Transition metal/dECM hydrogel complexation for large-sized cell spheroid

Decellularized extracellular matrix (dECM) hydrogels are attractive biomaterials for tissue engineering due to their intrinsic tissue-specific characteristics and the complex three-dimensional microarchitecture of the original tissue. However, their limited mechanical stability in vitro hinders practical applications. In this study, we engineered porcine heart-derived dECM hydrogels reinforced with the transition metal compound potassium tetrachloroplatinate(II) (K₂PtCl₄). The incorporation of K₂PtCl₄ accelerated gelation and enhanced the structural stability of the hydrogels through coordination bonding between Pt ions and functional groups within dECM. Rheological analysis revealed concentration-dependent improvements in storage modulus, highlighting the tunable viscoelastic properties of the composites. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) confirmed the formation of Pt-dECM coordination molecular networks, while the native morphology of dECM was verified by scanning electron microscopy (SEM). Furthermore, the biocompatibility and functionality of cell spheroids prepared with metal/dECM hydrogel complex were validated, which exhibited stable morphology, high viability, and expressed E-cadherin-mediated cell-cell junctions within Pt-dECM hydrogels. These findings demonstrate that transition metal complexation effectively improves the mechanical and biological functionality of dECM hydrogels, thereby providing a versatile platform for 3D cell culture and regenerative medicine.