Disrupted bone metabolism can lead to delayed fracture healing or non-union, often requiring intervention to correct. Although the current clinical gold standard bone graft implants and commercial bone graft substitutes are effective, they possess inherent drawbacks and are limited in their therapeutic capacity for delayed union and non-union repair. Research into advanced biomaterials and therapeutic biomolecules has shown great potential for driving bone regeneration, although few have achieved commercial success or clinical translation. There are a number of therapeutics, which influence bone remodelling, currently licensed for clinical use. Providing an alternative local delivery context for these therapies, can enhance their efficacy and is an emerging trend in bone regenerative therapeutic strategies. This review aims to provide an overview of how biomaterial design has advanced from currently available commercial bone graft substitutes to accommodate previously licensed therapeutics that target local bone restoration and healing in a synergistic manner, and the challenges faced in progressing this research towards clinical reality. The combined use of biomaterial scaffolds with licensed pro-anabolic and anti-catabolic therapeutics to target local bone restoration and healing in a synergistic manner by enhancing osteoblast activity and reducing osteoclast activity. As a result, the deposition and formation of bone is expedited yielding improved stability and osseous bridging for non-union fracture repair. Display omitted