In the pancreas, extracellular matrix (ECM) components play an import role in providing mechanical and physiological support, and also contribute to the function of islets. These ECM-connections are damaged during islet-isolation from the pancreas and are not fully recovered after encapsulation and transplantation. To promote the functional survival of human pancreatic islets, we tested different ECMs molecules in alginate-encapsulated human islets. These were laminin derived recognition sequences, IKVAV, RGD, LRE, PDSGR, collagen I sequence DGEA (0.01-1.0 mM), and collagen IV (50-200 µg/ml). Interaction with RGD and PDSGR promoted islet viability and glucose induced insulin secretion (GIIS) when it was applied at concentrations ranging from 0.01- 1.0 mM (p<0.05). Also the laminin sequence LRE contributed to enhanced GIIS but only at higher concentrations of 1 mM (p<0.05). Collagen IV also had beneficial effects but only at 50 µg/ml and no further improvement was observed at higher concentrations. IKVAV and DGEA had no effects on human islets. Synergistic effects were observed by adding Collagen(IV)-RGD, Collagen(IV)-LRE, and Collagen(IV)-PDSGR to encapsulated human islets. Our results demonstrate the potential of specific ECM components in support of functional survival of human encapsulated and free islet grafts. This article is protected by copyright. All rights reserved.