Extracellular matrix‐blood composite injection reduces post‐traumatic osteoarthritis after anterior cruciate ligament injury in the rat

Abstract

Purpose The objective of this study was to determine if an injection of a novel extracellular matrix scaffold and blood composite (EMBC) after anterior cruciate ligament (ACL) injury would have a mitigating effect on post-traumatic osteoarthritis (PTOA) development in rat knees. Methods Lewis rats underwent unilateral ACL transection and were divided into three groups: 1) no further treatment (ACLT; n = 10), 2) an intraarticular injection of EMBC on day 0 (INJ0; n = 11), and 3) an intra-articular injection of EMBC on day 14 (INJ14; n = 11). Ten animals received capsulotomy only (n = 10, SHAM group). The OARSI histology scoring of the tibial cartilage and micro-CT of the tibial epiphysis were performed after 35 days. The ratio of intact/treated hind limb forces during gait was determined using a variable resistor walkway. Results The OARSI cartilage degradation sum score and total degeneration width were significantly greater in the ACLT group when compared to the INJ0 (P = 0.031, and P = 0.005) and INJ14 (P =0.022 and P =0.04) group. Weight bearing on the operated limb only decreased significantly in the ACLT group (P = 0.048). Conclusion In the rat ACL transection model, early or delayed injection of EMBC ameliorated the significant decrease in weight bearing and cartilage degradation seen in knees subjected to ACL transection without injection. The results indicate that the injection of EMBC may slow the process of PTOA following ACL injury and may provide a promising treatment for PTOA.

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model

“…The results with this method identified bone loss in the ACL transected knee, suggesting a global response of the bone to joint unloading, which agree with previous reports of bone loss in the medial compartment of the tibial epiphyses with ACL transection (Maerz et al, 2016; Mohan et al, 2016; Proffen et al, 2016). Previous studies suggest that decreases in BV/TV correspond to unloading of the ACL transected limb or due to an inflammatory response that affects bone resorption (Jay et al, 2012; Maerz et al, 2016; Proffen et al, 2016).…”

“…The results with this method identified bone loss in the ACL transected knee, suggesting a global response of the bone to joint unloading, which agree with previous reports of bone loss in the medial compartment of the tibial epiphyses with ACL transection (Maerz et al, 2016; Mohan et al, 2016; Proffen et al, 2016). Previous studies suggest that decreases in BV/TV correspond to unloading of the ACL transected limb or due to an inflammatory response that affects bone resorption (Jay et al, 2012; Maerz et al, 2016; Proffen et al, 2016). A limitation of our analysis is that we did not include a sham operated group; however, we previously found that the BV/TV values for the contralateral knees of the ACL transected group were equivalent to the BV/TV means of the sham group using the Whole Compartment Method (Proffen et al, 2016), and therefore the data presented here are from both knees of the ACL transected group only.…”

“…Previous studies suggest that decreases in BV/TV correspond to unloading of the ACL transected limb or due to an inflammatory response that affects bone resorption (Jay et al, 2012; Maerz et al, 2016; Proffen et al, 2016). A limitation of our analysis is that we did not include a sham operated group; however, we previously found that the BV/TV values for the contralateral knees of the ACL transected group were equivalent to the BV/TV means of the sham group using the Whole Compartment Method (Proffen et al, 2016), and therefore the data presented here are from both knees of the ACL transected group only. Another limitation was that scanning was performed at 30 μm.…”

“…The animals used for this analysis were a subset from a larger study evaluating changes in joint arthrosis following treatment with an extracellular matrix blood composite (Proffen et al, 2016). Twelve week old Lewis rats (n=10) underwent unilateral ACL transection surgery to induce joint arthrosis under an IACUC approved protocol.…”

Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage

“…Posttraumatic OA in animals often occurs within 1 month to 1 year after injury, with smaller animals developing macroscopic changes in cartilage structure sooner than larger animals. 39 , 49 Furthermore, animal joints can be opened to directly evaluate the integrity of the graft and articular cartilage. For these reasons, animal models have been long used to study ACL injuries, treatments, and associated complications.…”