Abstract: Disclosed are hyaluronic acid (HA) compositions including crosslinked, water-insoluble, hydrated HA gel particles. Also disclosed are methods of making the HA compositions, and methods of using the HA composition to augment tissue in a subject.

Abstract: A method of treating a subject having a musculoskeletal disorder includes administering to a subject's articular site in need thereof an effective amount of a hyaluronic acid (HA) composition. In one embodiment, the HA composition includes an HA derivative, wherein carboxyl functionalities of the hyaluronic acid derivative are each independently derivatized to include an N-acylurea or 0-acyl isourea, or both N-acylurea and 0-acyl isourea. In another embodiment, the HA composition includes a crosslinked HA gel that is prepared by reacting an uncrosslinked HA with a biscarbodiimide in the presence of pH buffer in a range of between about 4 and about 8. The composite can optionally include at least one second bioactive agent other than the HA derivative, such as a steroid.

Abstract: A hyaluronic acid (HA) composition includes crosslinked, water-insoluble, hydrated HA gel particles. The HA includes crosslinks represented by the following structural formula: HA—U—R2—U—HA The variables are defined herein. A method of augmenting tissue in a subject includes inserting a needle into a subject at a location in the subject that is in need of tissue augmentation, wherein the needle is coupled to a syringe loaded with the HA composition, and applying force to the syringe, to deliver the HA composition into the subject. A method of preparing the HA composition, includes forming water-insoluble, dehydrated crosslinked HA particles, separating the water-insoluble, dehydrated particles by average diameter, selecting a subset of particles by average diameter, and hydrating the subset of dehydrated particles with a physiologically compatible aqueous solution.