A Process to Make Collagen Scaffolds with an Artificial Circulatory System using Rapid Prototyping
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A Process to Make Collagen Scaffolds with an Artificial Circulatory System using Rapid Prototyping Eleftherios Sachlos1, Nuno Reis1,2, Chris Ainsley2, Brian Derby2 and Jan T. Czernuszka1 1 Department of Materials, University of Oxford, Parks Road, Oxford, OX1 3PH, U.K. 2 Manchester Materials Science Centre, University of Manchester and UMIST, Grosvenor St, Manchester, M1 7HS, U.K. ABSTRACT Tissue engineering aims to produce biological substitutes to restore or repair damaged human tissues or organs. The principle strategy behind tissue engineering involves seeding relevant cell(s) onto porous 3D biodegradable scaffolds. The scaffold acts as a temporary substrate where the cells can attach and then proliferate and differentiate. Collagen is the major protein constituent of the extracellular matrix in the human body and therefore an attractive scaffold material. Current collagen scaffolds are foams which limit the mass transport of oxygen and nutrients deep into the scaffold, and consequently cannot support the growth of thick-cross sections of tissue (greater than 500 µm). We have developed a novel process to make collagen and collagen-hydroxyapatite scaffolds containing an internal artificial circulatory system in the form of branching channels using a sacrificial mould, casting and critical point drying technique. The mould is made using a commercial rapid prototyping system, the Model-Maker II, and is designed to possess a series of connected shafts. The mould is dissolved away and the solvent itself removed by critical point drying with liquid carbon dioxide. Processed hydroxyapatite has been characterised by XRD and FTIR analysis. Tissue engineering with collagen scaffolds possessing controlled internal microarchitecture may be the key to growing thick cross-sections of human tissue. INTRODUCTION Tissue engineering has the potential to significantly improve clinical treatment of damaged human tissue, currently based on organ transplantation and biomaterial implantation, by producing an unlimited supply of immunologically-tolerant ‘biological substitutes’ that can repair or replace the defect site and grow with the patient. One of the strategies employed involves the expansion of human cells in vitro on biodegradable porous scaffolds. This serves as a substrate for cellular attachment and defines the macroscopic shape of the engineered tissue [1]. Proliferating cells are expected to occupy the freed space created during scaffold degradation and eventually produce a completely natural tissue. Most scaffolds used for tissue engineering are open-cell foam structures which have resulted in the growth of thin cross-sections of tissue. For example, bone has been grown in vitro to a thickness of 370-500µm [2, 3]. The small cellular penetration depth of scaffolds may be due to the lack of nutrient and oxygen diffusion deep into the interior of the scaffold; cell colonisation of the scaffold’s periphery can become a barrier, or limit, to the diffusion of these essential components. Thus cell migration and surviva
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