The goal of this work was to design a device for rapid screening of crosslinked thermoset polymers. This gradient curing platform is capable of yielding a library of polyesters with systematically varying mechanical and physicochemical properties and the resultant cellular response. A library of poly(xylitolsebacate) polyesters was prepared in this device by differential curing to yield a gradient polymer. The resultant polymer exhibits a gradient in the storage modulus (1 to 5 MPa), wettability (70° < water contact angle < 110°), degree of crosslinking, degradation rate (3–25% in 7 days), drug release and biological response (ability to support stem cell proliferation and differentiation) from one end of the polymer to the other. Primary human mesenchymal stem cells were cultured to assess the cellular response in vitro. Maximal stem cell proliferation and osteogenesis was observed on the highly crosslinked polyester segments that provide high stiffness, are hydrophobic and are slow degrading as compared to the lower cured counterparts. Under in vivo conditions, this material showed differential response across the gradient without displaying significant concerns for inflammation or infection. This gradient curing device is capable of ascertaining suitable curing conditions to obtain appropriate polymers for application specific requirements. This gradient platform was further used to identify optimal processing parameters to prepare three-dimensional tissue scaffolds such as electrospun fiber mats and porous foams. Thus, this versatile combinatorial platform is well suited for rapid screening of thermoset polymers for biomedical applications. © 2018 Elsevier B.V.