[en] Bone regeneration is the process whereby bone is able to (scarlessly) repair itself from trauma, such as fractures or implant placement. Despite extensive experimental research, many of the mechanisms involved still remain to be elucidated. Over the last decade, many mathematical models have been established to investigate the regeneration process in silico. The first models considered only the influence of the mechanical environment as a regulator of the healing process. These models were followed by the development of bioregulatory models where mechanics was neglected and regeneration was regulated only by biological stimuli such as growth factors. The most recent mathematical models couple the influences of both biological and mechanical stimuli. Examples are given to illustrate the added value of mathematical regeneration research, specifically in the in silico design of treatment strategies for non-unions. Drawbacks of the current continuum-type models, together with possible solutions in extending the models towards other time and length scales are discussed. Finally, the demands for dedicated and more quantitative experimental research are presented.
Aaron, A. D. 1996 Bone healing and grafting. In Orthopaedic knowledge update, vol. 5 (ed. J. R. Kasser), pp. 21-28. Rosemont, IL: American Academy of Orthopaedic Surgeons.
Adam, J. A. 1999 A simplified model of wound healing (with particular reference to the critical size defect). Math. Comput. Model. 30, 23-32. (doi:10.1016/S0895-7177 (99) 00145-4)
Adam, J. 2002 The effect of surface curvature on wound healing in bone: II. The critical size defect. Math. Comput. Model. 35, 1085-1094. (doi:10.1016/S0895-7177 (02) 00073-0)
Alarcon, T., Byrne, H. M. and Maini, P. K. 2004 Towards whole-organ modelling of tumour growth. Prog. Biophys. Mol. Biol. 85, 451-472. (doi:10.1016/j.pbiomolbio.2004.02.004)
Ambard, D. and Swider, P. 2006 A predictive mechano-biological model of the bone-implant healing. Eur. J. Mech. A/Solids 25, 927-937. (doi:10.1016/j.euromechsol.2006.02.006)
Ament, C. and Hofer, E. P. 2000 A fuzzy logic model of fracture healing. J. Biomech. 33, 961-968. (doi:10.1016/S0021-9290 (00) 00049-X)
An, Y. H., Friedman, R. J. and Draughn, R. A. 1999 Animal models of fracture or osteotomy. In Animal models in orthopaedic research (eds Y. H. An and R. J. Friedman), pp. 197-218. Boca Raton, FL: CRC Press.
Anderson, A. R. A. and Chaplain, M. A. J. 1998 Continuous and discrete mathematical models of tumor-induced angiogenesis. Bull. Math. Biol. 60, 857-900. (doi:10.1006/bulm.1998.0042)
Anderson, A. and Quaranta, V. 2008 Integrative mathematical oncology. Nat. Rev. Cancer 8, 227-234. (doi:10.1038/nrc2329)
Andreykiv, A., Prendergast, P. J., van Keulen, F., Swieszkowski, W. and Rozing, P. M. 2005 Bone ingrowth simulation for a concept glenoid component design. J. Biomech. 38, 1023-1033. (doi:10.1016/j.jbiomech.2004. 05.044)
Andreykiv, A., van Keulen, F. and Prendergast, P. J. 2007 Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells. Biomech. Model. Mechanobiol. 7, 443-461. (doi:10.1007/s10237-007-0108-8)
Arnold, J. S. and Adam, J. A. 1999 A simplified model of wound healing II: the critical size defect in two dimensions. Math. Comput. Model. 30, 47-60. (doi:10.1016/S0895-7177 (99) 00197-1)
Bailón-Plaza, A. and van der Meulen, M. C. H. 2001 A mathematical framework to study the effects of growth factor influences on fracture healing. J. Theor. Biol. 212, 191-209. (doi:10.1006/jtbi. 2001.2372)
Bailón-Plaza, A. and van der Meulen, M. C. H. 2003 Beneficial effects of moderate, early loading and adverse effects of delayed or excessive loading on bone healing. J. Biomech. 36, 1069-1077. (doi:10.1016/S0021-9290 (03) 00117-9)
Bellomo, C. 2003 Modelling wound healing in bone. Math. Comput. Model. 37, 901-906. (doi:10. 1016/S0895-7177 (03) 00105-5)
Blenman, P. R., Carter, D. R. and Beaupré, G. S. 1989 Role of mechanical loading in the progressive ossification of a fracture callus. J. Orthop. Res. 7, 398-407. (doi:10.1002/jor.1100070312)
Burger, E. H. and Klein-Nulend, J. 1999 Mechanotransduction in bone-role of the lacunocanalicular network. FASEB J. 13, S101-S112.
Byrne, H. M., Owen, M. R., Alarcon, T. A., Murphy, J. and Maini, P. K. 2006 Modelling the response of vascular tumours to chemotherapy: a multiscale approach. Math. Models Methods 16 (Suppl.), 1219-1241. (doi:10.1142/S0218202506001522)
Cañadell, J. and Forriol, F. 1997 The external fixator in the treatment of infected pseudoarthrosis and bone defects. Osteosynth. Int. 5, 221-225.
Carter, D. R. 1987 Mechanical loading history and skelet al. biology. J. Biomech. 20, 1095-1109. (doi:10.1016/0021-9290 (87) 90027-3)
Carter, D. R., Blenman, P. R. and Beaupré, G. S. 1988 Correlations between mechanical stress history and tissue differentiation in initial fracture healing. J. Orthop. Res. 6, 736-748. (doi:10. 1002/jor.1100060517)
Carter, D. R., Beaupré, G. S., Giori, N. J. and Helms, J. A. 1998 Mechanobiology of skelet al. regeneration. Clin. Orthop. Relat. Res. 355S, S41-S55. (doi:10.1097/00003086-199810001-00006)
Claes, L. E. and Heigele, C. A. 1999 Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. J. Biomech. 32, 255-266. (doi:10.1016/S0021-9290 (98) 00153-5)
Compston, J. E., Papapoulos, S. E. and Blanchard, F. 1998 Report on osteoporosis in the European Community: current status and recommendations for the future. Working Party from European Union Member States. Osteoporos. Int. 8, 531-534. (doi:10.1007/s001980050094)
Davies, J. E. 2003 Understanding peri-implant endosseous healing. J. Dent. Educ. 67, 932-949.
Duyck, J., De Cooman, M., Puers, R., Van Oosterwyck, H., Vander Sloten, J. and Naert, I. 2004 A repeated sampling bone chamber methodology for the evaluation of tissue differentiation and bone adaptation around titanium implants under controlled mechanical conditions. J. Biomech. 37, 1819-1822. (doi:10.1016/j.jbiomech.2004.02.044)
Duyck, J., Vandamme, K., Geris, L., Van Oosterwyck, H., De Cooman, M., Vander Sloten, J., Puers, R. and Naert, I. 2006 The influence of micro-motion on the tissue differentiation around immediately loaded cylindrical turned titanium implants. Arch. Oral Biol. 51, 1-9. (doi:10. 1016/j.archoralbio.2005.04.003)
Einhorn, T. A. 1995 Enhancement of fracture healing. J. Bone Joint Surg. Am. 77, 940-956.
Einhorn, T. A. 1998 The cell and molecular biology of fracture healing. Clin. Orthop. Relat. Res. 355S, S7-S21. (doi:10.1097/00003086- 199810001-00003)
Einhorn, T. A., Majeska, R. J., Rush, E. B., Levine, P. M. and Horowitz, M. C. 1995 The expression of cytokine activity by fracture callus. J. Bone Miner. Res. 10, 1272-1281.
Gabbay, J. S., Zuk, P. A., Tahernia, A., Askari, M., O'hara, C. M., Karthikeyan, T., Azari, K., Hollinger, J. O. and Bradley, J. P. 2006 In vitro microdistraction of preosteoblasts: distraction promotes proliferation and oscillation promotes differentiation. Tissue Eng. 12, 3055-3065. (doi:10.1089/ten. 2006.12.3055)
Garcia-Aznar, J. M., Kuiper, J. H., Gómez-Benito, M. J., Doblaré, M. and Richardson, J. B. 2007 Computational simulation of fracture healing: influence of interfragmentary movement on the callus growth. J. Biomech. 40, 1467-1476. (doi:10.1016/j.jbiomech.2006.06.013)
Gardner, M. J., van der Meulen, M. C., Demetrakopoulos, D., Wright, T. M., Myers, E. R. and Bostrom, M. P. 2006 In vivo cyclic axial compression affects bone healing in the mouse tibia. J. Orthop. Res. 24, 1679-1686. (doi:10.1002/jor.20230)
Gerhard, F. A., Webster, D. J., van Lenthe, G. H. and Müller, R. 2009 In silico biology of bone modelling and remodelling: adaptation. Phil. Trans. R. Soc. A 367, 2011-2030. (doi:10.1098 /rsta.2008.0297)
Geris, L., Van Oosterwyck, H., Vander Sloten, J., Duyck, J. and Naert, I. 2003 Assessment of mechanobiological models for the numerical simulation of tissue differentiation around immediately loaded implants. Comp. Methods Biomech. Biomed. Eng. 6, 277-288. (doi:10. 1080/10255840310001634412)
Geris, L., Andreykiv, A., Van Oosterwyck, H., Vander Sloten, J., van Keulen, F., Duyck, J. and Naert, I. 2004 Numerical simulation of tissue differentiation around loaded titanium implants in a bone chamber. J. Biomech. 37, 763-769. (doi:10.1016/j.jbiomech.2003.09.026)
Geris, L., Gerisch, A., Vander Sloten, J., Weiner, R. and Van Oosterwyck, H. 2008a Angiogenesis in bone fracture healing: a bioregulatory model. J. Theor. Biol. 251, 137-158. (doi:10.1016/j.jtbi. 2007.11.008)
Geris, L., Vandamme, K., Naert, I., Vander Sloten, J., Duyck, J. and Van Oosterwyck, H. 2008b Application of mechanoregulatory models to simulate peri-implant tissue formation in an in vivo bone chamber. J. Biomech. 41, 145-154. (doi:10.1016/j.jbiomech.2007.07.008)
Geris L., Vander Sloten, J. and Van Oosterwyck, H. 2008c Mathematical modelling of bone regeneration including angiogenesis: design of treatment strategies for atrophic nonunions. In Transactions of the 54th Annual Meeting of the Orthopaedic Research Society, New Orleans.
Geris, L., Vander Sloten, J. and Van Oosterwyck, H. 2008d An integrated mathematical modelling framework for the study of bone fracture healing. J. Biomech. 41, S107. (doi:10.1016/S0021-9290 (08) 70107-6)
Gerstenfeld, L. C., Cullinane, D. M., Barnes, G. L., Graves, D. T. and Einhorn, T. A. 2003 Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J. Cell. Biochem. 88, 873-884. (doi:10.1002/jcb.10435)
Glowacki, J. 1998 Angiogenesis in fracture repair. Clin. Orthop. Relat. Res. 355S, S82-S89. (doi:10. 1097/00003086-199810001-00010)
Gomez-Benito, M. J., Garcia-Aznar, J. M., Kuiper, J. H. and Doblaré, M. 2005 Influence of fracture gap size on the pattern of long bone healing: a computational study. J. Theor. Biol. 235, 105-119. (doi:10.1016/j.jtbi.2004.12.023)
Goodship, A. E. and Kenwright, J. 1985 The influence of induced micromovement upon the healing of experimental tibial fractures. J. Bone Joint Surg. 67B, 650-655.
Goodship, A. E., Cunningham, J. L. and Kenwright, J. 1998 Strain rate and timing of stimulation in mechanical modulation offracture healing. Clin. Orthop. Relat. Res. 355S, 105-115. (doi:10.1097 /00003086-199810001- 00012)
Gross, U. M. 1988 Biocompatibility: the interaction of biomaterials and host response. J. Dent. Educ. 52, 798-803.
Hadjiargyrou, M., Lombardo, F., Zhao, S., Ahrens, W., Joo, J., Ahn, H., Jurman, M., White, D. W. and Rubin, C. T. 2002 Transcriptional profiling of bone regeneration. J. Biol. Chem. 277, 30 177-30 182. (doi:10.1074/jbc. M203171200)
Harrison, L. J., Cunningham, J. L., Strömberg, L. and Goodship, A. E. 2003 Controlled induction of a pseudarthrosis: a study using a rodent model. J. Orthop. Trauma 17, 11-21. (doi:10.1097 /00005131-200301000- 00003)
Huiskes, R., Van Driel, W. D., Prendergast, P. J. and Søballe, K. 1997 A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation. J. Mater. Sci. Mater. Med. 8, 785-788. (doi:10.1023/A:1018520914512)
Hulth, A. 1989 Current concepts of fracture healing. Clin. Orthop. 249, 265-284. (doi:10.1097 /00003086-198912000-00028)
Hunter, P. J. and Borg, T. K. 2003 Integration from proteins to organs: the Physiome Project. Nat. Rev. Mol. Cell Biol. 4, 237-243. (doi:10.1038/nrm1054)
Idelsohn, S., Planell, J. A., Gil, F. J. and Lacroix, D. 2006 Development of a dynamic mechanoregulation model based on shear strain and fluid flow to optimize distraction osteogenesis. J. Biomech. 39 (Suppl. 1), S9-S10. (doi:10.1016/S0021-9290 (06) 82903-9)
Igarashi, A. and Yamaguchi, M. 1999 Increase in bone protein components with healing rat fractures: enhancement by zinc treatment. Int. J. Mol. Med. 4, 615-620.
Isaksson, H., Wilson, W., van Donkelaar, C., Huiskes, R. and Ito, K. 2006a Comparison of biophysical stimuli for mechano-regulation of tissue differentiation during fracture healing. J. Biomech. 39, 1507-1516. (doi:10.1016/j.jbiomech.2005.01.037)
Isaksson, H., van Donkelaar, C., Huiskes, R. and Ito, K. 2006b Corroboration of mechanoregulatory algorithms for tissue differentiation during fracture healing: comparison with in vivo results. J. Orthop. Res. 24, 898-907. (doi:10.1002/jor.20118)
Isaksson, H., Comas, O., van Donkelaar, C., Mediavilla, J., Wilson, W., Huiskes, R. and Ito, K. 2007 Bone regeneration during distraction osteogenesis: mechano-regulation by shear strain and fluid velocity. J. Biomech. 40, 2002-2011. (doi:10.1016/j.jbiomech.2006.09.028)
Isaksson, H., van Donkelaar, C. C., Huiskes, R. and Ito, K. 2008a A mechano-regulatory bonehealing model incorporating cell-phenotype specific activity. J. Theor. Biol. 252, 230-246. (doi:10.1016/j.jtbi.2008. 01.030)
Isaksson, H., van Donkelaar, C. C. and Ito, K. 2008b Influence of material properties when modeling tissue differentiation during bone healing. J. Biomech. 41, S105. (doi:10.1016/S0021-9290 (08) 70105-2)
Kalpakcioglu, B. B., Morshed, S., Engelke, K. and Genant, H. K. 2008 Advanced imaging of bone macrostructure and microstructure in bone fragility and fracture repair. J. Bone Joint Surg. 90, 68-78. (doi:10.2106/JBJS. G.01506)
Kasper, G. et al. 2007 Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells 25, 903-910. (doi:10.1634/stemcells.2006-0432)
Kelly, D. J. and Prendergast, P. J. 2005 Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects. J. Biomech. 38, 1413-1422. (doi:10.1016/j.jbiomech.2004. 06.026)
Kenwright, J. and Gardner, T. 1998 Mechanical influences on tibial fracture healing. Clin. Orthop. Relat. Res. 355S, 179-190. (doi:10.1097/00003086-199810001-00019)
Kuiper, J. H., Ashton, B. A. and Richardson, J. B. 2000 Computer simulation offracture callus formation and stiffness restoration. In Proc. 12th Conf. of the ESB, European Society of Biomechanics, Dublin.
Lacroix, D. and Prendergast, P. J. 2002 A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J. Biomech. 35, 1163-1171. (doi:10.1016 /S0021-9290 (02) 00086-6)
Lacroix, D., Prendergast, P. J., Li, G. and Marsh, D. 2002 Biomechanical model to simulate tissue differentiation and bone regeneration: application to fracture healing. Med. Biol. Eng. Comp. 40, 14-21. (doi:10.1007/BF02347690)
Landry, P. S. 2000 Effect of soft-tissue trauma on the early periosteal response of bone to injury. J. Trauma 48, 479-483. (doi:10.1097/00005373-200003000-00018)
Leucht, P., Kim, J. B., Wazen, R., Currey, J. A., Nanci, A., Brunski, J. B. and Helms, J. A. 2007 Effect of mechanical stimuli on skelet al. regeneration around implants. Bone 40, 919-930. (doi:10.1016/j.bone.2006.10. 027)
Loboa, E. G., Beaupré, G. S. and Carter, D. R. 2001 Mechanobiology of initial pseudarthrosis formation with oblique fractures. J. Orthop. Res. 19, 1067-1072. (doi:10.1016/S0736-0266 (01) 00028-6)
Makino, T., Hak, D. J., Hazelwood, S. J., Curtiss, S. and Reddi, H. A. 2005 Prevention of atrophic nonunion development by recombinant human bone morphogenetic protein-7. J. Orthop. Res. 23, 632-638. (doi:10.1016/j.orthres.2004.09.009)
Malizos, K. N. and Papatheodorou, L. K. 2005 The healing potential of the periosteum, molecular aspects. Injury 36S, S13-S19. (doi:10.1016/j.injury.2005.07.030)
Marsh, D., Buckwalter, J. A. and McCollister-Evarts, C. 1994 Delayed union, nonunion, malunion and avascular necrosis. In Complications in orthopaedic surgery (ed. C. H. Epps), pp. 183-211. Philadelphia, PA: J. B. Lippinscott.
Mayer-Kuckuk, P. and Boskey, A. L. 2006 Molecular imaging promotes progress in orthopedic research. Bone 39, 965-977. (doi:10.1016/j.bone.2006.05.009)
McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K. and Chen, C. S. 2004 Cell shape, cytoskelet al. tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483-495. (doi:10.1016/S1534-5807 (04) 00075-9)
McDougall, S. R., Anderson, A. R. and Chaplain, M. A. 2006 Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies. J. Theor. Biol. 241, 564-589. (doi:10.1016/j.jtbi.2005.12.022)
McKibbin, B. 1978 The biology of fracture healing in long bones. J. Bone Joint Surg. 60B, 150-162.
Minina, E., Wenzel, H. M., Kreschel, C., Karp, S., Gaffield, W., McMahon, A. P. and Vortkamp, A. 2001 BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development 128, 4523-4534.
Morgan, E. F., Longaker, M. T. and Carter, D. R. 2006 Relationships between tissue dilatation and differentiation in distraction osteogenesis. Matrix Biol. 25, 94-103. (doi:10.1016/j.matbio.2005. 10.006)
Moukoko, D., Pithioux, M. and Chabrand, P. 2007 Temporal evolution of mechanical properties of skelet al. tissue regeneration in rabbits: an experimental study. Med. Biol. Eng. Comput. 45, 989-995. (doi:10.1007/s11517-007-0237-3)
Mullender, M. G. and Huiskes, R. 1997 Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone 20, 527-532. (doi:10.1016/S8756-3282 (97) 00036-7)
Murray, J. D. 2002 Mathematical biology: I. An introduction, 3rd edn. New York, NY: Springer.
Nelson, C. M., Jean, R. P., Tan, J. L., Liu, W. F., Sniadecki, N. J., Spector, A. A. and Chen, C. S. 2005 From the cover: emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl Acad. Sci. USA 102, 11 594-11 599. (doi:10.1073/pnas.0502575102)
Oni, O. O., Stafford, H. and Gregg, P. J. 1989 An experimental study of the patterns of periosteal and endosteal damage in tibial shaft fractures using a rabbit trauma model. J. Orthop. Trauma 3, 142-147. (doi:10.1097/00005131-198906000-00009)
Overgaard, S. 2000 Calcium phosphate coatings for fixation of bone implants: evaluated mechanically and histologically by stereological methods. J. Orthop. Scand. 71 (Suppl. 297), 1-74. (doi:10.1080/ 000164700753759574)
Park, S. H., O'Connor, K., Sung, R., McKellop, H. and Sarmiento, A. 1999 Comparison of healing process in open osteotomy model and closed fracture model. J. Orthop. Trauma 13, 114-120. (doi:10.1097/00005131-199902000- 00008)
Pauwels, F. 1960 Eine neue Theorie über den Einfluß mechanischer Reize auf die Differenzierung der Stützgewebe. Z. Anat. Entwicklungsgeschichte 121, 478-515. (doi:10.1007/BF00523401)
Perren, S. M. 1979 Physical and biological aspects of fracture healing with special reference to internal fixation. Clin. Orthop. Relat. Res. 138, 175-195.
Perren, S. M. and Cordey, J. 1980 Concepts of interfragmentary strain. In Current concepts of internal fixation of fractures (ed. H. K. Uhthoff), pp. 63-77. New York, NY: Springer.
Plenk Jr, H. and Zitter, H. 1996 Material considerations. In Endosseous implants: scientific and clinical aspects (ed. G. Watzek), pp. 63-99. Chicago, IL: Quintessence Publishing Co.
Praemer, A., Furner, S. and Rice, D. P. 1999 Musculoskelet al. conditions in the United States. Rosemont, IL: American Academy of Orthopaedic Surgeons.
Prendergast, P. J., Huiskes, R. and Søballe, K. 1997 Biophysical stimuli on cells during tissue differentiation at implant interfaces. J. Biomech. 30, 539-548. (doi:10.1016/S0021-9290 (96) 00140-6)
Reed, A., Joyner, C. J., Brownlow, H. C. and Simpson, A. H. R. W. 2002 Human atrophic fracture non-unions are not avascular. J. Orthop. Res. 20, 593-599. (doi:10.1016/S0736-0266 (01) 00142-5)
Reginster, J. Y. and Burlet, N. 2006 Osteoporosis: a still increasing prevalence. Bone 38 (Suppl. 1), S4-S9. (doi:10.1016/j.bone.2005. 11.024)
Rodriguez-Merchan, E. C. and Forriol, F. 2004 Nonunion: general principles and experimental data. Clin. Orthop. Relat. Res. 419, 4-12. (doi:10.1097/00003086-200402000-00003)
Schenk, R. K. and Herrmann, R. W. 1984 Histologic studies on the incorporation of uncemented implants. In The cementless fixation of hip endoprostheses (ed. E. Morscher), pp. 52-58. Berlin, Germany: Springer.
Schwartz, Z., Kieswetter, K., Dean, D. D. and Boyan, B. D. 1997 Underlying mechanisms at the bone-surface interface during regeneration. J. Periodont. Res. 32, 166-171. (doi:10.1111/j.1600-0765.1997.tb01399.x)
Shefelbine, S. J., Augat, P., Claes, L. and Simon, U. 2005 Trabecular bone fracture healing simulation with finite element analysis and fuzzy logic. J. Biomech. 38, 2440-2450. (doi:10. 1016/j.jbiomech.2004.10.019)
Simon, U., Augat, P., Utz, M. and Claes, L. 2003 Simulation of tissue development and vascularisation in the callus healing process. In Transactions of the 49th Annual Meeting of the Orthopaedic Research Society, New Orleans.
Søballe, K. 1993 Hydroxyapatite ceramic coating for bone implant fixation. Acta Orthop. Scand. 64 (Suppl. 255), 1-48.
Southwood, L. L., Frisbie, D. D., Kawcak, C. E. and McIlwraith, C. W. 2004 Delivery of growth factors using gene therapy to enhance bone healing. Vet. Surg. 33, 565-578. (doi:10.1111/j.1532-950x.2004.04080.x)
Steflik, D. E., Corpe, R. S., Lake, F. T., Young, T. R., Sisk, A. L., Parr, G. R., Hanes, P. J. and Berkery, D. J. 1998 Ultrastructural analyses of the attachment (bonding) zone between bone and implanted biomaterials. J. Biomed. Mater. Res. 39, 611-620. (doi:10.1002 /(SICI) 1097-4636 (19980315) 39:4<611::AID-JBM16>3.0. CO;2-9)
Taguchi, K., Ogawa, R., Migita, M., Hanawa, H., Ito, H. and Orimo, H. 2005 The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model. Biochem. Biophys. Res. Commun. 331, 31-36. (doi:10.1016/j.bbrc.2005.03.119)
Weinand, C. et al. 2006 Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone. Bone 38, 555-563. (doi:10.1016/j.bone.2005.10.016)
Whiteside, L. A. 1978 The effects of extraperiosteal and subperiosteal dissection. II. On fracture healing. J. Bone Joint Surg. Am. 60, 26-30.
You, L., Cowin, S. C., Schaffler, M. B. and Weinbaum, S. 2001 A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J. Biomech. 34, 1375-1386. (doi:10.1016/S0021-9290 (01) 00107-5)