Abstract
Development of large, clinically sized tissue constructs with efficient mass transport is a tremendous need in tissue engineering. One major challenge in large tissue-engineered constructs is to support homogeneous delivery of oxygen and nutrients throughout the tissue scaffold while eliminating induced hypoxic regions in depth. To address this goal, we introduced an especial channeled architecture on porous silk-based tissue scaffolds to improve supplying of oxygen to the cells in central regions of the scaffolds. Oxygen gradients were measured and evaluated in three scaffold prototypes, namely, one unchanneled and two channeled scaffolds with different channel diameters (500 μm and 1000 μm). The channels were introduced into the constructs using stainless-steel rods arranged uniformly in stainless-steel mold, a fabrication method that enables precise control over channel diameter and the distance between channels. During 2-week culture of G292 cells, the 1000 μm channeled scaffolds demonstrated higher oxygen concentration at the center compared to 500 μm channeled prototype; however, the oxygen concentration approached the same level around the last days of culture. Nevertheless, homogenous oxygen distribution throughout the 1000 μm channeled constructs and the consequence of higher cell proliferation at day 14 postseeding corroborate the efficient elimination of induced hypoxic regions; and therefore, it holds promise for clinically relevant sized scaffold especially in bone tissue engineering.
Highlights
Considering the limited supply of autografts, immune response risk of allografts, and insufficient osteogenic capacity of bone substitutes, appropriate bioactive bone graft is crucially vital which still remains a major challenge in biomedical engineering [8–11]
An ideal scaffold for bone tissue engineering should mimic osteoblast extracellular matrix (ECM) in order to prepare an environment for cell growth and support the bone remodeling process
In comparison with unchanneled constructs, the results revealed that induced hypoxic regions in depth of our channeled scaffold were efficiently eliminated and cells were attached, grown, and proliferated remarkably through 3D structure
Summary
Tissue engineering is an ideal approach for the regeneration of damaged tissues and for the fabrication of artificial tissues to study biological functions in vitro [1] or even to be used as a replacement for animal models [2]. Scaffold-based bone tissue engineering is a promising alternative that uses cells and bioactive factors on 3D scaffold structures to regenerate damaged bone tissues, caused by, e.g., tumor, trauma, osteoarthritis, and osteonecrosis [6–8]. Considering the limited supply of autografts, immune response risk of allografts, and insufficient osteogenic capacity of bone substitutes, appropriate bioactive bone graft is crucially vital which still remains a major challenge in biomedical engineering [8–11]. An ideal scaffold for bone tissue engineering should mimic osteoblast extracellular matrix (ECM) in order to prepare an environment for cell growth and support the bone remodeling process. These scaffolds are basically fabricated from hyaluronic acid-based hydrogels, heparin-based hydrogels, fibrin-based hydrogels, chondroitin sulfate, or natural polymeric hydrogels [12–14]
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