A standardized, open-source, portable model for noninvasive joint injury in mice

Area of Science:

• Biomedical Engineering
• Orthopedics
• Preclinical Research

Background:

• Preclinical models are essential for osteoarthritis (OA) research and therapeutic development.
• Surgical models like destabilization of the medial meniscus (DMM) are established, but noninvasive joint loading models are gaining traction.
• Standardization of noninvasive mouse models is needed to improve reproducibility.

Purpose of the Study:

• To introduce the Mobile Joint-Injury Operator (MoJO) for standardized, noninvasive anterior cruciate ligament rupture (ACLR) induction in mice.
• To provide an open-source protocol, 3D-printable fixtures, and data for a low-cost, portable uniaxial testing system.
• To validate the MoJO system's accuracy, reproducibility, and its ability to generate a post-traumatic OA phenotype.

Main Methods:

• Developed and validated the MoJO system, including 3D-printable fixtures and a detailed loading protocol.
• Performed over 952 procedures to assess accuracy and inter-operator reproducibility.
• Characterized the post-traumatic OA phenotype using hyperalgesia testing, flow cytometry, micro-CT (μCT), and histology.

Main Results:

• The MoJO protocol achieved >99% success rate for ACLR with high accuracy and repeatability across operators and institutions.
• ACLR induction successfully generated a post-traumatic OA phenotype in male and female C57Bl/6 mice.
• Observed progressive hyperalgesia, cartilage damage, synovitis, osteophyte formation, and altered immune cell populations.

Conclusions:

• The MoJO system offers an affordable and highly reproducible method for implementing the mouse ACLR model.
• Standardization of joint injury via MoJO is crucial for refining OA animal models.
• This open-source approach facilitates wider adoption and advancement in OA research.