Perforated red blood cells enable compressible and injectable hydrogels as therapeutic vehicles

Abstract

Hydrogels engineered for medical use within the human body need to be delivered in a minimally invasive fashion without altering their biochemical and mechanical properties to maximize their therapeutic outcomes. In this regard, key strategies applied for creating such medical hydrogels include formulating precursor solutions that can be crosslinked in situ with physical or chemical cues following their delivery or forming macroporous hydrogels at sub-zero temperatures via cryogelation prior to their delivery. Here, we present a new class of injectable composite materials with shape recovery ability. The shape recovery is derived from the physical properties of red blood cells (RBCs) that are first modified via hypotonic swelling and then integrated into the hydrogel scaffolds before polymerization. The RBCs' hypotonic swelling induces the formation of nanometer-sized pores on their cell membranes, which enable fast liquid release under compression. The resulting biocomposite hydrogel scaffolds display high deformability and shape-recovery ability. The scaffolds can repeatedly compress up to ~87% of their original volumes during injection and subsequent retraction through syringe needles of different sizes; this cycle of injection and retraction can be repeated up to ten times without causing any substantial mechanical damage to the scaffolds. Our biocomposite material system and fabrication approach for injectable materials will be foundational for the minimally invasive delivery of drug-loaded scaffolds, tissue-engineered constructs, and personalized medical platforms that could be administered to the human body with conventional needle-syringe systems.