Macrophage Membrane-Biomimetic Multi-Layered Nanoparticles Targeting Synovial Angiogenesis for Osteoarthritis Therapy.

Osteoarthritis (OA) is an inflammatory and progressive joint disease characterized by angiogenesis-mediated sustained, chronic, and low-grade synovitis. Anti-angiogenesis is emerging as a strategy for attenuating OA progression, but is often compromised by poor targeted drug delivery and immune clearance. Recent studies have identified macrophages formed a "protective barrier" in the lining layer (LL) of synovium, which blocked the communication of joint cavity and sublining layer (SL) of synovium. Inspired by natural mimicry, macrophage membrane-camouflaged drug delivery is explored to avoid immune clearance. Based on the single cell RNA sequencing, the CD34+ synovial cells are identified as "sentinel cells" for synovium angiogenesis. Consequently, CD34 antibody-modified macrophage membrane is constructed to target new angiogenesis. Hence, a biomimetic multi-layered nanoparticle (NP) is developed that incorporates axitinib-loaded poly(lactic-co-glycolic) acid (PLGA) with CD34 antibody modified macrophage membrane (Atb@NP@Raw@CD34) to specifically deliver axitinib (Atb) to the SL and sustain inhibiting angiogenesis without immune elimination. It is found that the Atb@NP@Raw@CD34 can pass through macrophage "barrier", specifically targeting CD34+ cells, continuously releasing Atb and anti-angiogenesis in OA synovitis. Furthermore, in vivo data demonstrated that Atb@NP@Raw@CD34 can attenuate joint degeneration by inhibiting synovium angiogenesis-mediated synovitis. In conclusion, local injection of Atb@NP@Raw@CD34 presents a promising approach for clinically impeding OA progression.

Lubricin-Inspired Nanozymes Reconstruct Cartilage Lubrication System with an "In-Out" Strategy.

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly-2-acrylamide-2-methylpropanesulfonic acid sodium salt-grafted aminofullerene, is developed to restore the cartilage lubrication system using an "In-Out" strategy. The "Out" aspect involves reducing friction through a combination of hydration lubrication and ball-bearing lubrication. Simultaneously, the "In" aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions.

Improving insulin resistance by sulforaphane via activating the Bacteroides and Lactobacillus SCFAs-GPR-GLP1 signal axis.

Background: Insulin resistance (IR) is closely associated with non-alcoholic fatty liver disease (NAFLD), and the gut microbiome contributes to the development of NAFLD. Sulforaphane (SFN) is a phytochemical in cruciferous vegetables that could improve lipid metabolism disorder. However, whether SFN can alleviate IR in NAFLD by regulating the intestinal flora remains unclear. Methods: SFN was administered to high fat diet (HFD)-fed Wistar rats for 10 weeks. Gut microbiota was analysed by 16S rRNA sequencing and the short chain fatty acids (SCFAs) by gas chromatography. The expression of tight junction protein and the numbers of Lactobacillus, Bacteroides and Bifidobacterium were determined by qPCR. The expression of G-protein-coupled receptor 41/43 (GPR41/43) was determined by western blot. A randomized controlled trial (RCT) was conducted in NAFLD patients with broccoli seed tablets (rich in SFN, 42 mg d-1) as intervention for 12 weeks. Thirty-six volunteers with abnormal glucose before the broccoli seed tablet treatment were selected in the intervention group to analyze their blood glucose, insulin, homeostasis model assessment-insulin resistance index (HOMA-IRI), homeostasis model assessment-insulin sensitivity index (HOMA-ISI) and glucagon-like peptide (GLP-1). Results: SFN reduced blood glucose and HOMA-IRI while increasing insulin sensitivity in HFD rats. SFN reduced glycogen synthase kinase 3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK) activity, and phosphorylation of serine residues of IRS-2 induced by HFD. SFN reshaped the gut microbiota composition of HFD-induced rats and, especially, increased the content of Bacteroidaceae, Lactobacillaceae and Bifidobacteriaceae, which are related to the improvement from SFN of the blood glucose and HOMA-IRI. The increased numbers of Bacteroides and Lactobacillus were the targets of SFN to enhance the expression of tight junction proteins ZO-1 and occludin, thereby lowering lipopolysaccharide content to reduce inflammation, ultimately alleviating IR. Bacteroides and Lactobacillus produced SCFAs, which activated GPR41/43 to secrete GLP1. Moreover, it was also confirmed in RCT that SFN intervention increased the level of GLP1 in NAFLD patients, which was positively correlated with the reduction of blood glucose and HOMA-IR. Conclusions: SFN alleviated IR in NAFLD via the Bacteroides and Lactobacillus SCFAs-GPR41/43-GLP1 axis and protected the intestinal mucosal barrier to decrease inflammation.

Bone and Joint-on-Chip Platforms: Construction Strategies and Applications.

Organ-on-a-chip, also known as "tissue chip," is an advanced platform based on microfluidic systems for constructing miniature organ models in vitro. They can replicate the complex physiological and pathological responses of human organs. In recent years, the development of bone and joint-on-chip platforms aims to simulate the complex physiological and pathological processes occurring in human bones and joints, including cell-cell interactions, the interplay of various biochemical factors, the effects of mechanical stimuli, and the intricate connections between multiple organs. In the future, bone and joint-on-chip platforms will integrate the advantages of multiple disciplines, bringing more possibilities for exploring disease mechanisms, drug screening, and personalized medicine. This review explores the construction and application of Organ-on-a-chip technology in bone and joint disease research, proposes a modular construction concept, and discusses the new opportunities and future challenges in the construction and application of bone and joint-on-chip platforms.

Nano-Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications.

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron-scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro-robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano-micron combinations are summarized, and the latest applications of these advanced nano-micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano-micron combined HMs are provided.

Microvesicles-hydrogel breaks the cycle of cellular senescence by improving mitochondrial function to treat osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of increasing senescent cells. Stem cell therapy has proven effective in addressing cellular senescence, however, it still has issues such as immune rejection and ethical concerns. Microvesicles (MVs) constitute the primary mechanism through which stem cell therapy exerts its effects, offering a cell-free approach that circumvents these risks and has excellent anti-ageing potential. Nonetheless, MVs have a short in vivo half-life, and their secretion composition varies considerably under diverse conditions. This study aims to address these issues by constructing a ROS-responsive hydrogel loaded with pre-stimulant MVs. Through responding to ROS levels this hydrogel intelligently releases MVs, and enhancing mitochondrial function in chondrocytes to improving cellular senescence. RESULT: We employed Interferon-gamma (IFN-γ) as a stem cell-specific stimulus to generate IFN-γ-microvesicles (iMVs) with enhanced anti-ageing effects. Simultaneously, we developed a ROS-responsive carrier utilising 3-aminophenylboronic acid (APBA)-modified silk fibroin (SF) and polyvinyl alcohol (PVA). This carrier served to protect MVs, prolong longevity, and facilitate intelligent release. In vitro experiments demonstrated that the Hydrogel@iMVs effectively mitigated cell senescence, improved mitochondrial function, and enhanced cellular antioxidant capacity. In vivo experiments further substantiated the anti-ageing capabilities of the Hydrogel@iMVs. CONCLUSION: The effect of MVs can be significantly enhanced by appropriate pre-stimulation and constructing a suitable carrier. Therefore, we have developed a ROS-responsive hydrogel containing IFN-γ pre-stimulated iMVs to target the characteristics of ageing chondrocytes in OA for therapeutic purposes. Overall, this novel approach effectively improving mitochondrial dysfunction by regulating the balance between mitochondrial fission and fusion, and the accumulation of reactive oxygen species was reduced, finally, alleviates cellular senescence, offering a promising therapeutic strategy for OA.

Injectable smart stimuli-responsive hydrogels: pioneering advancements in biomedical applications.

Hydrogels have established their significance as prominent biomaterials within the realm of biomedical research. However, injectable hydrogels have garnered greater attention compared with their conventional counterparts due to their excellent minimally invasive nature and adaptive behavior post-injection. With the rapid advancement of emerging chemistry and deepened understanding of biological processes, contemporary injectable hydrogels have been endowed with an "intelligent" capacity to respond to various endogenous/exogenous stimuli (such as temperature, pH, light and magnetic field). This innovation has spearheaded revolutionary transformations across fields such as tissue engineering repair, controlled drug delivery, disease-responsive therapies, and beyond. In this review, we comprehensively expound upon the raw materials (including natural and synthetic materials) and injectable principles of these advanced hydrogels, concurrently providing a detailed discussion of the prevalent strategies for conferring stimulus responsiveness. Finally, we elucidate the latest applications of these injectable "smart" stimuli-responsive hydrogels in the biomedical domain, offering insights into their prospects.

The application and prospects of 3D printable microgel in biomedical science and engineering.

Three-dimensional (3D) bioprinting technology is one of the most advanced techniques currently applied in tissue engineering and regenerative medicine and has developed rapidly in the past few years. Despite many breakthroughs, there are still several challenges of 3D bioprinting technology awaiting to be addressed, and one of them is the urgency of optimizing bioinks (natural or synthetic hydrogel), which are critical elements in 3D bioprinting, for specific properties. Different from traditional hydrogels, microgels, which are a new type of bioink, are micron-sized gels with excellent mechanical and biological properties, which make them great candidates for applications in 3D bioprinting. Different from the dense and limited pore size of traditional hydrogels, the pore structure of microgel is adjustable, enabling better cell loading before 3D bioprinting, and the printed pores are conducive to the exchange of metabolic substances and cell migration. The "bottom-up" modular microgel has stronger customizable characteristics, and it can freely adjust its mechanical properties, such as hardness, toughness, and rheological properties. In this review, we review the application of microgels in the field of biomedicine and discuss the future development of microgels in 3D bioprinting.

An ultra-sensitive photoelectrochemical sensor for chlorpyrifos detection based on a novel BiOI/TiO2 n-n heterojunction.

Due to widespread application of chlorpyrifos for controlling pests in agriculture, the continuous accumulation of chlorpyrifos residue has caused serious environmental pollution.The detection of chlorpyrifos is of great significance for humans and environment because it can arise a series of diseases by inhibiting acetylcholinesterase (AChE) activity. Photoelectrochemical sensing, as an emerging sensing technology, has great potential in the detection of chlorpyrifos. It is urgent that find a suitable photoelectric sensing strategy to effectively monitor chlorpyrifos. Herein, an n-n heterojunction was constructed by uniformly immobilizing n-type 3DBiOI, which had loose porous structure composed of numerous small and thin nanosheets, on the surface of TiO2 with anatase/rutile (AR-TiO2) heterophase junction. Under light irradiation, the proposed BiOI/AR-TiO2 n-n heterojunction exhibited excellent optical absorption characteristics and photoelectrochemical activity. Additionally, the photoelectrochemical sensing platform demonstrated excellent analytical performance in monitoring chlorpyrifos. Under optimized conditions, it showed a wide detection range of 1 pg mL-1- 200 ng mL-1 and a detection limit (S/N = 3) as low as 0.24 pg mL-1, with superior selectivity and stability. The ultra-sensitivity and great specificity for detection of chlorpyrifos can be ascribed to chelation between Bi (Ⅲ) and C=N and P=S bonds in chlorpyrifos, which had been confirmed in this work. Meanwhile, the PEC sensor also had potential application value for monitoring chlorpyrifos in water samples, lettuce and pitaya, which the recoveries of samples ranged from 96.9% to 104.7% with a relative standard deviation (RSD) of 1.11%-5.93%. This sensor provided a novel idea for constructing heterojunctions with high photoelectric conversion efficiency and had a high application prospect for the detection of chlorpyrifos and other structural analogues.

The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype.

Macrophages (Mφs) play a crucial role in the pathological progression of osteoarthritis (OA) by regulating inflammation and tissue repair. Decreasing pro-inflammatory M1-Mφs and increasing anti-inflammatory M2-Mφs can alleviate OA-related inflammation and promote cartilage repair. Apoptosis is a natural process associated with tissue repair. A large number of apoptotic bodies (ABs), a type of extracellular vesicle, are produced during apoptosis, and this is associated with a reduction in inflammation. However, the functions of apoptotic bodies remain largely unknown. In this study, we investigated the role of M2-Mφs-derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in a mouse model of OA. Our data show that M2-ABs can be targeted for uptake by M1-Mφs, and this reprograms M1-to-M2 phenotypes within 24 h. The M2-ABs significantly ameliorated the severity of OA, alleviated the M1-mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis in mice. RNA-seq revealed that M2-ABs were enriched with miR-21-5p, a microRNA that is negatively correlated with articular cartilage degeneration. Inhibiting the function of miR-21-5p in M1-Mφs significantly reduced M2-ABs-guided M1-to-M2 reprogramming following in vitro cell transfection. Together, these results suggest that M2-derived apoptotic bodies can prevent articular cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response caused by M1 macrophages. The mechanism underlying these findings may be related to miR-21-5p-regulated inhibition of inflammatory factors. The application of M2-ABs may represent a novel cell therapy, and could provide a valuable strategy for the treatment of OA and/or chronic inflammation.

Injectable Self-Setting Ternary Calcium-Based Bone Cement Promotes Bone Repair.

Bone defects, especially large ones, are clinically difficult to treat. The development of new bone repair materials exhibits broad application prospects in the clinical treatment of trauma. Bioceramics are considered to be one of the most promising biomaterials owing to their good biocompatibility and bone conductivity. In this study, a self-curing bone repair material having a controlled degradation rate was prepared by mixing calcium citrate, calcium hydrogen phosphate, and semi-hydrated calcium sulfate in varying proportions, and its properties were comprehensively evaluated. In vitro cell experiments and RNA sequencing showed that the composite cement activated PI3K/Akt and MAPK/Erk signaling pathways to promote osteogenesis by promoting the proliferation and osteoblastic differentiation of mesenchymal stem cells. In a rat model with femoral condyle defects, the composite bone cement showed excellent bone repair effect and promoted bone regeneration. The injectable properties of the composite cement further improved its practical applicability, and it can be applied in bone repair, especially in the repair of irregular bone defects, to achieve superior healing.

Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.

BACKGROUND: Psoralea corylifolia is a medicinal leguminous plant that has long been used to treat various diseases. Psoralidin (PSO) is the main extract compound of P. corylifolia and exhibits antibacterial, antitumor, anti-inflammatory, antioxidant, and other pharmacological activities. PSO has demonstrated inhibitory effects in several cancers; however, its inhibitory effect on osteosarcoma has not been reported. This study aimed to evaluate the inhibitory effect of PSO on osteosarcoma and elucidate the underlying molecular mechanisms. METHODS: Crystal violet, cell counting kit-8 (CCK8), and 5-Ethynyl-2'-deoxyuridine (EdU) staining assays were used to assess the inhibitory effect of PSO on the proliferation of 143B and MG63 osteosarcoma cells. Wound healing and Transwell assays were conducted to evaluate the effects of PSO on osteosarcoma cell migration and invasion. The cell cycle and apoptosis were analyzed using flow cytometry. To determine the possible molecular mechanisms, RNA-sequencing was performed and protein expression was analyzed by western blotting. The inhibitory effect of PSO on osteosarcoma in vivo was analyzed using a mouse model of orthotopic osteosarcoma and immunohistochemistry. RESULTS: PSO inhibited osteosarcoma cell proliferation in a concentration-dependent manner, inhibited cell migration and invasion, and induced cell-cycle arrest and apoptosis. Mechanistically, PSO treatment significantly inhibited the focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways by downregulating ITGB1 expression in both MG63 and 143B cells. Furthermore, we demonstrated that PSO restrained osteosarcoma growth in vivo. CONCLUSION: PSO may suppress osteosarcoma via the FAK and PI3K/Akt signaling pathways by downregulating ITGB1 expression.

Total Hip Arthroplasty Patients with Distinct Postoperative Fibrinolytic Phenotypes Require Different Antifibrinolytic Strategies.

Bleeding patients exhibit different fibrinolytic phenotypes after injury, and the universal use of tranexamic acid (TXA) is doubted. We aimed to evaluate the efficacy of postoperative antifibrinolytic treatment in total hip arthroplasty (THA) patients with different fibrinolytic phenotypes. A retrospective analysis was conducted in 238 patients who underwent THA. Patients were divided into two groups by different fibrinolytic phenotypes (non-fibrinolytic shutdown and fibrinolytic shutdown), determined by the LY30 level on postoperative day 1 (POD1). The two groups were further stratified into four sub-groups based on different postoperative TXA regimens (Group A received no TXA postoperatively, while Group B did). Hidden blood loss (HBL), decline of hemoglobin (ΔHb), D-dimer (D-D), fibrinogen/fibrin degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), and demographics were collected and compared. The clinical baseline data were comparable between the studied groups. In patients who presented non-fibrinolytic shutdown postoperatively, Group B suffered significantly lower HBL and ΔHb than Group A on POD3 and POD5. In patients who presented postoperative fibrinolytic shutdown, Group B failed to benefit from the postoperative administration of TXA when compared to Group A. No difference was found in postoperative levels of D-D, FDP, PT, and APTT. Postoperative antifibrinolytic therapy is beneficial for THA patients who presented non-fibrinolytic shutdown postoperatively, while the efficacy and necessity should be considered with caution in those with fibrinolytic shutdown. LY30 is a promising parameter to distinguish different fibrinolytic phenotypes and guide TXA administration. However, further prospective studies are needed to confirm these findings.

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis.

Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication. However, these boundary layers can be damaged by shear, resulting in decreased lubrication. Here, a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib (CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid (HA) hydrogels (CLX@Lipo@HA-gel). The dynamic cross-linked network enables the hydrogel to get restructured in response to shear, and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces, which results in the formation of boundary layers to provide stable lubrication. Moreover, hydration shells formed surrounding the hydrogel can retard the degradation process, thus helping in sustaining lubrication. Furthermore, in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance, alleviate cartilage wear, and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication. Overall, CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis.

Circular RNA circRNF169 functions as a miR-30c-5p sponge to promote cellular senescence.

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-ß-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.

Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis.

Introducing hydration layers to hydrogel microspheres (HMs) by coating the surface with liposomes can effectively reduce friction. However, the lubrication can be inactivated when the surface coatings are damaged. To endow HMs with the ability to form self-renewable hydration layers and maintain cellular homeostasis, rapamycin-liposome-incorporating hyaluronic acid-based HMs (RAPA@Lipo@HMs) were created using microfluidic technology and photopolymerization processes. The RAPA@Lipo@HMs improve joint lubrication by using a smooth rolling mechanism and continuously exposing liposomes on the outer surface to form self-renewable hydration layers via frictional wear. In addition, the released autophagy activator (rapamycin)-loaded cationic liposomes can target negatively charged cartilage through electrostatic interactions and maintain cellular homeostasis by increasing autophagy. Furthermore, the in vivo data showed that the RAPA@Lipo@HMs can alleviate joint wear and delay the progression of osteoarthritis. The RAPA@Lipo@HMs can provide efficient lubrication and potentially alleviate friction-related diseases such as osteoarthritis.

Not all patients benefit from the postoperative antifibrinolytic treatment: clinical evidence against the universal use of tranexamic acid following total knee arthroplasty.

BACKGROUND: The empirical use of tranexamic acid (TXA) for bleeding remains controversial because of the distinct fibrinolytic phenotypes observed after injury. This study sought to assess the efficacy of postoperative TXA in patients presenting with different fibrinolytic phenotypes after total knee arthroplasty (TKA). METHODS: This retrospective study included 270 patients who underwent primary TKA. The patients were divided into two groups: Group A, received no postoperative TXA, and Group B, received postoperative TXA; they were further categorized into four subgroups based on postoperative fibrinolytic phenotypes (non-fibrinolytic shutdown [NFSD] and fibrinolytic shutdown [FSD]). Fibrinolytic phenotypes were determined using percentage of clot lysis 30 min after maximum strength (LY30) level measured on postoperative day 1 (POD1). Data on perioperative hidden blood loss (HBL), decrease in the hemoglobin level (ΔHb), allogeneic blood transfusion (ABT) rate, fibrin degradation product (FDP) level, D-dimer (D-D) level, prothrombin time (PT), and activated partial thromboplastin time (APTT) as well as clinical baseline data were collected and compared. RESULTS: No differences in baseline clinical data were noted. Among patients presenting with NFSD, those in Group B had significantly lower HBL and ΔHb on POD1 and POD3 than those in Group A. Among patients presenting with FSD, perioperative HBL and ΔHb were similar between the two groups. No differences were observed in perioperative ABT rate, FDP level, D-D level, PT, and APTT. CONCLUSIONS: Patients exhibit various fibrinolytic phenotypes after TKA. Postoperative antifibrinolytic strategies may be beneficial for patients presenting with NFSD, but not for those presenting with FSD. The LY30 level may guide targeted TXA administration after TKA. However, well-designed prospective randomized controlled trials are needed to obtain more robust data.