Four-Dimensional Printing Hierarchy Scaffolds with Highly Biocompatible Smart Polymers for Tissue Engineering Applications.

The objective of this study was to four-dimensional (4D) print novel biomimetic gradient tissue scaffolds with highly biocompatible naturally derived smart polymers. The term "4D printing" refers to the inherent smart shape transformation of fabricated constructs when implanted minimally invasively for seamless and dynamic integration. For this purpose, a series of novel shape memory polymers with excellent biocompatibility and tunable shape changing effects were synthesized and cured in the presence of three-dimensional printed sacrificial molds, which were subsequently dissolved to create controllable and graded porosity within the scaffold. Surface morphology, thermal, mechanical, and biocompatible properties as well as shape memory effects of the synthesized smart polymers and resultant porous scaffolds were characterized. Fourier transform infrared spectroscopy and gel content analysis confirmed the formation of chemical crosslinking by reacting polycaprolactone triol and castor oil with multi-isocyanate groups. Differential scanning calorimetry revealed an adjustable glass transition temperature in a range from -8°C to 35°C. Uniaxial compression testing indicated that the obtained polymers, possessing a highly crosslinked interpenetrating polymeric networks, have similar compressive modulus to polycaprolactone. Shape memory tests revealed that the smart polymers display finely tunable recovery speed and exhibit greater than 92% shape fixing at -18°C or 0°C and full shape recovery at physiological temperature. Scanning electron microscopy analysis of fabricated scaffolds revealed a graded microporous structure, which mimics the nonuniform distribution of porosity found within natural tissues. With polycaprolactone serving as a control, human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and differentiation greatly increased on our novel smart polymers. The current work will significantly advance the future design and development of novel and functional biomedical scaffolds with advanced 4D printing technology and highly biocompatible smart biomaterials.

[1]  Michael F. Toney,et al.  Structure and Mechanism of Strength Enhancement in Interpenetrating Polymer Network Hydrogels , 2011 .

[2]  Michael Wegener,et al.  Soft Polymers for Building up Small and Smallest Blood Supplying Systems by Stereolithography , 2012, Journal of functional biomaterials.

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

[4]  C. Laurencin,et al.  VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[5]  Judith R. Meakin,et al.  Fused deposition models from CT scans , 2004 .

[6]  Ron Pelrine,et al.  Interpenetrating Polymer Networks for High‐Performance Electroelastomer Artificial Muscles , 2006 .

[7]  Matthew C. Phipps,et al.  Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. , 2012, Biomaterials.

[8]  Giacomo Ceccone,et al.  Plasma modification of PCL porous scaffolds fabricated by solvent-casting/particulate-leaching for tissue engineering , 2014 .

[9]  Jason A Inzana,et al.  3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration. , 2014, Biomaterials.

[10]  Skylar Tibbits,et al.  4D Printing: Multi‐Material Shape Change , 2014 .

[11]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[12]  Qi Ge,et al.  Active materials by four-dimension printing , 2013 .

[13]  P. Supaphol,et al.  Development of polycaprolactone porous scaffolds by combining solvent casting, particulate leaching, and polymer leaching techniques for bone tissue engineering. , 2013, Journal of biomedical materials research. Part A.

[14]  J. A. Lewis.  Direct Ink Writing of 3D Functional Materials , 2006 .

[15]  T. Maekawa,et al.  POLYMERIC SCAFFOLDS IN TISSUE ENGINEERING APPLICATION: A REVIEW , 2011 .

[16]  S. Landgraeber,et al.  Osteogenic differentiation and proliferation of bone marrow-derived mesenchymal stromal cells on PDLLA + BMP-2-coated titanium alloy surfaces. , 2016, Journal of biomedical materials research. Part A.

[17]  M. Dadsetan,et al.  Nanocomposite bone scaffolds based on biodegradable polymers and hydroxyapatite. , 2015, Journal of biomedical materials research. Part A.

[18]  K. Yao,et al.  Poly(D,L-lactic acid) surfaces modified by silk fibroin: effects on the culture of osteoblast in vitro. , 2002, Biomaterials.

[19]  Dong-Woo Cho,et al.  Solid freeform fabrication technology applied to tissue engineering with various biomaterials , 2012 .

[20]  Patrick T. Mather,et al.  Chemically Cross-Linked Polycyclooctene: Synthesis, Characterization, and Shape Memory Behavior , 2002 .

[21]  Nathan J. Castro,et al.  Design of a Novel 3D Printed Bioactive Nanocomposite Scaffold for Improved Osteochondral Regeneration , 2015, Cellular and molecular bioengineering.

[22]  J. Seppälä,et al.  Synthesis and Characterization of a Biodegradable Thermoplastic Poly(ester−urethane) Elastomer , 1997 .

[23]  Jean-Pierre Kruth,et al.  Additively manufactured porous tantalum implants. , 2015, Acta biomaterialia.

[24]  Rosa Akbarzadeh,et al.  Effects of processing parameters in thermally induced phase separation technique on porous architecture of scaffolds for bone tissue engineering. , 2014, Journal of biomedical materials research. Part B, Applied biomaterials.

[25]  A. Bandyopadhyay,et al.  Bone tissue engineering using 3D printing , 2013 .

[26]  D. Hutmacher,et al.  Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae. , 2013, Biomaterials.

[27]  Moustapha Kassem,et al.  Surface-modified functionalized polycaprolactone scaffolds for bone repair: in vitro and in vivo experiments. , 2014, Journal of biomedical materials research. Part A.

[28]  Ping Wang,et al.  Soybean oil‐based polyurethane networks as candidate biomaterials: Synthesis and biocompatibility , 2012 .

[29]  Keri M Petersen,et al.  A bioactive "self-fitting" shape memory polymer scaffold with potential to treat cranio-maxillo facial bone defects. , 2014, Acta biomaterialia.

[30]  S. Miao,et al.  Ethyl rhamnolipids as a renewable source to produce biopolyurethanes , 2015 .

[31]  L G Machado,et al.  Medical applications of shape memory alloys. , 2003, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[32]  Scott J. Hollister,et al.  Controllable mineral coatings on PCL scaffolds as carriers for growth factor release. , 2012, Biomaterials.

[33]  P. Supaphol,et al.  Development of polycaprolactone porous scaffolds by combining solvent casting, particulate leaching, and polymer leaching techniques for bone tissue engineering: Development Of Polycaprolactone Porous Scaffolds , 2014 .

[34]  D. Cho,et al.  Improvement of bone regeneration capability of ceramic scaffolds by accelerated release of their calcium ions. , 2014, Tissue engineering. Part A.

[35]  Kaufui Wong,et al.  A Review of Additive Manufacturing , 2012 .