Progress in Polymer Science 36 (2011) 238–268 Contents lists available at ScienceDirect Progress in Polymer Science journal homepage: www.elsevier.com/locate/ppolysci Design of artificial extracellular matrices for tissue engineering Byung-Soo Kim a,1, In-Kyu Park b,1, Takashi Hoshiba c, Hu-Lin Jiang d, Yun-Jaie Choi e, Toshihiro Akaike f,∗, Chong-Su Cho e,∗∗ a School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, South Korea b Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-746, South Korea c Biomaterials Center, National Institute for Materials Science, Tsukuba 305-0044, Japan d College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea e Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea f Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501, Japan article info abstract Article history: The design of artificial extracellular matrix (ECM) is important in tissue engineering because Received 25 May 2010 artificial ECM regulates cellular behaviors, including proliferation, survival, migration, Received in revised form and differentiation. Artificial ECMs have several functions in tissue engineering, includ- 22 September 2010 ing provision of cell-adhesive substrate, control of three-dimensional tissue structure, and Accepted 7 October 2010 Available online 20 October 2010 presentation of growth factors, cell-adhesion signals, and mechanical signals. Design cri- teria for artificial ECMs vary considerably depending on the type of the engineered tissue. This article reviews the materials and methods that have been used in fabrication of artifi- Keywords: Artificial extracellular matrix cial ECMs for engineering of specific tissues, including liver, cartilage, bone, and skin. This Naturally-derived polymer article also reviews artificial ECMs used for modulation of stem cell behaviors for tissue Stem cells engineering applications. Synthetic polymer © 2010 Elsevier Ltd. All rights reserved. Tissue engineering Contents 1. Introduction ........................................................................................................................ 239 1.1. Significance of artificial extracellular matrix in tissue engineering applications .......................................... 239 1.2. General requirements of artificial ECMs for tissue engineering............................................................ 239 1.3. Classification of artificial ECMs ............................................................................................. 239 2. Liver ................................................................................................................................. 240 2.1. Mechanism of specific interaction between hepatocytes and galactose moieties ......................................... 240 2.2. Classification of artificial ECMs for liver tissue engineering................................................................ 241 2.2.1. Synthetic polymers ................................................................................................ 241 2.2.2. Naturally-derived polymers....................................................................................... 242 2.3. Parameters affecting hepatocellular behavior .............................................................................. 245 ∗ Corresponding author. Tel.: +81 45 924 5790; fax: +81 45 924 5815. ∗∗ Corresponding author. Tel.: +82 2 880 4868; fax: +82 2 875 2494. E-mail addresses: [email protected] (T. Akaike), [email protected] (C.-S. Cho). 1 These authors contributed equally to this work. 0079-6700/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.progpolymsci.2010.10.001 B.-S. Kim et al. / Progress in Polymer Science 36 (2011) 238–268 239 2.3.1. Galactose density and microdistribution of galactose ............................................................ 246 2.3.2. Topology of artificial ECMs ........................................................................................ 247 3. Cartilage ............................................................................................................................ 248 3.1. Natural material-based artificial ECMs ..................................................................................... 248 3.2. Synthetic material-based artificial ECMs ................................................................................... 251 3.2.1. Poly(ethylene glycol) (PEG) hydrogels ............................................................................ 252 3.2.2. Injectable hydrogels ............................................................................................... 252 3.3. Composite artificial ECMs ................................................................................................... 253 4. Bone ................................................................................................................................. 253 4.1. Artificial ECMs for bone tissue engineering ................................................................................ 253 4.1.1. Design criteria of artificial ECMs for bone tissue engineering .................................................... 253 4.1.2. Non-polymeric materials ......................................................................................... 253 4.1.3. Synthetic polymeric materials .................................................................................... 254 4.1.4. Naturally-derived polymers....................................................................................... 254 4.1.5. Composite materials .............................................................................................. 254 4.2. Regulation of cellular functions by artificial ECMs ......................................................................... 254 4.2.1. Importance of regulation of cellular function by artificial ECMs ................................................. 254 4.2.2. Regulation of osteoblast functions ................................................................................ 254 4.3. Artificial ECMs for osteochondral defects .................................................................................. 255 5. Skin ................................................................................................................................. 255 5.1. Naturally-derived materials ................................................................................................ 256 5.2. Synthetic polymeric materials .............................................................................................. 256 5.3. Future challenges in skin tissue engineering ............................................................................... 256 6. Stem cells ........................................................................................................................... 256 6.1. Delivery of soluble factors using artificial ECMs............................................................................ 256 6.2. Cell adhesion signal presentation by artificial ECMs ....................................................................... 258 6.3. Chemistry of artificial ECMs ................................................................................................ 258 6.4. Architecture of artificial ECMs .............................................................................................. 259 6.5. Mechanical properties of artificial ECMs ................................................................................... 259 6.6. Control of cell shape and size with artificial ECMs ......................................................................... 260 6.7. Mechanical signal loading on artificial ECMs ............................................................................... 261 7. Concluding remarks ................................................................................................................ 262 Acknowledgements ................................................................................................................ 262 References .......................................................................................................................... 262 1. Introduction 1.2. General requirements of artificial ECMs for tissue engineering 1.1. Significance of artificial extracellular matrix in tissue engineering applications Artificial ECMs should be designed to guide cell attachment, proliferation, and differentiation for tissue Tissue engineering, which aims to reconstruct living tis- regeneration [8]. Material and biological requirements sues for replacement of damaged or lost tissues/organs should be considered for each tissue engineering applica- of living organisms, has recently emerged as an exciting tion, even though the exact requirements differ according interdisciplinary area in the life sciences [1]. To achieve to organ [9–11]. For the material side, there are several this aim, it is necessary to use cells together with biosig- requirements for artificial ECMs: artificial ECMs should be nalling molecules and extracellular matrix (ECM) into or biocompatible and non-toxic, and have a desired degrada- onto which cells will develop, organize, and behave as if tion rate, surface properties, processability, porosity, and they are in their native tissue [2]. Tissue engineering