rational scaffold design for skeletal tissue engineering - a modelling and experimental approach
The availability of donor material is a worldwide problem. The potential solutions of allografts and xenografts suffer from the severe disadvantage of a potential immunological response. Autografts could circumvent these disadvantages but the associated limited quantity and donor site morbidity limits their use. A promising alternative to donor material is tissue engineering.
For musculoskeletal tissue engineering a scaffold provides an environment for cells to form tissue. A scaffold provides temporary mechanical stability for the tissue to develop and has the ability to influence cell behavior and subsequently tissue formation. The effect of biophysical loading on cell differentiation and tissue formation in an imaged 3D scaffold was predicted with Finite Element Analysis. Initially, cells experience 2D strains as they are attached to the scaffold surface and it was shown that 2D strains are significantly lower than 3D strains, commonly used in literature. In-silico experiments of several scaffold designs showed significant effects on the stress and strain distribution during biophysical loading. Through the scaffold design, regions for specific tissue formation could be appointed. In-vitro experiments with a scaffold made of a shape memory polymer, which possessed a one-time intrinsic mechanical stimulus, showed the feasibility of culturing cells on such a scaffold and already showed an effect on cell orientation.
Besides sustaining biophysical loading, the scaffold also initially replaces the local tissue function upon implantation. In (osteo)chondral sites the friction coefficient of the tissue is an important parameter. Common used biomaterials and scaffold designs were tested biologically and tribologically for replacing (osteo)chondral defects. The scaffold design had a significant influence as the loading was not supported in some designs or reduced the friction coefficient in other designs. The chemical structure and bulk stiffness influenced cell behavior as well. Changing the molecular weight of a biomaterial, the bulk stiffness of the scaffold changed correspondingly, while the chemical structure remained the same. Decreasing the molecular weight resulted in a lower stiffness and a stronger tendency of hypertrophic chondrogenic differentiation.
The scaffold design and biophysical loading have a significant influence on cell behavior and can be tailored to control stem cell activity and tissue regeneration.
Starting time 16.30h in Building Waaier Prof.dr. G. van Berkhoff-zaal
