The present disclosure provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a biological macromolecule comprising one or more thiol groups; and (b) a molecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure also provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a molecule comprising one or more thiol groups; and (b) a biological macromolecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure further provides a covalently modified biological macromolecule prepared by any of the disclosed methods. The covalently modified biological macromolecules may be further crosslinked to form a scaffold.