In this study, we used human mesenchymal stem cells (MSC) derived from bone marrow in conjunction with three different protein scaffolds (unmodified collagen, cross-linked collagen, silk), and three different culture environments (static culture, well-mixed spinner flasks, perfused cartridges) to study osteogenesis under controlled in vitro conditions. The pattern of bone formation correlated with the conditions of fluid flow, an important finding for the design and set-up of bioreactors, needed to promote mass transfer even into the scaffold center. Furthermore, the orientation of the formed bone was directed by and parallel to the direction of the fluid flow vector. However, our hypothesis that constructs grown in perfused cartridges—the most efficient transport within the scaffold center—are structurally superior to those grown in spinner flasks was not confirmed, in contrast to previous studies demonstrating a strong mineralization of nondegradable materials in perfused cartridges. This highlights the importance of finding a suitable balance between scaffold design and bioreactor conditions in order to yield optimal engineered tissue outcomes. These finding, among others, should have their impact on the design of future tissue engineering strategies, including a refocus on seeing the whole picture rather than merely individual aspects for successful tissue engineering outcomes.

The clinical demand for tissue-engineered bone is extremely wide across the general population. In the United States, approximately one million fractures are annually treated in hospitals as fractures at risk of non-healing. Tissue engineering may provide functional substitutes of native tissues which can serve as grafts for implantation. Also, engineered bone can serve as a high fidelity model for biological research. In contrast to most tissues, bone tissue engineering research and practice has had a reduced focus on in vitro formation of bone constructs. In vitro studies have been dedicated to screening new scaffolds for use in vivo to guide the infiltration of host cells and enhance bone regeneration. Our study demonstrated the feasibility of modulating osteogenesis in vitro, and stressed the need to optimize the conditions for bone tissue engineering in future approaches in the field.

Bone engineering—due to the amazing potential of bone for self-reconstruction—is most likely one of the first tissues that we will be able to engineer by means of tissue engineering. For me, a good reason to join this area of research was the motivation to help patients. My doctoral thesis at the ETH Zurich was focused on the formulation and design of drug delivery systems for osteoinductive growth factors and, still being fascinated by this area, I wanted to extend my research to the use of mesenchymal stem cells during my postdoc with Gordana Vunjak Novakovic and with Robert Langer at MIT and David Kaplan at Tufts University as well as within a second doctoral program with a focus on Orthopedics at the University of Frankfurt. So, research for me became more and more interdisciplinary and international and also more exciting.

Stem cell-based tissue engineering involves very different aspects, e.g., stem cell biology, biomaterials, drug formulation and delivery, and fluid mechanics/bioreactors. This automatically results in the need for others to succeed in the field, the need to form teams, and the need to truly communicate which is driven by the need to comprehend languages of originally unrelated scientific disciplines. I experienced the possibility of working under such conditions as an invaluable privilege made possible because of the fact that many different research backgrounds—each one being dependent on the others—thrive at the same goal: the (re)construction of human tissues and organs, with the promise of helping the relief of pain, and restoring the ability to lead a normal life to numerous patients. This is truly motivating and has always inspired and driven our efforts and, last but not least, was one key element resulting in a number of wonderful friendships that came from these shared beliefs. On moving back to ETH, I was fortunate to rapidly build up a research team at the interface of tissue engineering and drug formulation and delivery, with a particular focus on growth factor stability and delivery kinetics in order to maximize cellular responses in a desired way. My research team and I continue to feel the excitement of tissue engineering research and the good feeling of working together with wonderful friends in this shared effort, some of whom co-authored and largely contributed to this featured publication.