One of the outcomes of the past few decades of focus on the development of tissue engineering and cell therapies is an increased understanding of what can be achieved with nanomaterials, meaning any manufactured substance or structure with nanoscale features that can engage with cells in a defined way. The use of nanoscale scaffolding to emulate aspects of the extracellular matrix in order to support transplanted cells is a going concern, for example. Another line of research and development is the use of nanoparticles that are engineered to steer tissue penetration in specific directions, release cargo in response to specific stimuli, and interact with cells to alter their behavior. Here, researchers review the state of the art in the context of developing therapies for osteoarthritis, the age-related degeneration of joint tissues.
Osteoarthritis (OA) is no longer viewed as a mere "wear-and-tear" disease, but rather as a multifactorial joint failure syndrome driven by cellular senescence, metabolic dysregulation, and low-grade chronic inflammation. These pathological pillars synergistically disrupt cartilage homeostasis, subchondral bone remodeling, and synovial inflammation, collectively fueling disease progression. While conventional therapies offer only symptomatic relief, they fail to reverse or reprogram the underlying pathological microenvironment. Consequently, there is an urgent need to develop disease-modifying interventions that can simultaneously target these pathological pillars.
Here, we critically examine how nanomaterial-based platforms - leveraging tailorable surface chemistry, cartilage-penetrating dimensions, and stimuli-responsive cargo release - enable precision targeting of these interconnected mechanisms. We highlight advances in senolytic delivery for senescent cell clearance, redox-modulating nanozymes for metabolic reprogramming, and immunoregulatory strategies for macrophage repolarization, emphasizing designs that transcend passive drug delivery to actively remodel the joint microenvironment. By integrating mechanistic insights with engineering innovation, this review outlines a roadmap for next-generation disease-modifying nanomedicines that promise not merely to slow OA progression, but to restore the biological clock of the joint. We also discuss current translational barriers and propose future directions for personalized OA therapy.
Link: https://doi.org/10.2147/IJN.S584027
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