Modeling dECM-based inflammatory cartilage microtissues in vitro for drug screening

Compared to traditional 3D models lacking the native cellular microenvironment, cartilage decellularized extracellular matrix (dECM) has shown great advantages in understanding complex mechanisms of cartilage inflammatory diseases and drug treatment by providing an extracellular matrix and mesenchymal-like microenvironment. Herein, dECM replicates the cartilage tissue microenvironment by remodeling the cartilage matrix. We developed an efficient, rapid, and highly controllable cartilage inflammation model by dECM-based PLGA porous microspheres (dECM-PLGA PMs). Cartilage modular units prepared based on dECM were induced by lipopolysaccharide (LPS) to mimic cartilage inflammation in vivo. Subsequently, three different types of classical anti-inflammatory drugs, curcumin (Cur), icariin (ICA), and berberine hydrochloride (BH), were evaluated for their therapeutic effects, separately. Notably, the dECM-PLGA model showed significantly different pharmacological sensitivities to the three anti-inflammatory agents, along with ICA showing the highest therapeutic effect on cartilage inflammation. The effects of the different anti-inflammatory drugs were further verified in vivo using a rat model. In conclusion, these findings showed the constructed multicellular aggregates of dECM-PLGA PMs are promising for drug screening.