Injectable Bi-layered Cryogel Scaffolds for Targeted Adhesion to Tissues

We present a simple strategy to fabricate injectable bi-layered hyaluronic acid cryogel scaffolds for use in biomedical applications. Specifically, bi-layered cryogel scaffolds were formed via the sequential freezing, layering, and photo-cross-linking of individual macromer solutions, introducing defined interfaces without compromising scaffold porosity and mechanical integrity. We leveraged this fabrication technique to create an easily deployable Janus patch that is non-adhesive on one side and adhesive to tissues (via electrostatic and covalent bonding) on the other side. This is of particular interest in the development of cardiac patches that should adhere to the epicardial surface of the heart but not to other tissues. Once applied with the adhesive side in contact with the heart muscle, the patch remained adhered for over 2 weeks ex vivo, whereas the non-adhesive side resisted tissue adhesion. As a further proof-of-concept, the scaffold was injected into the fluid-filled pericardial space of explanted hearts and showed directional adhesion.