Three-dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues.

A novel approach has been demonstrated to construct biocompatible, macroporous 3-D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(D,L-lactic-co-glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nano-phase material (PLGA encapsulating CaCO(3) or TiO(2) nanoparticles) were used for the construction of microsphere-based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO(3)/TiO(2) were fabricated via an ethanol sintering technique. The controllable mechanical characteristics and biocompatible nature of these scaffolds warrants further investigation for interfacial tissue engineering applications.