Abstract: A method of making a modified hyaluronate composition including providing an aqueous solution of uncrosslinked hyaluronic acid or sodium hyaluronate in unbuffered 135 to 200 mM NaCl, crosslinking the uncrosslinked hyaluronic acid or sodium hyaluronate in the aqueous solution with a dialdehyde or disulfide crosslinking agent to provide crude modified hyaluronate having a soluble fraction and a crosslinked fraction with a 10% to 98% degree of crosslinking, centrifuging the crude modified hyaluronate and removing at least a portion of the soluble fraction, and optionally repeating the centrifuging and removing until the modified hyaluronate has less than 10% by weight of the soluble fraction based on the total weight of hyaluronate, with a soluble fraction polydispersity (Mw/Mn) of 1 to 1.6, an Rh of the crosslinked fraction of 150 nm to 2000 nm, and an Rz of the crosslinked fraction of 50 nm to 700 nm, wherein Rh>Rz.

Abstract: A method of making a modified hyaluronate composition including providing an aqueous solution of uncrosslinked hyaluronic acid or sodium hyaluronate in unbuffered 135 to 200 mM NaCl, crosslinking the uncrosslinked hyaluronic acid or sodium hyaluronate in the aqueous solution with a dialdehyde or disulfide crosslinking agent to provide crude modified hyaluronate having a soluble fraction and a crosslinked fraction with a 10% to 98% degree of crosslinking, centrifuging the crude modified hyaluronate and removing at least a portion of the soluble fraction, and optionally repeating the centrifuging and removing until the modified hyaluronate has less than 10% by weight of the soluble fraction based on the total weight of hyaluronate, with a soluble fraction polydispersity (Mw/Mn) of 1 to 1.6, an Rh of the crosslinked fraction of 150 nm to 2000 nm, and an Rz of the crosslinked fraction of 50 nm to 700 nm, wherein Rh>Rz.