Other relevant doodles: Joe Swift on Lamins & tissue properties
Invited external talk at the Glasgow Biomaterials Seminar Series
October 27th 2015
Dr. Ansgar Petersen
Abstract by Ansgar Petersen on his talk:
In the last decade the understanding how cells sense their microenvironment and respond to it has increased remarkably. Mechanical signals like substrate stiffness but also surface topography were recognized as important additional “flavors” that, next to biochemical signals, direct cell behavior. While micro-topographical features on surfaces have been studied intensively, relatively little is still known how 3D geometries on length scales larger than the cell size influence cell and extracellular matrix properties. Macroporous biomaterials offer the possibility to exploit 3D geometry as a parameter to guide cell behavior. They can be utilized as a tool to understand cell response but also as an in vivo strategy to guide cells towards tissue regeneration.
We used 2.5D and 3D biomaterials produced by stereolithography or directional freezing / freeze drying to investigate how mesenchymal stromal cells and fibroblasts respond to biomaterial architecture. For this we analyzed cell migration, differentiation, geometric organization, and formation of extracellular matrix in vitro. We found evidence that cell function is influenced remarkably by the material’s surface curvature via alterations in cell geometry and surface adhesion. Furthermore, the structure of newly formed extracellular matrix was closely linked to cell organization in the 3D environment. The findings were incorporated into a biomaterial strategy for the treatment of critical size bone defects in rats. Using macroporous collagen scaffolds with low stiffness and highly orientated pore architecture, we were able to recapitulate a developmental bone growth process. More precisely, the scaffold’s specific pore architecture induced endochondral ossification with a structural organization that closely mimicked the growth plate. It was found that the material-guided collagen fiber alignment at the interface between non-mineralized and mineralized tissue was decisive for the occurrence of the growth process. This example illustrates how biomaterial mechanics and pore architecture can contribute to tissue regeneration next to cell therapeutic or growth factor based approaches. Increasing freedom in the technical realization of more complex architectures will in future open new possibilities to employ geometry for instructive biomaterials in tissue regeneration.
Papers mentioned in the talk:
Kilian, K. A., Bugarija, B., Lahn, B. T., & Mrksich, M. (2010). Geometric cues for directing the differentiation of mesenchymal stem cells. PNAS, 107, 4872–4877. doi:10.1073/pnas.0903269107
Joe Swift et al. Science Vol. 341 no. 6149 DOI: 10.1126/science.1240104
Willie, B. M., Petersen, A., Schmidt-Bleek, K., Cipitria, A., Mehta, M., Strube, P., … Duda, G. (2010). Designing biomimetic scaffolds for bone regeneration: why aim for a copy of mature tissue properties if nature uses a different approach? Soft Matter, 6(20), 4976. doi:10.1039/c0sm00262c
Schmidt-Bleek, K., Petersen, A., Dienelt, A., Schwarz, C., & Duda, G. N. (2014). Initiation and early control of tissue regeneration - bone healing as a model system for tissue regeneration. Expert Opinion on Biological Therapy, 14(2), 247–59.