X-ray imaging optimization of 3D tissue engineering scaffolds via combinatorial fabrication methods.

We have developed a combinatorial method for determining optimum tissue scaffold composition for several X-ray imaging techniques. X-ray radiography and X-ray microcomputed tomography enable non-invasive imaging of implants in vivo and in vitro. However, highly porous polymeric scaffolds do not always possess sufficient X-ray contrast and are therefore difficult to image with X-ray-based techniques. Incorporation of high radiocontrast atoms, such as iodine, into the polymer structure improves X-ray radiopacity but also affects physicochemical properties and material performance. Thus, we have developed a combinatorial library approach to efficiently determine the minimum amount of contrast agent necessary for X-ray-based imaging. The combinatorial approach is demonstrated in a polymer blend scaffold system where X-ray imaging of poly(desaminotyrosyl-tyrosine ethyl ester carbonate) (pDTEc) scaffolds is improved through a controlled composition variation with an iodinated-pDTEc analog (pI(2)DTEc). The results show that pDTEc scaffolds must include at least 9%, 16%, 38% or 46% pI(2)DTEc (by mass) to enable effective imaging by microradiography, dental radiography, dental radiography through 0.75cm of muscle tissue or microcomputed tomography, respectively. Only two scaffold libraries were required to determine these minimum pI(2)DTEc percentages required for X-ray imaging, which demonstrates the efficiency of this new combinatorial approach for optimizing scaffold formulations.

[1]  R Langer,et al.  Selective cell transplantation using bioabsorbable artificial polymers as matrices. , 1988, Journal of pediatric surgery.

[2]  Newell R Washburn,et al.  Combinatorial screening of cell proliferation on poly(L-lactic acid)/poly(D,L-lactic acid) blends. , 2005, Biomaterials.

[3]  Dominique Bernard,et al.  Non-destructive quantitative 3D analysis for the optimisation of tissue scaffolds. , 2007, Biomaterials.

[4]  J. Vacanti,et al.  Tissue engineering. , 1993, Science.

[5]  Carl G. Simon,et al.  Combinatorial Polymer Scaffold Libraries for Screening Cell‐Biomaterial Interactions in 3D , 2008 .

[6]  J M Bidlack,et al.  An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library. , 1994, Science.

[7]  P. Rüegsegger,et al.  Direct Three‐Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  Alamgir Karim,et al.  Combinatorial characterization of cell interactions with polymer surfaces. , 2003, Journal of biomedical materials research. Part A.

[9]  B. Vázquez,et al.  The effect of cross-linking agents on acrylic bone cements containing radiopacifiers. , 2001, Biomaterials.

[10]  T. W. Ridler,et al.  Picture thresholding using an iterative selection method. , 1978 .

[11]  J. Klawitter,et al.  Application of porous ceramics for the attachment of load bearing internal orthopedic applications , 1971 .

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

[13]  Robert Langer,et al.  Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction. , 2005, Biomaterials.

[14]  S. Deb,et al.  Radiopacity in bone cements using an organo-bismuth compound. , 2002, Biomaterials.

[15]  P. Törmälä,et al.  Mechanical properties and in vitro degradation of self-reinforced radiopaque bioresorbable polylactide fibres , 2003, Journal of biomaterials science. Polymer edition.

[16]  Matthew L Becker,et al.  Fabrication of combinatorial polymer scaffold libraries. , 2007, The Review of scientific instruments.

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

[18]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[19]  D. Rüfenacht,et al.  Radiopaque polymeric materials for medical applications. Current aspects of biomaterial research. , 1999, Investigative radiology.

[20]  R G Smith,et al.  Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. , 1998, Science.

[21]  Carl G. Simon,et al.  Characterization of Combinatorial Polymer Blend Composition Gradients by FTIR Microspectroscopy , 2004, Journal of research of the National Institute of Standards and Technology.

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

[23]  S Brocchini,et al.  Structure-property correlations in a combinatorial library of degradable biomaterials. , 1998, Journal of biomedical materials research.

[24]  Tadashi Kokubo,et al.  Pore throat size and connectivity determine bone and tissue ingrowth into porous implants: three-dimensional micro-CT based structural analyses of porous bioactive titanium implants. , 2006, Biomaterials.

[25]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[26]  J. Kohn,et al.  Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. , 1994, Journal of biomedical materials research.

[27]  R. Sabesan,et al.  Infrared characterization of 2,6-diaryl-4-piperidones , 2006 .

[28]  Sheng Lin-Gibson,et al.  Systematic investigation of porogen size and content on scaffold morphometric parameters and properties. , 2007, Biomacromolecules.

[29]  N. Weber,et al.  Viscoelastic properties of fibrinogen adsorbed to the surface of biomaterials used in blood-contacting medical devices. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[30]  Esmaiel Jabbari,et al.  Quantitative analysis of interconnectivity of porous biodegradable scaffolds with micro-computed tomography. , 2004, Journal of biomedical materials research. Part A.