The effect of pore size within fibrous scaffolds fabricated using melt electrowriting on human bone marrow stem cell osteogenesis

Abstract

Limitations associated with current bone grafting materials has necessitated the development of synthetic scaffolds that mimic the native tissue for bone repair. Scaffold parameters such as pore size, pore interconnectivity, fibre diameter, and fibre stiffness are crucial parameters of fibrous bone tissue engineering (BTE) scaffolds required to replicate the native environment. Optimum values vary with material, fabrication method and cell type. Melt electrowriting (MEW) provides precise control over extracellular matrix (ECM)-like fibrous scaffold architecture. The goal of this study was to fabricate and characterise poly-ε-caprolactone (PCL) fibrous scaffolds with 100, 200, and 300 μm pore sizes using MEW and determine the influence of pore size on human bone marrow stem cell (hMSC) adhesion, morphology, proliferation, mechanosignalling and osteogenesis. Each scaffold was fabricated with a fibre diameter of 4.01 ± 0.06 μm. The findings from this study highlight the enhanced osteogenic effects of controlled micro-scale fibre deposition using MEW, where the benefits of 100 μm square pores in comparison with larger pore sizes are illustrated, a pore size traditionally reported as a lower limit for osteogenesis. This suggests a lower pore size is optimal when hMSCs are seeded in a 3D ECM-like fibrous structure, with the 100 μm pore size optimal as it demonstrates the highest global stiffness, local fibre stiffness, highest seeding efficiency, maintains a spread cellular morphology, and significantly enhances hMSC collagen and mineral deposition. Similarly, this platform represents an effective in vitro model for the study of hMSC behaviour to determine the significant osteogenic benefits of controlling ECM-like fibrous BTE scaffold pore size using MEW.

Development of a New Bone‐Mimetic Surface Treatment Platform: Nanoneedle Hydroxyapatite (nnHA) Coating

“…Melt electrowriting (MEW) is a recently developed 3D printing technology which overcomes the above limitations of FDM and electrospinning, being capable of fabricating and controlling the deposition of micrometer-scale fibers. [27][28][29] This facilitates the manufacture of complex fibrous microarchitectures [30][31][32][33][34] consistent with that seen in native extracellular matrix (ECM) including that of bone. We recently utilized MEW to fabricate scaffolds with bone inspired fiber diameters of 10 µm and investigated whether the fiber architecture in terms of degrees of alignment could influence stem/stromal cell behavior.…”

Stem Cell Mechanobiology and the Role of Biomaterials in Governing Mechanotransduction and Matrix Production for Tissue Regeneration

“…It was proposed that this was due to the importance of topography as a determinant of cellular behavior. One study aimed to investigate the precise effect of pore size (100, 200, and 300 µm) within 3D fibrous ECM-like scaffolds, fabricated using melt electrowriting (MEW), on the osteogenic potential of hBMSCs (Brennan et al, 2019). Human BMSCs were seeded onto MEW scaffolds and assessed to determine an optimum pore size.…”

Processing variables of direct-write, near-field electrospinning impact size and morphology of gelatin fibers

“…These results add to the growing body of literature using electrowriting to engineer tissues and study cell-biomaterial interactions (9,18,30–32,40–42). Importantly, these gelatin fibers are on the diameter range of collagen fibers which is the domain where the fibroblast would reside, while also providing a more natural biomaterial than synthetic polymers (10).…”