Modulating mechanical behaviour of 3D-printed cartilage-mimetic PCL scaffolds: influence of molecular weight and pore geometry

Three-dimensional (3D)-printed poly(ε)-caprolactone (PCL)-based scaffolds are increasingly being explored for cartilage tissue engineering (CTE) applications. However, ensuring that the mechanical properties of these PCL-based constructs are comparable to that of articular cartilage that they are meant to regenerate is an area that has been under-explored. This paper presents the effects of PCL's molecular weight (MW) and scaffold's pore geometric configurations; strand size (SZ), strand spacing (SS), and strand orientation (SO), on mechanical properties of 3D-printed PCL scaffolds. The results illustrate that MW has significant effect on compressive moduli and yield strength of 3D-printed PCL scaffolds. Specifically, PCL with MW of 45 K was a more feasible choice for fabrication of visco-elastic, flexible and load-bearing PCL scaffolds. Furthermore, pore geometric configurations; SZ, SS, and SO, all significantly affect on tensile moduli of scaffolds. However, only SZ and SS have statistically significant effects on compressive moduli and porosity of these scaffolds. That said, inverse linear relationship was observed between porosity and mechanical properties of 3D-printed PCL scaffolds in Pearson's correlation test. Altogether, this study illustrates that modulating MW of PCL and pore geometrical configurations of the scaffolds enabled design and fabrication of PCL scaffolds with mechanical and biomimetic properties that better mimic mechanical behaviour of human articular cartilage. Thus, the modulated PCL scaffold proposed in this study is a framework that offers great potentials for CTE applications.

[1]  A. Grodzinsky,et al.  Biosynthetic response of cartilage explants to dynamic compression , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  Rosa Akbarzadeh,et al.  Solvent-free polymer/bioceramic scaffolds for bone tissue engineering: fabrication, analysis, and cell growth , 2014, Journal of biomaterials science. Polymer edition.

[3]  Dong-Woo Cho,et al.  Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering. , 2014, Journal of the mechanical behavior of biomedical materials.

[4]  R L Reis,et al.  Melt-based compression-molded scaffolds from chitosan-polyester blends and composites: Morphology and mechanical properties. , 2009, Journal of biomedical materials research. Part A.

[5]  Lorenzo Moroni,et al.  Combinatorial approaches to controlling cell behaviour and tissue formation in 3D via rapid-prototyping and smart scaffold design. , 2009, Combinatorial chemistry & high throughput screening.

[6]  Dong-Woo Cho,et al.  An additive manufacturing‐based PCL–alginate–chondrocyte bioprinted scaffold for cartilage tissue engineering , 2015, Journal of tissue engineering and regenerative medicine.

[7]  L. Moroni,et al.  Influence of PCL molecular weight on mesenchymal stromal cell differentiation , 2015 .

[8]  S. Ferreira,et al.  Box-Behnken design: an alternative for the optimization of analytical methods. , 2007, Analytica chimica acta.

[9]  B. Eames,et al.  Using synchrotron radiation inline phase-contrast imaging computed tomography to visualize three-dimensional printed hybrid constructs for cartilage tissue engineering. , 2016, Journal of synchrotron radiation.

[10]  Albert C. Chen,et al.  Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering. , 2011, Biomaterials.

[11]  J. Karger‐Kocsis.  Dependence of the fracture and fatigue performance of polyolefins and related blends and composites on microstructural and molecular characteristics , 1999 .

[12]  C A van Blitterswijk,et al.  3D fiber-deposited scaffolds for tissue engineering: influence of pores geometry and architecture on dynamic mechanical properties. , 2006, Biomaterials.

[13]  F. Guilak,et al.  Cartilage degeneration in post‐collapse cases of osteonecrosis of the human femoral head: Altered mechanical properties in tension, compression, and shear , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[14]  B B Seedhom,et al.  The 'instantaneous' compressive modulus of human articular cartilage in joints of the lower limb. , 1999, Rheumatology.

[15]  Xiaoyu Tian,et al.  A brief review of dispensing-based rapid prototyping techniques in tissue scaffold fabrication: role of modeling on scaffold properties prediction , 2009, Biofabrication.

[16]  J. Feijen,et al.  AFM-based mechanical testing of electrospun PCL fibers , 2009 .

[17]  Yuejin Wu,et al.  Enhanced enzymatic saccharification of rice straw by microwave pretreatment. , 2009, Bioresource technology.

[18]  Wei Sun,et al.  Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering , 2009, Biofabrication.

[19]  Y. Kuo,et al.  Effects of Composition, Solvent, and Salt Particles on the Physicochemical Properties of Polyglycolide/Poly(lactide‐co‐glycolide) Scaffolds , 2006, Biotechnology progress.

[20]  K. Yoon,et al.  The Effect of Molecular Weight of Polycaprolactone on the Ester Interchange Reactions during Melt Blending with Poly(ethylene terephthalate) , 2002 .

[21]  A.C.W. Lau,et al.  Precision extruding deposition and characterization of cellular poly‐ε‐caprolactone tissue scaffolds , 2004 .

[22]  Jaroslav Kováčik,et al.  Correlation between Young's modulus and porosity in porous materials , 1999 .

[23]  P. Nagy,et al.  Towards the understanding of the molecular weight dependence of essential work of fracture in semi-crystalline polymers: A study on poly(ε-caprolactone) , 2014 .

[24]  M. Guthold,et al.  Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique. , 2016, Materials science & engineering. C, Materials for biological applications.

[25]  I. Zein,et al.  Fused deposition modeling of novel scaffold architectures for tissue engineering applications. , 2002, Biomaterials.

[26]  J Malda,et al.  Bioprinting of hybrid tissue constructs with tailorable mechanical properties , 2011, Biofabrication.

[27]  D. J. Walsh,et al.  Calculations of the phase diagrams of polyethylene dissolved in supercritical solvents , 1988 .

[28]  B B Seedhom,et al.  The relationship of the compressive modulus of articular cartilage with its deformation response to cyclic loading: does cartilage optimize its modulus so as to minimize the strains arising in it due to the prevalent loading regime? , 2001, Rheumatology.

[29]  Michele M. Temple,et al.  Age- and site-associated biomechanical weakening of human articular cartilage of the femoral condyle. , 2007, Osteoarthritis and cartilage.

[30]  M. Raghunath,et al.  Electro-spinning of pure collagen nano-fibres - just an expensive way to make gelatin? , 2008, Biomaterials.

[31]  Shaun Eshraghi,et al.  Mechanical and microstructural properties of polycaprolactone scaffolds with one-dimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering. , 2010, Acta biomaterialia.

[32]  Deok‐Ho Kim,et al.  Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink , 2014, Nature Communications.

[33]  Zohreh Izadifar,et al.  Analyzing Biological Performance of 3D-Printed, Cell-Impregnated Hybrid Constructs for Cartilage Tissue Engineering. , 2016, Tissue engineering. Part C, Methods.

[34]  R. Schneiderman,et al.  Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density. , 2001, Osteoarthritis and cartilage.

[35]  Xiaoyan Yuan,et al.  Preparation and Characterization of Poly(L-lactide)/ Poly(-caprolactone) Fibrous Scaffolds for Cartilage Tissue Engineering , 2004 .

[36]  N. Kawazoe,et al.  Cartilage tissue engineering using funnel-like collagen sponges prepared with embossing ice particulate templates. , 2010, Biomaterials.

[37]  M. Wong,et al.  Cyclic compression of articular cartilage explants is associated with progressive consolidation and altered expression pattern of extracellular matrix proteins. , 1999, Matrix biology : journal of the International Society for Matrix Biology.

[38]  M. Bennink,et al.  Mechanical testing of electrospun PCL fibers. , 2012, Acta biomaterialia.

[39]  Tae Gwan Park,et al.  Hyaluronic acid modified biodegradable scaffolds for cartilage tissue engineering. , 2005, Biomaterials.

[40]  Andrei L. Turinsky,et al.  Effect of Voxel Size on 3D Micro-CT Analysis of Cortical Bone Porosity , 2007, Calcified Tissue International.

[41]  Stefan Lohfeld,et al.  Predicting the Elastic Properties of Selective Laser Sintered PCL/β-TCP Bone Scaffold Materials Using Computational Modelling , 2013, Annals of Biomedical Engineering.

[42]  Robert E Guldberg,et al.  Microarchitectural and mechanical characterization of oriented porous polymer scaffolds. , 2003, Biomaterials.

[43]  Albert C. Chen,et al.  Effect of initial cell seeding density on 3D-engineered silk fibroin scaffolds for articular cartilage tissue engineering. , 2011, Biomaterials.

[44]  F. J. Dzida,et al.  Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage , 1991, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[45]  S. Rimdusit,et al.  Effects of polycaprolactone molecular weights on thermal and mechanical properties of polybenzoxazine , 2015 .

[46]  T M Quinn,et al.  Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage. , 2006, Osteoarthritis and cartilage.

[47]  G. Bowlin,et al.  Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications , 2008, Biomedical materials.

[48]  Robert L Sah,et al.  Mechanical asymmetry during articulation of tibial and femoral cartilages: local and overall compressive and shear deformation and properties. , 2010, Journal of biomechanics.

[49]  Albert C. Chen,et al.  Depth‐dependent confined compression modulus of full‐thickness bovine articular cartilage , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[50]  D. Hutmacher,et al.  The return of a forgotten polymer : Polycaprolactone in the 21st century , 2009 .

[51]  Lin Lu,et al.  Porogen-based solid freeform fabrication of polycaprolactone-calcium phosphate scaffolds for tissue engineering. , 2006, Biomaterials.

[52]  V C Mow,et al.  Tensile properties of human knee joint cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus , 1986, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[53]  JULIAN F. Johnson,et al.  Influence of molecular weight and molecular weight distribution on mechanical properties of polymers , 1982 .

[54]  Hideki Harada,et al.  Surfactant-enhanced anaerobic acidogenesis of Canna indica L. by rumen cultures. , 2008, Bioresource technology.

[55]  Jack G. Zhou,et al.  A novel sucrose porogen‐based solid freeform fabrication system for bone scaffold manufacturing , 2010 .

[56]  D. J. Walsh,et al.  Mechanical properties of low molecular weight polymers as a function of temperature , 1988 .

[57]  C. V. van Blitterswijk,et al.  Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique. , 2004, Biomaterials.

[58]  J. L. Gomez Ribelles,et al.  Biodegradable polycaprolactone scaffold with controlled porosity obtained by modified particle-leaching technique , 2008, Journal of materials science. Materials in medicine.

[59]  V. Guarino,et al.  Porosity and mechanical properties relationship in PCL porous scaffolds. , 2008, Journal of applied biomaterials & biomechanics : JABB.

[60]  C. V. van Blitterswijk,et al.  The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage. , 2005, Biomaterials.

[61]  C. V. van Blitterswijk,et al.  Chitosan scaffolds containing hyaluronic acid for cartilage tissue engineering. , 2011, Tissue engineering. Part C, Methods.

[62]  M. Ourak,et al.  Influence of porosity on Young's modulus and Poisson's ratio in alumina ceramics , 2001 .

[63]  J. Kováčik.  Correlation Between Elastic Modulus, Shear Modulus, Poisson's Ratio and Porosity in Porous Materials , 2008 .

[64]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[65]  Jack G. Zhou,et al.  Mechanical Study of Polycaprolactone-hydroxyapatite Porous Scaffolds Created by Porogen-based Solid Freeform Fabrication Method , 2014, Journal of applied biomaterials & functional materials.

[66]  Scott A. Rodeo,et al.  The Basic Science of Articular Cartilage , 2009, Sports health.

[67]  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.