Immunomodulation-based development engineering for advancing metal soft tissue implants

Metal materials have been widely applied clinically due to their superior mechanical properties. However, the integration of metallic implants with surrounding soft tissue remains challenging and may lead to severe infections and failure of treatments. Development of natural exemplar suggests that the establishment of the soft tissue integration around hard surfaces is a complex scenario associated with the coordination of epithelial tissue, connective tissue and immune cells. In addition, the influence of the peri-implant immune microenvironment on soft tissue integration reparative process has received increasing attention. Given that the properties of the metal implant could effectively modulate immune response, it is predictable to regulate the immune microenvironment around metal implants for optimized soft tissue integration. This review firstly compared the establishment of natural biological hard surface-soft tissue integration with metal implants, in which the important role of epithelial tissue, connective tissue and immune cells were emphasized. Furthermore, up-to-date research outcomes in the closely connections between the immune microenvironment and soft tissue integration were discussed and summarized. From the view of natural soft-hard tissue integration development and reparative process, the immunomodulation-based strategy is proposed to manipulate the immune microenvironment for the enhancement of soft tissue-metal implant integration.