Microrobotics and MEMS-Based Fabrication Techniques for Scaffold-Based Tissue Engineering Han Zhang, 1 Dietmar W. Hutmacher,* 2 Franck Chollet, 3 Aun Neow Poo, 1 Etienne Burdet 1,4 1 Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, Engineering Drive 1, Singapore 119260, Singapore 2 Division of Bioengineering, Faculty of Engineering, Department of Orthopaedic Surgery, Faculty of Medicine, National University of Singapore, Engineering Drive 1, Singapore 119260, Singapore Fax: 65-6872 3069; E-mail: biedwh@nus.edu.sg 3 MicroMachines Centre, School of Mechanical & Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore 4 Department of Bioengineering, Imperial College London, London, United Kingdom Received: November 17, 2004; Revised: March 24, 2005; Accepted: March 24, 2005; DOI: 10.1002/mabi.200400202 Keywords: biodegradable polymers; micro-assembly; rapid prototyping; scaffold; tissue engineering Introduction Tissue engineering allows us to look into a potential future of medicine in which surgeons will routinely repair or replace failing or aging body parts with laboratory grown tissues. With this technology, it will become possible to regenerate or replace damaged tissues with tissue engi- neered constructs (TEC) such as bone, cartilage, blood vessels, and skin (Figure 1). The most common concepts underlying tissue engineering combine living cells, biolo- gically active molecules, and a scaffold, forming a TEC which aims to promote the repair and regeneration of tissue. The scaffold is expected to support cell colonization, mig- ration, growth, and differentiation, and to guide the devel- opment of the required tissue. It is beyond the scope of this review to discuss in detail the biological issues related to scaffold based tissue engineering. The important factors governing scaffold properties include matrix morphology, mechanical strength, surface structure, degradation kinetics and biological factors. There is probably no universal scaffold morphology for all appli- cations; in contrast, each tissue/organ needs a specific and individual matrix design with appropriate material proper- ties. A minimal set of requirements for biochemical and physical properties of scaffolds for tissue engineering (TE) does, however exist. First, they must provide sufficient mechanical strength and stiffness for initial substitution of the wound contraction forces and later remodeling of the tissue. [1] Second, the scaffold architecture should be designed to allow the following: initial cell attachment Summary: Scaffold based tissue engineering strategies use cells, biomolecules and a scaffold to promote the repair and regeneration of tissues. Although scaffold-based tissue engi- neering approaches are being actively developed, most are still experimental, and it is not yet clear what defines an ideal scaffold/cell construct. Solid free form fabrication (SFF) techniques can precisely control matrix architecture (size, shape, interconnectivity, branching, geometry and orienta- tion). The SFF methods enable the fabrication of scaffolds with various designs and material compositions, thus provid- ing a control of mechanical properties, biological effects and degradation kinetics. This paper reviews the application of micro-robotics and MEMS-based fabrication techniques for scaffold design and fabrication. It also presents a novel robotic technique to fabricate scaffold/cell constructs for tissue engineering by the assembly of microscopic building blocks. Scaffold design for a single step pop-up assembly. Macromol. Biosci. 2005, 5, 477–489 DOI: 10.1002/mabi.200400202 ß 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Review 477