Decoupled control of degradation and mechanical properties of in situ forming and fast dissolving polyaspartamide hydrogels

Abstract

Hydrogels are widely used in various biomedical applications such as scaffolds for cell and tissue culture, drug delivery systems, and biosensor platforms. Most hydrogels are created by crosslinking monomers or macromers via chemical reactions that require toxic initiation process. Therefore, the reactions that can proceed without initiators and are mild enough to minimize toxic effects, while still allowing hydrogel formation under aqueous conditions, are highly desired. Herein, a polyaspartamide-based crosslinker system that can undergo “in situ” forming chemical reactions to form hydrogels is presented. Polyaspartamide crosslinkers presenting amino functional groups with varying lengths and degrees of substitutions are efficiently synthesized by nucleophilic reactions with polysuccinimide. These crosslinkers are reacted with gel-forming polymers via Michael addition or Schiff base formation under physiological and biocompatible conditions (e.g. neutral pH, room temperature, no initiators). In addition, modulating the graft parameters allows the control of mechanical and degradational properties of resulting hydrogels in a wide range. Their biomedical potential as an injectable delivery system is demonstrated using ex vivo tissue model, in which the injection of precursor solution and subsequent hydrogel formation within the tissue are demonstrated.