Stem cell implantation strategy has exhibited potential to treat the myocardial infarction (MI), however, the low retention and survival limit their applications due to the reactive oxygen species (ROS) microenvironment after MI. In this study, the fullerenol nanoparticles are introduced into alginate hydrogel to create an injectable cell delivery vehicle with antioxidant activity. Results suggest that the prepared hydrogels exhibit excellent injectable and mechanical strength. In addition, the fullerenol/alginate hydrogel can effectively scavenge the superoxide anion and hydroxyl radicals. Based on these results, the biological behaviors of brown adipose-derived stem cells (BADSCs) seeded in fullerenol/alginate hydrogel were investigated in the presence of HO. Results suggest that the fullerenol/alginate hydrogels have no cytotoxicity effects on BADSCs. Moreover, they can suppress the oxidative stress damage of BADSCs and improve their survival capacity under ROS microenvironment via activating the ERK and p38 pathways while inhibiting JNK pathway. Further, the addition of fullerenol can improve the cardiomyogenic differentiation of BADSCs even under ROS microenvironment. To assess its therapeutic effects in vivo, the fullerenol/alginate hydrogel loaded with BADSCs were implanted in the MI area in rats. Results suggest that the fullerenol/alginate hydrogel can effectively decrease ROS level in MI zone, improve the retention and survival of implanted BADSCs, and induce angiogenesis, which in turn promote cardiac functional recovery. Therefore, the fullerenol/alginate hydrogel can act as injectable cell delivery vehicles for cardiac repair.

Hydrogels based on supramolecular noncovalent interactions have attracted great research interest but are still limited by relatively low mechanical strength and performance deterioration at subzero temperatures because of the formation of ice crystallization. In this study, an antifreezing and mechanically strong gelatin supramolecular organohydrogel is prepared via a simple strategy of immersing a gelatin pre-hydrogel in the citrate (Cit) water/glycerol mixture solution. In the organohydrogel, a part of water molecules are replaced by glycerol, which inhibits the formation of ice crystallization even at extremely low temperature. In addition, the formation of noncovalent interactions such as the hydrophobic aggregation induced by the salting-out effect, ionic interactions between the −NH 3 + of gelatin and Cit 3− anions, and hydrogen bonding between gelatin chains and glycerol endows the organohydrogels with high mechanical strength and toughness. The supramolecular organohydrogel can maintain its mechanical flexibility even at −80 °C or be stored for a long time. Moreover, the nature of noncovalent interactions endows the organohydrogel with intriguing thermoplasticity, good healable ability, and excellent adhesive behavior at various substrate surfaces.

The high mechanical strength and long-term resistance to the fibrous capsule formation are two major challenges for implantable materials. Unfortunately, these two distinct properties do not come together and instead compromise each other. Here, we report a unique class of materials by integrating two weak zwitterionic hydrogels into an elastomer-like high-strength pure zwitterionic hydrogel via a “swelling” and “locking” mechanism. These zwitterionic-elastomeric-networked (ZEN) hydrogels are further shown to efficaciously resist the fibrous capsule formation upon implantation in mice for up to 1 year. Such materials with both high mechanical properties and long-term fibrous capsule resistance have never been achieved before. This work not only demonstrates a class of durable and fibrous capsule–resistant materials but also provides design principles for zwitterionic elastomeric hydrogels.