Inkjet-based biopatterning of bone morphogenetic protein-2 to spatially control calvarial bone formation.

The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or (125)I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns.

[1]  T A Einhorn,et al.  Enhancement of fracture-healing. , 1995, The Journal of bone and joint surgery. American volume.

[2]  C. J. Lewis,et al.  Cyanine dye labeling reagents: sulfoindocyanine succinimidyl esters. , 1993, Bioconjugate chemistry.

[3]  P. Campbell,et al.  Insulin-like growth factor (IGF)-binding protein-5-(201-218) region regulates hydroxyapatite and IGF-I binding. , 1997, American journal of physiology. Endocrinology and metabolism.

[4]  S. Feng,et al.  [Surgical treatment of craniosynostosis]. , 1995, Zhonghua zheng xing shao shang wai ke za zhi = Zhonghua zheng xing shao shang waikf [i.e. waike] zazhi = Chinese journal of plastic surgery and burns.

[5]  J. Gurdon,et al.  Morphogen gradient interpretation , 2001, Nature.

[6]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[7]  M. Gonzalez-Gaitan,et al.  Morphogen Gradient Formation and Vesicular Trafficking , 2002, Traffic.

[8]  C. Rider.  Heparin/heparan sulphate binding in the TGF-beta cytokine superfamily. , 2006, Biochemical Society transactions.

[9]  N. K. Sinsel,et al.  Effect of unilateral partial facial paralysis on periosteal growth at the muscle-bone interface of facial muscles and facial bones. , 2003, Plastic and reconstructive surgery.

[10]  J. Price,et al.  The cell biology of bone growth. , 1994, European journal of clinical nutrition.

[11]  Yingcui Li,et al.  Heparan sulfate proteoglycans including syndecan-3 modulate BMP activity during limb cartilage differentiation. , 2006, Matrix biology : journal of the International Society for Matrix Biology.

[12]  S. Cohen,et al.  Wingless gradient formation in the Drosophila wing , 2000, Current Biology.

[13]  B. Mroczkowski,et al.  Recombinant human epidermal growth factor precursor is a glycosylated membrane protein with biological activity , 1989, Molecular and Cellular Biology.

[14]  M. G. Vicker.  Gradient and temporal signal perception in chemotaxis. , 1989, Journal of cell science.

[15]  Susan W Herring.  Mechanical influences on suture development and patency. , 2008, Frontiers of oral biology.

[16]  Benjamin Wu,et al.  MicroCT evaluation of three-dimensional mineralization in response to BMP-2 doses in vitro and in critical sized rat calvarial defects. , 2007, Tissue engineering.

[17]  P. Wilkinson.  How do leucocytes perceive chemical gradients? , 1990, FEMS microbiology immunology.

[18]  W. Sebald,et al.  Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. , 1996, European journal of biochemistry.

[19]  N. Ferrara,et al.  The Role of Vascular Endothelial Growth Factor in Angiogenesis , 2002, Acta Haematologica.

[20]  L A Opperman,et al.  Cranial sutures as intramembranous bone growth sites , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  K. Lyons,et al.  Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. , 2006, Human molecular genetics.

[22]  S. -. Lee,et al.  Cytokine delivery and tissue engineering. , 2000, Yonsei medical journal.

[23]  A. Economides,et al.  0163-769X/03/$20.00/0 Endocrine Reviews 24(2):218–235 Printed in U.S.A. Copyright © 2003 by The Endocrine Society doi: 10.1210/er.2002-0023 Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton , 2022 .

[24]  K Basler,et al.  Compartment boundaries: at the edge of development. , 1999, Trends in genetics : TIG.

[25]  Yan Peng,et al.  AlloDerm versus DermaMatrix in Immediate Expander-Based Breast Reconstruction: A Preliminary Comparison of Complication Profiles and Material Compliance , 2009, Plastic and reconstructive surgery.

[26]  J. Hicks,et al.  A comparative, long term assessment of soft tissue substitutes: AlloDerm, Enduragen, and Dermamatrix. , 2009, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[27]  Eric D. Miller,et al.  Microenvironments Engineered by Inkjet Bioprinting Spatially Direct Adult Stem Cells Toward Muscle‐ and Bone‐Like Subpopulations , 2008, Stem cells.

[28]  V. P. Kumar,et al.  The anatomy of the anterior origin of the deltoid. , 1997, The Journal of bone and joint surgery. British volume.

[29]  Benjamin M. Wu,et al.  Evolving concepts in bone tissue engineering. , 2005, Current topics in developmental biology.

[30]  C. Tickle,et al.  Morphogen gradients in vertebrate limb development. , 1999, Seminars in cell & developmental biology.

[31]  D. Greenhalgh,et al.  Cutaneous Wound Healing , 2007, Journal of burn care & research : official publication of the American Burn Association.

[32]  A. Sahni,et al.  Binding of Basic Fibroblast Growth Factor to Fibrinogen and Fibrin* , 1998, The Journal of Biological Chemistry.

[33]  R. Clark.  Synergistic signaling from extracellular matrix-growth factor complexes. , 2008, The Journal of investigative dermatology.

[34]  D. Summerbell,et al.  Positional signalling and specification of digits in chick limb morphogenesis , 1975, Nature.

[35]  A. Sahni,et al.  FGF‐2 but not FGF‐1 binds fibrin and supports prolonged endothelial cell growth , 2003, Journal of thrombosis and haemostasis : JTH.

[36]  E. L. Ferguson,et al.  Morphogen gradients: new insights from DPP. , 1999, Trends in genetics : TIG.

[37]  M. Nishiguchi,et al.  Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin. , 2008, Bone.

[38]  C. Zachariae.  Chemotactic cytokines and inflammation. Biological properties of the lymphocyte and monocyte chemotactic factors ELCF, MCAF and IL-8. , 1993, Acta dermato-venereologica. Supplementum.

[39]  Y. Ito,et al.  Gradient micropattern immobilization of heparin and its interaction with cells , 2001, Journal of biomaterials science. Polymer edition.

[40]  Phil G. Campbell,et al.  Extracellular Matrix-mediated Signaling by Dentin Phosphophoryn Involves Activation of the Smad Pathway Independent of Bone Morphogenetic Protein* , 2006, Journal of Biological Chemistry.

[41]  A. Ullrich,et al.  Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor , 1983, Nature.

[42]  A. Teleman,et al.  Shaping Morphogen Gradients , 2001, Cell.

[43]  J. Ralphs,et al.  The skeletal attachment of tendons--tendon "entheses". , 2002, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[44]  Eric D. Miller,et al.  Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell organization. , 2005, Biomaterials.

[45]  C. A. Evans,et al.  Histologic study of the attachment of muscles to the rat mandible. , 1982, Archives of oral biology.

[46]  D. Powell,et al.  Insulin-like Growth Factor-binding Protein-3 Binds Fibrinogen and Fibrin* , 1999, The Journal of Biological Chemistry.

[47]  Lee E. Weiss,et al.  Bayesian computer-aided experimental design of heterogeneous scaffolds for tissue engineering , 2005, Comput. Aided Des..

[48]  M. Botta,et al.  Fibroblast growth factors and their inhibitors. , 2000, Current pharmaceutical design.

[49]  T. Skaar,et al.  Secretion of insulin-like growth factor-I (IGF-I) and IGF-binding proteins from bovine mammary tissue in vitro. , 1991, The Journal of endocrinology.

[50]  A. Sahni,et al.  Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires alphavbeta3. , 2004, Blood.

[51]  Phil G Campbell,et al.  Tissue engineering with the aid of inkjet printers , 2007, Expert opinion on biological therapy.

[52]  P. Billings,et al.  Heparan Sulfate Proteoglycans (HSPGs) Modulate BMP2 Osteogenic Bioactivity in C2C12 Cells* , 2007, Journal of Biological Chemistry.

[53]  Eric D. Miller,et al.  Dose-dependent cell growth in response to concentration modulated patterns of FGF-2 printed on fibrin. , 2006, Biomaterials.

[54]  C. Rider.  Heparin/heparan sulphate binding in the TGF-β cytokine superfamily , 2006 .

[55]  Eric D. Miller,et al.  Inkjet printing of growth factor concentration gradients and combinatorial arrays immobilized on biologically-relevant substrates. , 2009, Combinatorial chemistry & high throughput screening.

[56]  Tetsuya Tabata,et al.  Morphogens, their identification and regulation , 2004, Development.

[57]  A. Sahni,et al.  Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires αvβ3 , 2004 .

[58]  S. Goldring,et al.  Skeletal tissue response to cytokines. , 1990, Clinical orthopaedics and related research.