Mechanical Aspects of Tissue Engineering

ABSTRACT

Tissue engineering describes an initiative whereby a deficit of tissue may be replaced with an engineered construct, typically thought to be some combination of a structural support element and a cellular element. There are several mechanical aspects that come into play during the design of such a construct. First, the way in which the mechanical behavior of a tissue is characterized varies depending on the tissue type. For example, one would not consider the ultimate strength of a non-load-bearing tissue such as adipose. However, in bone, where this property helps to describe a functional role, it is of paramount importance. In addition, the arrangement of material chosen to represent the design space has implications regarding the mechanical performance of the scaffold on several different size scales, from the cellular toward the macroscopic. The loading experienced by the implant must also be within the native tissue's mechanical usage window. Future knowledge gained on this subject will continue to characterize the mechanical requirements of various tissues, so that engineering solutions, such as computer-aided tissue engineering, may be utilized from this knowledge. In this article we describe some of these requirements and solutions using bone tissue as an example.

KEYWORDS

Computer-aided tissue engineering - mechanical - scaffold - bone - mechanobiology

REFERENCES

• 1 Smith D H, Wolf J A, Meaney D F. A new strategy to produce sustained growth of central nervous system axons: continuous mechanical tension.  Tissue Eng. 2001;  7 131-139
• 2 Huiskes R, Ruimerman R, van Lenthe G H, Janssen J D. Effects of mechanical forces on maintenance and adaptation of form in trabecular bone.  Nature. 2000;  405 704-706
• 3 Mullender M G, Huiskes R. Proposal for the regulatory mechanism of Wolff's law.  J Orthop Res. 1995;  13 503-512
• 4 Prendergast P J, Huiskes R. The biomechanics of Wolff's law: recent advances.  Ir J Med Sci. 1995;  164 152-154
• 5 Frost H M. From Wolff's law to the Utah paradigm: insights about bone physiology and its clinical applications.  Anat Rec. 2001;  262 398-419
• 6 Hung C T, Pollack S R, Reilly T M, Brighton C T. Real-time calcium response of cultured bone cells to fluid flow.  Clin Orthop Relat Res. 1995;  (313) 256-269
• 7 Hudlicka O. Mechanical factors involved in the growth of the heart and its blood vessels.  Cell Mol Biol Res. 1994;  40 143-152
• 8 Liu S Q. Biomechanical basis of vascular tissue engineering.  Crit Rev Biomed Eng. 1999;  27 75-148
• 9 Kim J, Hadlock T, Cheney M, Varvares M, Marler J. Muscle tissue engineering for partial glossectomy defects.  Arch Facial Plast Surg. 2003;  5 403-407
• 10 Hickey D G, Frenkel S R, Di Cesare P E. Clinical applications of growth factors for articular cartilage repair.  Am J Orthop. 2003;  32 70-76
• 11 Woo S L, Hildebrand K, Watanabe N, Fenwick J A, Papageorgiou C D, Wang J H. Tissue engineering of ligament and tendon healing.  Clin Orthop Relat Res. 1999;  (367 suppl) S312-S323
• 12 Butler D L, Goldstein S A, Guilak F. Functional tissue engineering: the role of biomechanics.  J Biomech Eng. 2000;  122 570-575
• 13 Sikavitsas V I, Bancroft G N, Lemoine J J, Lieberschner M A, Dauner M, Mikos A G. Flow perfusion enhances the calcified matrix deposition of marrow stromal cells in biodegradable nonwoven fiber mesh scaffolds.  Ann Biomed Eng. 2005;  33 63-70
• 14 Angele P, Schumann D, Angele M et al.. Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds.  Biorheology. 2004;  41 335-346
• 15 Mauck R L, Soltz M A, Wang C C et al.. Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels.  J Biomech Eng. 2000;  122 252-260
• 16 Hung C T, Mauck R L, Wang C C, Lima E G, Ateshian G A. A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading.  Ann Biomed Eng. 2004;  32 35-49
• 17 Darling E M, Athanasiou K A. Biomechanical strategies for articular cartilage regeneration.  Ann Biomed Eng. 2003;  31 1114-1124
• 18 Fan J, Walsh K B. Mechanical stimulation regulates voltage-gated potassium currents in cardiac microvascular endothelial cells.  Circ Res. 1999;  84 451-457
• 19 Curi M A, Skelly C L, Meyerson S L et al.. Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels.  J Surg Res. 2002;  108 198-202
• 20 Akhyari P, Fedak P W, Weisel R D et al.. Mechanical stretch regimen enhances the formation of bioengineered autologous cardiac muscle grafts.  Circulation. 2002;  106(12, suppl 1) I137-I142
• 21 Papadaki M. Cardiac muscle tissue engineering.  IEEE Eng Med Biol Mag. 2003;  22 153-154
• 22 Neumann T, Hauschka S D, Sanders J E. Tissue engineering of skeletal muscle using polymer fiber arrays.  Tissue Eng. 2003;  9 995-1003
• 23 Cowin SC Bone Mechanics Handbook. 2nd ed. Boca Raton, FL; CRC Press 1989
• 24 Marcus R. Clinical review 76: the nature of osteoporosis.  J Clin Endocrinol Metab. 1996;  81 1-5
• 25 Johnston Jr C C, Slemenda C W. Pathogenesis of osteoporosis.  Bone. 1995;  17(2 suppl) 19S-22S
• 26 Groger A, Klaring S, Merten H A, Holste J, Kaps C, Sittinger M. Tissue engineering of bone for mandibular augmentation in immunocompetent minipigs: preliminary study.  Scand J Plast Reconstr Surg Hand Surg. 2003;  37 129-133
• 27 Sanders K M, Pasco J A, Ugoni A M et al.. The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study.  J Bone Miner Res. 1998;  13 1337-1342
• 28 Frost H M. Changing views about ‘osteoporoses’ (a 1998 overview).  Osteoporos Int. 1999;  10 345-352
• 29 Wolff J. Das Gesetz der Transformation der Knochen. Berlin; Hirschwald Verlag 1892
• 30 Turner C H. Functional determinants of bone structure: beyond Wolff's law of bone transformation.  Bone. 1992;  13 403-409
• 31 Cowin S C. A resolution restriction for Wolff's law of trabecular architecture.  Bull Hosp Jt Dis Orthop Inst. 1989;  49 205-212
• 32 Frost H M. Bone's mechanostat: a 2003 update.  Anat Rec A Discov Mol Cell Evol Biol. 2003;  275 1081-1101
• 33 Frost H M. The skeleton's mechanical usage window. In: The Utah Paradigm of Skeletal Physiology. Athens, Greece; International Society of Musculoskeletal and Neuronal Interactions 2004: 224-241
• 34 Lanyon L E, Hampson W G, Goodship A E, Shah J S. Bone deformation recorded in vivo from strain gauges attached to the human tibial shaft.  Acta Orthop Scand. 1975;  46 256-268
• 35 Frost H M. Bone “mass” and the “mechanostat”: a proposal.  Anat Rec. 1987;  219 1-9
• 36 Jee W. Integrated bone tissue physiology: anatomy and physiology. In: Cowin SC Bone Biomechanics Handbook. Boca Raton, FL; CRC Press LLC 2001: (1)1-(1)68
• 37 Duyck J, Ronold H J, Van Oosterwyck H, Naert I, Vander Sloten J, Ellingsen J E. The influence of static and dynamic loading on marginal bone reactions around osseointegrated implants: an animal experimental study.  Clin Oral Implants Res. 2001;  12 207-218
• 38 Mahmoudifar N, Doran P M. Tissue engineering of human cartilage in bioreactors using single and composite cell-seeded scaffolds.  Biotechnol Bioeng. 2005;  91 338-355
• 39 Forwood M R, Owan I, Takano Y, Turner C H. Increased bone formation in rat tibiae after a single short period of dynamic loading in vivo.  Am J Physiol. 1996;  270(3 Pt 1) E419-E423
• 40 Liebschner M AK, Wettergreen M A. Optimization of bone scaffold engineering for load bearing application. In: Ashammakhi N, Ferretti P Topics in Tissue Engineering. Oulu, Finland; University of Oulu 2003: 1-39
• 41 Majeska R. Cell biology of bone. In: Cowin SC Bone Biomechanics Handbook. Boca Raton, FL; CRC Press LLC 2001: (2)1-(2)24
• 42 Liebschner M A. Biomechanical considerations of animal models used in tissue engineering of bone.  Biomaterials. 2004;  25 1697-1714
• 43 van Rietbergen B, Huiskes R. Elastic constants of cancellous bone. In: Cowin SC Bone Biomechanics Handbook. Boca Raton, FL; CRC Press LLC 2001: 15(1)-15(24)
• 44 Lucchinetti E. Composite models of bone properties. In: Cowin SC Bone Biomechanics Handbook Boca Raton, FL; CRC Press LLC 2001: 12(1)-12(19)
• 45 Guo X E. Mechanical properties of cortical bone and cancellous bone tissue. In: Cowin SC Bone Biomechanics Handbook. Boca Raton, FL; CRC Press LLC 2001: 10(1)-10(23)
• 46 Frost H M. On Wolff's law and some related matters.  In: The Utah Paradigm of Skeletal Physiology. Athens, Greece; International Society of Musculoskeletal and Neuronal Interactions 2004: 41-73
• 47 Grande D A, Halberstadt C, Naughton G, Schwartz R, Manji R. Evaluation of matrix scaffolds for tissue engineering of articular cartilage grafts.  J Biomed Mater Res. 1997;  34 211-220
• 48 Weinbaum S, Cowin S C, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses.  J Biomech. 1994;  27 339-360
• 49 Perren S M. Physical and biological aspects of fracture healing with special reference to internal fixation.  Clin Orthop Relat Res. 1979;  (138) 175-196
• 50 Prendergast P J, Huiskes R, Soballe K. ESB Research Award 1996. Biophysical stimuli on cells during tissue differentiation at implant interfaces.  J Biomech. 1997;  30 539-548
• 51 You J, Yellowley C E, Donahue H J, Zhang Y, Chen Q, Jacobs C R. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow.  J Biomech Eng. 2000;  122 387-393
• 52 Cowin S C, Weinbaum S. Strain amplification in the bone mechanosensory system.  Am J Med Sci. 1998;  316 184-188
• 53 You L, Cowin S C, Schaffler M B, Weinbaum S. A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix.  J Biomech. 2001;  34 1375-1386
• 54 Kunnel J G, Gilbert J L, Stern P H. In vitro mechanical and cellular responses of neonatal mouse bones to loading using a novel micromechanical-testing device.  Calcif Tissue Int. 2002;  71 499-507
• 55 Ruimerman R, Van Rietbergen B, Hilbers P, Huiskes R. The effects of trabecular-bone loading variables on the surface signaling potential for bone remodeling and adaptation.  Ann Biomed Eng. 2005;  33 71-78
• 56 Hollister S J, Levy R A, Chu T M, Halloran J W, Feinberg S E. An image-based approach for designing and manufacturing craniofacial scaffolds.  Int J Oral Maxillofac Surg. 2000;  29 67-71
• 57 Biggemann M, Hilweg D, Brinckmann P. Prediction of the compressive strength of vertebral bodies of the lumbar spine by quantitative computed tomography.  Skeletal Radiol. 1988;  17 264-269
• 58 Sun W, Starly B, Darling A, Gomez C. Computer-aided tissue engineering: application to biomimetic modelling and design of tissue scaffolds.  Biotechnol Appl Biochem. 2004;  39 49-58
• 59 Wettergreen M, Bucklen B, Starly B, Yuksel E, Sun W, Liebschner M A. Creation of a unit block library of architectures for use in assembled scaffold engineering.  Computer-Aided Design. 2005;  37 1141-1149
• 60 Wettergreen M, Bucklen B, Templetion A, Liebschner M A. Computer-aided tissue engineering of a human vertebral body.  Ann Biomed Eng. 2005;  , In press
• 61 Hutmacher D W. Scaffolds in tissue engineering bone and cartilage.  Biomaterials. 2000;  21 2529-2543
• 62 Sun W, Darling A, Starly B, Nam J. Computer-aided tissue engineering: overview, scope and challenges.  Biotechnol Appl Biochem. 2004;  39 29-47
• 63 Hollister S J, Maddox R D, Taboas J M. Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints.  Biomaterials. 2002;  23 4095-4103
• 64 Belytschko T, Xiao S P, Parimi C. Topology optimization with implicit functions and regularization.  Int J Numer Methods Eng. 2003;  57 1177-1196
• 65 Bendsoe M P, Kikuchi N. Generating optimal topologies in structural design using a homogenization method.  Comput Methods Appl Mech Eng. 1988;  71 197-224
• 66 Van Rietbergen B, Muller R, Ulrich D, Ruegsegger P, Huiskes R. Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions.  J Biomech. 1999;  32 443-451
• 67 Mattheck C. Design in nature.  Interdiscip Sci Rev. 1994;  19 298-314
• 68 Mattheck C, Bethge K, Tesari I, Scherrer M, Kraft O. Is there a universal optimum notch shape?.  Materialwiss Werkstofftech. 2004;  35 582-586
• 69 Lin C Y, Kikuchi N, Hollister S J. A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity.  J Biomech. 2004;  37 623-636