Development and characterization of an immunomodulatory and injectable system composed of collagen modified with trifunctional oligourethanes and silica
Immunomodulatory biomaterials have emerged as a promising approach to engineer wound healing. To achieve this task, the bioactivity of the biomaterials and an easy application are two key desirable characteristics. This work reports an injectable gel system containing immune cells primed for wound healing. By combining the self-assembly of type I collagen, crosslinked with trifunctional oligourethanes, and silica particle entrapment, the structured collagen network acts as a delivery vehicle for macrophages. This structured collagen network primes the macrophages towards an anti-inflammatory response. Rheological measurements suggest that the mixture of liquid precursors can be safely stored at low temperature and low pH (4°C, pH 3) for at least one month. After pH neutralization and injection, gels with a storage modulus of 50-80 Pa are obtained in five minutes. Several immunocytochemistry and ELISA tests strongly suggest, mouse and human macrophages are stimulated by the material to up-regulate the production of anti-inflammatory cytokines, while down-regulating the production of pro-inflammatory cytokines. The injection of gel in an ex vivo inflammation model of intervertebral disc demonstrated that it is possible to transit from a pro-inflammatory to an anti-inflammatory micro-environment. Altogether, the results suggest that this gel can polarize the macrophage response and promoting a surrounding anti-inflammatory micro-environment ready for injection for wound healing applications.