Journal of Orthopaedic Research®最新文献

Cementless total knee arthroplasty implants offer advantages over cemented implants, such as bone preservation and easier revision procedures. However, the optimal interference fit required to achieve a good press-fit fixation, essential for both primary and long-term stability, remains uncertain. This study uses finite element analysis to investigate the effects of two interference fits (350 µm and 700 µm) on micromotions, gap behavior, and plastic deformation at the bone-implant interface of a cementless femoral component under various loading conditions. Finite element models were developed using paired cadaveric femurs, incorporating microCT and optical scans. Micromotions were quantified as shear displacement, while gaps were quantified as normal displacement. Bone response was assessed by quantifying the volume of bone experiencing total equivalent plastic strain. The models showed moderate correlation with experimental results, predicting 35% of displacement variability. Although high interference fit implants slightly reduced micromotions and gaps, these differences were not statistically significant (p = 0.252 and p = 0.759, respectively). The high interference fit implants exhibited significantly greater plastic deformation (+15.7%, p = 0.031), particularly at the posterior femoral condyles. These findings suggest that while an increased interference fit does not enhance primary stability, it may lead to more plasticity in the bone, potentially leading to more damage. Thus, optimizing the interference fit is crucial to balance implant fixation and minimize bone damage.

Joint replacement is one of the most successful complex surgical procedures, in large part due to innovations in implant materials and designs. Understanding how implants perform in vivo and why some fail has been crucial to continuous improvement. Analysis of implants retrieved at revision surgery can determine mechanisms driving both performance and failure and suggest necessary changes to address problems. Retrieval analysis can also serve as the earliest warning that an implant system has failed to meet expectations and that a regulatory recall may be the prudent decision. In this review, we provide a history of how retrieval analysis has been leveraged to provide mechanistic answers to design and material problems, to advance implant design and practice, and to provide warnings of early failures. We describe methods to conduct failure analysis of revised implants from subjective observations to quantitative techniques that span engineering, imaging, and pathology. We then present ways in which retrieval analysis has advanced biomaterials and design improvements using the development of polyethylene-based materials and the discovery of implant tribocorrosion and subsequent mitigation strategies as examples. We also discuss how retrieval analysis was combined with finite element modeling in the evolution of four generations of knee implant design. Finally, we discuss how retrieval analysis can continue to be a valuable resource for joint replacement surgery and implant manufacturing.

Detecting microstructural damage in ligaments remains a challenging case when no visible tearing occurs. This study introduces a novel application of micro-CT for ligament evaluation in wet tissue state with potential for clinical translation. We utilize neutral iodixanol and cationic tantalum oxide nanoparticles (Ta₂O₅-cNPs) for quantitative and qualitative imaging of microdamaged bovine ligaments. We hypothesize that neutral iodixanol reflects the ligament's functional alterations, while Ta₂O₅-cNPs will depict ligament structure by highlighting biphasic differences between the interfascicular matrix and fascicular regions. To examine these hypotheses, bovine anterior (N = 6) and posterior (N = 5) cruciate ligaments were assigned to control and damaged groups. All samples underwent biomechanical tensile testing to quantify the functional properties. Ligaments in the damaged group were strained up to 16% to create microdamage. Young's modulus was significantly reduced by 68% in the damaged group relative to the healthy group (p < 0.001). Samples were then separately immersed in each contrast agent and imaged using micro-CT at several timepoints during diffusion. The neutral iodixanol diffused faster compared to Ta₂O₅-cNPs, while Ta₂O₅-cNPs achieved approximately three times higher maximum partition. Although statistically significant differences in contrast agent partition between control and damaged groups were not observed, the findings demonstrate that (1) P_max of neutral iodixanol showed correlation with biomechanical properties specifically phase shift at frequencies of 0.1, 0.5, and 2 Hz indicating sensitivity to viscoelastic changes of the tissues, and (2) Ta₂O₅-cNPs enable visualization of the ligament's structures, supporting their potential for three-dimensional histological assessment.

Rotator cuff tears (RCTs) often require surgical intervention; however, surgical outcome is frequently insufficient due to poor healing of the tendon-bone enthesis, leading to high retear rates. Previously, the recombinant human amelogenin protein (rHAM⁺) regenerated injured or diseased musculoskeletal tissues including ligaments and osteochondral injuries. We therefore hypothesized that rHAM⁺ can also induce regeneration of the biomechanical and structural properties of the enthesis. The right shoulder infraspinatus tendon of 75 rats was fully-transected, and treated either with 0.5 mg/mL rHAM⁺ dissolved in propylene glycol alginate (PGA) carrier (n = 30), or with PGA carrier alone (n = 30). Fifteen unoperated rats were additionally evaluated. Four- and eight-weeks posttreatment, the degree of regeneration was evaluated using biomechanical and histological analyses. rHAM⁺ induced full recovery of biomechanical properties 8 weeks posttreatment, with the transected tendon demonstrating similar averaged tensile strength as the unoperated contralateral tendon, while PGA brought about substantially inferior biomechanical outcome. Eight weeks after treatment with rHAM⁺, progressive structural improvement was observed, including parallel type I collagen fibers with orientation and width similar to the uninjured group, restoration of the fibrocartilage zone, bone ingrowth, and a detectable tidemark, contrary to poor tissue maturation of the PGA-treated tendons. Furthermore, rHAM⁺ led to significantly less fatty degeneration of the infraspinatus muscle compared to PGA. rHAM⁺ induced regeneration of biomechanical strength and promoted maturation of the enthesis of fully transected rat RCT. Therefore, we recommend further evaluation of amelogenin as possible adjunct therapeutic strategy to improve the healing and reduce retears in clinical RC repair.

Post-traumatic osteoarthritis (PTOA) develops following severe knee trauma like anterior cruciate ligament (ACL) injury. PTOA can be identified by measuring morphology (thickness) and matrix composition of articular cartilage. Morphological MRI has been used to measure cartilage thickness, while quantitative magnetic resonance imaging (qMRI) has been used to measure cartilage matrix composition. In hopes of utilizing a single MRI technique to obtain both measurements simultaneously, this study explored whether cartilage thickness measurements from qMRI sequences were comparable to those from a morphological MRI sequence. Healthy participants with atraumatic, normal knees underwent three MRI acquisitions on their left knee: a three-dimensional (3D) morphological MRI sequence (T1-weighted Fast Field Echo [T1FFE]) and two 3D quantitative MRI sequences (T1ρ, T2*). The images were manually segmented to characterize the articular cartilage surface and subchondral bone-cartilage interface. 3D articular cartilage thickness maps were developed for each acquisition for the lateral and medial compartments of the tibia and femur. The qMRI thickness maps were compared to the morphological MRI thickness maps within subjects at fixed anatomical points. T1ρ cartilage thickness maps showed strong agreement with T1FFE maps as evidenced by ICCs exceeding 0.8 for 11 of 12 regions of interest (ROIs). In addition, mean thickness differences smaller than the in-plane pixel size of the reconstructed images, indicated minimal bias. There was inferior agreement between the T2* and T1FFE maps, and statistically significant bias observed for 8 of 12 ROIs. T1ρ qMRI sequences can simultaneously provide quantitative and comparable morphological measurements of knee articular cartilage thickness.

When significant structural defects (such as post tumor removal or severe bone defect) exceed the body's inherent capacity for self-repair, orthopedic implants remain an effective clinical option for restoring skeletal structural integrity and mechanical function. Conventional subtractive manufacturing, however, often lacks the precision, customization, and structural complexity demanded by modern implant design. Additive manufacturing (AM) has emerged as a transformative alternative, enabling layer-by-layer fabrication tailored to patient-specific anatomy. This review explains the underlying principles of AM and its application to orthopedic implant design, highlighting how the technology surpasses traditional machining in accuracy, design freedom, and personalization. We outline end-to-end workflow that couples computer-aided design with detailed patient-specific anatomical data to produce bespoke implants, and we compare major AM modalities-powder bed fusion, material extrusion, directed energy deposition, and stereolithography-focusing on their strengths, limitations, and clinical suitability. Recent clinical deployments and research advances are surveyed to illustrate the positive impact of AM on postoperative recovery, implant longevity, and patient comfort. Finally, we discuss the challenges of scaling AM for mass production and consider future directions, emphasizing opportunities for interdisciplinary collaboration that could broaden the technology's reach in personalized orthopedic care.

This manuscript summarizes over 30 years of research that began with the novel concept of using intra-articular gene transfer to treat joint diseases. A notable milestone in this journey was the first-in-human transfer of an exogenous gene to a joint, accomplished by the ex vivo delivery of cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) to joints of patients with rheumatoid arthritis. Responding to lessons learned from this study and the prevailing clinical landscape we next developed an in vivo gene delivery system based on adeno-associated virus (AAV) with osteoarthritis (OA) as the target disease. The safety and efficacy of this vector, sc-rAAV2.5IL-1Ra, was demonstrated in the joints of rats and horses leading to a successful IND application to the FDA. In this clinical trial (ClinicalTrials. gov Identifier: NCT02790723) sc-rAAV2.5IL-1Ra was injected at escalating doses into the knee joints of nine patients with OA who were followed for 1 year. This trial met its primary outcome measure, safety, and demonstrated that sustained expression of transgenic IL-1Ra was possible after a single injection of the vector. Patient-reported outcomes improved, but without a control group it is not possible to determine the influence of a placebo effect. This and other unresolved matters are addressed in a recently-completed Phase Ib trial (ClinicalTrials. gov Identifier: NCT05835895). Beyond OA, sc-rAAV2.5IL-1Ra has potential therapeutic value in a variety of degenerative, inflammatory, fibrotic and autoimmune conditions. More generally, gene therapy holds much promise in the field of regenerative medicine, including regenerative orthopaedics. Trial Registration: (ClinicalTrials. gov Identifier: NCT02790723, NCT05835895).

The interplay between mechanical stability and healing response in critical-size bone defects is poorly studied. The objective of this study was to investigate the relationship between Ratfix^TM constructs' stiffness in a rodent model of critical size defect (CSD) in femurs. We hypothesized that lower stiffness would result in improved bone regeneration. To test our hypothesis, we created CSD in male Fischer 344 rats and randomly assigned animals to rigid, intermediate, or flexible Ratfix^TM construct groups. In vivo radiographs were obtained every 2 weeks, and all animals were euthanized at 8 weeks for microCT analysis, histology, and biomechanical testing. At the end of the experiment, 73% of the flexible stiffness group, 100% of the intermediate stiffness group, and 63% of the rigid group demonstrated radiographic union. The intermediate group formed significantly more bone volume (BV) and callus volume (CV) than the rigid group, but was not significantly higher than the flexible group. Torsional stiffness and torque to failure of the intermediate group were over three-fold higher than the rigid group, but not significantly greater than the flexible group. Our study suggests that when treating CSD, mechanical stability is an important factor to facilitate bone regeneration, with optimal stiffness being critical, as both overly flexible and overly rigid constructs can impair healing.

Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty (TJA), one of the most frequently performed surgical procedures worldwide. Management of acute PJI commonly involves debridement, antibiotics, and implant retention (DAIR), though failure rates remain high due to antibiotic-tolerant biofilms. Chronic PJI is typically treated with two-stage revision using antibiotic-loaded spacers, but this approach carries substantial morbidity, especially during the interstage period. Preventative strategies include preoperative patient optimization, antibiotic prophylaxis, tranexamic acid, antiseptic skin preparation, and local antibiotic powders and rinses. To improve outcomes, emerging innovations include biofilm-active antimicrobial agents, targeted postoperative antibiotic delivery, intraarticular irrigation protocols, and one-stage revision strategies. While biofilm is a significant contributor to persistent infection, technologies to combat this problem include antibacterial implant surfaces, mechanically disruptive shockwave and magnetic fields, bioactive glass, and induction heating. In cases of treatment failure, salvage options remain limited, but novel approaches such as pathogen-specific bacteriophage therapy offer promising new directions.

Tendinopathy is a complex, painful condition that affects up to 5% of the general population in their lifetime. Antibiotic treatment with fluoroquinolones has been associated with the onset of tendinopathy and tendon rupture. The mechanisms behind fluoroquinolone induced tendinopathy remain unclear. To probe activation of potentially causative pathways, we treated juvenile mice with ciprofloxacin in drinking water for 4 weeks and performed RNA sequencing on tail tendons. We discovered that ciprofloxacin-treated mice had upregulated genes relating to nerve development. Additionally, treated mice showed downregulation of genes associated with extracellular matrix (ECM) processes. We further explored ECM changes using histological and mechanical testing methods on patellar tendons. We found that ciprofloxacin treatment led to altered cell morphology and proteoglycan density. These changes translated to a decrease in mechanical properties of the patellar tendons. Furthermore, ciprofloxacin-treated mice had a higher percentage of apoptotic cells, and we confirmed increased presence of nerve cells (Plexin B1⁺) in the patellar tendons compared to controls. Taken together, we showed that ciprofloxacin treatment in juvenile mice induces structural and biological phenotypes commonly associated with fluoroquinolone-induced tendinopathy and identify the axis of pathological neural activation as a promising area for further exploration. Clinical significance: Oral administration of ciprofloxacin in mice presents a clinically relevant model for studying mechanisms of tendinopathy in humans.