Hyaluronic acid macromer molecular weight dictates biophysical properties and in vitro cellular response to semi-synthetic hydrogels

In situ forming hydrogels present a promising approach for minimally invasive cell transplantation and tissue regeneration. Amongst prospective materials, hyaluronic acid (HyA) has displayed great potential, owing to its inherent biocompatibility, biodegradation and ease of chemical modification. However, current studies in the literature use a broad range of HyA macromer molecular weights (MWs) from u003c100 kDa to 1 MDa with no consensus regarding an optimal MW for a specific application. We investigated the effects of different HyA macromer MW on key biophysical properties of semi-synthetic hydrogels, such as viscosity, gelation time, shear storage modulus, molecular diffusion, and degradation. Using higher MW HyA macromers leads to quicker gelation times and stiffer, more stable hydrogels with a smaller mesh sizes. Assessment of the potential for HyA hydrogels to support network formation by encapsulated vascular cells derived from human induced pluripotent stem cells (hiPSCs) in vitro reveals key differe...