Dendritic macromolecules are well-defined highly branched macromolecules synthesized via a divergent or convergent approach. A salient feature of the macromolecules described herein, and a goal of our research effort, is to prepare dendritic macromolecules suitable for in vitro and in vivo use by focusing on biocompatible building blocks and biodegradable linkages. These dendritic macromolecules can be subsequently crosslinked to form hydrogels using a photochemical acrylate-based or a chemical ligation strategy. The properties—mechanical, swelling, degradation, and so forth—of the hydrogels can be tuned by altering the composition, crosslinking chemistry, wt %, generation number and so forth. The utility and diverse applicability is demonstrated through successful use of these hydrogels in three unique applications: hydrogel adhesives for repairing corneal wounds, hydrogel scaffolds for cartilage tissue engineering, and hydrogel reaction chambers for high throughput screening of molecular recognition events. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 383–400, 2008.