WO2009116950A1 - Moule pour couler des échafaudages d'ingénierie tissulaire et son procédé de génération - Google Patents

Moule pour couler des échafaudages d'ingénierie tissulaire et son procédé de génération Download PDF

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Publication number
WO2009116950A1
WO2009116950A1 PCT/SG2008/000081 SG2008000081W WO2009116950A1 WO 2009116950 A1 WO2009116950 A1 WO 2009116950A1 SG 2008000081 W SG2008000081 W SG 2008000081W WO 2009116950 A1 WO2009116950 A1 WO 2009116950A1
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WO
WIPO (PCT)
Prior art keywords
mould
images
dimensional
bitmap
templates
Prior art date
Application number
PCT/SG2008/000081
Other languages
English (en)
Inventor
Chin Sim Leo
Chi Mun Cheah
Original Assignee
Nanyang Polytechnic
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanyang Polytechnic filed Critical Nanyang Polytechnic
Priority to PCT/SG2008/000081 priority Critical patent/WO2009116950A1/fr
Publication of WO2009116950A1 publication Critical patent/WO2009116950A1/fr

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    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F30/00—Computer-aided design [CAD]
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F2113/00—Details relating to the application field
    • G06F2113/22—Moulding

Definitions

  • the present invention generally relates to technologies of designing and fabricating three-dimensional tissue engineering scaffolds, and more particularly to a mould for casting tissue engineering scaffolds and a process of generating the mould for casting tissue engineering scaffolds, and further to a tissue engineering scaffold fabricated by the mould for casting tissue engineering scaffolds.
  • One embodiment of the present invention provides a process for designing a customized three-dimensional porous mould for casting a three-dimensional porous scaffold for an object, wherein the customized three-dimensional porous mould comprises a wall and an internal structure with internal pores and internal channels connecting the internal pores.
  • the process comprises the steps of creating bitmap templates offline, wherein the bitmaps templates are created according to the desired shapes and dimensions of the pores and channels within the mould, preparing two-dimensional images of the object, pre-process the two-dimensional images to remove unwanted portions according to predetermined thresholds, generating the internal structure, and generating the wall of the mould; thereby the customized three-dimensional porous mould is designed.
  • the number of the bitmap templates depends on the size of the scaffold for the object, the resolution of the two-dimensional images of the object, the slice thickness of the two-dimensional images of the object, and the complexity of the internal pores and channels of the mould.
  • the step of creating bitmap templates performs manual drawing of the bitmap templates with any computer graphic software that supports a bitmap file format or using a short algorithm to automatically generate the bitmap templates.
  • the two-dimensional images are medical images that are generated from a technique selected from the group consisting of
  • CT computed tomography
  • MRI Magnetic resonance Imaging
  • Ultrasound or computer-based medical imaging systems
  • the two-dimensional images are stored in Digital Imaging and Communications in Medicine (DICOM) format.
  • DICOM Digital Imaging and Communications in Medicine
  • the two-dimensional images are firstly modified by intersecting them with appropriately selected bitmap templates via Boolean operation, resulting in the transferring of the grid pattern on the bitmap template onto the images, and then the internal (micro- O architecture) and external (external geometry) contour data of the modified images are extracted to reconstruct a three-dimensional surface model of the mould.
  • the three-dimensional surface model of the mould is reconstructed by surface patching technique.
  • the step of generating the wall of the mould includes creating the cup structure of the mould and expanding the edges of the wall to a required thickness.
  • the step of the creating of the cup structure of the mould for each slice, two sets of image data are kept, wherein one set is the cleaned images from the step of pre-process the two-dimensional images to remove unwanted portions according to predetermined thresholds without Boolean and the other set is the Boolean images, and wherein no Boolean operation is done for the last slice image that is the base of the cup.
  • Another embodiment of the present invention provides a customized three- dimensional porous mould for casting a three-dimensional porous scaffold for an object, wherein the customized three-dimensional porous mould comprises a wall and an internal structure with internal pores and internal channels connecting the internal pores, and wherein the customized three-dimensional porous mould is designed by the process comprising the steps of creating bitmap templates offline, wherein the bitmaps templates are created according to the desired shapes and dimensions of the pores and channels within the mould, preparing two-dimensional images of the object, pre-process the two- dimensional images to remove unwanted portions according to predetermined thresholds, the internal structure, and generating the wall of the mould; thereby the customized three- dimensional porous mould is designed.
  • the number of the bitmap templates depends on the size of the scaffold for the object, the resolution of the two-dimensional images of the object, the slice thickness of the two-dimensional images of the object, and the complexity of the internal pores and channels of the mould.
  • the step of creating bitmap templates performs manual drawing of the bitmap templates with any computer graphic software that supports a bitmap file format or using a short algorithm to automatically generate the bitmap templates.
  • the two-dimensional images are medical images that are generated from a technique selected from the group consisting of CT, MRI, Ultrasound or computer-based medical imaging systems.
  • the two-dimensional images are stored in Digital Imaging and Communications in Medicine (DICOM) format.
  • DICOM Digital Imaging and Communications in Medicine
  • the two-dimensional images are firstly modified by intersecting them with appropriately selected bitmap templates via Boolean operation, resulting in the transferring of the grid pattern on the bitmap template onto the images, and then the internal (micro- architecture) and external (external geometry) contour data of the modified images are extracted to reconstruct a three-dimensional surface model of the mould.
  • the three-dimensional surface model of the mould is reconstructed by surface patching technique.
  • the step of generating the wall of the mould includes creating the cup structure of the mould and expanding the edges of the wall to a required thickness.
  • the step of the creating of the cup structure of the mould for each slice, two sets of image data are kept, wherein one set is the cleaned images from the step of pre-process the two-dimensional images to remove unwanted portions according to predetermined thresholds without Boolean and the other set is the Boolean images, and wherein no Boolean operation is done for the last slice image that is the base of the cup.
  • FIG 1 is a flowchart showing the main steps of the designing and fabricating a mould for casting a three-dimensional porous scaffold in accordance with one embodiment of the present invention.
  • FIG 2 shows a sample of the DICOM medical images.
  • FIG 3 shows a sample of the pre-processed medical image after having removed the unwanted data from the DICOM medical image as shown in FIG 2.
  • FIG 4 is a diagram showing the refinement of the slice thicknesses.
  • FIG 5a shows one bitmap template.
  • FIG 5b shows the negative of the bitmap template shown in FIG 5 a.
  • FIG 5c shows a diagrammatic view of forming square pores by overlaying the bitmap templates of FIG 5a and FIG 5b.
  • FIG 5d shows the result of intersecting the Medical Image of FIG 3 with the bitmap template as shown in FIG 5a.
  • FIGS 6a and 6b show an enlarged part of the image of FIG 5d before and after the morphological operation.
  • FIG 7 shows a graphical illustration of the creation of the cup structure of the mould in accordance with one embodiment of the present invention.
  • FIG 8 shows a graphical illustration of the increase of the wall thickness of the mould in accordance with one embodiment of the present invention.
  • FIG 9 shows a mould around the jaw area fabricated by a Rapid Prototyping machine.
  • the present invention provides processes for designing and fabricating a three-dimensional porous mould that can be used for casting a three-dimensional porous scaffold, where the mould can be fabricated using a Rapid Prototyping system.
  • FIG 1 is a flow chart showing the main steps of the process. It is to be appreciated that while the following description will use specific computer terms and programs for the convenience of explanation, other computer programs may be used if they are applicable for the method of the present invention, hi addition, the order of steps in the flow chart is designated only for the convenience of narration. The present invention can be practiced without following the order of steps depicted in FIG 1.
  • the process 1 may start by creating bitmap templates offline 10.
  • a three-dimensional porous mould comprises internal pores and internal channels connecting the internal pores.
  • One aspect of the present invention is to utilize the bitmap templates to create the desired internal pores and channels.
  • the bitmap templates are created according to the desired shapes and dimensions of the pores and channels within the mould.
  • the number of different bitmap templates that have to be created for a mould depends on many factors including the size of the scaffold, the resolution of the medical images, the slice thickness, and the complexity of the pores and channels. For example, if a square-shaped pore is required, two different bitmap templates that are exact negatives of one another will be prepared, as shown in FIG 5a and FIG 5b.
  • the three-dimensional square pore structure is then achieved by arranging the two different bitmap templates in an alternating manner, as shown in FIG 5 c.
  • the shape and dimension of the pores and channels can be controlled by specifying the width of the grids and the spacing between the grids in the bitmap templates. It is apparent that the bitmap templates can be employed to create pores and channels within a mould with any shapes and complexity. However, creating pore shapes with more complex geometries demands more different bitmap templates and more complex arrangements of the different bitmap templates.
  • bitmap templates can be manual drawing of the template design by using any computer graphic software that supports a bitmap file format.
  • a short algorithm can also be used to automatically generate the required bitmap templates.
  • the methods and algorithms for generating and manipulating the bitmap templates are well known to those skilled in the art, so that no further details will be provided herein.
  • the bitmap templates generated consist of uniform arrays of grids representing the internal structure of the mould and the voids in between the structures.
  • a wide variety of bitmap templates can be created by changing the size, spacing and shape of the grids to give rise to different mould internal micro-architecture designs which possess different micro- structural properties (e.g., porosity, pore shape and distribution and interconnectivity) to suit various Tissue Engineering applications.
  • two-dimensional images are prepared 20. While medical images from CT, MRI or Ultrasound are used to illustrate the application of the principles of the present invention, it is to be appreciated that the present invention is not so limited.
  • the two-dimensional medical imaging slice data can be generated either by CT, MRI or other types of computer-based medical imaging systems.
  • the generated image slices are stored using a standard file format known as the Digital Imaging and Communications in Medicine (DICOM).
  • FIG 2 shows a sample of the DICOM medical image.
  • Each individual image slice is stored in a single DICOM file.
  • the scanned profile data of a patient is contained in a series of DICOM files, each showing a particular cross-section of the patient's body.
  • Each image slice is separated by a fixed user determined interval known as the slice thickness.
  • the slice thickness directly affects the resolution and accuracy of any three-dimensional models generated using the imaging data slices as an input.
  • the DICOM medical images may be generated by actual scanning or obtained from public databases.
  • FIG 3 shows a sample of the pre-processed medical image after having removed the unwanted data from the DICOM medical image as shown in FIG 2.
  • the removal of unwanted data can also be carried out manually using a specially written algorithm or any image editing software that supports DICOM file format.
  • the imaging data slices are firstly modified by intersecting them with appropriately selected bitmap templates via Boolean operation. This will result in the transferring of the grid pattern on the bitmap template onto the image slice.
  • the internal (micro-architecture) and external (external geometry) contour data of the modified image slices are extracted. Surface patching technique is then applied between the contours to create a three-dimensional closed surface model of the mould.
  • the slice thickness has to be refined.
  • the refinement may be accomplished in many different ways.
  • One exemplary refinement is shown in FIG 4.
  • the refinement is done by duplicating the sets of the pre-processed DICOM image slice files and filling the slice thicknesses by inserting the duplicated DICOM image slices into the slice thickness 50.
  • the number of duplicates to be made for each slice is determined by the thickness of the pre-processed DICOM image slice and the slice thickness.
  • the image header data of all the slices has to be re-designated by the user. This modification is necessary to ensure that the inserted slices would be deemed as being a continuous set of 2D images.
  • bitmap templates are created and the image slices are pre-processed
  • a Boolean intersection operation is then performed between the bitmap templates and the image slices 60.
  • the grid pattern of the bitmap templates will be transferred onto the image slices and will appear as two- dimensional array of pores and channels.
  • FIGS 5a and 5b two sets of bitmap templates being exact negatives of one another are used to generate the squared pores and channels as illustrated in FIG 5c.
  • FIG 5d shows the result of intersecting the Medical Image of FIG 3 and the Bitmap Template 1 of FIG 5a.
  • Different bitmap templates for intersection with the image slices will be required for different geometrical shape and size of the pores generated in the scaffold structure.
  • FIGS 6a and 6b show an enlarged part of the image of FIG 5d before and after the morphological operation.
  • the operations of generating the external (wall) structure of the mould will be described in detail.
  • the operation of generating the wall comprises two steps: creating the cup structure of the mould 80 and expanding the edges of the wall to a required thickness 90.
  • the creating of the cup structure of the mould 80 For each slice, two sets of image data are kept; one set is the cleaned image from step 30 without Boolean and the other set is the Boolean image from step 60. No Boolean operation shall be done for the last slice; the last slice is the base of the cup.
  • FIG 7 there is provided a graphical illustration of the creation of the cup structure of the mould in accordance with one embodiment of the present invention.
  • two sets of image data are generated as shown in FIG 7(a).
  • FIG 7(b) cleaned image of previous slice; cleaned image of current slice; and Boolean image of current slice.
  • the Boolean operation comprises two steps: 1) as shown in FIG 7(c), the previous cleaned slice and current Boolean slice are Booleaned to generate an initial resultant slice; and 2) as shown in FIG 7(d), the initial resultant slice and current cleaned slice are Booleaned to generate a resultant slice, hi other embodiments, instead of doing step 1 in the Boolean operation, the previous Boolean slice can be used as the initial resultant slice. For the last slice, no Boolean operation is necessary as a solid base is required.
  • FIG 8 there is provided a graphical illustration of the increase of the wall thickness of the mould in accordance with one embodiment of the present invention.
  • a segmentation technique is first used to create the image boundary as shown in FIG 8(a) and FIG 8(b).
  • wall thickness is being increased by using morphological dilation and erosion. Depending on the thickness required, the process repeats accordingly.
  • the series of in- sequenced Boolean slices together with increased wall thickness slices are then used as inputs to some third party software that converts it into STL file which is suitable for Rapid Prototyping.
  • FIG 9 shows a mould around the jaw area fabricated by a Rapid Prototyping machine using the InkJet printing technique.
  • the materials that are applicable for the scaffold are not limited to any specific type. It could be biodegradable if the scaffold is to be used in providing a support for tissue growth in vivo.
  • materials that can be prepared into slurry/solutions include ceramics, polymers and combination of both materials. The selection of a specific material or materials for making a scaffold depends upon the characteristics of the desired scaffold.

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  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Theoretical Computer Science (AREA)
  • Computer Hardware Design (AREA)
  • Evolutionary Computation (AREA)
  • Geometry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

L'invention porte sur un procédé pour mettre au point un moule poreux tridimensionnel personnalisé pour couler un échafaudage poreux tridimensionnel pour un objet. La présente invention porte en outre sur un moule poreux tridimensionnel personnalisé pour couler un échafaudage poreux tridimensionnel pour un objet, le moule poreux tridimensionnel personnalisé comprenant une paroi et une structure interne avec des pores internes et des canaux internes reliant les pores internes.
PCT/SG2008/000081 2008-03-17 2008-03-17 Moule pour couler des échafaudages d'ingénierie tissulaire et son procédé de génération WO2009116950A1 (fr)

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PCT/SG2008/000081 WO2009116950A1 (fr) 2008-03-17 2008-03-17 Moule pour couler des échafaudages d'ingénierie tissulaire et son procédé de génération

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PCT/SG2008/000081 WO2009116950A1 (fr) 2008-03-17 2008-03-17 Moule pour couler des échafaudages d'ingénierie tissulaire et son procédé de génération

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2013202686B2 (en) * 2012-04-05 2015-06-18 Howmedica Osteonics Corp Surface modified unit cell lattice structures for optimized secure freeform fabrication
US9135374B2 (en) 2012-04-06 2015-09-15 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US9456901B2 (en) 2004-12-30 2016-10-04 Howmedica Osteonics Corp. Laser-produced porous structure
US11155073B2 (en) 2002-11-08 2021-10-26 Howmedica Osteonics Corp. Laser-produced porous surface
US11298747B2 (en) 2017-05-18 2022-04-12 Howmedica Osteonics Corp. High fatigue strength porous structure
US12011355B2 (en) 2005-12-06 2024-06-18 Howmedica Osteonics Corp. Laser-produced porous surface

Citations (2)

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Publication number Priority date Publication date Assignee Title
US6454811B1 (en) * 1998-10-12 2002-09-24 Massachusetts Institute Of Technology Composites for tissue regeneration and methods of manufacture thereof
WO2003000857A2 (fr) * 2001-06-22 2003-01-03 The Regents Of The University Of Michigan Procede de conception d'echafaudages de genie tissulaire et d'implants de biomateriaux

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
US6454811B1 (en) * 1998-10-12 2002-09-24 Massachusetts Institute Of Technology Composites for tissue regeneration and methods of manufacture thereof
WO2003000857A2 (fr) * 2001-06-22 2003-01-03 The Regents Of The University Of Michigan Procede de conception d'echafaudages de genie tissulaire et d'implants de biomateriaux

Non-Patent Citations (1)

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Title
DIETMAR W. HUTMACHER ET AL.: "Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems", TRENDS IN BIOTECHNOLOGY, vol. 22, no. 7, July 2004 (2004-07-01), pages 354 - 362, XP002395574 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11155073B2 (en) 2002-11-08 2021-10-26 Howmedica Osteonics Corp. Laser-produced porous surface
US11510783B2 (en) 2002-11-08 2022-11-29 Howmedica Osteonics Corp. Laser-produced porous surface
US11186077B2 (en) 2002-11-08 2021-11-30 Howmedica Osteonics Corp. Laser-produced porous surface
US9456901B2 (en) 2004-12-30 2016-10-04 Howmedica Osteonics Corp. Laser-produced porous structure
US11660195B2 (en) 2004-12-30 2023-05-30 Howmedica Osteonics Corp. Laser-produced porous structure
US12011355B2 (en) 2005-12-06 2024-06-18 Howmedica Osteonics Corp. Laser-produced porous surface
AU2013202686B2 (en) * 2012-04-05 2015-06-18 Howmedica Osteonics Corp Surface modified unit cell lattice structures for optimized secure freeform fabrication
US10614176B2 (en) 2012-04-06 2020-04-07 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US9180010B2 (en) 2012-04-06 2015-11-10 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US9135374B2 (en) 2012-04-06 2015-09-15 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US11759323B2 (en) 2012-04-06 2023-09-19 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US12102538B2 (en) 2012-04-06 2024-10-01 Howmedica Osteonics Corp. Surface modified unit cell lattice structures for optimized secure freeform fabrication
US11298747B2 (en) 2017-05-18 2022-04-12 Howmedica Osteonics Corp. High fatigue strength porous structure
US11684478B2 (en) 2017-05-18 2023-06-27 Howmedica Osteonics Corp. High fatigue strength porous structure

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