Sesión oral en la Industriales Research Meeting 2016 en la que el autor muestra sus últimas investigaciones

Díaz Lantada, Andrés

Servicio de Coordinación de Bibliotecas de la Universidad Politécnica de Madrid

1“Biomedical microsystems for 
interacting at a cellular level”
Prof. Dr. Andrés Díaz Lantada
* Contact: adiaz@etsii.upm.es
Product Development Lab – Mechanical Engineering Department,
ETSI Industriales – Universidad Politécnica de Madrid
Industriales Research Meeting 2016, Madrid, April 20th
2General index
1. Introduction: Cells and biomaterials
2. Biomimetic modeling & manufacturing strategies
3 C t h ll d f t l. urren c a enges an  u ure proposa s
4. Main conclusions
5. Personal note
2
Industriales Research Meeting 2016, Madrid, April 20th
31.- Introduction: Cells and biomaterials
1.1.- The cell: A comple multi-scale and multi-physical/biochemical living system 
The eukaryotic cell: The basic unit of life, which operates on the basis of its
genetic information and of the complex interactions with the local micro-
environment that provides physical and chemical support and signals for 
survival and regulation (cell niche).
Stem cells: are defined as cells with self-
renewal abilities and with the capability of 
differentiation into specialized cell types. 
These cells are fundamental in tissue repair 
and regeneration strategies.
The behavior and fate of stem cells is not 
just dependent on genetic information, but is 
also regulated by other biochemical and 
mechanical cues and signals (epigenetic 
cues), which come from their micro-Pic. Standard license agreement: 
3
environment. [blueringmedia]© 123RF.com
Industriales Research Meeting 2016, Madrid, April 20th
41.- Introduction: Cells and biomaterials
1.2.- Biomaterials and biodevices for interacting with cells and driving their behavior
Natural materials and man-made materials are different in terms of:
Æ Elasticity and strength
Æ Structure – porosity – morphology
Æ Surface topography / texture
Æ Fatigue performance
Æ Self-healing abilities
Æ Aesthetics
Current trends for biomimetic and biomechanic solutions: 
Pics. sources: American Medical Association & M.A. Meyers
Design, modeling and manufacture of (bio)materials and related (bio)devices with: 
1) porous and lattice geometries; 2) functional gradients of properties; 
3) controlled surface topographies; and 4) geometries defined at different scales
(among other trends including surface biofunctionalization biofabrication )
4
, …
Industriales Research Meeting 2016, Madrid, April 20th
52.- Biomimetic modeling & manufacturing strategies
2.1.- Modeling and manufacturing porous and lattice (bio)materials and (bio)devices
Conventional prostheses vs. human materials
Mechanical mismatchesÆ Inadequate epigenetic cues for cells and tissues
Potential benefits of biomimetic and biomechanical materials for enhanced response 
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Industriales Research Meeting 2016, Madrid, April 20th
62.- Biomimetic modeling & manufacturing strategies
2.1.- Modeling and manufacturing porous and lattice (bio)materials and (bio)devices
Computer-aided design and engineering of porous and lattice structures
Bi i ti CAD lib i idl bt i d b f t i t l
- Díaz Lantada, A.; Lafont Morgado, P..- “Rapid prototyping for biomedical engineering: Current capabilities and 
challenges”. Annual Review of Biomedical Engineering, 14, 73-96, 2012. 
- Díaz Lantada A ; Pareja Sánchez B ; Gómez Murillo C ; Urbieta Sotillo J - “Fractals in tissue engineering: toward
om me c  rar es rap y o a ne y means o  parame r c oo s
The use of boolean operations easily promotes connection with final applications
6
, .  , .  , .  , ..      
biomimetic cell-culture matrices, microsystems and microstructured implants”. Expert Review of Medical Devices, 10(5), 
629-648, 2013. 
Industriales Research Meeting 2016, Madrid, April 20th
72.- Biomimetic modeling & manufacturing strategies
2.1.- Modeling and manufacturing porous and lattice (bio)materials and (bio)devices
Computer-aided design and engineering of porous and lattice structures
Systematically developed CAD libraries + assessment via modeling resources
leads to fundamental information regarding the adequacy for final applications
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Industriales Research Meeting 2016, Madrid, April 20th
82.- Biomimetic modeling & manufacturing strategies
2.1.- Modeling and manufacturing porous and lattice (bio)materials and (bio)devices
Processes based on phase-
separation, particle leaching…
Current trends based on additive
manufacturing approaches
Cell cultures & pics. 
Courtesy of Prof
- Díaz Lantada, A.; Alarcón Iniesta, H.; Pareja Sánchez, B.; García-Ruíz, J.P..- “Free-form rapid-prototyped PDMS 
 . 
García-Ruíz, UAM
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scaffolds incorporating growth factors promote chondrogenesis”. Advances in Materials Science and Engineering, Vol. 
2014, ID 612976, 2014. 
Industriales Research Meeting 2016, Madrid, April 20th
92.- Biomimetic modeling & manufacturing strategies
2.1.- Modeling and manufacturing porous and lattice (bio)materials and (bio)devices
Lattices with functional gradients
of mechanical properties by AMT
Combined materials and technologies
towards biomimetic constructs
- Díaz Lantada, A.; Alarcón Iniesta, H.; García-Ruíz, J.P..- “Composite scaffolds for osteochondral repair obtained by 
Cell culture: Prof. García-Ruíz, UAM
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combination of additive manufacturing, particle leaching and hMSC-CM functionalization”. Materials Science and 
Engineering C: Materials in Biology and Medicine, 59, 218-217, 2016.  
- Díaz Lantada, A.; De Blas Romero, A.; Schwentenwein, M.; Jelinek, C.; Homa, J..- “Lithography-based ceramic 
manufacture (LCM) of auxetic structures: present capabilities and challenges”. Smart Materials and Structures, 25 (5), 
2016.  
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2.- Biomimetic modeling & manufacturing strategies
2.2.- Modeling and manufacturing porous and lattice biomaterials and biodevices
Computer-aided design and engineering of lattice and porous structures
Manufacturing resorting to additive apporaches
Different CAD modeling strategies also enable biomimetic 
gradients of mechanical properties, density, porosity… 
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- Hengsbach, S.; Díaz Lantada, A..- “Direct laser writing of auxetic structures: Present capabilities and challenges”. 
Smart Materials and Structures, 23, 085033, 2014. 
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2.- Biomimetic modeling & manufacturing strategies
2.3.- Modeling and manufacturing microtextured (bio)materials and (bio)devices
Computer-aided design and engineering of microtextures and topographies
Fractal models for modeling texture
Brownian surface model with
control parameter “alfa” 
- Díaz Lantada A ; Pareja Sánchez B ; Gómez Murillo C ; Urbieta Sotillo J - “Fractals in tissue engineering: toward
∑∞
=
− +++=
1
0 ]))·sin()·cos([·sin(·),(
k
kkk
kk
k AByBxCzyxz λλ α
11
, .  , .  , .  , ..      
biomimetic cell-culture matrices, microsystems and microstructured implants”. Expert Review of Medical Devices, 10(5), 
629-648, 2013. 
Industriales Research Meeting 2016, Madrid, April 20th
12
2.- Biomimetic modeling & manufacturing strategies
2.3.- Modeling and manufacturing microtextured (bio)materials and (bio)devices
Additive manufacturing applied to obtaining micro-textures and topographies
Prototype of microtextured surface microtextured
- Hengsbach S ; Díaz Lantada A - “Direct laser writing of fractal surfaces: Strategy to design and manufacture textured
  ,  
mold insert and mass-produced microsystem
Linking additive manufacturing and mass production
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, .  , ..             
materials”. Advanced Engineering Materials, 17(2), 172-180, 2015. 
- Díaz Lantada, A.; Piotter, V.; Plewa, K.; Barié, N.; Guttmann, M.; Wissmann, M..- “Towards mass production of 
microtextured microdevices: Linking rapid prototyping with microinjection molding”. Int. Journal of Adv. Manufacturing 
Tech., 2014, Sept. 2014. 
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2.- Biomimetic modeling & manufacturing strategies
2.3.- Modeling and manufacturing microtextured (bio)materials and (bio)devices
Additive manufacturing applied to obtaining micro-textures and topographies
300 μm
Cell cultures & pics. 
Courtesy of Prof García-Ruíz UAM
13
 . , 
Industriales Research Meeting 2016, Madrid, April 20th
-Díaz Lantada, A.; Alarcón Iniesta, H.; García-Ruíz, J.P..- “Multi-channeled polymeric microsystem for 
studying the impact of surface topography on cell adhesion and motility”. Polymers, 7(11), 2371-2388, 2015. 
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2.- Biomimetic modeling & manufacturing strategies
2.4.- Modeling and manufacturing multi-scale (bio)materials and (bio)devices
Combined manufacturing processes applied to obtaining multi-scale geometries
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- Hengsbach, S.; Díaz Lantada, A..- “Rapid prototyping of multi-scale biomedical microdevices by combining additive 
manufacturing technologies”. Biomedical Microdevices, 16(4), 617-627, 2014. 
Industriales Research Meeting 2016, Madrid, April 20th
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2.- Biomimetic modeling & manufacturing strategies
2.4.- Modeling and manufacturing multi-scale (bio)materials and (bio)devices
Combining additive manufacturing, laser ablation and metallization towards
mass production via micro-injection molding: Application to organs-on-chips
Liver-on-chip device
Cell cultures & pics.
15
  
Courtesy of Prof. García-Ruíz, UAM
- Díaz Lantada, A.; Begasse, G.; Morss Clyne, A.; Hengsbach, S.; Piotter, V.; Smyrek, P.; Plewa, K.; Guttmann, M.; 
Pfleging, W..- “Towards reliable organs-on-chips and humans-on-chips”. Spriger’s Handbook on Biomedical Microdevices 
for Interacting at a Cellular Level. In press, 2016. 
16
2.- Biomimetic modeling & manufacturing strategies
2.4.- Modeling and manufacturing multi-scale (bio)materials and (bio)devices
Combining additive manufacturing, laser ablation and metallization towards
mass production via micro-injection molding: Application to organs-on-chips
Blood-brain barrier on chip
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Laser stereolithography + soft lithography Direct laser writing for enhanced precision
Industriales Research Meeting 2016, Madrid, April 20th
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3.- Current challenges and future proposals
3.1.- Current technological limits and challenges
Multi-scale modeling and manufacturing processes are needed
Precision and part size are linked in micro-/nano-manufacturing technologies
Cell cultures & pics. 
Courtesy of Prof García-Ruíz UAM
17- Díaz Lantada, A.; Muslija, A.; García-Ruíz, J.P..- “Auxetic tissue engineering scaffolds with nanometric features and 
resonances in the megaHertz range”. Smart Materials and Structures, 24, 2015.
 . , 
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3.- Current challenges and future proposals
3.1.- Current technological limits and challenges
Multi-scale modeling and manufacturing processes are needed
Precision and part size are linked in micro-/nano-manufacturing technologies
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Nano “playground” for cells: Multi-culture platform for studying the impact
of several extracellular matrices on cell behavior in a single experiment
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3.- Current challenges and future proposals
3.2.- Future proposals and research directions
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4.- Main conclusions
Main conclusions: 
-Designing, modeling and manufacturing biomimetic materials may enhance the
performance of several types of biomedical devices.
-Strategies for taking into account the common porosities, hierarchical
geometries and textures of biomaterials have been described.
-Computer aided design and engineering resources help to model and assess the
potential performance of the proposed biomaterials, even integrated into
complex devices.
-Combining advanced manufacturing resources constitutes a very adequate
approach for the development of new biomaterials and their integration into
biomedical microdevices for enhanced performance.
-Solutions developed on the basis of biomimetic approaches have impact in 
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several industries, inlcuding: health, transport, energy, space.
Industriales Research Meeting 2016, Madrid, April 20th
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5.- Personal note
Acknowledgements:
Machines Engineering Division, Product Development Lab, ETSI Industriales UPM: 
Pilar Lafont, Pilar Leal, Socorro Martín, Silvia Ortega, Juan Manuel Muñoz, José Luis Muñoz, 
Javier Echavarri, Enrique Chacón, Julio Muñoz, Pedro Ortego, Antonio Sillero, Adrián de Blas, 
Alejandro Abou-Assali, Ely Dannier V. Niño
Karlsruhe Nano-Micro Facility, Helmholtz Research Facility, Karlsruhe Institute of Technology:
Dieter Maas, Stefan Hengsbach, Alban Muslija, Volker Piotter, Klaus Bade, Markus Guttmann, 
Wilhelm Pfleging, Klaus Plewa, Markus Wissmann, Peter Smyrek, Nicole Barie, Thomas Schaller, 
Jürgen Mohr, colleagues from KNMF & KIT
Molec. Biology Dpt., Univ. Autónoma de Madrid: 
Josefa Predestinación García Ruíz, Hernán Alarcon Iniesta
Institute of Materials Science and Technology, Lithoz GmbH:
Tech. Univ. of Viena: Jürgen Stampfl Johannes Homa, Martin Schwentenwein
Vascular Kinetics Lab. Drexel University: 
Alisa Morss Clyne H2020 Tomax Project: 
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SENTI, University of Cranfield: 
José Luis Endrino
Tool-less manufacture 
of complex geometries
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Biomedical microsystems for interacting at a cellular level
THANKS FOR YOUR 
ATTENTION
Product Development Lab
Mechanical Engineering Department
Universidad Politécnica de Madrid
*Contact: Andrés Díaz Lantada
adiaz@etsii.upm.es
22
Industriales Research Meeting 2016, Madrid, April 20th


Biomedical microsystems for interacting at a cellular level

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Biomedical microsystems for interacting at a cellular level

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