Dietmar W. Hutmacher, Michael Sittinger and Makarand V. Risbud- Scaffold-based tissue engineering:...

Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems Dietmar W. Hutmacher 1 , Michael Sittinger 2 and Makarand V. Risbud 3 1 Divisi on of Bioeng ineeri ng and Department of Orthopa edic Surgery, National University of Singap ore, 119260, Singap ore 2 German Rheumatism Research Center and Experimental Rheumatolog y and Tissue Engineering Laboratory, Department of Rheumatology and Clinical Immunology, Charite ´ , Humboldt University of Berlin, 101 17 Berlin, Germany 3 Graduate Program in Cell and Tissue Engineering and Department of Orthopa edic Surgery, Thomas Jeff erson University, Philadelphia 19107, USA One of the milestones in tissue engineering has been the development of 3D scaffolds that guide cells to form functi onal tissue. Rece ntly, mouldless manuf actur ing techniques, known as solid free-form fabrication (SFF), or rap id protot ypi ng, have been suc ces sfully used to fabricate complex scaffolds. Similarly, to achieve simul- taneous addition of cells during the scaffold fabrication, novel robotic assembly and automated 3D cell encapsu- lation techn iques are being deve loped . As a resul t of these techn ologi es, tissu e-eng ineered constr ucts can be prepared that contain a controlled spatial distribu- tion of cells and growth factors, as well as engineered gradients of scaffold materials with a predicted micro- struc ture. Here, we revi ew the appli catio n, advance- ment and fut ure direc tio ns of SFF techniqu es in the des ign and cre ati on of scaf fol ds for use in cli nic all y driven tissue engineering. Curre ntly , scaf fold-b ased tissu e engin eerin g strategies are expanding to encompass cells, bioacti ve molec ules and str uct ura l mat rices. Eac h of these component s is combin ed into a ‘constru ct’ that promo tes repair and – in the best case scenar io – reg enerat ion of damage d or dis eas ed tissues. Because many scaffold-based tissue-engineering approaches are still experimental, it is not yet clear what defines a so-called ‘ideal scaffold’. Fac tor s gov erning scaf fol d des ign are complex and include considerations of matri x archi tectur e, pore size and mor pho logy , mec han ics versus por osi ty , sur fac e properties and degradation products. Moreover, because scaffolds are often composite structures, other confound- ing variables include the composition of biological components and vari at ion of thes e and ot her factors wi th ti me. It could be argued that there is no ‘ideal scaffold’ design pe r se, ins tea d eac h tis sue req uir es a specifi c matrixdes ign with defined material properties. Scaffold design should theref ore be gi n wi th at least a set of mi ni mum bi ochemi cal and physical requirements [1]. The scaffold must provide sufficient mechanical strength and stiffness to substitute initially for wound contraction forces, and later for the remodelling of the tissue. Furthermore, scaffold architec- ture should enhance initi al cell atta chment and subse - que nt mig rat ion into the matrix; it must also enhance the mass trans fer of metab olite s and provide suf ficient space for remodelling of the organized tissue matrix and development of a vasculature. To achieve this goal, the scaffold degradation profile should be designed so that it supports the constr uct unt il neo tis sue (cel ls plu s organi zed extracellular matri x witho ut vascu lariz ation ) is formed [1]. A second important considerati on is that if the degradation profile is slow the 3D matrix will maintain structural integrity and mechanical properties during the in vitr o and/or in vi vo remod ellin g proces s. Facto rs affecting the rate of remodelling include the type of tissue and the anatomy and physiology of the host tissue [2]. The external siz e and shape of the constr uct must als o be considered, particularly if the scaffold or cell construct is customised for an individual patient. It is also imperative that scaffo lds are manu factur ed in a reprod ucibl e, con- trolle d, and cost-effe ctive fashion with the flexibility to accommodate the presence of biological components, such as cel ls and gro wth fac tor s, in cert ain applic ati ons [3,4]. T o date, two methods of incorporating cells into scaffolds are being explored: (i) seeding of cells onto the surface of the scaffold following fabrication and (ii) the incorporation of cel ls int o the sca ff old fab rica tio n pro cess. In ter ms of organ printi ng, the secon d proces s is of consi derab le interest. However, early results reflect success with printing cell monolayers and not a complete 3D tissue or organ [5]. Basic considerations for scaffold fabrication by SFF Advanced mou ldl ess man ufacturing techni que s, com- monly known as solid free-form fabrication (SFF), rapid prototyping (RP) or, more colloquially, art to part technol- ogy [6] have recently been used for fabricating complex shaped scaffolds. Unlike conventional machining, which involves constant removal of materials, SFF builds parts by selectively adding materials, layer by layer , as specified by a comput er program. Eac h lay er represents the shape of the cros s-se cti on of the model at a specifi c level. T oday , SFF is viewed as an efficient way of reproducibly generating scaffolds of desired properties on a large scale [4,7,8]. In Correspond ing author: Dietmar W. Hutmacher ([email protected]. sg). Review TRENDS in Biotechnology Vol.22 No.7 July 2004 www.sciencedirect.com 0167-7799/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1 016/j.ti btech.2004.05.005

Dietmar W. Hutmacher, Michael Sittinger and Makarand V. Risbud- Scaffold-based tissue engineering:...

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