Advanced Biomaterial-Based In Vitro Osteoarthritis Models: Integrating Sex as a Biological Variable in Hormonal,...

Area of Science:

• Bioengineering
• Materials Science
• Cell Biology
• Translational Medicine

Background:

• Osteoarthritis (OA) disproportionately affects women, yet current in vitro models lack sex-specific considerations.
• Hormonal changes and subchondral bone remodeling, which differ between sexes, significantly influence OA progression.
• Existing experimental systems fail to fully replicate sex-dependent OA mechanisms, hindering research.

Purpose of the Study:

• To highlight the limitations of current sex-neutral in vitro OA models.
• To emphasize the need for sex-specific variables in OA research.
• To propose next-generation in vitro systems for improved OA mechanistic understanding and therapy development.

Main Methods:

• Review of existing in vitro osteoarthritis models and their limitations.
• Analysis of sex-specific factors influencing OA pathogenesis, including hormonal fluctuations and subchondral bone.
• Conceptualization of advanced in vitro systems integrating material properties, dynamic loading, and hormonal modulation.

Main Results:

• Current in vitro OA models do not adequately account for sex-specific biological differences.
• Sex-neutral assumptions in model design limit the capture of divergent OA disease trajectories.
• Advanced biomaterials and tunable conditions are necessary to address these limitations.

Conclusions:

• Next-generation in vitro systems integrating material properties, dynamic loading, and hormonal conditions are essential.
• These advanced models can improve mechanistic understanding of OA and enhance drug screening reliability.
• Developing sex-specific OA therapies requires a multidisciplinary approach combining bioengineering, materials science, and cell biology.