Novel Techniques and Future Perspective for Investigating Critical-Size Bone Defects.

A critical-size bone defect is a challenging clinical problem in which a gap between bone ends will not heal and will become a nonunion. The current treatment is to harvest and transplant an autologous bone graft to facilitate bone bridging. To develop less invasive but equally effective treatment options, one needs to first have a comprehensive understanding of the bone healing process. Therefore, it is imperative to leverage the most advanced technologies to elucidate the fundamental concepts of the bone healing process and develop innovative therapeutic strategies to bridge the nonunion gap. In this review, we first discuss the current animal models to study critical-size bone defects. Then, we focus on four novel analytic techniques and discuss their strengths and limitations. These four technologies are mass cytometry (CyTOF) for enhanced cellular analysis, imaging mass cytometry (IMC) for enhanced tissue special imaging, single-cell RNA sequencing (scRNA-seq) for detailed transcriptome analysis, and Luminex assays for comprehensive protein secretome analysis. With this new understanding of the healing of critical-size bone defects, novel methods of diagnosis and treatment will emerge.

Applying deep learning to quantify empty lacunae in histologic sections of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a disease in which inadequate blood supply to the subchondral bone causes the death of cells in the bone marrow. Decalcified histology and assessment of the percentage of empty lacunae are used to quantify the severity of ONFH. However, the current clinical practice of manually counting cells is a tedious and inefficient process. We utilized the power of artificial intelligence by training an established deep convolutional neural network framework, Faster-RCNN, to automatically classify and quantify osteocytes (healthy and pyknotic) and empty lacunae in 135 histology images. The adjusted correlation coefficient between the trained cell classifier and the ground truth was R = 0.98. The methods detailed in this study significantly reduced the manual effort of cell counting in ONFH histological samples and can be translated to other fields of image quantification.

Replication of the tensile behavior of knee ligaments using architected acrylic yarn.

Knee ligament injury diagnosis is achieved by a comparison between the laxity levels sensed by a clinician in the injured and healthy limb. This is a difficult-to-learn task that requires hands-on practice to achieve proficiency. The inclusion of a physical knee simulator with biomechanically realistic passive components such as knee ligaments could provide consistent training for medical students and lead to improved care for knee injury patients. In this study, we developed a material construct that is both adaptable to a physical knee model and capable of replicating the non-linear mechanical behavior of knee ligaments with the use of helically arranged acrylic yarn. The microstructure of four different types of acrylic yarn were measured and then tested under uniaxial tension. While the fiber twist angle was similar amongst the four yarn types (range = 17.9-18.8°), one yarn was distinct with a low ply twist angle (15.2 ± 1.6°) and high packing fraction (Φ=0.32±0.08). These microstructural differences yielded a lower toe length and higher stiffness and best corresponded to ligament mechanical behavior. We then made looped-yarn constructs to modulate the sample's toe length and stiffness. We found that the load-displacement curve of the construct can be tuned by changing the loop length and loop number of the looped-yarn constructs, matching the load-displacement curve of specific knee ligaments. This study shows how spun yarn can be used to replicate the mechanical behavior of knee ligaments, creating synthetic ligament constructs that could enable the construction of biomechanically realistic joints.

Outcomes of Arthroscopic All-Inside Repair Versus Observation in Older Patients With Meniscus Root Tears.

BACKGROUND: Meniscus root tears lead to de-tensioning of the meniscus, increased contact forces, and cartilage damage. Management of older patients with root tears is controversial and the efficacy of different treatment options is unclear. PURPOSE: To compare the clinical outcomes of patients with moderate knee osteoarthritis who underwent an all-inside meniscus root repair technique versus nonoperative management for either medial or lateral meniscus root tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients with a diagnosed posterior meniscus root tear who underwent arthroscopic repair (AR: 30 knees) or nonoperative treatment with observation (O: 18 knees) were followed for a minimum of 2 years (mean follow-up, 4.4 years). The arthroscopic repair included all-inside sutures to reduce the root back to its remnant (reduction sutures), thereby re-tensioning the meniscus, and 1 mattress suture to strengthen the repair by reapproximating the construct to the posterior capsule. The data collected included the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Tegner, and Veterans RAND 12-Item Health Survey (VR-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and conversion to total knee arthroplasty (TKA). RESULTS: Medial meniscus root tears comprised 80.0% of the AR group and 77.8% of the O group. The average Kellgren-Lawrence grade was 2 in both groups. The baseline scores for the KOOS Symptoms subscale were lower for AR (50.2 ± 19.3) than for O (66.5 ± 16.1) (P = .003), as were the KOOS Knee-Related Quality of Life scores (AR, 26.7 ± 16.1; O, 39.6 ± 22.1) (P = .046). No differences were found between groups for the absolute values at follow-up except that follow-up Tegner scores were lower in the O group than in the AR group (P = .004). Significant improvements were seen in the AR group from baseline to ultimate follow-up in average KOOS subscale scores (P < .001), Lysholm scores (P < .001), Tegner scores (P = .0002), and VR-12 PCS scores (P < .001), whereas the O group had a significant improvement only in average KOOS Pain (P = .003), KOOS Function in Daily Living (P = .006), and VR-12 PCS (P = .038) scores. Compared with the O group, the AR group had a significantly larger improvement from baseline to follow-up in average KOOS Pain (P = .009), KOOS Symptoms (P = .029), and Lysholm scores (P = .016). During follow-up, 3.3% of the AR group underwent a TKA compared with 33.3% of the O group (P = .008). The hazard ratio of TKA conversion was 93.2% lower for the AR group compared with the O group (P = .013). CONCLUSION: All-inside medial or lateral meniscus root repair showed improved functional outcomes and decreased TKA conversion rates compared with nonoperative treatment and may be considered as a treatment option for the management of meniscus root tears in older patients with moderate osteoarthritis.

Evaluation of the Consistency and Composition of Commercially Available Bone Marrow Aspirate Concentrate Systems.

BACKGROUND: Bone marrow aspirate (BMA) concentrate (BMAC) has gained popularity as a treatment modality for various orthopaedic conditions; however, there are still inconsistencies in its reported therapeutic efficacy. This may be because of the many different commercial BMAC preparation systems used clinically, which generate dissimilar concentrate products. PURPOSE: To compare 3 commercially available BMAC preparation systems: Harvest SmartPrep 3, Biomet BioCUE, and Arthrex Angel. We evaluated the consistency of each of these systems and compared the composition of their concentrate products. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 10 patients donated whole blood and BMA, which were combined and processed with the 3 different BMAC preparation systems. Samples were taken before and after processing for the measurement of white blood cells (WBC), platelets (PLT), CD34+ cells, and colony-forming unit-fibroblast (CFU-F). To evaluate consistency, the variances of cell yield and concentration increase from baseline for each cell type were compared between systems. To compare concentrate product composition, differences between the systems' mean cell yield and concentration increase from baseline for each cell type were evaluated. RESULTS: The Harvest system (variance, 0.25) concentrated WBC more consistently than the Arthrex system (variance, 3.25) (P = .024), but no other differences in consistency were noted between the 3 systems. The Harvest system recovered the greatest percentage of CFU-F (82.4% ± 18.2%), CD34+ cells (81.1% ± 28.5%), and WBC (77.3% ± 8.6%), whereas the Biomet system recovered the greatest percentage of PLTs (92.9% ± 27.3%). The Arthrex system concentrated PLT to the greatest degree (11.10 ± 2.05 times baseline), while the Biomet system concentrated WBC to the greatest degree (5.99 ± 1.04 times baseline). CONCLUSION: The consistency of the 3 systems was similar for all but 1 of the evaluated cell types. However, the composition of the concentrate products differed across systems. This may grant each system unique advantages without having to sacrifice reproducibility. CLINICAL RELEVANCE: Understanding the consistency of different BMAC preparation systems and their product makeup may aid in determining optimal therapeutic doses of different cell types.