Turning Nature's own processes into design strategies for living bone implant biomanufacturing: a decade of Developmental Engineering

Abstract

A decade after the term developmental engineering (DE) was coined to indicate the use of developmental processes as blueprints for the design and development of engineered living implants, a myriad of proof-of-concept studies demonstrate the potential of this approach in small animal models. This review provides an overview of DE work, focusing on applications in bone regeneration. Enabling technologies allow to quantify the distance between in vitro processes and their developmental counterpart, as well as to design strategies to reduce that distance. By embedding Nature's robust mechanisms of action in engineered constructs, predictive large animal data and subsequent positive clinical outcomes can be gradually achieved. To this end, the development of next generation biofabrication technologies should provide the necessary scale and precision for robust living bone implant biomanufacturing.

Keywords: Automation; Biofabrication; Biomanufacturing; Clinical translation; Endochondral ossification; In silico tools; Omics; Scale-up; Tissue engineering.