Pediatric anterior cruciate ligament (ACL) injuries are a major problem in the pediatric and adolescent populations. Approximately one-quarter of these injuries only extend through only part of the tissue cross-section. Yet, there is very limited data to inform clinical treatments for pediatric partial ACL tears. In particular, understanding how injury severity impacts long-term degenerative changes in the joint is unknown. In this study, we leverage a skeletally immature preclinical porcine model to evaluate joint biomechanics, tissue remodeling, and degeneration after partial (isolated anteromedial (AM) or posterolateral (PL) bundle) or complete (full thickness) ACL injury. Six months after injury, joint laxity increases were minimal for PL bundle injury, minor for AM bundle injury, and major for ACL injury. In both partial injury cases, the remaining bundle remodeled through an increase in CSA to attempt to restore ACL function and stabilize the knee joint. Joint degeneration (evaluated by cartilage T1 relaxation, macroscopic cartilage degeneration, and meniscal hypertrophy) was minimal after PL bundle injury, moderate after AM bundle injury, and substantial after ACL injury. Further analysis with subjects grouped by Lachman grade (indicating the extent of joint destabilization) indicated that degeneration was associated with the extent of biomechanical destabilization, irrespective of the injury type. These findings point to the importance of considering the results of joint laxity exams when creating treatment plans for young patients with significant growth remaining, particularly those with partial ACL injuries.
Engineered scaffolds are commonly used to assist in cellular transplantations, providing crucial support and specific architecture for a variety of tissue engineering applications. Photopolymerization as a fabrication technique for cell scaffolds enables precise spatial and temporal control of properties and structure. One simple technique to achieve a two-dimensional structure is the use of a patterned photomask, which results in regionally selective photo-cross-linking. However, the relationships between photopolymerization parameters like light intensity and exposure time and outcomes like structural fidelity and mechanical properties are not well-established. In this work, we used photopolymerization to generate degradable polycaprolactone triacrylate (PCLTA) scaffolds with a defined microstructure. We examined the impact of light intensity and exposure time on scaffold properties such as shear modulus and micropore structure. To assess feasibility in a specific application and determine the relationship between parameter-driven properties and cell loading, we cultured retinal progenitor cells on the PCLTA scaffolds. We found that light intensity and polymerization time directly impact the scaffold stiffness and micropore structure, which in turn influenced the cell loading capacity of the scaffold. Because material stiffness and topography are known to impact cell viability and fate, understanding the effect of scaffold fabrication parameters on mechanical and structural properties is critical to optimizing cell scaffolds for specific applications.
Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 1-2 weeks after birth or were left intact (boars). Post-euthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars (p<0.001 for all measures). ACL cross-sectional area (CSA), length, volume, and stiffness all increased with age (p<0.0001), as did ACL anteromedial (AM) bundle percent contribution to resisting applied loads (p=0.012). Boar ACL and AM bundle volumes were 18% (p=0.003) and 24% (p=0.004) larger than barrows across ages. However, CSA, stiffness, and bundle contribution were similar between boars and barrows (p>0.05). The barrows had smaller temporal increases in AM bundle percent function than boars, but these data were highly variable. Thus, early and sustained loss in testosterone leads to subtle differences in ACL morphology, but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.
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