Hip arthroplasty (HA) has been popularized worldwide since it was initiated in the 1960s, and the number of operations has increased rapidly (1). With the acceleration of population aging and the increase in the incidence of musculoskeletal diseases worldwide, hip arthroplasty has become an irreplaceable treatment for femoral neck fracture, femoral head necrosis, inflammatory arthritis and other diseases. Professor Charnley introduced Polymethyl methacrylate (PMMA) bone cement in the mid-20th century, and it has been widely used in the field of joint arthroplasty (2). PMMA bone cement has been pivotal to the early success of hip arthroplasty. However, failures of bone cement implants were historically misattributed to “bone cement disease”, a generalized critique that inadvertently promoted the rise of cementless prostheses. Advances in materials, design, and technology, have enhanced the durability of cementless fixation (3), leading to a global decline in cemented hip prosthesis usage. Nevertheless, evidence supporting superior clinical outcomes for cementless fixation remains inconclusive (4, 5). With increasing adoption of cementless implants, their limitations—particularly in elderly populations—have become apparent. Cementless fixation exhibits higher revision rates compared to cemented fixation in elderly patients (6–8), a trend corroborated by the 2018 Australian Orthopaedic Association National Joint Replacement Registry report, which identified significantly elevated revision risks for cementless prostheses in patients over 80 years old, especially within the first three postoperative months (9). Periprosthetic fractures, particularly involving femoral components, are the most common revision trigger. Burnett et al. reported that the surgical complication risk of cementless HA for femoral neck fracture is higher than cemented HA, with an 11-fold increased risk of periprosthetic fracture compared to cemented HA (10). These findings underscore PMMA's irreplaceable role in managing elderly patients with compromised bone quality or femoral neck fractures.

PMMA bone cement, however, poses systemic risks, including circulatory- and coagulation-system toxicity (11). Methyl methacrylate (MMA) monomer toxicity and exothermic polymerization-induced thermal necrosis synergistically damage bone cells and surrounding tissues. Necrotic debris, combined with histamine and prostaglandin release, exacerbates systemic dysregulation, elevating pulmonary embolism risks (12). Furthermore, thermal necrosis byproducts and cement particles provoke local inflammation, while excessive inflammatory responses and necrotic accumulation drive bone resorption at the bone-cement interface, increasing aseptic loosening risks.

To mitigate these adverse effects, Sun et al. developed enoxaparin sodium (ES)-loaded PMMA (ES-PMMA) by physically embedding ES into PMMA's porous matrix (13). ES-PMMA releases therapeutically relevant ES concentrations within 24 h, achieving antithrombotic efficacy via CD40 protein suppression in vascular endothelial cells (14). Additionally, ES-PMMA induces macrophage M2 polarization, enhances anti-inflammatory mediator secretion (15), and promotes interfacial osteogenesis, reducing loosening risks (16). Collectively, these studies validate ES's capacity to counteract PMMA's side effects.

Despite these advances, ES-PMMA suffers from burst-release kinetics and transient therapeutic windows. While effective for short-term thrombosis prevention, its rapid drug depletion fails to sustain the prolonged anti-inflammatory and osteogenic modulation required for bone repair. To address this, we incorporated chitosan (CS)—a cost-effective, biodegradable polymer with high drug-loading capacity (17)—as a sustained-release carrier. By conjugating ES with CS to form drug-loaded microspheres and integrating them into PMMA, we engineered enoxaparin sodium-chitosan-polymethyl methacrylate (ES-CS-PMMA) bone cement. Compared to ES-PMMA, ES-CS-PMMA exhibits attenuated burst release, prolonged release duration, and enhanced capacity to continuously suppress inflammation and stimulate peri-implant osteogenesis.

However, additive incorporation into bone cement alters its mechanical properties, potentially affecting in vivo stress distribution (18). Montserrat et al. mixed 3.5 g bupivacaine hydrochloride with 40.8 g PMMA and measured the mechanical properties of bone cement. The results showed that the addition of bupivacaine hydrochloride significantly reduced the flexural strength of bone cement, which fell short of the minimum flexural strength value (19). Kwong et al. added 6 g vancomycin to 43 g Copal PMMA cement and found that the flexural strength of the drug-loaded cement was significantly lower than the ISO standard (20). Finite element analysis (FEA), a tool superior to animal models for simulating physiological implant behavior, has been extensively applied in hip arthroplasty research. While prior FEA studies predominantly focus on prosthesis materials and designs (21, 22), biomechanical comparisons between PMMA and modified bone cements remain scarce, partly due to limited material parameter data. This study thus aims to characterize PMMA and ES-CS-PMMA material parameters and employ FEA to compare their stress distribution profiles post-hip arthroplasty, addressing a critical gap in functionalized bone cement optimization. As a preliminary study, this work establishes a computational framework that paves the way for future investigations, including multiscale modeling of long-term bone adaptation, integration of patient-specific dynamic loading patterns, and experimental validation through fatigue testing coupled with microstructural damage analysis. These extensions will enhance the clinical translatability of computational predictions in advanced bone cement development.

Hip arthroplasty has become essential for treating femoral neck fractures and joint diseases, with cemented prostheses regaining attention due to higher revision risks in cementless alternatives (29). While PMMA bone cement revolutionized joint arthroplasty, its exothermic reaction during implantation causes thermal necrosis, inflammation, and loosening (11, 12). Nevertheless, Modified bone cements, such as ES-PMMA, were developed to mitigate these effects by promoting osteogenesis and reducing inflammation (13–16). However, ES-PMMA's short release duration led to the creation of ES-CS-PMMA, which uses chitosan microspheres to prolong drug release and enhance biocompatibility. Despite these advantages, additives may compromise mechanical strength, necessitating thorough evaluation before clinical use to ensure surgical success.

The three-dimensional FE model shows that, compared with that of the natural femur, the stress distribution of the femur is different for both the PMMA bone cement and the ES-CS-PMMA bone cement. According to Wolff's law, a reduction in the bone load causes the bone to adapt itself by reducing its mechanical strength or decreasing its trabecular size (30). From a biomechanical point of view, the implanted prosthesis will inevitably redistribute the stress value of the femur. Subsequently, the reduced stress and debris induced around the prosthetic stem make the surrounding bones prone to osteoporosis and bone resorption. These two skeletal reactions usually worsen the stable environment of the prosthetic stem (31). However, in hip arthroplasty, prosthesis implantation inevitably leads to femoral load transfer. In the natural femur, the stress is mainly concentrated in the cortical bone, and the cortical load gradually increases from the proximal region to the distal region and is distributed along the anteromedial and posterolateral sides. When the prosthesis is implanted, the stress in the proximal and middle bone cortex is unloaded and transferred to the femoral shaft, but there is no significant difference in the mean stress among the three models. In the distal region, the mean stress of the femur after prosthesis implantation is significantly lower than that of the natural femur. The reduction in stress increases the risk of periprosthetic fractures in the distal region of the prosthesis to some extent, but this cannot be avoided in hip arthroplasty.

However, there was no significant difference in the femoral stress distribution between the two FE models, whether in the PMMA cement group or ES-CS-PMMA cement group. These findings indicate that adding an appropriate amount of CS microspheres or other substances to the bone cement does not significantly affect the stress distribution in the femur. In contrast, the addition of chitosan microspheres has a positive effect and reduces the side effects of bone cement during or after implantation. From a biomechanical point of view, these findings also indirectly confirm the efforts of other scholars in the modification of bone cement.

Nevertheless, comparison with other FEA studies must be interpreted cautiously due to the diversities in the loading conditions, bone-implant interface, age and weight of the subjects and experimental results.

Other FEA methods for hip arthroplasty focus mostly on simulating the static situation of standing on one leg after hip arthroplasty, and the applied force is relatively simple, which is different from the patient's postoperative motion state (32, 33). Aguilisa et al. applied a single force to the femoral head to compare the fatigue analysis results of different materials (26). This simplified loading condition ignores the influence of muscles and ligaments on the results. In patients after hip arthroplasty, walking slowly is more basic and commonly used than standing on one leg. In this study, we compared the effects of PMMA cement and ES-CS-PMMA cement on the femoral stress distribution after hip arthroplasty. Although applying a single force does not significantly reduce the accuracy, we still consider the role of the iliopsoas muscle and abductor muscle in exercise in the FE models to minimize the impact of load conditions on the research results. Although our model incorporates to simulate slow walking—surpassing single-leg stance simplifications—it does not fully replicate the multidirectional loading environment of the hip. Critical omissions include twisting force and dynamic shear forces. These simplifications likely underestimate shear stress at the stem-cement interface and obscure direction-specific micromotion patterns, particularly affecting stability assessments of anti-rotation implant designs. Nevertheless, since the core objective was comparing biomechanical responses between PMMA and ES-CS-PMMA cement under identical loading simplifications, such systematic bias minimally impacts the intergroup difference conclusions.

Regarding interfacial modeling, frictional face-to-face contact and frictionless node-to-node contact are used to describe the bone-implant interface. In this study, the implant–bone cement and bone cement–bone interfaces are completely bonded, which does not consider the micromotion of the implant. This idealized assumption may lead to an over-simplified characterization of interfacial stress transfer mechanisms. Interfacial micromotion can induce dynamic stress redistribution: at the proximal bone cement–bone interface, the fully bonded assumption may result in an underestimation of shear stress; conversely, at the distal stem–bone cement interface, this assumption could overestimate the peak compressive stress (34). Consequently, our findings are more applicable to evaluating the prosthesis mechanical performance during initial fixation, but cannot accurately reflect long-term effects such as micromotion-induced bone remodeling or bone cement fatigue failure risks. Subsequent research should integrate multimodal loading conditions and employ frictional contact models to quantify interface slippage effects on mechanical responses.

Although the FE analysis adopted gait loading for a 70 kg adult male, patient weight and age critically alter the biomechanical response. Increasing weight elevates dynamic hip joint force substantially, raising cement mantle stress significantly with interface micromotion potentially exceeding the bone resorption threshold (35). Elderly patients exhibit markedly lower trabecular bone modulus, increasing proximal femoral stress shielding and intensifying shear stress concentration at stem-cement interfaces (36). These findings indicate that obese patients require high-strength cement with optimized fixation. Although our fixed-parameter model reveals cement performance trends, future weight-age gradient models should quantify failure probability in high-risk cohorts.

Importantly, the FE predictions provide targeted guidance for subsequent experiments: Comparable cement mantle stress distributions between ES-CS-PMMA and PMMA groups suggest similar fatigue failure mechanisms in the modified cement. This consistency indicates that in vitro testing should prioritize monitoring interface crack propagation beyond 1 million cycles over short-term strength degradation. Limitations regarding omitted dynamic loads will be addressed in validation studies using hexapod simulators to replicate multi-axis loading environments, establishing a comprehensive biomechanical evaluation framework.

In summary, the Young's modulus and Poisson's ratio of PMMA bone cement and ES-CS-PMMA bone cement were measured in this study, laying a foundation for follow-up studies of bone cement implants or bone cement hip arthroplasty. The Young's modulus of PMMA was 4,127 MPa with a Poisson's ratio of 0.25; ES-CS-PMMA exhibited an Young's modulus of 4,331 MPa and a Poisson's ratio of 0.28. Moreover, regardless of whether PMMA bone cement or ES-CS-PMMA bone cement is used as an adhesive for hip arthroplasty, the stress distribution of the cement sheath and femur after prosthesis implantation has not changed. This finding shows that adding a proper amount of drugs or other active substances into bone cement does not reduce the mechanical properties of the bone cement.