Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering

Three-dimensional printing (3DP) is a rapid prototyping technique that can create complex 3D structures by inkjet printing of a liquid binder onto powder biomaterials for tissue engineering scaffolds. Direct fabrication of scaffolds from 3DP, however, imposes a limitation on material choices by manufacturing processes. In this study, we report an indirect 3DP approach wherein a positive replica of desired shapes was printed using gelatin particles, and the final scaffold was directly produced from the printed mold. To create patient-specific scaffolds that match precisely to a patient's external contours, we integrated our indirect 3DP technique with imaging technologies and successfully created custom scaffolds mimicking human mandibular condyle using polycaprolactone and chitosan for potential osteochondral tissue engineering. To test the ability of the technique to precisely control the internal morphology of the scaffolds, we created orthogonal interconnected channels within the scaffolds using computer-aided-design models. Because very few biomaterials are truly osteoinductive, we modified inert 3D printed materials with bioactive apatite coating. The feasibility of these scaffolds to support cell growth was investigated using bone marrow stromal cells (BMSC). The BMSCs showed good viability in the scaffolds, and the apatite coating further enhanced cellular spreading and proliferation. This technique may be valuable for complex scaffold fabrication.

[1]  Shinji Sakai,et al.  An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. , 2009, Biomaterials.

[2]  H. Seitz,et al.  Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[3]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. , 2002, Tissue engineering.

[4]  H. Fritz,et al.  Plasticizing polylactide—the effect of different plasticizers on the mechanical properties , 1999 .

[5]  J. J. Coleman,et al.  Cranial Reconstruction with Computer‐Generated Hard‐Tissue Replacement Patient‐Matched Implants: Indications, Surgical Technique, and Long‐Term Follow‐Up , 2002, Plastic and reconstructive surgery.

[6]  T Fannin,et al.  Medical rapid prototyping and 3D CT in the manufacture of custom made cranial titanium plates. , 1999, Journal of medical engineering & technology.

[7]  H. S. Azevedo,et al.  Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends , 2007, Journal of The Royal Society Interface.

[8]  J. Suh,et al.  Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. , 2000, Biomaterials.

[9]  Xiaobing Fu,et al.  Naturally derived materials-based cell and drug delivery systems in skin regeneration. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[10]  L G Griffith,et al.  Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition. , 2001, Tissue engineering.

[11]  Min Lee,et al.  Beta-tricalcium phosphate particles as a controlled release carrier of osteogenic proteins for bone tissue engineering. , 2012, Journal of biomedical materials research. Part A.

[12]  Emanuel M. Sachs,et al.  Solid free-form fabrication of drug delivery devices , 1996 .

[13]  L. Reimer,et al.  Scanning Electron Microscopy , 1984 .

[14]  Boon Chin Heng,et al.  Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model , 2009, Biomedical materials.

[15]  Benjamin M. Wu,et al.  Scaffold fabrication by indirect three-dimensional printing. , 2005, Biomaterials.

[16]  J. Planell,et al.  High-resolution PLA-based composite scaffolds via 3-D printing technology. , 2013, Acta biomaterialia.

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

[18]  Y. Ikada,et al.  Effects of bFGF incorporated into a gelatin sheet on wound healing , 2005, Journal of biomaterials science. Polymer edition.

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

[20]  Y. Kawashima,et al.  Aqueous colloidal polymer dispersions of biodegradable DL-lactide/glycolide copolymer as basis for latex films: A new approach for the development of biodegradable depot systems , 1995 .

[21]  Miqin Zhang,et al.  Chitosan-based hydrogels for controlled, localized drug delivery. , 2010, Advanced drug delivery reviews.

[22]  M. Lück,et al.  Partial solubility parameters of poly(D,L-lactide-co-glycolide). , 2004, International journal of pharmaceutics.

[23]  Michael J. Cima,et al.  Effects of solvent-particle interaction kinetics on microstructure formation during three-dimensional printing , 1999 .

[24]  Emanuel M. Sachs,et al.  Computer-derived microstructures by 3D Printing: Sio- and Structural Materials , 1994 .

[25]  Tabatabaei Qomi,et al.  The Design of Scaffolds for Use in Tissue Engineering , 2014 .

[26]  R. Hollins,et al.  Cranial reconstruction with computer-generated hard-tissue replacement patient-matched implants: indications, surgical technique, and long-term follow-up. , 2003, Archives of facial plastic surgery.

[27]  Tejraj M Aminabhavi,et al.  Recent advances on chitosan-based micro- and nanoparticles in drug delivery. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[28]  R. Gross,et al.  Citrate esters as plasticizers for poly(lactic acid) , 1997 .

[29]  V. Dodane,et al.  Pharmaceutical applications of chitosan , 1998 .

[30]  V. B. Konkimalla,et al.  Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[31]  C K Chua,et al.  Fabrication of porous polymeric matrix drug delivery devices using the selective laser sintering technique , 2001, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[32]  Jacob K. White,et al.  Cell-delivery therapeutics for liver regeneration. , 2010, Advanced drug delivery reviews.

[33]  Harri Korhonen,et al.  Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography. , 2011, Acta biomaterialia.

[34]  Jun Li,et al.  Poly(lactic acid) scaffold fabricated by gelatin particle leaching has good biocompatibility for chondrogenesis , 2008, Journal of biomaterials science. Polymer edition.

[35]  L. Draghi,et al.  Microspheres leaching for scaffold porosity control , 2005, Journal of materials science. Materials in medicine.

[36]  K. Leong,et al.  Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. , 2003, Biomaterials.

[37]  L G Griffith,et al.  Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion. , 1998, Journal of biomaterials science. Polymer edition.

[38]  A Colin,et al.  A novel tool for rapid prototyping and development of simple 3D medical image processing applications on PCs. , 1997, Computer methods and programs in biomedicine.

[39]  D. Hutmacher,et al.  Scaffold development using 3D printing with a starch-based polymer , 2002 .

[40]  Scott C. Brown,et al.  A three-dimensional osteochondral composite scaffold for articular cartilage repair. , 2002, Biomaterials.

[41]  Benjamin M Wu,et al.  Effect of scaffold architecture and pore size on smooth muscle cell growth. , 2008, Journal of biomedical materials research. Part A.

[42]  Benjamin M. Wu,et al.  The effect of pH on the structural evolution of accelerated biomimetic apatite. , 2004, Biomaterials.

[43]  Antonios G Mikos,et al.  Gelatin as a delivery vehicle for the controlled release of bioactive molecules. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[44]  D. Chorvat,et al.  Chitosan based hydrogel microspheres as drug carriers. , 2007, Macromolecular Bioscience.

[45]  Eleanor Stride,et al.  Controlled microchannelling in dense collagen scaffolds by soluble phosphate glass fibers. , 2007, Biomacromolecules.

[46]  E. Duek,et al.  The microscopical characterization of membranes poly (l-glycolic-co-lactic acid) with and without added plasticizer: an in vivo study , 2008, Journal of materials science. Materials in medicine.

[47]  Rajeev Bhat,et al.  Gelatin alternatives for the food industry: recent developments, challenges and prospects , 2008 .

[48]  Á. Gali,et al.  Computational design of in vivo biomarkers , 2014, Journal of physics. Condensed matter : an Institute of Physics journal.

[49]  DW Hutmacher,et al.  Concepts of scaffold-based tissue engineering—the rationale to use solid free-form fabrication techniques , 2007, Journal of cellular and molecular medicine.

[50]  M. Cima,et al.  Carbon dioxide extraction of residual chloroform from biodegradable polymers. , 2002, Journal of biomedical materials research.

[51]  R. A. Jain,et al.  Controlled release of drugs from injectable in situ formed biodegradable PLGA microspheres: effect of various formulation variables. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[52]  E. Duek,et al.  In vivo interaction of cells on poly L-(lactic acid) membranes containing plasticizer , 2002, Journal of materials science. Materials in medicine.

[53]  Hyejin Park,et al.  Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications. , 2012, Journal of biomedical materials research. Part A.

[54]  L G Griffith,et al.  In Vitro Organogenesis of Liver Tissue a , 1997, Annals of the New York Academy of Sciences.

[55]  Y. Kato,et al.  Application of chitin and chitosan derivatives in the pharmaceutical field. , 2003, Current pharmaceutical biotechnology.

[56]  J. Fisher,et al.  Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model. , 2002, Journal of biomedical materials research.

[57]  E. Tan,et al.  Proliferation and Differentiation of Human Osteoblasts within 3D printed Poly-Lactic-co-Glycolic Acid Scaffolds , 2009, Journal of biomaterials applications.

[58]  H. Burt,et al.  An in vitro study of plasticized poly(lactic-co-glycolic acid) films as possible guided tissue regeneration membranes: material properties and drug release kinetics. , 2010, Journal of biomedical materials research. Part A.

[59]  P H Krebsbach,et al.  Tissue engineering osteochondral implants for temporomandibular joint repair. , 2005, Orthodontics & craniofacial research.

[60]  L G Griffith,et al.  Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels. , 1998, Annals of surgery.

[61]  Yang-Jo Seol,et al.  Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[62]  M. Xanthos,et al.  An overview of additives and modifiers for polymer blends: Facts, deductions, and uncertainties , 1992 .

[63]  Benjamin M. Wu,et al.  In vitro response of MC3T3-E1 pre-osteoblasts within three-dimensional apatite-coated PLGA scaffolds. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[64]  Benjamin M. Wu,et al.  Biomimetic apatite-coated alginate/chitosan microparticles as osteogenic protein carriers. , 2009, Biomaterials.

[65]  W. Park,et al.  Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. , 1995, Biomaterials.

[66]  L. P. Tan,et al.  Controlled release of sirolimus from a multilayered PLGA stent matrix. , 2006, Biomaterials.

[67]  R Langer,et al.  Biomimetic approach to cardiac tissue engineering , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[68]  Jiabing Fan,et al.  Anionic carbohydrate-containing chitosan scaffolds for bone regeneration. , 2013, Carbohydrate polymers.