Self-healing injectable gelatin hydrogels for localized therapeutic cell delivery

Self-healing injectable hydrogel biomaterials uniquely enable precise therapeutic deposition and deployment at specific bodily locations through versatile and minimally invasive processes that can preserve cargo integrity and cell viability. Despite the distinct advantages that injectable hydrogels offer in tissue engineering and therapeutic delivery, exceptionally few have been created using components naturally present in the cellular niche. In this work, we introduce a shear-thinning hydrogel based on guest-host complexation of gelatin. As a biocompatible, biodegradable, and nonimmunogenic biopolymer derived from the most abundant extracellular matrix protein (collagen), gelatin offers great utility as the structural component of biomaterials. Taking advantage of reversible guest-host interactions between beta-cyclodextrin (CD) and adamantane (AD) on modified gelatins, we report the first strategy to afford a self-healing material based solely on a functionalized extracellular matrix protein. By varying the initial material formulation, hydrogels were synthesized with variable moduli and shear-thinability across a broad range. Gels were demonstrated to exhibit shear-thinning and self-healing properties, supporting protection of clinically relevant stem-cell-derived cardiomyocytes during injection. These materials are expected to expand clinical opportunities in cell delivery for in vivo tissue regeneration.