Organ and bio 3D printing

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Organ and bio 3D printing

  1. 1. le centre collectif de l’industrie technologique belgeThe Collective Centre of the Belgian Technology IndustryAdditive Manufacturing Department3D Bio-printing
  2. 2. 2The future is not that far away...CENG02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  3. 3. 3Bio-printingCENGAgenda• What is « bio-printing » ?• What is the market and who would be interested?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  4. 4. What is « bio-printing » ?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 4What is “bio-printing”?“ The ability to print various biological materials and cells along with varioustissue scaffold materials”Tissue Engineering:Its goal is to produce functional cell, tissue and organ to repair, replace orenhance biological function that has been lost by disease and injury. It is alsoone of the most promising approaches to solve the problems of shortage ofsuitable organs for transplantation.Engineered and « 3D printed » bio-scaffolds:Temporal architectural 3D structures for cell adhesion and cell growthUsually: biodegradable (poly-glycolic acid and poly-lactic acid)CENG
  5. 5. What is « bio-printing » ?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 5Bio-scaffolds & cells:• Cells are seeded onto the scaffolds and cultured in vitro in advance beforeimplantation.• After cell adhesion, the cell-adhered scaffolds are implanted into therecipients.• After implementation, biodegradable materials are degraded and finally onlythe implanted cells remain and form functional tissues in vivo.Remaining obstacles to overcome & reach the goal:• Find cells that will not be rejected by the host’s immune system• How to organize specialized cells into 3D tissues ?• How to bring nutriments (oxygen, minerals, blood, cell signals, …) to theprinted cells?• How to transport them and keep them sterilized to the O.R. ?• Results are depending on the 3D printing technology !CENG
  6. 6. 6Bio-printingCENGAgenda• What is « bio-printing » ?• What is the market and who would be interested?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  7. 7. What is the market and who would beinterested?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 7Examples:• Hair• Contact lenses• Artificial eye, cornea, cristalline• Surgery in general (artifical organs, tissue repair, …) in forms of implants:• External implants, internal implants, bone subistitutes, …CENG
  8. 8. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 8CENGExamples:• Gynecology, obstetrics, urology• Aesthetic surgery• Tissue graft assistance : liver, kidney, pancreas, nerve, spinal cord,...• Pharmaceutical : "Drug Delivery Devices"• Cardiovascular field : vessels, pacemaker, artificial heart, valves, stents, coils,balloon, glue, mirobeads, blood, catheters,...• Orthopaedic surgery : plate, rode, screw, pin, cement, protheses, ligaments,tendons• Cell chips (electronics)• Cosmetic applications (direct cosmetic print on skin)What is the market and who would beinterested?
  9. 9. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 9What is the market and who would beinterested ?CENG• Alternative to donor waiting list• Limited available « material » resource (skin, organs, cells, …)
  10. 10. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 10What is the market and who would beinterested ?CENGSome facts:• It would take 1,690,912,929,600 hours to print a liver for every member ofthe human race using today’s processes.• Every year, the number of people on the waiting list for an organ transplantincreases, yet the amount of donors and available organs remains at a low.• USA: more than 114,300 (2012) people on the waiting list as candidates• More than 73,000 active waiting list candidates• In 2005, 1848 patients died waiting for a donated liver to become available(USA)• 17000 adults and children have been medically approved for liver transplantsand are waiting for donated livers to become available (January 2012)• Drug industry problem:• Each year, the industry spends more than $50 billion (USA, 2012) on R&Dand approximately 20 new drugs are approved by the FDA• A new drug, on average costs $1.2 billion and takes 12 years to develop
  11. 11. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 11What is the market and who would beinterested ?CENG
  12. 12. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 12• From a monetary standpoint, tissue engineering and regenerative medicineresearch are now mainstream disciplines that receive nearly $200 million ayear in funding from the United States alone (2001).Why is 3D important?:• 2D cell culture: unnatural behavior in monolayers on plastic• 3D cell culture: mimics natural state for tissues in the body• A reliable, easy to use and inexpensive method for 3D cell growth willmake 2D methods obsolete !Use of 3D cell culture: explosive growth:• Total cell culture market: $520M (2004)• Market growing at 13%/year to $780M (2007)• 3D product citations (PubMed) and market share growing exponentially• Growth limited by product availabilityCENGWhat is the market and who would beinterested ?
  13. 13. Organ printing: the future of medecine !02/05/2013© Sirris | www.sirris.be | info@sirris.be | 13Conclusions:3D bioprinting technology has the potential to significantly impact the speed,predictiability and consequently the cost of successful drug discovery !CENG
  14. 14. 14Bio-printingCENGAgenda• What is « bio-printing » ?• What is the market and who would be interested?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  15. 15. State of the art – current results andachievements02/05/2013© Sirris | www.sirris.be | info@sirris.be | 15CENG
  16. 16. State of the art – current results andachievementsEvolution of Tissue Engineering and « Bioprinting »02/05/2013© Sirris | www.sirris.be | info@sirris.be | 16CENGCharles Hull invented SLADr. Gabor Forgacs (ONVO founder) andcolleagues made the observation that cellsstick together during embryonicdevelopment and move together in clumpswith liquid-like properties. ManufacturingprogramThe first human patientsunderwent urinary bladderaugmentation using a syntheticscaffold seeded with thepatient’s own cells (engineering,not printed)Thomas Boland’s lab atClemson modified an inkjetprinter to accomodate anddispense cells in scaffoldsDR. Forgacs developednew technology toengineer 3D tissue withonly cells, no scaffoldsOrganovo creates theNovoGEN MMX Bioplotterusing Forgacs technologyOrganovo prints the firsthuman blood vesselwithout the use of scaffoldsOrganovo develops multipledrug discovery platforms,3D bioprinted diseasemodels made from humancells1984 1996 2000 2003 2004 2006 2009 2010 2011World’s first “3Dprinted” artificialbladder implantedFirst lung tissuepatch2012First cardiacsheet orpatchFirst nerveguides
  17. 17. State of the art – current results andachievementsEvolution of Tissue Engineering and « Bioprinting »02/05/2013© Sirris | www.sirris.be | info@sirris.be | 17CENGToday 2011-2012:Small-scale tissues fordrug discovery andtoxicity testingTomorrow 2013-2015:Simple tissues for implant(e.g. cardiac patches orsegments of tubes, likeblood vesselsFuture 2015-2030:Lobs or pieces oforgansVery future 2030>:Full organs
  18. 18. 18CENG02/05/2013Case study (USA): Artificial bladder (2006)• World’s first articial bladders built by an 3D printingtechnology in lab !• Development of artifical bladder first tested on dogs (1999)• Transplantation was successful (but no post-reports)• 2006: Transplantation on 7 human patients• No risk of transplantation rejection (patient’s own cells)• Procedure: « Orthotopic Neobladder Procedure »• CT-Scan of the bladder (for the geometry)• Tissue sample is taken from the patient’s bladder• Biodegradable scaffolds are built using ink-jet printer• Cells are grown into biodegradable scaffold (hydrogels)• Transplantation of the artifical bladder• Scaffold is safely degraded within the patient’s body• Ink-jet printer: cartridges used stem cells & cross-linker[Source: Wake Forest University School of Medicine]© Sirris | www.sirris.be | info@sirris.be |State of the art – current results andachievements
  19. 19. 19CENG02/05/2013Case study (USA): Artificial liver (2009)• Bio-engineering of human liver (5.7g)• 3D printing of collagen skeleton• Application of human liver cells on skeleton matrix• Artificial liver is then placed in a bioreactor (nutrients & oxygen)• After one week: widespread cell growth inside the bioengineered organwith progressive formation of liver tissue as well as liver-associatedfunctions.[Source: Wake Forest University School of Medicine]© Sirris | www.sirris.be | info@sirris.be |State of the art – current results andachievements
  20. 20. 20CENG02/05/2013Case study (Europe): Artifical trachea (2011)• World’s first articial trachea built by an additivemanufacturing technology !• Bioartifical matrix (CT-Scan to CAD file)• Stem cells sprayed on matrix• Swedish hospital & european team (University Hospitalof Karolinska – Prof. Paolo Macchiariini)• Operation time: 12h• Trauma: cancer (size of a golf ball)• Material of the matrix: Synthetic nanocomposite polymer[Source: Karolinska Institute in Stockholm ]© Sirris | www.sirris.be | info@sirris.be |State of the art – current results andachievements
  21. 21. 21CENG02/05/2013Case study: In situ skin bio-printing for burn wounds (2011)• Portable skin printing system• Uses living cells to create tissue-engineered skin grafts to cover burn wounds• Future application: battlefield burn wounds• Fibroblasts and keratinocytes are printed directly onto skin• Suspensions with cells are mixed with fibrinogen, type 1 collagen andthrombin at the moment of application• Application already tested on mice© Sirris | www.sirris.be | info@sirris.be |State of the art – current results andachievements[Source: Wake Forest University School of Medicine]
  22. 22. 22Bio-printingCENGAgenda• What is « bio-printing » ?• What is the market and who would be interested?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  23. 23. What is necessary to print an organ ?• The need to consider:• Histology and anatomy in general• What cells should be used?• Conservation of the functionality• What scaffold should be printed?• What technology should be used?• Organs are:1) 3D structures2) They have characteristic micro-structures required to fulfill the particularfunction of an organ3) They are composed of multiple type of cells and extra-cellular matrices4) They have a complex vascular network to sustain the cells in the organsWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 23CENG
  24. 24. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 24What is necessary to print an organ ?1. Preprocessing:• CAD, blueprints, preconditioning2. Processing:• Actual 3D printing, solidification3. Postprocessing:• Perfusion (bioreactor), postconditioning, accelerated tissue maturationCENGWhat is required and how to print?
  25. 25. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 25What is necessary to print an organ ?Three potential human stem cell sources are emerging:• Human embryonic stem cells (politically controversial)• Resident stem cells (isolated from organs)• Circulated bone marrow derived adult stem cellsSo far: 30 =/= Cells have already been tested (2D array):• Chondrocytes, C17.2, PC6, AML12, C166, HL1, HeLa, neural precursor cells,mesenchymal stem cells, mouse embryonic stem cells, …)• No significant difference in cell viability (all >95%) compared to manuallyplated cells, suggesting that our cell printing technique can be generallyapplied to most of cell typesCENGWhat is required and how to print?
  26. 26. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 26What is necessary to print an organ ?Requirements (2D-array bio-printing:• use of a pneumatically-driven electromechanical valves for the use of liquidmaterials (viscosity up to 200 Pa*s)• Independant temperature control for the dispenser itself• A wide range of hydrogel materials that needs to be crosslinkedCENG
  27. 27. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 27What is necessary to print an organ ?Requirements for direct 3D-Printing of organs:• Include growth factors in the scaffolds• Have biodegradable scaffolds rather than non-ones (bioactive as well?)• Having nano-modifications on the scaffolds for better cell ingrowth?• Needs to be included in the scaffold: extracellular matrix, growth factors,vascular network and different cell types)• Living cells will be patterned into hydrogel tissue scaffoldsCENG+ growth factors(…)Cell type A Cell type Z+ agentslayer 01layer 10^9
  28. 28. Current and possible technologies:1. Scaffold based approaches1. Porogen leaching2. Phase-separated scaffolds3. Gas foaming2. Textile technologies1. Electrospinning2. Knitting and braiding3. Direct « 3D-printing » technologies1. Stereolithography2. Selective laser sintering3. Three-dimensional printing (3DP) (inkjet printing)4. Systems based on extrusion/direct writing5. Indirect 3D printingWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 28CENG
  29. 29. 1. Scaffold based approaches: Basic principlesCombination of:• Viable cells• Biomolecules• Structural scaffoldWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 29CENG
  30. 30. 1. Scaffold based approaches: Basic principlesScaffolds serve a purpose:• Support cell migration• Growth and differentiation• Guide tissue development• Organization into a mature and healthy stateRequirements of scaffolds:• Biomechanical (e.g.: wound contraction forces; vascularization; in vitro and mostof all in vivo growth dynamics)• Chemical (cell and tissue remodeling: interaction between cell type and scaffoldtype material (e.g.: skin v.s. bone cell type))• Physical (mechanical strength & stiffness)• Biological (cell attachment, mass transfer, degradation and resporption kinetics)What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 30CENG
  31. 31. 1. Scaffold based approaches: Basic principlesCurrent state of progress:• still infancy (experimental);• no certain knowledge about the scaffold geometries…• What about patient-custom tissue engineering ? And patient activity ?• What about multi-material printing (scaffolds) ?Drawbacks:• Cell distribution and cell composition inside of the scaffold cannot becontrolled• Morphogenesis of essential tissue architecture especially microstructures iscompletely dependent upon cells alone: Very difficult to fabricatephysiologically functional tissues which have special micro-3D structuresusing the scaffold based approach.• A new approach is necessary! – Or more basic research on scaffolds…What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 31CENG
  32. 32. 1. Scaffold based approaches: Basic principlesWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 32CENG
  33. 33. 1. Scaffold based approaches: Basic principlesWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 33CENG
  34. 34. 1. Scaffold based approaches: Basic principlesCharacteristics that need to be understood, defined and verified:• Material compositions• Porous architecture• Structural mechanics• Surface properties• Degradation properties and their resulting products in the body• Composition with other agents? (multi-material printing)• Changes of all these factors in time (kinetics)• Manufacturing technology and technology readinessConclusions:• There is no scaffold serving universal applications !• Scaffolds should be defined in function of the future growing cells?What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 34CENG
  35. 35. 1. Scaffold based approaches: Basic principlesMorphology and architecture;• Mechanical properties of porous scaffolds depend on:• Relative density (depending on stiffness and yield strength incompression)• Properties of the material (pore edges & walls need to be considered)• Stiffness : E• Yield strength in compression: sE=C1(100-P)^n ; s=C2(100-P)^nPorosity definition:• Compromise between porosity and mechanical properties• Pore interconnectivity is a critical factor !• Necessary for: cell migration and proliferation (initial stages)• Scaffolds should have 100% interconnecting pore volume !What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 35CENG
  36. 36. 1. Scaffold based approaches: Basic principlesPorosity definition:• Recent studies demonstrate that pore size is less important for boneformation• Optimal pore sizes of 200-600µm are required to support bone growth (localsupport for vasculature)• This is true for 3D scaffolds with nondesigned, random collection of pores,varying in size and interconnectivity• With 3D scaffolds built by 3D printers with 100% of interconnecting pores andhomogeneous pore architecture, no significant difference in bone formationwith varying pore size between 300-1200µmQuestion:• Is there an optimal biomaterial and architecture for regeneration of specifictissues ?What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 36CENG
  37. 37. 1. Scaffold based approaches: Porogen leachingPrinciple:• Dispersing a template (particles) within a polymericor monomeric solution, gelling or fixing the structure,and removal of the templateResult:• Porous scaffoldTechnical aspects:• Cheap technique• Possible to produce structures with locally porousinternal architectures• Porosities up to 300µm in diam.• Only local interconnection and non-controlled possible• No control on the shape/geometry of the pores and the mechanical propertiesWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 37CENG
  38. 38. 1. Scaffold based approaches : Phase-separated scaffoldsPrinciple:• Relies on the controlled phase separation of polymersolutions into high and low concentration regionsupon cooling. (high concentration = solidification);(low concentration = formation of pores)Result:• Porous scaffold with variable morphological natureTechnical aspects:• Liquid-liquid phase separation• Solid-liquid phase separation• Polymerization-induced phase separationWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 38CENG
  39. 39. 1. Scaffold based approaches : Gas foamingPrinciple:• Solvent-free formation of porous materials through generation of gas bubleswithin a polymer.• The polymers are pressurized with a gas (CO2) until saturation.• The release of the pressure results in nucleationResult:• Porous scaffold with more or less controlled pore sizes but uncontrolledinterconnectivityTechnical aspects:• Pore sizes up to 100µm in diam.What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 39CENG
  40. 40. 02/05/2013© Sirris | www.sirris.be | info@sirris.be | 40Limitations of these scaffold based approaches:• inability to control cell distribution in the 3D structures• inability to control positioning of multiple cell types• inability to control composition of the scaffold at specific locations• inability to control local concentration of growth factors• inability to control induction of blood capillaries• inability to control enhancement of the target organ cells at specific locations• inability to control biodegradation of the scaffold material (not always true)CENGWhat is required and how to print?
  41. 41. Current and possible technologies:1. Scaffold based approaches1. Porogen leaching2. Phase-separated scaffolds3. Gas foaming2. Textile technologies1. Electrospinning2. Knitting and braiding3. Direct « 3D-printing » technologies1. Stereolithography2. Selective laser sintering3. Three-dimensional printing (3DP) (inkjet printing)4. Systems based on extrusion/direct writing5. Indirect 3D printingWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 41CENG
  42. 42. 2. Textile technologies: ElectrospinningPrinciple:• A continuous fiber is produced by extruding a polymermelt or solution through a spinneret and thenmechanically drawn onto a winder or a series of windersand collected on a spool.Result:• Polymeric sheets with high permeabilityTechnical aspects:• The diameter can be controlled by the extrusion diameter• The extrusion will affect the crystallinity of the polymer, this will influence themechanical strength and degradation behavior• Possible to control the orientation of the fiber segments (neural tissueengineering)What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 42CENG
  43. 43. 2. Textile technologies: Knitting and braidingPrinciple:• Individual fibers or multifilament yarns are woven, knitted or braided intopatterns with variable pore sizes.Result:• Structures with poor mechanical strength that need to be filled with asecondary scaffold such as collagen gel or electrospun fibers.Technical aspects:• The knitted structures only serve as a mechanical support for a secondary,interstitial scaffold that might be damaged otherwise.• Still experimentalWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 43CENG
  44. 44. Current and possible technologies:1. Scaffold based approaches1. Porogen leaching2. Phase-separated scaffolds3. Gas foaming2. Textile technologies1. Electrospinning2. Knitting and braiding3. Direct « 3D-printing » technologies1. Stereolithography2. Selective laser sintering3. Three-dimensional printing (3DP) (inkjet printing)4. Systems based on extrusion/direct writing5. Indirect 3D printingWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 44CENG
  45. 45. 3. Direct « 3D-printing » technologies :What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 45CENG
  46. 46. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 46CENG
  47. 47. 3. Direct « 3D-printing » technologies :Principle:• Various “3D-Printing” methods.Result:• Scaffolds with highly reproducible architecture and compositional variationacross the entire matrix due to CAD controlled fabrication.Technical aspects:• Results highly depending on the technology and materials that can beprocessed !• Most of the technologies have to be adapted (Bioprinter, SLA, SLS, …)• Possible to fabricate biphasic or triphasic matrix systems (SLA): high potentialof micro-SLA (future)• SLS: mostly used for calcium-phosphate scaffolds (or others: PEEK; PEAK;PEKK, …)What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 47CENG
  48. 48. 3. Direct « 3D-printing » technologies : Powder based technologiesMain drawbacks of powder based technologies :• Open pores must be able to allow the internal unbound powders to beremoved (SLS, ZCorp, LBM, EBM, …) if the part is designed to be porous.• Surface roughness and the aggregation of the powdered materials affect theefficiency of removal of trapped materials.• Resolution of printers is limited by the specification of the nozzle size andposition control (print head movement).• Particle size of the powder used defines the layer thickness (100-400µm)• Most materials are not available or suited for tissue engineering (need to beestablished in-house).Conclusions:• Inkjet-printing is promising but must be adapted for tissue engineeringWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 48CENG
  49. 49. 3. Direct « 3D-printing » technologies : Extrusion technologiesPrinciple:• Extrusion of filaments or plotting of dots in 3D withoutincorporation of cells.• Variety of polymers possible• Hot melts as well as pastes/slurries possibleMain drawbacks of powder based techniques :• Only idea here is to build a physical scaffold• Only a certain range of thermoplastics for tissue engineering usable• Cells or other biological agents cannot be encapsulated into the scaffoldmatrix during fabrication process• Design of pores is limited (diameter of extruded filament, physical connectionbetween the layers, turning points, …)What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 49CENG
  50. 50. 3. Direct « 3D-printing » technologies : Ink-jet technologiesInk-jet technologies : Considered as the « true organ printing »Two possible methods: ink-jet printing or laser-printing technologyPrinciple:• Gelation technique of ink-jet printing:• Need to use two different types of gel solution, gel precursor and gel reactant.• Aqueous sodium alginate solution forms a hydrogel in contact with Ca2+ ions.(0.8-1% Sodium alginate on 2% CaCl2 solution)• Alginate hydrogel is one of the biocompatible hydrogels• They provide both structural strength for 3D structures and an aqueousenvironment for cellsWhat is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 50CENG
  51. 51. 3. Direct « 3D-printing » technologies : Ink-jet technologiesInk-jet:• Modified commercial version of buble jet or piezoelectric printer to dispensecells on the hydrogel materialLaser-technology:• Based on focusing a high-energy laser pulse onto a post above the cell-ladengel and subsequent dispensing of the cells underneath the evaporated spot.• -What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 51CENG
  52. 52. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 52CENG3. Direct « 3D-printing » technologies : Ink-jet technologiesWhy hydrogels:• Good candidate for non-skeletal tissue engineering• Facilitate the transport of oxygen through diffusion and integrate readily intothe surrounding extracellular matrix• Controllable dissociation/biodegradation of hydrogels in physiologicalenvironments• Useful for ex for chondrocytes and hepatocytesDrawbacks:• ink drying (inkjet droplets are so small that they dry immediately)• ink bleeding in wet conditions (if cells are printed onto wet substrates toprevent drying, the printed cells spread out and lose print resolution)• how to fabricate 3D structures with an inkjet printer?
  53. 53. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 53CENG3. Direct « 3D-printing » technologies : Ink-jet technologiesAdvantages for tissue engineering fabrication:• High resolution fabrication (pico-liter sized ink droplets)• Fabrication of composite products with different cells, materials and growthfactors• Fabrication of large-sized products (rapidly)• Easy to apply CAD bio-fabrication• Printable onto gels, aqueous solution, cells or directly onto the targetswounds during surgical operation• Usability of reactive gel material and reactive two materials.• Biomaterials: cells, proteins, DNA, bio-polymers, drugs, …• Direct cell printing, handling and positioning
  54. 54. What is required and how to print?02/05/2013© Sirris | www.sirris.be | info@sirris.be | 54CENG3. Direct « 3D-printing » technologies : Ink-jet technologiesFuture directions:• Main challenge: obtaining a homogenous distribution of cells throughout theentire 3D scaffold volume.• Two possibilities of incorporating cells into scaffolds (organ printing):1) Seeding of cells onto the surface of the scaffold (after fabrication)2) Incorporation of cells onto the scaffold fabrication process• -
  55. 55. 55Bio-printingCENGAgenda• What is « bio-printing » ?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• What is the market and who would be interested?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  56. 56. 56CENGOrgan printing – Conclusions and perspectives02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  57. 57. 57CENG« Medical Additive Manufacturing & Rapid Prototyping »« Sirris »02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  58. 58. 58Sirris Additive Manufacturing: ContactCENGCarsten ENGELBiomedical EngineerDepartment of Additive ManufacturingMail: carsten.engel@sirris.beMobile: +32 498 91 94 50Skype: Carsten-EngelSIRRISRue Auguste Piccard, 20B-6041 GOSSELIES BELGIUMhttp://www.sirris.be02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  59. 59. 59Bio-printingCENGAgenda• What is « bio-printing » ?• State of the art – current results and achievements• What is required and how to print 3D bio-materials ?• What is the market and who would be interested?• Conclusions• Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be |
  60. 60. Bibliography02/05/2013© Sirris | www.sirris.be | info@sirris.be | 60• T. Billiet et al., “A review of trends and limitations in hydrogel-rapid prototyping for tissueEngineering”, Biomaterials 33 (2012) 6020-6041• F. P.W. Melchels et al., “Additive manufacturing of tissues and organs”, Progress in PolymerScience 37 (2012) 1079–1104• M. Schuster et al., “Biofunctional Photopolymers for Micro-Stereolithography”, Proceedings ofLPM20007-the 8th International Symposium on Laser Precision Microfabrication• L. De Bartolo et al., “Bio-hybrid organs and tissues for patient therapy: A future vision for2030”, Chemical Engineering and Processing 51 (2012) 79– 87• K. J.L. Burg et al., “Biomaterial developments for bone tissue engineering”, Biomaterials 21(2000) 2347-2359• S. M. Warren et al., “Biomaterials for Skin and Bone Replacement and Repair in Plastic Surgery”,Operative Techniques in Plastic and Reconstructive Surgery, Vol 9, No 1: pp IO-15 (2003)• P. Bartolo et al., “Biomedical production of implants by additive electro-chemical and physicalprocesses”, CIRP Annals - Manufacturing Technology 61 (2012) 635–655• S. Bose et al., “Calcium phosphate ceramic systems in growth factor and drug delivery forbone tissue engineering: A review”, Acta Biomaterialia 8 (2012) 1401–1421• R. Gaetani et al., “Cardiac tissue engineering using tissue printing technology and humancardiac progenitor cells”, Biomaterials 33 (2012) 1782-1790CENG
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