Patterns of multiscale molecular transport in cartilage with superficial zone damage under static conditions.

Articular cartilage, a typical avascular porous tissue, maintains metabolic homeostasis primarily through solute diffusion across tissue interfaces. The superficial zone (SFZ), the outermost structural interface of cartilage, plays a critical role in regulating molecular transport. However, the quantitative mechanisms by which SFZ damage affects size-dependent diffusion remain unclear. Here, two graded SFZ damage models, namely enzymatic degradation and 10% thickness mechanical removal, are established to systematically quantify the transport kinetics of small (479 Da), intermediate (40 kDa), and large (150 kDa) solutes along both surface (axial) and lateral pathways. Through systematic experimental characterization, this study reveals a pronounced, transport direction-dependent "decoupling effect" induced by SFZ damage. As the SFZ becomes progressively impaired, the overall tracer concentration within cartilage increases, penetration depth is significantly enhanced, and effective diffusivity is markedly elevated. Concurrently, the size-dependent sieving sensitivity of cartilage gradually diminishes, allowing large molecules to more readily accumulate in the deep regions of damaged tissue. Building on these findings, an anisotropic diffusion model is further developed, enabling effective prediction of macromolecular transport behavior under varying degrees of SFZ damage. These findings highlight the essential role of SFZ structural integrity in regulating intra-cartilage molecular transport and provide a theoretical framework for optimizing intra-articular delivery of therapeutic agents with varying molecular sizes.