Search bioRxiv⌕ Search

Biology subjects

Paschall, L. N.

Publications and source records attributed to Paschall, L. N..

2 recordsLinked to original sources

Allograft and Autograft Anterior Cruciate Ligament Reconstructions Exhibit a Similar Biological Response to Cyclic Loading

ObjectiveAnterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. While outcomes are similar in the general patient population, the rerupture rate of non-irradiated allografts are 3-4 times higher than autografts in young active individuals. Previous studies suggest that the difference in clinical performance between graft types is due to impaired remodeling in allografts in response to loading. The objective of this study was to compare the remodeling response of autografts and allografts to cyclic loading. Furthermore, given that allografts are a foreign object and that immune cell signaling affects fibroblast mechanobiology, we compared markers of the immune cell composition between graft types. MethodsACL reconstructions were performed on New Zealand white rabbits, harvested 8 weeks post-surgery, and cyclically loaded to 2 MPa in a tensile bioreactor. Expression of markers for anabolic and catabolic tissue remodeling, as well as inflammatory cytokines and immune cells, were quantified using quantitative reverse transcription polymerase chain reaction. ResultsWe found that the expression of markers for tissue remodeling were not different between allografts and autografts. Similarly, we found that the expression of markers for immune cells were not different between allografts and autografts. ConclusionsThese data suggest that the poor clinical outcomes and impaired remodeling of allograft reconstructions compared to autografts is not due to a difference in graft mechanobiology.

bioengineering↗

Cyclic Loading Induces Anabolic and Catabolic Gene Expression in ACLs in a Load-Dependent and Sex-Specific Manner

Anterior cruciate ligament (ACL) injuries are historically thought to be a result of a single acute overload or traumatic event. However, recent studies suggest that ACL failure may be a consequence of fatigue damage. Additionally, the remodeling response of ACLs to fatigue loading is unknown. Therefore, the objective of this study was to investigate the remodeling response of ACLs to cyclic loading. Furthermore, given that women have an increased rate of ACL rupture, we investigated whether this remodeling response is sex specific. ACLs were harvested from male and female New Zealand white rabbits and cyclically loaded in a tensile bioreactor mimicking the full range of physiological loading (2, 4, and 8 MPa). Expression of markers for anabolic and catabolic tissue remodeling, as well as inflammatory cytokines, was quantified using RT-qPCR. We found that the expression of markers for tissue remodeling of the ACL is dependent on the magnitude of loading and is sex specific. Male ACLs activated a tissue remodeling response to cyclic loading below 4 MPa loads but turned off remodeling at 8 MPa. These data support the hypothesis that noncontact ACL injury is a consequence of failed tissue remodeling and inadequate repair of microtrauma resulting from fatigue loading. Conversely, female ACLs downregulate genes responsible for tissue remodeling in response to cyclic loading at all magnitudes, which may explain the increased rate of ACL tears in women. Together, these data provide insight into the remodeling response of ACLs in vivo and potentially offer novel approaches for preventing ACL rupture.

bioengineering↗