Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts.

Correlating massive bone graft strength to parameters derived from non-invasive imaging is important for pre-clinical and clinical evaluation of therapeutic adjuvants designed to improve graft repair. Towards that end, univariate and multivariate regression between measures of graft and callus geometry from micro-CT imaging and torsional strength and rigidity were investigated in a mouse femoral graft model. Four millimeter mid-diaphyseal defects were grafted with live autografts or processed allografts and allowed to heal for 6, 9, 12, or 18 weeks. We observed that allograft remodeling and incorporation into the host remained severely impaired compared to autografts mainly due to the extent of callus formation around the graft, the rate and extent of the graft resorption, and the degree of union between the graft and host bone as judged by post-mechanical testing analysis of the mode of failure. The autografts displayed greater ultimate torque and torsional rigidity compared to the allografts over time. However the biomechanical properties of allografts were equivalent to autografts by 9 weeks but significantly decreased at 12 and 18 weeks. Multivariate regression analysis demonstrated significant statistical correlations between combinations of the micro-CT parameters (graft and callus volume and cross-sectional polar moment of inertia) with the measured ultimate torque and torsional rigidity (adjusted R(2)=44% and 50%, respectively). The statistical correlations approach used in this mouse study could be useful in guiding future development of non-invasive predictors of the biomechanical properties of allografts using clinical CT.

[1]  J. Chalmers Transplantation immunity in bone homografting. , 1959, The Journal of bone and joint surgery. British volume.

[2]  W. Enneking,et al.  Freeze-dried allogeneic segmental cortical-bone grafts in dogs. , 1978, The Journal of bone and joint surgery. American volume.

[3]  E. Schwarz,et al.  A novel murine segmental femoral graft model , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  Pelker Rr,et al.  Biomechanical aspects of bone autografts and allografts. , 1987 .

[5]  R. Guldberg,et al.  Periosteal stem cells are essential for bone revitalization and repair. , 2005, Journal of musculoskeletal & neuronal interactions.

[6]  Matthew E. Cunningham,et al.  Modern biologics used in orthopaedic surgery , 2006, Current opinion in rheumatology.

[7]  D. Vanel,et al.  Imaging of vascularized fibula autograft placed inside a massive allograft in reconstruction of lower limb bone tumors. , 2004, AJR. American journal of roentgenology.

[8]  B. Masri,et al.  The biology of bone grafting. , 1999, Instructional course lectures.

[9]  R. Lindsey,et al.  Case reports: management of large segmental tibial defects using a cylindrical mesh cage. , 2006, Clinical orthopaedics and related research.

[10]  M. Viceconti,et al.  Mechanical strength of a femoral reconstruction in paediatric oncology: A finite element study , 2003, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[11]  M. Gebhardt,et al.  Infection in bone allografts. Incidence, nature, and treatment. , 1988, The Journal of bone and joint surgery. American volume.

[12]  E. Chao,et al.  The determination of bone fracture properties by dual-energy X-ray absorptiometry and single-photon absorptiometry: A comparative study , 1991, Calcified Tissue International.

[13]  R. Guldberg,et al.  Periosteal Progenitor Cell Fate in Segmental Cortical Bone Graft Transplantations: Implications for Functional Tissue Engineering , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  R. Guldberg,et al.  Biological effects of rAAV-caAlk2 coating on structural allograft healing. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[15]  D. Wise,et al.  Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction. , 2002, Tissue engineering.

[16]  A. Weiland,et al.  Bone Grafts: A Radiologic, Histologic, and Biomechanical Model Comparing Autografts, Allografts, and Free Vascularized Bone Grafts , 1984, Plastic and reconstructive surgery.

[17]  V. Goldberg,et al.  The biology of bone grafts. , 1993, Seminars in arthroplasty.

[18]  M. Gebhardt,et al.  Fractures of allografts. Frequency, treatment, and end-results. , 1990, The Journal of bone and joint surgery. American volume.

[19]  J. Broz,et al.  Effects of rehydration state on the flexural properties of whole mouse long bones. , 1993, Journal of biomechanical engineering.

[20]  Matthew J. Silva,et al.  Growing C57Bl/6 Mice Increase Whole Bone Mechanical Properties by Increasing Geometric and Material Properties , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  B. Brigman,et al.  Allografts about the Knee in Young Patients with High-Grade Sarcoma , 2004, Clinical orthopaedics and related research.

[22]  M. Panjabi,et al.  Allograft incorporation: A biomechanical evaluation in a rat model , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  W. Enneking,et al.  Allograft Bone Decreases in Strength In Vivo over Time , 2005, Clinical orthopaedics and related research.

[24]  G. Friedlaender Bone allografts: the biological consequences of immunological events. , 1991, The Journal of bone and joint surgery. American volume.

[25]  A. van Lingen,et al.  New segmental long bone defect model in sheep: Quantitative analysis of healing with dual energy X‐ray absorptiometry , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[26]  Jeffrey Bonadio,et al.  Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration , 1999, Nature Medicine.

[27]  K. Sell,et al.  Bone allograft antigenicity in an experimental model and in man. , 1978, Acta medica Polona.

[28]  Hiromu Ito,et al.  Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy , 2005, Nature Medicine.

[29]  A. Tamhane,et al.  Statistics and Data Analysis: From Elementary to Intermediate , 1999 .

[30]  W. Enneking,et al.  Biomechanical evaluation of retrieved massive allografts: preliminary results. , 2001, Biomedical sciences instrumentation.

[31]  A. van Lingen,et al.  Evaluation of Strength of Healing Fractures With Dual Energy Xray Absorptiometry , 2000, Clinical orthopaedics and related research.

[32]  C. Delloye,et al.  Canine cortical bone autograft remodeling in two simultaneous skeletal sites , 2004, Archives of orthopaedic and traumatic surgery.

[33]  P J Nicholls,et al.  X-ray diagnosis of healing fractures in rabbits. , 1979, Clinical orthopaedics and related research.

[34]  H. Burchardt The biology of bone graft repair. , 1983, Clinical orthopaedics and related research.

[35]  C. L. Mallows Some comments on C_p , 1973 .

[36]  R. Pelker,et al.  Biomechanical properties of bone allografts. , 1983, Clinical orthopaedics and related research.

[37]  David L. Helfet,et al.  Instructional Course Lectures , 2008 .

[38]  L. Claes,et al.  Prediction of fracture callus mechanical properties using micro-CT images and voxel-based finite element analysis. , 2005, Bone.