In this article, we describe the development of multifunctional, water-soluble hyperbranched polyglycerols containing redox-sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co) polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2-((2-oxiran-2-ylmethoxy) ethyl) disulfanyl) ethan-1-ol. Polymerizations were optimized at 65 degrees C unlike the homopolymerization of glycidol. Both low (5-10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2-carboxyethyl) phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules. (C) 2015 Wiley Periodicals, Inc.