Biomineralization Guided by Paper Templates

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.

Redefining Chinese calligraphy rice paper: an economical and cytocompatible substrate for cell biological assays

“…Remarkably, the CiGiP model has been applied to investigate interactions between broblasts and human lung cancer, 8 chemotaxis of cancer cells in an oxygen gradient, 9 and differentiation of human-induced pluripotent stem cells. 10 In addition, a paper sheet has been fabricated into versatile microdevices to investigate cellular phosphorylation, 11 biomineralization of articial bone tissues, 12 and high-throughput testing of the effect of soluble compounds. 13 Paper as a substrate for a cell culture platform and its emerging biomedical applications has been well reviewed by Dr Xu 14 and Dr Cheng.…”

Engineered Paper‐Based Cell Culture Platforms

“…Although there are diverse 3D platforms for culturing and analysis of cells, they commonly use sophisticated procedures, costly materials, tedious protocols, and laborious steps . To address these limitations, paper has been used as a 3D scaffold to culture cells of mammalian origin (e.g., immortalized cell lines, primary cells, and stem cells) as well as bacteria, yeast, algae, and plants …”

“…Patterned paper is then baked to melt the wax that forms hydrophobic boundaries for the patterns and the hydrophilic sample zones. This method has been extensively used in paper‐based cell culture platforms, and paper microfluidics for disease diagnostics . Another technique to fabricate paper scaffolds is hot embossing.…”

“…Due to various reasons (e.g., aging, trauma, disease, accidents and degeneration), there could be bone loss in the body . Although there are a number of strategies that can be used to fabricate scaffolds for regeneration of bone, those approaches use specialized equipment, costly materials, and long optimization protocols . Typically, scaffolds generated by these methods include heterogeneously distributed cells and demonstrate diffusion limitations.…”

“…In this work, Camci‐Unal et al used an origami‐inspired tissue engineering approach and utilized paper as a scaffold for bone tissue engineering ( Figure ) . Paper is an exceptionally flexible substrate that can easily be creased, folded, patterned, cut, or manipulated to generate 3D free‐standing structures.…”