Browsing by Author "Ahn, Taeyong"

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    Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice
    (Sage, 2023) Ahn, Taeyong; Loflin, Benjamin E.; Nguyen, Nicholas B.; Miller, Ciena K.; Colglazier, Kaitlyn A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of Medicine
    Background: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. Study design: Controlled laboratory study. Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors' hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. Clinical relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.
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    An Adolescent Murine In Vivo Anterior Cruciate Ligament Overuse Injury Model
    (Sage, 2023) Loflin, Benjamin E.; Ahn, Taeyong; Colglazier, Kaitlyn A.; Banaszak Holl, Mark M.; Ashton-Miller, James A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of Medicine
    Background: Overuse ligament and tendon injuries are prevalent among recreational and competitive adolescent athletes. In vitro studies of the ligament and tendon suggest that mechanical overuse musculoskeletal injuries begin with collagen triple-helix unraveling, leading to collagen laxity and matrix damage. However, there are little in vivo data concerning this mechanism or the physiomechanical response to collagen disruption, particularly regarding the anterior cruciate ligament (ACL). Purpose: To develop and validate a novel in vivo animal model for investigating the physiomechanical response to ACL collagen matrix damage accumulation and propagation in the ACL midsubstance, fibrocartilaginous entheses, and subchondral bone. Study design: Controlled laboratory study. Methods: C57BL/6J adolescent inbred mice underwent 3 moderate to strenuous ACL fatigue loading sessions with a 72-hour recovery between sessions. Before each session, randomly selected subsets of mice (n = 12) were euthanized for quantifying collagen matrix damage (percent collagen unraveling) and ACL mechanics (strength and stiffness). This enabled the quasi-longitudinal assessment of collagen matrix damage accrual and whole tissue mechanical property changes across fatigue sessions. Additionally, all cyclic loading data were quantified to evaluate changes in knee mechanics (stiffness and hysteresis) across fatigue sessions. Results: Moderate to strenuous fatigue loading across 3 sessions led to a 24% weaker (P = .07) and 35% less stiff (P < .01) ACL compared with nonloaded controls. The unraveled collagen densities within the fatigued ACL and entheseal matrices after the second and third sessions were 38% (P < .01) and 15% (P = .02) higher compared with the nonloaded controls. Conclusion: This study confirmed the hypothesis that in vivo ACL collagen matrix damage increases with tissue fatigue sessions, adversely impacting ACL mechanical properties. Moreover, the in vivo ACL findings were consistent with in vitro overloading research in humans. Clinical relevance: The outcomes from this study support the use of this model for investigating ACL overuse injuries.
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    Endurance running during late murine adolescence results in a stronger anterior cruciate ligament and flatter posterior tibial slopes compared to controls
    (Springer, 2022-01-03) Ochocki, Danielle N.; Loflin, Benjamin E.; Ahn, Taeyong; Colglazier, Kaitlyn A.; Young, Andrew R.; Snider, Anna A.; Bueckers, Elizabeth P.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of Medicine
    Background: Anterior cruciate ligament (ACL) injury rates continue to rise among youth involved in recreational and competitive athletics, requiring a better understanding of how the knee structurally and mechanically responds to activity during musculoskeletal growth. Little is understood about how anatomical risk factors for ACL injury (e.g., small ACL size, narrow intercondylar notch, and steep posterior tibial slope) develop and respond to increased physical activity throughout growth. We hypothesized that the ACL-complex of mice engaged in moderate to strenuous physical activity (i.e., endurance running) throughout late adolescence and young adulthood would positively functionally adapt to repetitive load perturbations. Methods: Female C57BL6/J mice (8 weeks of age) were either provided free access to a standard cage wheel with added resistance (n = 18) or normal cage activity (n = 18), for a duration of 4 weeks. Daily distance ran, weekly body and food weights, and pre- and post-study body composition measures were recorded. At study completion, muscle weights, three-dimensional knee morphology, ACL cross-sectional area, and ACL mechanical properties of runners and nonrunners were quantified. Statistical comparisons between runners and nonrunners were assessed using a two-way analysis of variance and a Tukey multiple comparisons test, with body weight included as a covariate. Results: Runners had larger quadriceps (p = 0.02) and gastrocnemius (p = 0.05) muscles, but smaller hamstring (p = 0.05) muscles, compared to nonrunners. Though there was no significant difference in ACL size (p = 0.24), it was 13% stronger in runners (p = 0.03). Additionally, both the posterior medial and lateral tibial slopes were 1.2 to 2.2 degrees flatter than those of nonrunners (p < 0.01). Conclusions: Positive functional adaptations of the knee joint to moderate to strenuous exercise in inbred mice offers hope that that some anatomical risk factors for ACL injury may be reduced through habitual physical activity. However, confirmation that a similar response to loading occurs in humans is needed.