suitable i.a. injection concentrations. The toxic effect of Rapamycin encapsulated in these NPs on both articular cells was dose-dependent. After Rapamycin-loaded NPs i.a. administration, local retention, in situ safety, and systemic release should be evaluated with experimental in vivo models.

Tranexamic acid (TXA), an antifibrinolytic drug, is usually administered intravenously; however, intra-articular administration has recently been proven to be as effective as intravenous administration. Limited information regarding the pharmacokinetics (PK) of TXA after intra-articular administration has been reported.

The aim of this study was to develop a population PK model of TXA administered as a single intra-articular dose and as two intravenous doses, and to study the sources of interindividual variability (IIV) in the PK processes of TXA. The developed model was used to simulate PK profiles of TXA at different dosage regimens and in patients with renal impairment.

Patients who underwent primary unilateral total knee replacement (TKR) received 1 g/10 mL (concentration of 100 mg/mL) of TXA applied directly to the surgical field before wound closure, or 2 g (two doses of 1 g) of intravenous TXA. A population PK model was developed using a nonlinear mixed-effects approach and sources of IIV, such as sex, age, body weight, height, body mass index (BMI), preoperative haemoglobin, preoperative haematocrit, and creatinine clearance.

Twenty-four patients were included, 12 in each group. Twenty patients were female, mean age (standard deviation) was 73.7 years (5.6). The disposition of TXA was best described as a two-compartment model with clearance dependent on creatinine clearance. Bootstrap results indicated that the model was stable and robust. The estimated bioavailability for intra-articular administration was 81%. Simulations indicated that 100% of patients would have plasma concentrations associated with partial fibrinolysis at 8 h post-administration with the dosages and routes of administration used in the present study. Intra-articular administration would produce complete inhibition of fibrinolysis in only 12% of patients compared with 72.5% with intravenous administration. No adverse events were reported.

This population PK model demonstrated that a single dose of high-concentration, low-volume intra-articular TXA can achieve antifibrinolytic plasma concentrations of the drug for 8 h, providing both local and systemic effects in patients undergoing TKR. TXA administration to the surgical field could be an alternative to the intravenous; route for patients undergoing TKR; however, clinical studies are needed to assess the toxic local effects of TXA.

Spanish Clinical Studies Registry Number: 2017-004059-22. Date of registration: 12 April 2018.

In spinal surgery, considerable blood loss is increasingly treated with the local application of tranexamic acid (TXA). However, little is known about its cytotoxicity and effect on human fibroblasts. This study was to identify the effect of TXA solution on human fibroblast at different concentrations and exposure times in vitro.

To mimic the actual clinical situation, human fibroblasts were subjected to both limited and chronic exposure to various clinically relevant concentrations of TXA to mimic different ways of topical administration. At time points after treatment, the viability, proliferation, apoptosis, collagen synthesis, adhesion, and migration of fibroblasts were analyzed in vitro.

Limited exposure (10 minutes) to a high concentration of TXA (100 mg/mL) did not affect the viability, proliferation, and apoptosis of fibroblasts, and chronic exposure to low concentration of TXA (≤12.5 mg/mL) exerted little effect on viability, proliferation, apoptosis, collagen synthesis, adhesion, and migration of human fibroblasts (P > 0.05). However, the chronic exposure to a high concentration of TXA (≥25 mg/mL) can inhibit the viability, proliferation, collagen synthesis, adhesion and migration, and induce apoptosis of fibroblasts.

Although limited exposure to high concentration of TXA and chronic exposure to low concentration of TXA exerted little effect on fibroblasts, chronic exposure to high concentration of TXA can lead to fibroblast injury.