Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material.

Abstract

The biomaterials-host interaction is a dynamic process in which macrophages play a vital role of regulation. Depending on the biochemical signals they sense, these highly plastic cells can mediate the immune response against the implanted scaffolds and/or exert regenerative potency to varying extent. Designing appropriate 'exterior signals' for scaffolds may exploit the power of endogenous macrophages to aid the regeneration of engineered tissues. To realise this goal, this study devised an injectable, instantaneously-solidifying coating material (acBSP) based on a unique, macrophage-affinitive glucomannan polysaccharide. Coating of three-dimensional hydrogel constructs with acBSP was rapid, neat and complete, requiring neither chemical reactions nor harsh conditions. Comprehensive in vitro analyses indicated that acBSP efficiently facilitated the adhesion and activation of macrophages and notably induced the macrophages to express pro-osteogenic/-angiogenic genes. Further in vivo assessment of acBSP-coated, mesenchymal stem cells-laden hydrogels in a murine dorsal subcutaneous pocket model demonstrated efficient macrophage activation, desirable scaffold-tissue integration and improved osteogenic differentiation in the delivered cells. In summary, by activating macrophages into a pro-osteogenic phenotype, the acBSP coating has demonstrated its competency as an innovative, open and efficacious platform to harness the power of host immunity for enhancing the regenerative performance of engineered tissue constructs.