Critical size defects in bone and osteochondral defects in articular cartilage do not heal without clinical intervention. Current clinical treatments of both defect types are associated with strong limitations, which could be addressed by the development of tissue engineering (TE) treatment strategies. Collagen scaffolds with a highly aligned architecture have been previously shown to induce bone formation by endochondral ossification in large bone defects in vivo. The establishment of the endochondral ossification process has been proven to depend on the aligned architecture of the collagen scaffolds, without the need for the inclusion of additional biochemical factors. However, the direct clinical application of these collagen scaffolds is hindered by their extremely low stiffness (low kPa range), which determines the easy alteration of the aligned architecture by means of tissue forces and extracellular matrix deposition within the scaffold pores. Here, the limitations of the collagen scaffolds with highly aligned architecture are addressed by incorporation of a stiffer synthetic support structure, generating multiscale hybrid scaffolds. The aim of the support structure is not limited to the improvement of the mechanical stiffness of the scaffold system at tissue level, but it extends also to the steering of the tissue regeneration process by means of different scaffold-dependent mechanical cues, which could be achieved by different types of support structures, e.g. a stiff and a compliant one. In fact, the development of bone through endochondral ossification happens by first establishing a cartilaginous template, which is then mineralized. Moreover, the formation of bone and cartilage has been associated to mechanical stimuli of lower and higher magnitude, respectively. Therefore, mechanical cues determined by the stiffness at tissue level of the hybrid scaffolds are intended to be used to guide tissue formation towards either bone or cartilage. The successful establishment of this approach would enable the use of controlled mechanics for applications beyond bone defect healing, e.g. in the treatment of osteochondral defects. In this thesis, a stiff and a compliant support structure to be included in the hybrid scaffolds were designed. Thereafter, the production of the support structures by selective laser sintering from poly(ε-caprolactone) was optimized in terms of material choice and resulting support structure properties. Moreover, stiff and compliant support structure architectures with significant differences in stiffness and fatigue resistance in in vivo-like conditions were designed. Subsequently, stiff and compliant hybrid scaffolds were produced and characterized in terms of morphology of the collagen walls, mechanical properties, and in vitro cell-material interactions. Concurrently, the ideal mechanical and architectural properties of scaffolds for osteochondral defect regeneration were here investigated by means of a computational model.
Design and characterization of multiscale hybrid scaffolds for endochondral ossification
Design und Charakterisierung von Multiskalen-Hybridscaffolds für die enchondrale Ossifikation
2021
Sonstige
Elektronische Ressource
Englisch
DDC: | 629 |
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