Biomaterials 24 (2003) 1487–1497 Novel collagen scaffolds with predefined internal morphology made by solid freeform fabrication E. Sachlos a, *, N. Reis a,b , C. Ainsley b , B. Derby b , J.T. Czernuszka a a Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH, UK b Manchester Materials Science Centre, UMIST and University of Manchester, Grosvenor Street, Manchester M1 7HS, UK Received 28 June 2002; accepted 15 October 2002 Abstract Novel collagen scaffolds possessing predefined and reproducible internal channels with widths of 135 mm and greater have been produced. The process employed to make the collagen scaffold utilises a sacrificial mould, manufactured using solid freeform fabrication technology, and critical point drying technique. A computer aided design (CAD) file of the mould to be produced is created. This mould is manufactured using a phase change ink-jet printer. A dispersion of collagen is then cast into the mould and frozen. The mould is dissolved away with ethanol and the collagen scaffold is then critical point dried with liquid carbon dioxide. The effect of processing on the tertiary structure of collagen is assessed by monitoring the wavenumber of the N–H stretching vibration peak using Fourier transform infra-red spectroscopy and it is found that processing does not denature the collagen. Ultraviolet-visual spectroscopy was used to detect the presence of any contamination from the sacrificial mould on the collagen. The ability to use computer aided design and manufacture (CAD/CAM) provides a route to optimise scaffold designs using collagen in tissue engineering applications. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: Tissue engineering; Collagen; Scaffold; Rapid prototyping; Solid freeform fabrication 1. Introduction Tissue engineering aims to produce biological sub- stitutes which may overcome the limitations of conven- tional clinical treatments for damaged tissues or organs. One of the principle methods behind tissue engineering involves growing the relevant cell(s) in vitro to form the required tissue, or organ, before inserting into the body. To achieve this goal the cells must attach to a three- dimensional (3D) substrate, known as a scaffold. This scaffold provides the initial extracellular matrix required to support the cells and may also define the micro- and macro-structure of the desired-engineered structure [1]. The scaffold therefore is a key component of tissue engineering. Several requirements have been identified as crucial for the production of tissue engineering scaffolds. These are that the scaffold should: (1) have appropriate surface chemistry to favour cellular attach- ment, differentiation and proliferation; (2) be made from a biodegradable or bioresorbable material, that degrades at an appropriate rate with no undesirable by- products, so that tissue will eventually replace the scaffold; (3) possess adequate mechanical properties to match the intended site for implantation and handling, (4) be easily fabricated into a variety of shapes and sizes and (5) possess interconnecting porosity so as to favour tissue integration and vascularisation [2]. Synthetic biodegradable polymers, such as aliphatic polyesters, e.g. polyglycolic acid, polylactic acid and their copolymers, are the most commonly used polymers for tissue engineering scaffold applications. Several processing techniques have been developed to make porous structures from these synthetic scaffold materi- als, namely: solvent casting-particulate leaching [3], phase separation [4], gas foaming [5], emulsion freeze drying [6] and fibre meshes [7]. However, these synthetic polymers possess a surface chemistry that does not promote cell adhesion. In addition, they produce a high local concentration of acidic by-products during *Corresponding author. Tel.: +44-1865-273768; fax: +44-1865- 273789. E-mail address: eleftherios.sachlos@materials.ox.ac.uk (E. Sachlos). 0142-9612/02/$-see front matter r 2002 Elsevier Science Ltd. All rights reserved. PII:S0142-9612(02)00528-8