Drop-on-demand printing of cells and materials for designer tissue constructs Thomas Boland a, ⁎ , Xu Tao a , Brook J. Damon b , Brian Manley a , Priya Kesari a , Sahil Jalota c , Sarit Bhaduri c a Department of Bioengineering, Clemson University, Clemson SC 29634, United States b Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, United States c School of Material Science and Engineering, Clemson University, Clemson SC 29634, United States Available online 1 September 2006 Abstract Adapting bottom-up approaches to tissue engineering is a real challenge. Since the first application of fused deposition modeling for tissue engineering scaffolds, considerable effort has been focused on printing synthetic biodegradable scaffolds. Concurrently a variety of rapid prototyping techniques have been developed to define macroscopically the shapes of deposited biomaterials, including photolithography, syringe- based gel deposition, and solid freeform fabrication. These designed scaffolds have shown promise in regenerating tissues at least equivalent to other scaffolding methods. An exciting advance in scaffold aided tissue regeneration is presented here, that of cell and organ printing, which allows direct printing of cells and proteins within 3D hydrogel structures. Cell printing opens the possibility to programmed deposition of scaffold structure and cell type, thus controlling the type of tissue that can be regenerated within the scaffold. Several examples of printed tissues will be presented including contractile cardiac hybrids. The hybrid materials have properties that can be tailored in 3D to achieve desired porosities, mechanical and chemical properties. The materials include alginate hydrogels with controlled microshell structures that can be built by spraying cross-linkers onto ungelled alginic acid. Endothelial cells were seen to attach to the inside of these microshells. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Finite element modeling was used to predict the mechanical properties and to generate CAD models with properties matching cardiac tissue. These results suggest that the printing method could be used for hierarchical design of functional cardiac patches, balanced with porosity for mass transport and structural support. © 2006 Elsevier B.V. All rights reserved. Keywords: Ink jet; 3D; Printing; Cells; Alginate 1. Introduction Computer aided scaffold topology design has recently gained attention as a viable option to achieve function and mass transport requirements within tissue engineering scaffolds. This hierarchi- cal design technique allows conceiving complex 3D structures with controlled architecture and pore sizes which can then be assembled using solid free-form fabrication (SFF) techniques. Several recent articles have reviewed and compared SFF scaffold fabrication techniques [1–5]. All SFF systems build a 3D struc- ture by layering a 2D material onto a moving platform. Recently, biomaterial scientists have used a number of these methods to fabricate tissue engineering scaffolds, including physical models of hard and soft tissues and custom-made tissue implant prostheses. Many of the SFF techniques can offer effective ways to precisely control matrix architecture (size, shape, interconnectivity, geometry and orientation) of a scaffold, yield- ing biomimetic structures of varying design and material com- position. Hierarchical design of the scaffolds with micron to millimeter features have demonstrated that enhanced control over mechanical properties, biological effects and degradation kinetics of the scaffolds is possible [4]. Moreover, SFF techniques can be easily automated and in- tegrated with imaging techniques to produce constructs that are customized in size and shape allowing tissue-engineering grafts to be tailored for specific applications or individuals [1]. Several groups have used computer aided design (CAD) based ap- proaches to design and build scaffolds with controlled architec- ture, mostly for hard tissues [6–8]. Materials Science and Engineering C 27 (2007) 372 – 376 www.elsevier.com/locate/msec ⁎ Corresponding author. Tel.: +1 864 656 7639; fax: +1 864 656 4466. E-mail address: tboland@clemson.edu (T. Boland). 0928-4931/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.msec.2006.05.047