Bone remodelling in vitro: Where are we headed? -A review on the current understanding of mimicking physiological bone remodelling and inflammation in vitro and the future strategies for testing biomaterials in vitro.

Bone remodelling is a dynamic process required for the maintenance of bone architecture in response to the changing mechanical needs. It is also a vital process during the repair of bone tissue following injury. Clinical intervention in terms of autografting or allografting is often required to heal bone injuries where physiological healing fails. The use of biomaterials as alternatives to autografts and allografts has spurred a significant research interest into further development of biomaterials for better clinical outcomes. Unfortunately, many biomaterials fail to make it to the clinic or fail after implantation due to the inconsistencies observed between in vitro and in vivo studies. It is therefore important to mimic the in vivo situation as closely as possible in an in vitro setting for testing biomaterials. The current in vitro models focus mostly on investigating the behaviour of osteoblast progenitors with the biomaterial under development as well as assessing the behaviour of osteoclasts, endothelial cells etc. However, the sequence of events that take place during bone healing or remodelling are not incorporated into the current in vitro models. This review highlights our current understanding of the physiological bone remodelling and the bone healing process followed by strategies to incorporate both the physiological and pathophysiological events into an in vitro environment. Here, we propose three main strategies for the assessment of biomaterials for bone, which includes; (1) testing biomaterials in the presence of immune cells, (2) testing biomaterials for osteogenesis, and (3) testing biomaterials in the presence of osteoclasts followed by osteoblasts to recapitulate the physiological events of bone resorption prior to bone formation. The focus of this review is to discuss the third strategy in details as the first two strategies are currently incorporated into a majority of in vitro experiments.