The development of renal-targeting delivery systems has shown great potential to improve the therapeutic efficacy to treat kidney diseases. However, current nanocarriers often exhibit poor targeting efficiency or short renal retention, limiting their use in drug delivery. Herein, we report the simplified preparation of poly(DL-serine) (PSer) bearing hydroxyl side chains, which showed enhanced accumulation in kidney in the first several hours post intravenous injection. Starting from unprotected amino acids, the hydrophilic polypeptides were prepared in a two-step synthesis without tedious protection/deprotection procedures. With the improved uptake by renal tubular epithelial cells, PSer outperformed its threonine analogue, with the kidney-to-liver ratio of up to 7.7 (∼9% injected dose in kidney). Finally, the conjugates of PSer with dexamethasone exhibited enhanced therapeutic efficacy than free drug in an animal model of acute kidney injury. We believe this work improves our understanding to design nanomedicine with enhanced kidney accumulation, boosting its use to treat renal diseases.
Addressing the challenge of diagnosing incipient bearing faults amidst significant noise, a novel diagnostic approach is introduced, leveraging a Rank Constrained Low-Rank and Sparse Decomposition ( RCLRSD ) model tailored for weak fault detection in bearings. Initially, we raised the Autocorrelation Function of the Square Envelope in Frequency Domain as an innovative method for the estimation of fault frequencies. Subsequently, we constructed a two-dimensional observation matrix, which is formulated independently of predefined assumptions. Then, we examine the configuration and distribution patterns of bearing fault signals, uncovering the low-rank nature of fault characteristics within a designated two-dimensional transform domain. Moreover, we found the noise signal to exhibit sparsity and an approximate Gaussian distribution. Based on this, a rank-constrained low-rank sparse decomposition model is established, and rank-constrained low-rank regular constraints for feature information and sparse regular constraints and Gaussian constraints for interference signals are constructed respectively. Ultimately, we employed the Gray Wolf Optimization algorithm to refine the model parameters, and we deduced the model's solver via the Alternating Direction Method of Multipliers. The proposed RCLRSD model decomposes bearing fault data into three constituents: low-rank, sparse, and Gaussian components, effectively addressing the challenge of extracting weak fault signatures from bearings. The weak feature extraction capability of the RCLRSD model is verified using a multi-interference simulation model and experimental data of bearing failures under strong noise conditions; the generalization of the model is verified by the classification effect of the Support Vector Machine under two bearing failure datasets. Comparison with various algorithms confirms the superiority of the proposed algorithm.
In osteoporotic bones, the stability of orthopedic implants is compromised, and excessive M1 macrophage polarization at the bone-implant interface disrupts bone-immune homeostasis, leading to implant loosening or failure. To address this, this study develops a bionic magnesium alloy internal fixation coating inspired by the "brick-and-mortar" structure of pearl, aiming to improve bone-implant integration and vascularization in osteoporotic conditions. The multifunctional coating consists of a calcium phosphate (Ca-P) "brick" layer, which serves as a mineralization template and corrosion barrier, and fibronectin-mimetic peptides (Fn-mimetic peptides) as the "mortar" to promote cell adhesion, regulate immune responses, and stimulate angiogenesis. This bionic multilayer structure not only alleviates oxidative stress in the osteoporotic microenvironment but also fosters immune regulation-osteogenesis coupling and improves the bone-vascular-immune microenvironment. It precisely controls the degradation rate of Mg alloys and enhances tissue repair. The CaP layer reduces rapid degradation and prevents hydrogen gas release and local alkalinization, whereas Fn-mimetic peptides enhance early bone integration and vascularization. The synergistic effect of the magnesium alloy implant and bionic coating significantly improved bone implant stability, regeneration, and vascularization, as demonstrated in osteoporotic rat models, offering a promising strategy for the design of bone repair materials under pathological conditions.
Poly(ethylene glycol) (PEG)-polypeptide drug nanocarriers have garnered increasing attention during last decades. However, the tedious polymer synthesis and the stability issue greatly limit their further development. Herein the biphasic polymerization platform is reported for the easy access of a series of crosslinked PEG-polypeptide nanoparticles for enhanced drug loading and selective drug release. The accelerated polymerization allows for the preparation of a library of PEG-polypeptides from crude monomers with different polypeptide segments for structural optimization. Nanocarriers with redox-responsive de-crosslinking and enhanced drug loading are therefore obtained based on the model drug, doxorubicin, which exhibits selective killing of cancer cells. This study provides a synthetic method for efficient preparation of PEG-polypeptide nanocarriers, benefiting the downstream drug loading and therapeutic studies.
The structural and surface properties of nanomedicines play an important role in determining their biological fate. Surface chemistry of nanomedicines is one of the key parameters, where researchers used various strategies such as PEGylation to avoid the undesired clearance of nanoparticles (NPs) for enhanced targeting effect. Nevertheless, the fine-tuning of surface chemistry through polymer functionalization remains largely unexplored. In this concise report, we find that the incorporation of only 10 mol% valine residues into the surface-anchored poly(L-glutamic acid) significantly lowered the macrophage uptake of NPs. The introduction of other hydrophobic amino acid residues, however, increased the NPs internalization instead. The chirality and the side-chain structure of valine played an important role in the unexpected uptake behavior. We believe this work highlights the impact of slight changes of the surface-anchored polymer structure on the behavior of NPs, drawing people's attention to the careful design of surface chemistry to optimize the nanomedicine design.
miRNAs regulate several life activities and they have emerged as biomarkers in cancer diagnosis. Pursuing highly sensitive sensing platforms for detecting miRNAs, signal amplification strategies are the most frequently utilized means. In this research, a click chemistry-mediated variable temperature amplification (CCVTA) biosensor was developed for the highly selective and sensitive detection of miRNA-21. Sensing depended on enzyme-free amplification and copper-free type click chemistry, which greatly simplified the pre-treatment procedure and the conditions for sensing. In addition, the amplification products were used to output two signals, which are electrochemical and colorimetric modes. The dual-mode biosensor respectively achieved a detection limits of 0.57 and 17.19 fmol/mL, as well as excellent selectivity, stability, and applicability. It can be expected that CCVTA-biosensor sparkle with attractive prospects in the sensing field.
Despite the fact that homogeneous biosensing strategies have been proven to be advantageous, it remains a difficult task to identify multiple tumor biomarkers. Our proposition entails the creation of a groundbreaking biosensor that combines electrochemical and fluorescent techniques, enabling simultaneous detect multiple biomarkers with label- and enzyme-free assistance in a single step. Porous UIO-66-NH2 nanovessels loaded with 3,3 ',5,5 ' -tetramethylbenzidine (TMB) and methylene blue (MB) double signal dyes, along with double-stranded DNA (dsDNA) formed by the aptamer chain of human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) and its complementary chain as a gated switch to the envelope MOFs, were utilized to create functional MOFs (dsDNA@MB@UIO and dsDNA@TMB@UIO). When HER2 and ER targets are present, the chain replacement reaction led to the formation of a biomarker-aptamer complex, resulting in the destruction of the dsDNA structure on the surface of MOF and the liberation of MB and TMB. The concentration of the two target biomarkers determines the strength of the electrochemical and fluorescent signals produced. By combining targeted biomarkers, signal enhancement, and dual-signal detection into one unified process, the amount of test error caused by the multi-step detection needed in prior studies is significantly decreased. We executed the detect HER2 and ER, achieving detection limits of 4.7 and 5.9 fg/mL in 4.7-1000 pg/mL linear range with good selectivity, stability, reproducibility, and acceptable applicability. The proposed biosensor for developing dsDNA@MB@UIO and dsDNA@TMB@UIO is promising for the early and sensitive detection of cancer biomarkers.
Introduction Inflammatory diseases, such as diabetes mellitus, rheumatoid arthritis, and inflammatory bowel disease, lead to systemic immune microenvironment disturbances, contributing to bone loss, yet the mechanisms by which specific receptors regulate this process in inflammatory bone loss remain poorly understood. As a G-protein-coupled receptor, the Apelin receptor plays a crucial role in the regulation of inflammation and immune microenvironment. However, the precise mechanisms governing its role in inflammatory bone loss remain incompletely understood. Objective This study aims to investigate how APJ regulates macrophage polarization to mitigate inflammatory bone loss. Methods Lipopolysaccharide induced systemic inflammatory bone loss model in mice was used to explore the relationship between bone loss and osteoclast activation, macrophage polarization and APJ. In vitro studies, Bone marrow derived macrophages and siRNA were used to elucidate the regulatory influence of APJ on the immune microenvironment and osteoclast differentiation, while high-throughput sequencing is leveraged to uncover the underlying mechanisms through which APJ modulates macrophage polarization. Results Our study established a link between APJ and macrophage M1 polarization in systemic inflammatory bone loss mice. The activation of APJ effectively mitigated M1 polarization in macrophages, suppressed excessive osteoclast activation, and alleviated systemic inflammatory bone loss. In vitro high-throughput sequencing analysis revealed that APJ modulates macrophage polarization, linking to mitochondrial autophagy and the NOD-like receptor signaling pathway and the involvement of the AMPK and MAPK signaling pathways in signal transduction after APJ activation was also suggested. Subsequent experiments substantiated that APJ predominantly enhances mitophagy and diminishes the accumulation of reactive oxygen species by regulating the AMPK/BNIP3/PINK1/PARKIN axis, thereby suppressing the activation of macrophage M1 polarization and osteoclastogenesis. Conclusion This study elucidated the underlying mechanism by which APJ modulates macrophage polarization, thereby proposing a new therapeutic target for addressing inflammatory bone loss.
Heteropolypeptides bearing two or more functional side chains are promising polymeric materials for various biomedical applications. However, conventional preparation of heteropolypeptides relies on the synthesis and purification of each N-carboxyanhydride (NCA) monomer in a separate manner, which substantially increases the time and cost. Herein, we report the facile preparation of heteropolypeptides with up to 86% yield within several hours, which are obtained from a mixture of crude NCA monomers. The combination of n-hexane precipitation and biphasic segregation effectively removed >90% impurities from crude NCA mixtures, allowing for the successful polymerization process. Various heteropolypeptides with monomodal distribution and narrow dispersity were efficiently prepared, whose compositions were predetermined by the feeding ratios of amino acids. We believe that this work significantly simplifies the preparation of various heteropolypeptides, boosting the downstream studies of these promising materials.
Anionic synthetic polypeptides are promising candidates as standalone bone-targeting drug carriers. Nevertheless, the structure-property relationship of the bone-targeting ability of polypeptides remains largely unexplored. Herein we report the optimization of the in vitro and in vivo bone-targeting ability of poly(glutamic acid)s (PGAs) by altering their chain lengths and backbone chirality. PGA 100-mers exhibited higher hydroxyapatite affinity in vitro, but their rapid macrophage clearance limited their targeting ability. Shorter PGA was therefore favored in terms of in vivo bone targeting. Meanwhile, the backbone chirality showed less significant impact on the in vitro and in vivo targeting behavior. This study highlights the modulation of structural parameters on the bone-targeting performance of anionic polypeptides, shedding light on the future design of polypeptide-based carriers.
Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration of cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, and lysosomal phagocytosis, oligonucleotide therapy remains a formidable challenge. The discovery of cationic peptides has provided innovative insights for the effective delivery of oligonucleotides, yet the stable, efficient, and convenient assembly of peptides and oligonucleotides remains an elusive goal, referred to as the "Holy Grail" challenge in the field. Addressing this challenge, it has pioneered the development of a straightforward and highly efficient engineering carrier-free covalent peptide-oligonucleotide nano-conjugates (PONs) through a mild click reaction. Notably, this PONs can realize self-assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase resistance and surprisingly effective intracellular oligonucleotide delivery as well as lysosomal escape. Based on this strategy, a PONs named CPP-(DOPA)(6)-miRNA-223 is synthesized, which demonstrates rapid and effective cellular uptake, swift lysosomal escape in macrophage, remarkable accumulation in inflammatory regions and excellent therapeutic effect in an inflammatory arthritis model. Therefore, this work may provide a breakthrough for the clinical application of all oligonucleotide delivery therapies and expanding the applications in gene therapy.
Simultaneous detection of multiple tumor markers is of great significance for an accurate diagnosis and early treatment of cancer. Electrochemical homogeneous biosensing strategies have been shown to have advantages, such as high sensitivity and no electrode modification, but they are still a challenge in the field of simultaneous detection of multiple tumor markers. The ER, PR, HER2, and Ki67 proteins are the standard biomarkers for the clinical molecular typing of breast cancer. Precise, sensitive, and simultaneous detection of these four biomarkers is of great importance in the molecular typing of breast cancer, which helps in the creation of personalized treatment plans. In the present study, we developed an electrochemical homogeneous electrochemical bioplatform based on metal ions/SiO2NPs/magnetic beads for detection of the four biomarkers and simultaneous diagnosis of the 10 types of breast cancer directly in human serum at one system by a single electrode. The electrochemical bioplatform has a short detection time of 140 min; however, the current clinical tissue testing time takes about 1 week. Also, the electrochemical bioplatform selectively detects HER2, ER, Ki67, and PR in a range of 0-1000 pg/mL with detection limits of 2, 1.8, 10.36, and 1.33 pg/mL, respectively.
As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both bone formation by osteoblasts and bone resorption by osteoclasts constitute bone reconstruction homeostasis. The equilibrium of bone homeostasis is governed by many complicated signaling pathways that weave together to form an intricate network. These pathways coordinate the meticulous processes of bone formation and resorption, ensuring the structural integrity and dynamic vitality of the skeletal system. Dysregulation of the bone homeostatic regulatory signaling network contributes to the development and progression of many skeletal diseases. Significantly, imbalanced bone homeostasis further disrupts the signaling network and triggers a cascade reaction that exacerbates disease progression and engenders a deleterious cycle. Here, we summarize the influence of signaling pathways on bone homeostasis, elucidating the interplay and crosstalk among them. Additionally, we review the mechanisms underpinning bone homeostatic imbalances across diverse disease landscapes, highlighting current and prospective therapeutic targets and clinical drugs. We hope that this review will contribute to a holistic understanding of the signaling pathways and molecular mechanisms sustaining bone homeostasis, which are promising to contribute to further research on bone homeostasis and shed light on the development of targeted drugs.
Polypeptides obtained from the ring-opening polymerization of N-carboxyanhydrides, as the synthetic analogues of natural proteins, have drawn broad interests during the recent three decades. Unlike other synthetic polymers, polypeptides form ordered secondary structures like alpha-helices and 8-sheets, which offer conformation-specific functions that are not observed in unstructured polymers. In this article, we summarized the unique structural features of alpha-helical polypeptides compared to their random-coiled analogues, and reviewed the helix-associated assembly behaviors and biomedical functions based on the structural differences. In addition, the characterization and modulation of polypeptide conformations were also discussed. We believe this review will shed light on the future design of synthetic polypeptides with helix-specific properties, further expanding the scope of polypeptide materials.
An ultra-sensitive ratiometric electrochemical aptasensor was constructed based on metal-organic frameworks (MOFs) and bimetallic oxides for the detection of the human epidermal growth factor receptor 2 (HER2), a breast cancer marker. The aluminum metal-organic framework (Al-MOF) and cerium-metal-organic framework (CeMOF) have higher specific surface area, which is conducive to load more aptamers or complementary DNA (cDNA), and realize the amplification of internal reference signal Fc. Furthermore, nanoflower-like bismuth copper oxide (Bi2CuO4) with abundant active sites was introduced to modify more aptamers on its surface, which were then fixed to the glassy carbon electrode (GCE) to amplify the detection signal. The quantitative detection of HER2 was achieved by differential pulse voltammetry (DPV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The materials were characterized by scanning electron microscope, transmission electron microscope, Zeta potential analyzer, X-ray diffraction and X-ray photoelectron spectroscopy. The ratiometric electrochemical aptasensor based on nanomaterial and chain displacement signal amplification technology could discern HER2 in a very wide range (0.001-20.0 ng/mL) with an extremely low detection limit (0.049 pg/mL) and has demonstrated good performance in clinical serum analysis. This strategy also provides a feasible idea for sensitive analysis of other clinical tumor markers.
Implant-associated infection (IAI) is increasingly emerging as a serious threat with the massive application of biomaterials. Bacteria attached to the surface of implants are often difficult to remove and exhibit high resistance to bactericides. In the quest for novel antimicrobial strategies, conventional antimicrobial materials often fail to exert their function because they tend to focus on direct bactericidal activity while neglecting the modulation of immune systems. The inflammatory response induced by host immune cells was thought to be a detrimental force impeding wound healing. However, the immune system has recently received increasing attention as a vital player in the host's defense against infection. Anti-infective strategies based on the modulation of host immune defenses are emerging as a field of interest. This review explains the importance of the immune system in combating infections and describes current advanced immune-enhanced anti-infection strategies. First, the characteristics of traditional/conventional implant biomaterials and the reasons for the difficulty of bacterial clearance in IAI were reviewed. Second, the importance of immune cells in the battle against bacteria is elucidated. Then, we discuss how to design biomaterials that activate the defense function of immune cells to enhance the antimicrobial potential. Based on the key premise of restoring proper host-protective immunity, varying advanced immune-enhanced antimicrobial strategies were discussed. Finally, current issues and perspectives in this field were offered. This review will provide scientific guidance to enhance the development of advanced anti-infective biomaterials.
Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.
Objective To estimate the early effectivenss of computer navigation-assisted total knee arthroplasty (TKA) by comparing with traditional TKA. Methods The clinical data of 89 patients (100 knees) underwent primary TKA between October 2017 and July 2018 were analyzed retrospectively, including 44 patients (50 knees) who completed the TKA under the computer-assisted navigation system as the navigation group and 45 patients (50 knees) treated with traditional TKA as the control group. There was no significant difference between the two groups ( P>0.05) in gender, age, body mass index, diagnosis, side, disease duration, Kellgren-Lawrence classification of osteoarthritis, and preoperative American Hospital for Special Surgery (HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA) deviation. The operation time, incision length, difference in hemoglobin before and after operation, postoperative hospital stay, and the complications were recorded and compared between the two groups. The HSS score, ROM, and joint forgetting score (FJS-12) were used to evaluate knee joint function in all patients. Unilateral patients also underwent postoperative time of up and go test and short physical performance battery (SPPB) test. At 1 day after operation, the HKA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), sagittal femoral component angle (sFCA), and sagittal tibial component angle (sTCA) were measured and calculated the difference between the above index and the target value (deviation); and the joint line convergence angle (JLCA) was also measured. Results The operations of the two groups were successfully completed, and the incisions healed by first intention. The operation time and incision length of the navigation group were longer than those of the control group ( P<0.05); the difference in difference of hemoglobin before and after the operation and the postoperative hospital stay between groups was not significant ( P>0.05). Patients in the two groups were followed up 27-40 months, with an average of 33.6 months. Posterior tibial vein thrombosis occurred in 1 case in each of the two groups, and 1 case in the control group experienced repeated knee joint swelling. The HSS scores of the two groups gradually increased after operation ( P<0.05); HSS scores in the navigation group at 1 and 2 years after operation, and knee ROM and FJS-12 scores at 2 years were significantly higher than those in the control group ( P<0.05). There was no significant difference in the postoperative time of up and go test and SPPB results between the two groups at 7 days after operation ( P>0.05); the postoperative time of up and go test of the navigation group was shorter than that of the control group at 2 years ( t=-2.226, P=0.029), but there was no significant difference in SPPB ( t=0.429, P=0.669). X-ray film measurement at 1 day after operation showed that the deviation of HKA after TKA in the navigation group was smaller than that of the control group ( t=-7.392, P=0.000); among them, the HKA deviations of 50 knees (100%) in the navigation group and 36 knees (72%) in the control group were less than 3°, showing significant difference between the two groups ( χ 2=16.279, P=0.000). The JLCA and the deviations of mLDFA, mMPTA, sFCA, and sTCA in the navigation group were smaller than those in the control group ( P<0.05). Conclusion Compared with traditional TKA, computer navigation-assisted TKA can obtain more accurate prosthesis implantation position and lower limb force line and better early effectiveness. But there is a certain learning curve, and the operation time and incision length would be extended in the early stage of technology application.
Periprosthetic osteolysis (PPO) remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles. Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses. Additionally, the NLRP3 inflammasome is activated by prosthetic particles. Sirtuin3, an NAD+-dependent deacetylase of mitochondria, regulates the function of mitochondria in diverse activities. However, whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported. Therefore, we investigated the role of SIRT3 during the process of titanium (Ti) particle-induced osteolysis. We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro. Moreover, we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway. Collectively, these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.
OBJECTIVE:To estimate the early effectivenss of computer navigation-assisted total knee arthroplasty (TKA) by comparing with traditional TKA. METHODS:The clinical data of 89 patients (100 knees) underwent primary TKA between October 2017 and July 2018 were analyzed retrospectively, including 44 patients (50 knees) who completed the TKA under the computer-assisted navigation system as the navigation group and 45 patients (50 knees) treated with traditional TKA as the control group. There was no significant difference between the two groups ( P>0.05) in gender, age, body mass index, diagnosis, side, disease duration, Kellgren-Lawrence classification of osteoarthritis, and preoperative American Hospital for Special Surgery (HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA) deviation. The operation time, incision length, difference in hemoglobin before and after operation, postoperative hospital stay, and the complications were recorded and compared between the two groups. The HSS score, ROM, and joint forgetting score (FJS-12) were used to evaluate knee joint function in all patients. Unilateral patients also underwent postoperative time of up and go test and short physical performance battery (SPPB) test. At 1 day after operation, the HKA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), sagittal femoral component angle (sFCA), and sagittal tibial component angle (sTCA) were measured and calculated the difference between the above index and the target value (deviation); and the joint line convergence angle (JLCA) was also measured. RESULTS:The operations of the two groups were successfully completed, and the incisions healed by first intention. The operation time and incision length of the navigation group were longer than those of the control group ( P<0.05); the difference in difference of hemoglobin before and after the operation and the postoperative hospital stay between groups was not significant ( P>0.05). Patients in the two groups were followed up 27-40 months, with an average of 33.6 months. Posterior tibial vein thrombosis occurred in 1 case in each of the two groups, and 1 case in the control group experienced repeated knee joint swelling. The HSS scores of the two groups gradually increased after operation ( P<0.05); HSS scores in the navigation group at 1 and 2 years after operation, and knee ROM and FJS-12 scores at 2 years were significantly higher than those in the control group ( P<0.05). There was no significant difference in the postoperative time of up and go test and SPPB results between the two groups at 7 days after operation ( P>0.05); the postoperative time of up and go test of the navigation group was shorter than that of the control group at 2 years ( t=-2.226, P=0.029), but there was no significant difference in SPPB ( t=0.429, P=0.669). X-ray film measurement at 1 day after operation showed that the deviation of HKA after TKA in the navigation group was smaller than that of the control group ( t=-7.392, P=0.000); among them, the HKA deviations of 50 knees (100%) in the navigation group and 36 knees (72%) in the control group were less than 3°, showing significant difference between the two groups ( χ 2=16.279, P=0.000). The JLCA and the deviations of mLDFA, mMPTA, sFCA, and sTCA in the navigation group were smaller than those in the control group ( P<0.05). CONCLUSION:Compared with traditional TKA, computer navigation-assisted TKA can obtain more accurate prosthesis implantation position and lower limb force line and better early effectiveness. But there is a certain learning curve, and the operation time and incision length would be extended in the early stage of technology application.