Endochondral ossification (EO) is a process of bone formation taking place in humans during foetal development and childhood growth, but not in adulthood. Previous studies(1) reported that a collagen scaffold with channel-like pores was able to induce EO in a rat osteotomy model, representing a promising strategy for the treatment of large bone defects. However, a translation to the clinics is hindered by the low stiffness of the biomaterial scaffold, which might lead to a breakdown of the pore architecture before full defect healing. Here, we include a stiff polymeric support structure into the collagen scaffolds to generate a hybrid scaffold that is load bearing at the tissue-level, while maintaining favourable biological properties at the cell-level.
Support structures were produced from polyamide by selective laser sintering. Hybrid scaffolds were obtained by immersing the support structure into a collagen suspension before directional freezing and freeze-drying. Collagen scaffolds, support structures and hybrid scaffolds were characterized concerning their mechanical stiffness and pore architecture and studied concerning their ability to support cell migration and ECM deposition.
Mechanical compression tests showed a 1000-fold increase of the elastic modulus for hybrid compared to collagen scaffolds, measuring 6 MPa and 5kPa, respectively. After two weeks of cell culture, the characteristic pore architecture was maintained only in hybrid scaffolds, leading to an aligned network of extracellular matrix. Collagen scaffolds showed strong volume loss, with the resulting impairment of pore architecture.
The here-introduced hybrid scaffold represents a multiscale system in which properties at tissue-level (support structure) and cell-level (collagen scaffold) can be varied independently. This allows a multi-scale optimization of the mechanical environment to support EO in bone defects. Future work will assess the hybrid scaffolds ability to induce EO in vivo.
(1)Petersen et al, Nat Commun, 9:4430, DOI: 10.1038/s41467-018-065042018