On scaffold designing for bone regeneration: A computational multiscale approach.

Scaffold design for bone tissue engineering applications involves many parameters that directly influence the rate of bone tissue regeneration onto its microstructural surface. To improve scaffold functionality, increasing interest is being focused on in vitro and in vivo research in order to obtain the optimal scaffold design for a specific application. However, the evaluation of the effect of each specific scaffold parameter on tissue regeneration using these techniques requires costly protocols and long-term experiments. In this paper, we elucidate the effect of some scaffold parameters on bone tissue regeneration by means of a mathematically based approach. By virtue of in silico experiments, factors such as scaffold stiffness, porosity, resorption kinetics, pore size and pre-seeding are analyzed in a specific bone tissue application found in the literature. The model predicts the in vivo rate of bone formation within the scaffold, the scaffold degradation and the interaction between the implanted scaffold and the surrounding bone. Results show an increasing rate of bone regeneration with increasing scaffold stiffness, scaffold mean pore size and pre-seeding, whereas the collapse of the scaffold occurs for a faster biomaterial resorption kinetics. Requiring further experimental validation, the model can be useful for the assessment of scaffold design and for the analysis of scaffold parameters in tissue regeneration.

[1]  P J Prendergast,et al.  Biophysical stimuli on cells during tissue differentiation at implant interfaces , 1997 .

[2]  Pedro Moreo,et al.  Modeling mechanosensing and its effect on the migration and proliferation of adherent cells. , 2008, Acta biomaterialia.

[3]  A. Caplan,et al.  Osteogenesis in Marrow-Derived Mesenchymal Cell Porous Ceramic Composites Transplanted Subcutaneously: Effect of Fibronectin and Laminin on Cell Retention and Rate of Osteogenic Expression , 1992, Cell transplantation.

[4]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[5]  M. Lafage-Proust,et al.  Modulation of the responses of human osteoblast-like cells to physiologic mechanical strains by biomaterial surfaces. , 2005, Biomaterials.

[6]  M. V. D. van der Meulen,et al.  A mathematical framework to study the effects of growth factor influences on fracture healing. , 2001, Journal of theoretical biology.

[7]  Noboru Kikuchi,et al.  Characterization of the mechanical behaviors of solid-fluid mixture by the homogenization method , 1998 .

[8]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[9]  D P Fyhrie,et al.  Trabecular bone density and loading history: regulation of connective tissue biology by mechanical energy. , 1987, Journal of biomechanics.

[10]  G S Beaupré,et al.  An approach for time‐dependent bone modeling and remodeling—theoretical development , 1990, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  John A. Kanis,et al.  Bone and Mineral Research , 1991 .

[12]  Paolo A. Netti,et al.  The performance of poly-ε-caprolactone scaffolds in a rabbit femur model with and without autologous stromal cells and BMP4 , 2007 .

[13]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[14]  H. Grootenboer,et al.  Adaptive bone-remodeling theory applied to prosthetic-design analysis. , 1987, Journal of biomechanics.

[15]  D. Pavlin,et al.  Effect of mechanical loading on periodontal cells. , 2001, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[16]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[17]  F. Pauwels,et al.  Gesammelte Abhandlungen zur funktionellen Anatomie des Bewegungsapparates , 1965 .

[18]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[19]  Mark Taylor,et al.  Computational modelling of cell spreading and tissue regeneration in porous scaffolds. , 2007, Biomaterials.

[20]  S. Hollister Porous scaffold design for tissue engineering , 2005, Nature materials.

[21]  José Manuel García-Aznar,et al.  Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: fabrication, mechanical properties, and finite element modeling. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[22]  Josep A Planell,et al.  Simulation of tissue differentiation in a scaffold as a function of porosity, Young's modulus and dissolution rate: application of mechanobiological models in tissue engineering. , 2007, Biomaterials.

[23]  Lin Tang,et al.  Effects of different magnitudes of mechanical strain on Osteoblasts in vitro. , 2006, Biochemical and biophysical research communications.

[24]  José Manuel García-Aznar,et al.  Micro–macro numerical modelling of bone regeneration in tissue engineering , 2008 .

[25]  A I Caplan,et al.  Stem cell technology and bioceramics: from cell to gene engineering. , 1999, Journal of biomedical materials research.

[26]  A. Caplan,et al.  Porous ceramic vehicles for rat-marrow-derived (Rattus norvegicus) osteogenic cell delivery: effects of pre-treatment with fibronectin or laminin. , 1993, The Journal of oral implantology.

[27]  Masao Tanaka,et al.  Simulation of Trabecular Surface Remodeling based on Local Stress Nonuniformity. , 1997 .

[28]  Xuesi Chen,et al.  Composites of poly(lactide-co-glycolide) and the surface modified carbonated hydroxyapatite nanoparticles. , 2007, Journal of biomedical materials research. Part A.

[29]  P H Krebsbach,et al.  Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds. , 2003, Biomaterials.

[30]  D. Biskobing COPD and osteoporosis. , 2002, Chest.

[31]  R E Guldberg,et al.  The accuracy of digital image-based finite element models. , 1998, Journal of biomechanical engineering.

[32]  H. Takita,et al.  Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis. , 1997, Journal of biochemistry.

[33]  Chad Johnson,et al.  The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. , 2004, Biomaterials.

[34]  Antonios G Mikos,et al.  Modulation of cell differentiation in bone tissue engineering constructs cultured in a bioreactor. , 2006, Advances in experimental medicine and biology.

[35]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[36]  Jeff Houck,et al.  Rabbit knee joint biomechanics: Motion analysis and modeling of forces during hopping , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  R. Reis,et al.  Bioinert, biodegradable and injectable polymeric matrix composites for hard tissue replacement: state of the art and recent developments , 2004 .

[38]  D Kaspar,et al.  Tissue engineering of bone: effects of mechanical strain on osteoblastic cells in type I collagen matrices. , 2005, Biomaterials.

[39]  I Zein,et al.  Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. , 2001, Journal of biomedical materials research.

[40]  David Williams,et al.  Benefit and risk in tissue engineering , 2004 .

[41]  T. Adachi,et al.  Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration. , 2006, Biomaterials.

[42]  S. Hollister,et al.  Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. , 2002, Biomaterials.

[43]  H. Takita,et al.  Geometry of Carriers Controlling Phenotypic Expression in BMP-Induced Osteogenesis and Chondrogenesis , 2001, The Journal of bone and joint surgery. American volume.

[44]  N. Kikuchi,et al.  A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity. , 2004, Journal of biomechanics.

[45]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[46]  S J Hollister,et al.  Trabecular surface remodeling simulation for cancellous bone using microstructural voxel finite element models. , 2001, Journal of biomechanical engineering.

[47]  Kyriacos Zygourakis,et al.  Cell population dynamics modulate the rates of tissue growth processes. , 2006, Biophysical journal.

[48]  Patrick J Prendergast,et al.  Prediction of the optimal mechanical properties for a scaffold used in osteochondral defect repair. , 2006, Tissue engineering.

[49]  M J Gómez-Benito,et al.  Influence of fracture gap size on the pattern of long bone healing: a computational study. , 2005, Journal of theoretical biology.

[50]  J. A. Sanz-Herrera,et al.  A mathematical model for bone tissue regeneration inside a specific type of scaffold , 2008, Biomechanics and modeling in mechanobiology.

[51]  Eric A Nauman,et al.  Effect of porosity on the fluid flow characteristics and mechanical properties of tantalum scaffolds. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[52]  A. Göpferich,et al.  Polymer Bulk Erosion , 1997 .

[53]  M. Lewandowska-Szumieł,et al.  Osteoblast response to the elastic strain of metallic support. , 2007, Journal of biomechanics.

[54]  A. Friedenstein,et al.  Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. , 1968, Transplantation.