Injectable "smart" materials are emerging as promising platforms for minimally invasive cell delivery and tissue regeneration. A novel thermoresponsive complex coacervate was engineered through electrostatic interactions between natural polysaccharides grafted with poly(N-isopropylacrylamide) (PNIPAAm). The resulting biopolymeric-derived coacervate exhibits pronounced shear-thinning behavior and undergoes a rapid sol-gel transition at physiological temperature. Rheological analysis revealed that the thermoresponsive PNIPAAm chains regulate network dynamics, with faster relaxation at 25°C and enhanced structuring at 37°C due to increased hydrophobic interactions. The designed complex coacervate provides an efficient transport vehicle for the in situ retention of liquid-core capsules (LC) loaded with human adipose stem cells, promoting autonomous and hierarchical tissue organization. This system retained its shear-thinning properties even at high LC volumetric ratios (up to 54%) and supported high cell viability at least for 7 days. This strategy enables cell encapsulation in a thermoresponsive injectable complex coacervate that can be loaded with virtually any, or even multiple, cell types, offering a highly modular and cytocompatible platform. Altogether, this work introduces a new paradigm for the design of bioinspired, thermoresponsive complex coacervates, offering hierarchical control over cellular organization enabling the decoupling of tissue-forming units from the transport matrix.
Monteiro et al. (2026) studied this question.