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Bone extracellular matrix (ECM) shows considerable promise as a material for bone graft substitutes, primarily due to its intrinsic osteoinductive properties, which naturally support the process of bone formation. Bone ECM can be processed into highly porous scaffolds that facilitate effective cell infiltration and nutrient transport. A potential limitation of bone ECM scaffolds is their relatively poor mechanical properties, which may restrict their use to non-load bearing activities. Furthermore, given the well-established role of matrix stiffness in regulating the differentiation of mesenchymal stromal/stem cells (MSCs), the relative softness of current bone ECM derived scaffolds may be suboptimal for supporting osteogenesis. Therefore, the first goal of this study was to develop solubilised bone ECM scaffolds with a range of mechanical properties. We then sought to determine how the stiffness of such bone ECM scaffolds modulates osteogenesis of MSCs.
To this end, we developed a protocol to extract decellularised bone ECM from porcine bone. This method yielded a material suitable for fabricating scaffolds with a unidirectional pore architecture, a design that further supports rapid cell infiltration and alignment within the scaffold structure. By producing scaffolds with varying ECM concentrations, we aimed to control and assess how changes in ECM density influence both their mechanical stiffness and capacity to support osteogenesis of MSCs in vitro.
Our findings indicate that scaffold stiffness can be modulated effectively by adjusting ECM concentration: higher ECM concentrations produce stiffer scaffolds while retaining elasticity, as evident by the minimal levels of permanent deformation observed following the application of large compressive strains. All scaffolds were able to retain at least the 95% of their original shape. Additionally, the Young’s modulus of the scaffolds increased from approximately 3 kPa for 2% ECM scaffolds to 14 kPa for 6% ECM scaffolds. These stiffer scaffolds supported robust cell proliferation and led to increased mineral and collagen deposition. Aligned collagen deposition parallel to the direction of the scaffold pores was observed, highlighting the role of pore orientation in guiding neo-tissue organisation.
In conclusion, this study demonstrates that by varying ECM concentration, bone ECM-derived scaffolds can be engineered to possess tunable stiffness and tailored porosity, making them highly supportive of the osteogenic differentiation of MSCs. The ability to modulate bone ECM scaffold stiffness provides a valuable tool for optimising scaffold performance for bone tissue engineering applications, where both material stiffness and cellular orientation play essential roles in effective bone regeneration.
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