Articular cartilage injuries (ACIs), which predominantly affect about 37% of young high-level athletes and around 40% of adults over the age of 65, consist of acute and intense joint loading causing sharp pain, joint dysfunction, effusion, and a potential progression to joint degeneration. ACIs are characterized by several severities of lesions, namely low-grade or chondral lesions (grades 1-3) that do not fully reach the bone and are characterized by cartilage swelling or partial-thickness loss, and full-thickness or subchondral lesions (grade 4) that do fully reach the bone. Although intrinsic healing is possible in both cases, these injuries collectively disrupt the integration of the cartilage extracellular matrix and consequently interrupt mechanical load distribution throughout the cartilage and joint as a whole. The mechanical mismatch can eventually lead to osteoarthritis, which leads to the progressive loss of cartilage, destruction of the subchondral bone, and deterioration of ligaments, among other damaging effects, as well as a detrimental loss of aggrecan, an important component of cartilage. Current interventions to aid in the repair of cartilage include microfracture,osteochondral autograft transplantation, and autologous chondrocyte implantation. These surgeries can aid in providing improved temporary comfort to the patient and artificial repairs to the site of injury but fail in significantly reintegrating the cartilage extracellular matrix and maintaining the mechanical load distribution present prior to the injury.

Therefore, this project seeks to utilize chondrocyte-binding peptide RLD-RLD to improve extracellular matrix integration at the interface between cartilage. The first part of the study consists of verifying the adsorption of RLD-RLD to ATDC5 chondrogenic cells. These cells were grown in both 2D as a monolayer and 3D as cell pellets, and the adsorption of RLD-RLD and VTK, a peptide previously identified to have a high affinity for apatite, was measured. After ensuring the adsorption of RLD-RLD to ATDC5 cells, 3D ATDC5 pellets were combined after a 7-day culture period and the peptide was added to chondrogenic media for 3- and 7-day periods. Pellets were then sectioned and stained to visualize the integration of ECM at the interface, and a quantitative scoring system was used to characterize the pellets with and without the use of the peptide. Finally, pellets were again grown for a 7-day period and then combined along with RLD-RLD for a 3-day period, and atomic force microscopy was performed on the pellets to determine the mechanical integration strength between the pellets.

Overall, the data demonstrated an increase in integration at the interface between pellets with the chondrocyte-binding peptide compared to the control group with no peptide. These findings can be utilized for future investigation of the use ofRLD-RLD in many cartilage applications, specifically in using a form of this peptide for integration at the cartilage-bone interface, which would be useful for the healing of subchondral lesions. It would also be beneficial to continue these studies in vivo with a mice model to investigate its advantage when applied directly to injured cartilage.

DATE: Thursday, April 21, 2022
TIME: 12:00 PM (Noon)
Zoom: https://umich.zoom.us/j/99821287326 (Passcode: 926901)
Chair: Prof. David Kohn