Finite element-based evaluation of the supraspinatus tendon biomechanical environment necessitates better clinical management based on tear location and thickness.

Partial-thickness rotator cuff tears are a common cause of pain and disability and are central to developing full-thickness rotator cuff tears. However, limited knowledge exists regarding the alterations to the mechanical environment due to these lesions. Computational models that study the alterations to the mechanical environment of the supraspinatus tendon can help advance clinical management to avoid tear progression and provide a basis for surgical intervention. In this study, we use three-dimensional validated finite element models from six intact specimens to study the effects of low- and high-grade tears originating on the articular and bursal surfaces of the supraspinatus tendon. Bursal-sided tears generally had a lower failure load, modulus, and strain than articular-sided tears. Thus, caution should be taken when managing bursal-sided tears as they may be more susceptible to tear progression.

Disparities in Rotator Cuff Tear Progression Definitions and Rates: A Systematic Review.

Background: While rotator cuff tears are prevalent in the general population, the natural history of this disease is unclear. Understanding rotator cuff tear progression is crucial for refining surgical indications and evaluating the necessity of early interventions. This study presents an in-depth analysis of the existing literature on the definitions and progression rates of rotator cuff tears, aiming to enhance clinical decision making and patient outcomes. Methods: A systematic literature search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using Medline (PubMed), Embase (Elsevier), and Web of Science databases on January 12, 2023. Articles were identified as relevant to the natural history and progression of asymptomatic and symptomatic partial-thickness (PT) and full-thickness (FT) rotator cuff tears. Those written in English reporting rotator cuff progression rates of tears in adults, based on magnetic resonance imaging (MRI) or ultrasound, were included. After reviewing the articles, the data on the rates of tear progression and associated risk factors were extracted, compiled, and analyzed. The risk of bias was determined using the Newcastle-Ottawa Scale. Results: Twenty-one articles met the inclusion criteria, with 1,831 tears included. The progression rate for all partial thickness tears was 26.7% ± 12.8% at an average follow-up of 2.2 ± 0.9 years, with 5 definitions for tear progression. For FT tears, the progression rate was 54.9% ± 18.6% at a follow-up time of 3.0 ± 2.0 years, with 8 definitions for tear enlargement. A significant difference (p < 0.0001) was found between the progression rates of PT and FT tears. Patients who were initially asymptomatic and became symptomatic had higher progression rates (33%-63%) than those who remained asymptomatic (4%-38%). Conclusion: Further research would benefit by identifying a clinically relevant and standardized definition of rotator cuff tear progression, to describe the natural history of rotator cuff disease, making results more comparable and optimizing treatment planning. Level of Evidence: Level II. See Instructions for Authors for a complete description of levels of evidence.

Stimulation of fracture mineralization by salt-inducible kinase inhibitors.

Introduction: Over 6.8 million fractures occur annually in the US, with 10% experiencing delayed- or non-union. Anabolic therapeutics like PTH analogs stimulate fracture repair, and small molecule salt inducible kinase (SIK) inhibitors mimic PTH action. This study tests whether the SIK inhibitor YKL-05-099 accelerates fracture callus osteogenesis. Methods: 126 female mice underwent femoral shaft pinning and midshaft fracture, receiving daily injections of PBS, YKL-05-099, or PTH. Callus tissues were analyzed via RT-qPCR, histology, single-cell RNA-seq, and µCT imaging. Biomechanical testing evaluated tissue rigidity. A hydrogel-based delivery system for PTH and siRNAs targeting SIK2/SIK3 was developed and tested. Results: YKL-05-099 and PTH-treated mice showed higher mineralized callus volume fraction and improved structural rigidity. RNA-seq indicated YKL-05-099 increased osteoblast subsets and reduced chondrocyte precursors. Hydrogel-released siRNAs maintained target knockdown, accelerating callus mineralization. Discussion: YKL-05-099 enhances fracture repair, supporting selective SIK inhibitors' development for clinical use. Hydrogel-based siRNA delivery offers targeted localized treatment at fracture sites.

The biomechanical assessment of two stemless shoulder arthroplasty prostheses in uniformly poor-quality bone mineral density cadaveric specimens.

BACKGROUND: Stemless shoulder arthroplasty offers several advantages, such as preserving bone stock and reducing periprosthetic fracture risk. However, implant motion can deter osteointegration and increase bone resorption, where micromotion less than 0.150 mm is crucial for bony ingrowth and vital to the success of the implant. The interaction between the implant and the metaphyseal bone and its effects on stability remains unclear. Therefore, this cadaveric study aims to assess the immediate stability of two stemless prostheses in low bone density specimens. METHODS: Twenty cadaveric shoulders were used to compare the stability of two stemless shoulder implants by Zimmer-Biomet (model A) and Exactech (model B), subjected to loads of 220 N, 520 N, and 820 N to assess strain and micromotion. FINDINGS: Micromotion at 220 N load was 0.061 ± 0.080 mm and 0.053 ± 0.050 mm, and at 520 N load, 0.279 ± 0.37 mm and 0.311 ± 0.35 mm for models A and B, respectively. The estimated mean force required to achieve a 150 µm micromotion was 356 ± 116 N and 315 ± 61 N for models A and B, respectively. Motion analysis revealed distinct movement patterns for each implant, with model B demonstrating better force distribution on the bone despite no significance. INTERPRETATION: Forces over 520 N (high postoperative rehabilitation force) could hinder bone integration with prostheses due to excessive micromotion. Conversely, forces around 220 N (preconditioning loading force) are considered safe for prosthesis stability even with low bone density. These insights may caution against using stemless implants when bone density is low, and help guide clinical decisions on the duration of rehabilitation and sling use after stemless arthroplasty.

Effect of Tear Size and Location on Supraspinatus Tendon Strain During Activities of Daily Living and Physiotherapy.

The supraspinatus tendon plays a crucial role in shoulder abduction, making it one of the common structures affected by injury. Clinically, crescent-shaped tears are the most commonly seen tear shape. By developing six specimen-specific, three-dimensional, supraspinatus-infraspinatus finite element model with heterogeneous material properties, this study aimed to examine the changes in tissue deformation (maximum principal strain) of the supraspinatus tendon due to specimen-specific material properties and rotator cuff tear size. FE models with small- and medium-sized full-thickness crescent-shaped tears were subjected to loads seen during activities of daily living and physiotherapy. Six fresh-frozen cadaveric shoulders were dissected to mechanically test the supraspinatus tendon and develop and validate FE models that can be used to assess changes in strain due to small (< 1 cm, equivalent to 20-30% of the tendon width) and medium-sized (1-3 cm, equivalent to 40-50% of the tendon width) tears that are located in the middle and posterior regions of the supraspinatus tendon. FE predictions of maximum principal strain at the tear tips were examined to determine whether failure strain was reached during activities of daily living (drinking and brushing teeth) and physiotherapy exercises (prone abduction and external rotation at 90° abduction). No significant differences were observed between the middle and posterior tear failure loads for small- and medium-sized tears. For prone abduction, there was a potential risk for tear progression (exceeded failure strain) for medium-sized tears in the supraspinatus tendon's middle and posterior regions. For external rotation at 90° abduction, one model with a middle tear and two with posterior tears experienced failure. For all daily activity loads, the strain never exceeded the failure strain. Our three-dimensional supraspinatus-infraspinatus FE model shows that small tears appear unlikely to progress based on the regional strain response; however, medium-sized tears are at higher risk during more strenuous physiotherapy exercises. Furthermore, differences in patient-specific tendon material properties are important in determining whether the tear will progress. Therefore, patient-specific management plans based on tear size may be beneficial to improve clinical outcomes.

Excellent accuracy of magnetic resonance imaging for diagnosis of discoid meniscus tears: A systematic review and meta-analysis.

Purpose: The discoid meniscus (DM) is distinguished by its thickened, disc-shaped formation, which extends over the tibial plateau. The likelihood of developing osteoarthritis escalates if a DM tear remains undiagnosed and untreated. While DM tears can be diagnosed through arthroscopy, the high cost, invasive nature and limited availability of this procedure highlight the need for a better diagnostic modality. This study aims to determine the accuracy of magnetic resonance imaging (MRI) in diagnosing DM tears. Methods: A systematic review was conducted to gather articles with at least 10 cases on the comparison of MRI and arthroscopy as the gold standard for DM tear diagnosis. Stata and MetaDisc were used to conduct the statistical analysis. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Five diagnostic performance studies, derived from four original research papers involving 305 patients, were evaluated. Based on the pooled data, the sensitivity, specificity, diagnostic odds ratio, positive limit of detection and negative limit of detection were found to be 0.87 (95% confidence interval [CI], 0.82-0.91) and 0.84 (95% CI, 0.75-0.90), 32.88 (95% CI, 5.81-186.02), 5.22 (95% CI, 1.71-15.92) and 0.18 (95% CI, 0.09-0.38), respectively. A hierarchical summary receiver operating characteristic curve with an area under the curve of 0.92 was generated. Conclusion: This meta-analysis demonstrates that MRI has excellent sensitivity and specificity for diagnosing DM tears. Despite its lower accuracy compared to arthroscopy, MRI can be used in symptomatic patients as a viable alternative to arthroscopy due to its inherent advantages. Level of Evidence: Level IV.

Detection and Localization of Spine Disorders from Plain Radiography.

Spine disorders can cause severe functional limitations, including back pain, decreased pulmonary function, and increased mortality risk. Plain radiography is the first-line imaging modality to diagnose suspected spine disorders. Nevertheless, radiographical appearance is not always sufficient due to highly variable patient and imaging parameters, which can lead to misdiagnosis or delayed diagnosis. Employing an accurate automated detection model can alleviate the workload of clinical experts, thereby reducing human errors, facilitating earlier detection, and improving diagnostic accuracy. To this end, deep learning-based computer-aided diagnosis (CAD) tools have significantly outperformed the accuracy of traditional CAD software. Motivated by these observations, we proposed a deep learning-based approach for end-to-end detection and localization of spine disorders from plain radiographs. In doing so, we took the first steps in employing state-of-the-art transformer networks to differentiate images of multiple spine disorders from healthy counterparts and localize the identified disorders, focusing on vertebral compression fractures (VCF) and spondylolisthesis due to their high prevalence and potential severity. The VCF dataset comprised 337 images, with VCFs collected from 138 subjects and 624 normal images collected from 337 subjects. The spondylolisthesis dataset comprised 413 images, with spondylolisthesis collected from 336 subjects and 782 normal images collected from 413 subjects. Transformer-based models exhibited 0.97 Area Under the Receiver Operating Characteristic Curve (AUC) in VCF detection and 0.95 AUC in spondylolisthesis detection. Further, transformers demonstrated significant performance improvements against existing end-to-end approaches by 4-14% AUC (p-values < 10-13) for VCF detection and by 14-20% AUC (p-values < 10-9) for spondylolisthesis detection.

Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions.

BACKGROUND: Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies. METHODS: Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time. RESULTS: Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points. CONCLUSION: Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

An Automated Vertebrae Localization, Segmentation, and Osteoporotic Compression Fracture Detection Pipeline for Computed Tomographic Imaging.

Osteoporosis is the most common chronic metabolic bone disease worldwide. Vertebral compression fracture (VCF) is the most common type of osteoporotic fracture. Approximately 700,000 osteoporotic VCFs are diagnosed annually in the USA alone, resulting in an annual economic burden of ~$13.8B. With an aging population, the rate of osteoporotic VCFs and their associated burdens are expected to rise. Those burdens include pain, functional impairment, and increased medical expenditure. Therefore, it is of utmost importance to develop an analytical tool to aid in the identification of VCFs. Computed Tomography (CT) imaging is commonly used to detect occult injuries. Unlike the existing VCF detection approaches based on CT, the standard clinical criteria for determining VCF relies on the shape of vertebrae, such as loss of vertebral body height. We developed a novel automated vertebrae localization, segmentation, and osteoporotic VCF detection pipeline for CT scans using state-of-the-art deep learning models to bridge this gap. To do so, we employed a publicly available dataset of spine CT scans with 325 scans annotated for segmentation, 126 of which also graded for VCF (81 with VCFs and 45 without VCFs). Our approach attained 96% sensitivity and 81% specificity in detecting VCF at the vertebral-level, and 100% accuracy at the subject-level, outperforming deep learning counterparts tested for VCF detection without segmentation. Crucially, we showed that adding predicted vertebrae segments as inputs significantly improved VCF detection at both vertebral and subject levels by up to 14% Sensitivity and 20% Specificity (p-value = 0.028).

Relaxin as a treatment for musculoskeletal fibrosis: What we know and future directions.

Fibrotic changes in musculoskeletal diseases arise from the abnormal buildup of fibrotic tissue around the joints, leading to limited mobility, compromised joint function, and diminished quality of life. Relaxin (RLX) attenuates fibrosis by accelerating collagen degradation and inhibiting excessive extracellular matrix (ECM) production. Further, RLX disrupts myofibroblast activation by modulating the TGF-ß/Smads signaling pathways, which reduces connective tissue fibrosis. However, the mechanisms and effects of RLX in musculoskeletal pathologies are emerging as increasing research focuses on relaxin's impact on skin, ligaments, tendons, cartilage, joint capsules, connective tissues, and muscles. This review delineates the actions of relaxin within the musculoskeletal system and the challenges to its clinical application. Relaxin shows significant potential in both in vivo and in vitro studies for broadly managing musculoskeletal fibrosis; however, challenges such as short biological half-life and sex-specific responses may pose hurdles for clinical use.

A graph model to describe the network connectivity of trabecular plates and rods.

Introduction: The trabecular network is perceived as a collection of interconnected plate- (P) and rod-like (R) elements. Previous research has highlighted how these elements and their connectivity influence the mechanical properties of bone, yet further work is required to elucidate better the deeply interconnected nature of the trabecular network with distinct element formations conducting forces per their mechanical boundary conditions. Within this network, forces act through elements: a rod or plate with force applied to one end will transmit this force to a component connected to the other end, defining the boundary conditions for the loading of each element. To that end, this study has two aims: First, to investigate the connectivity of individually segmented elements of trabecular bone with respect to their local boundary conditions as defined by the surrounding trabecular network and linking them directly to the bone's overall mechanical response during loading using a mathematical graph model of the plate and rod (PR) Network. Second, we use this model to quantify side artifacts, a known artifact when testing an excised specimen of trabecular bone, where vertical trabeculae lose their load-bearing capacity due to a loss of connectivity, ultimately resulting in a change of the trabecular network topology. Resuts: Connected elements derived from our model predicted apparent elastic modulus by fitting a linear regression (R 2 = 0.81). In comparison, prediction using conventional bone volume fraction results in a lower accuracy (R 2 = 0.72), demonstrating the ability of the PR Network to estimate compressive elastic modulus independent of specimen size or loading boundary condition. Discussion: PR Network models are a novel approach to describing connectivity within the trabecular network and incorporating mechanical boundary conditions within the morphological analysis, thus enabling the study of intrinsic material properties of trabecular bone. Ultimately, PR Network models may be an early predictor or provide further insights into osteo-degenerative diseases.

Metaverse, virtual reality and augmented reality in total shoulder arthroplasty: a systematic review.

PURPOSE: This systematic review aims to provide an overview of the current knowledge on the role of the metaverse, augmented reality, and virtual reality in reverse shoulder arthroplasty. METHODS: A systematic review was performed using the PRISMA guidelines. A comprehensive review of the applications of the metaverse, augmented reality, and virtual reality in in-vivo intraoperative navigation, in the training of orthopedic residents, and in the latest innovations proposed in ex-vivo studies was conducted. RESULTS: A total of 22 articles were included in the review. Data on navigated shoulder arthroplasty was extracted from 14 articles: seven hundred ninety-three patients treated with intraoperative navigated rTSA or aTSA were included. Also, three randomized control trials (RCTs) reported outcomes on a total of fifty-three orthopedics surgical residents and doctors receiving VR-based training for rTSA, which were also included in the review. Three studies reporting the latest VR and AR-based rTSA applications and two proof of concept studies were also included in the review. CONCLUSIONS: The metaverse, augmented reality, and virtual reality present immense potential for the future of orthopedic surgery. As these technologies advance, it is crucial to conduct additional research, foster development, and seamlessly integrate them into surgical education to fully harness their capabilities and transform the field. This evolution promises enhanced accuracy, expanded training opportunities, and improved surgical planning capabilities.

Proximal femur fracture detection on plain radiography via feature pyramid networks.

Hip fractures exceed 250,000 cases annually in the United States, with the worldwide incidence projected to increase by 240-310% by 2050. Hip fractures are predominantly diagnosed by radiologist review of radiographs. In this study, we developed a deep learning model by extending the VarifocalNet Feature Pyramid Network (FPN) for detection and localization of proximal femur fractures from plain radiography with clinically relevant metrics. We used a dataset of 823 hip radiographs of 150 subjects with proximal femur fractures and 362 controls to develop and evaluate the deep learning model. Our model attained 0.94 specificity and 0.95 sensitivity in fracture detection over the diverse imaging dataset. We compared the performance of our model against five benchmark FPN models, demonstrating 6-14% sensitivity and 1-9% accuracy improvement. In addition, we demonstrated that our model outperforms a state-of-the-art transformer model based on DINO network by 17% sensitivity and 5% accuracy, while taking half the time on average to process a radiograph. The developed model can aid radiologists and support on-premise integration with hospital cloud services to enable automatic, opportunistic screening for hip fractures.

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model.

BACKGROUND CONTEXT: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential nonopioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSE: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGN: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODS: Callus tissue was harvested 2- and 8-weeks postsurgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. µCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTS: µCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at 2 weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSION: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at 2 weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCE: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the postoperative setting following spinal fusions.

Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

BACKGROUND: Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. PURPOSE: To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. FIELD STRENGTH/SEQUENCE: 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, µCT imaging, and gravimetric measurements. ASSESSMENT: Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. STATISTICAL TESTS: ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. RESULTS: The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. DATA CONCLUSION: Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Tuning the Biodegradation Rate of Silk Materials via Embedded Enzymes.

Conventional thinking when designing biodegradable materials and devices is to tune the intrinsic properties and morphological features of the material to regulate their degradation rate, modulating traditional factors such as molecular weight and crystallinity. Since regenerated silk protein can be directly thermoplastically molded to generate robust dense silk plastic-like materials, this approach afforded a new tool to control silk degradation by enabling the mixing of a silk-degrading protease into bulk silk material prior to thermoplastic processing. Here we demonstrate the preparation of these silk-based devices with embedded silk-degrading protease to modulate the degradation based on the internal presence of the enzyme to support silk degradation, as opposed to the traditional surface degradation for silk materials. The degradability of these silk devices with and without embedded protease XIV was assessed both in vitro and in vivo. Ultimately, this new process approach provides direct control of the degradation lifetime of the devices, empowered through internal digestion via water-activated proteases entrained and stabilized during the thermoplastic process.

A Passive Ankle Dorsiflexion Testing System for an In Vivo Model of Overuse-induced Tendinopathy.

Tendinopathy is a chronic tendon condition that results in pain and loss of function and is caused by repeated overload of the tendon and limited recovery time. This protocol describes a testing system that cyclically applies mechanical loads via passive dorsiflexion to the rat Achilles tendon. The custom-written code consists of pre- and post-cyclic loading measurements to assess the effects of the loading protocol along with the feedback control-based cyclic fatigue loading regimen. We used 25 Sprague-Dawley rats for this study, with 5 rats per group receiving either 500, 1,000, 2,000, 3,600, or 7,200 cycles of fatigue loads. The percentage differences between the pre- and post-cyclic loading measurements of the hysteresis, peak stress, and loading and unloading moduli were calculated. The results demonstrate that the system can induce varying degrees of damage to the Achilles tendon based on the number of loads applied. This system offers an innovative approach to apply quantified and physiological varying degrees of cyclic loads to the Achilles tendon for an in vivo model of fatigue-induced overuse tendon injury.

Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses.

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.

Bacteriophage therapy and current delivery strategies for orthopedic infections: A SCOPING review.

OBJECTIVES: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized. METHODS: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central. RESULTS: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described. CONCLUSIONS: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.

Plastic and elastic biomechanical properties of anterior cruciate ligament autografts.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common orthopedic injury, occurring in roughly 68.6 per 100,000 persons annually, with the primary treatment option being ACL reconstruction. However, debate remains about the appropriate graft type for restoring the native biomechanical properties of the knee. Furthermore, plastic graft elongation may promote increased knee laxity and instability without rupture. This study aims to investigate the plastic properties of common ACL-R graft options. METHODS: Patellar tendon (PT), hamstring tendon (HT), and quadriceps tendon (QT) grafts were harvested from 11 cadaveric knees (6 male and 5 female) with a mean age of 71(range 55-81). All grafts were mechanically tested under uniaxial tension until failure to determine each graft's elastic and plastic biomechanical properties. RESULTS: Mechanically, the QT graft was the weakest, exhibiting the lowest failure force and the lowest failure stress (QT < HT, p = 0.032). The PT was the stiffest of the grafts, having a significantly higher stiffness (PT > QT, p = 0.0002) and Young's modulus (PT > QT, p = 0.001; PT > HT, p = 0.041). The HT graft had the highest plastic elongation at 4.01 ± 1.32 mm (HT > PT, p = 0.002). The post-yield behavior of the HT tendon shows increased energy storage capabilities with the highest plastic energy storage (HT > QT, p = 0.012) and the highest toughness (HT > QT, p = 0.032). CONCLUSION: Our study agrees with prior studies indicating that the failure load of all grafts is above the requirements for everyday activities. However, grafts may be susceptible to yielding before failure during daily activities. This may result in the eventual loss of functionality for the neo-ACL, resulting in increased knee laxity and instability.