Abstract
This work demonstrates the fabrication of partially mineralized scaffolds fabricated in 3D shapes using paper by folding, and by supporting deposition of calcium phosphate by osteoblasts cultured in these scaffolds. This process generates centimeter-scale free-standing structures composed of paper supporting regions of calcium phosphate deposited by osteoblasts. This work is the first demonstration that paper can be used as a scaffold to induce template-guided mineralization by osteoblasts. Because paper has a porous structure, it allows transport of O2 and nutrients across its entire thickness. Paper supports a uniform distribution of cells upon seeding in hydrogel matrices, and allows growth, remodelling, and proliferation of cells. Scaffolds made of paper make it possible to construct 3D tissue models easily by tuning material properties such as thickness, porosity, and density of chemical functional groups. Paper offers a new approach to study mechanisms of biomineralization, and perhaps ultimately new techniques to guide or accelerate the repair of bone.
Highlights
Bone serves multiple functions in vertebrates: it provides a mechanical structure, anchors muscles, stores minerals, and provides a compartment in which red and white blood cells form[1]
It is a suitable biomaterial for tissue engineering, cellulose has to be processed in order to fabricate scaffolds, which might require long and sequential procedures or optimization of protocols and labor
We previously reported a technique for culturing cells in gel-impregnated paper scaffolds[18]
Summary
Bone serves multiple functions in vertebrates: it provides a mechanical structure, anchors muscles, stores minerals, and provides a compartment in which red and white blood cells form[1]. Available synthetic scaffolds are not biocompatible without the incorporation of biological cues (e.g., functional groups that interact with cells, growth factors, small molecules, and the presence of minerals)[5]. Another major problem with existing bone scaffolds is the inability to promote vascularization within the scaffold[4]. Whatman paper is pure cellulose fiber, and does not include lignin, binder, brightener, or sizing agents[16,17] They have been explored for other aspects of cell biology[18,19,20,21,22], the simple and flexible features of paper-based materials have not been used to guide deposition of hydroxyapatite by osteoblasts. The scaffolds made of paper combine the simplicity of a biocompatible material with the ability to form free-standing structures
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