One of the critical challenge facing tissue enginering strategies relate to simultaneous generation of multiple tissues and its functional assembly that lead to complex organ systems[1]. The gradient of structural and mechanical properties present in tissues have led to engineering strategies that focus on this interface. The tissue-to-tissue interface is the most crucial parameter in the approach to multitissue repair. Tissue interfaces present a chemical hierarchical structure leading to different mechanical properties. The interface is the transition between two adjacent tissues as it presents a highly heterogenous structure of chemical and biological organization[2,3]. The hypothesis in this study is that differential functional properities can be engineered by modulation of macromolecules gradient in a cell seeded three-dimensional hydrogel system. Specifically, differential paracrine secretory profiles can be engineered using hBMSC. Hence, the specific objectives of this study are to: assemble the macromolecular gradient from natural materials (gellan gum, hyaluronic acid and collagen); to evaluate whether the gradient is suitable for hMSC encapsulation by cellular viability assessement; and screen the paracrine secretation of hBMSC over time within this gradient hydrogel system.