Bone chamber: in vivo or in vitro? Both

Ossicle in the bone chamber made by tissue engineering approaches
A 3D rendering of the ossicle generated for the B2B device.

In B2B two approaches have been planned in order to generate the ossicle for the bone chamber. The first, and more standardized, consists of the generation of the ossicle in vivo (in murine models) and only later to transfer it into the dedicated chamber. This approach starts with the insertion of patient-derived chondrocytes, the cell forming the cartilage, in mice with a weakened immune system, to reduce the chances of rejection. There, the human cartilage is slowly converted into an ossicle thanks to the action of the animal blood flow:  nutrients and bone-forming cells are brought in and they trigger the remodeling of the cellular mass into an ossicle – including the cavity to accommodate the bone marrow.

Besides this reliable and relatively standard approach, the team of Eric Farrell, Associate Professor at the Department of Oral and Maxillofacial Surgery at Erasmus University Medical Center (The Netherlands) and partner in B2B, has set the challenge to generate the ossicle without the support of animal models. “We hope in the future to generate as much as bone-like structure directly in vitro. But to achieve this, we first need to understand step by step how the transformation happens in animals and then mimic it in a test tube,” explains Dr. Farrell.  Besides avoiding animal experimentation, the in vitro approach brings other benefits: the system is more reproducible thus reducing the intrinsic variability associated with animal models; it’s easily scalable, enabling also high-throughput experiments, and, once the protocol is set-up, the process should take less time and effort to be completed compared to the animal counterpart.

“The level of complexity that we try to reach within the B2B project is quite new. In vitro scientists usually focus on the very early stages of the bone formation, for example, the mineralization step; our challenge is to include the blood vessels and other types of cells during this process, thus adding an extra layer of complexity.” At this stage of the project, the team at Erasmus MC is able to generate cartilage in vitro and is currently working on the mineralization step and the introduction of other types of cells e.g. immune cells, osteoclasts, blood vessels, etc. To ease this part, the initial idea was to host an expert on angiogenesis from Prof. Banfi’s group in Basel (link to the news about it), to support the co-culture of endothelial cells with the cartilage system; but the exchange had to be postponed due to the COVID-19 emergency. “In the meantime, we are dissecting the events that occur in vivo, step by step,” says Prof.Farrell. This approach will still set an important base for bone-generation in tissue engineering.

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