Development of 3D Co-culture Systems aiming to develop realistic 3D-bone tissue models

Bone loss can be promoted due to several diseases (e.g. osteoporosis) and trauma (e.g. tumor resection). To tackle this loss, the scientific community has been following different approaches  mostly focus on bone formation prompted by osteoblasts. However, bone remodelling is a continuous process that comprises not only bone formation (by osteoblasts), but also, bone resorption (by osteoclasts) [1]. Thus, urged the need to develop new strategies to accurately mimic the native bone tissue and the entire bone remodelling process.

In this sense, a three dimensional (3D) co-culture system of osteoblasts and osteoclasts would introduce the cells’ interactivity present in native bone tissue remodeling environment. To accomplish this goal, this project proposes the development of a 3D in vitro system composed of human bone marrow (hBM) derived osteoblasts and osteoclasts within Gellan Gum spongy-like hydrogels combined with hydroxyapatite (GG-HAp). In fact, it was shown previously that GG-HAp spongy-like hydrogels presented promising features for bone tissue engineering [2,3]. Additionally, this project will comprise the culture of the 3D in vitro system under dynamic conditions, to assure nutrients and oxygen transportation, and, under electrical stimulation, to potentiate osteogenic differentiation. Afterwards, this 3D model will be connected to a perfusion microfluidic system and it will be evaluated his ability as a drug screening system. Finally, the efficiency of the developed 3D model will be further tested in vivo as a proof-of-concept.The 3D in vitro system proposed in this project would allow fine-tuning the bone formation and resorption processes in vitro, emulating bone disorders, as osteoporosis, shedding important findings on such disorders’ molecular processes, as well as, on the development of new therapeutic approaches.