Direct-Write Construction of Tissue-Engineered Scaffolds

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Direct-Write Construction of Tissue-Engineered Scaffolds Anatoly M. Kachurin,1 Robert L. Stewart,1 Kenneth H. Church,1 William L. Warren,1 John P. Fisher,2 Antonios G. Mikos,2 Stine-Katherine Kraeft,3 and Lan Bo Chen3 1 Sciperio, Inc., 5202-2 North Richmond Hill Road, Stillwater, OK 74075, U.S.A. 2 Department of Bioengineering, Rice University, Houston, TX 77251, U.S.A. 3 Dana–Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, U.S.A. ABSTRACT A computer-controlled xyz dispensing system called the Biological Architecture Tool (BAT) has been extensively tested in the creation of multilayered and three-dimensional biological objects: tissue scaffolds and plain and patterned cellular-array slides. The BAT dispensing system has proven its versatility and reliability in tissue engineering and biological experiments. The potential employments of modified versions of the xyz dispensers for in vivo minimally invasive surgery and other in vitro aspects of biological and medical research are discussed. INTRODUCTION The modern tissue engineering (TE) community regards biodegradable supporting and shape-forming scaffolds as crucial parts of novel tissue constructs. The community acknowledges that in many cases the human body is unable to directly regenerate removed or lost tissue. Reconstructing the proper three-dimensional (3D) organization of cellular and extracellular elements is a necessity. Otherwise, the removed volume eventually will be filled with nonfunctional scar tissue, at best [1]. To fulfill successfully their structural and functional roles, tissue scaffolds should be highly penetrable to cells and vital fluids. Porous scaffolding constructs become a paradigm, which has stipulated the involvement of leaching and gas expansion techniques in the fabrication of scaffolds [2]. The in vitro construction of tissue scaffolds poses comparatively fewer problems. Molding and 3D-printing polymerization techniques allow the fabrication of sophisticated elements [3]. The injection of biodegradable plastics, hydrogels, and cellularized composites in bone reconstruction and orthodontic surgery can be regarded as simplified versions of in vivo scaffolding [2, 4]. However, the minimally invasive surgery (MIS) of the near future will inevitably require in vivo and in situ fabrication of complex, multicellular, spatially organized, and functional elements of tissue and organs [1, 5]. The study objective was to explore the potential of using the Sciperio Biological Architecture Tool (BAT) dispensing technology for future in vivo and in situ fabrication of tissue scaffolds and cell constructs. EXPERIMENT Poly(propylene fumarate) (PPF), poly(propylene fumarate-co-ethylene glycol) (PPF–PEG) hydrogel, and bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO) photoactivator were obtained from Rice University. Synthesis of these polymers has been described elsewhere [6]. Commercial sucrose sugar, in 200–500-µm and 5–30-µm grain-size brands, was used as leaching filler. A modified TL003 Facial Sunlamp (Saidel Inc., Rent