Projection Based Stereolithography Process for 3d Biomanufacturing of Biomaterials.
In:
Submitted By vaibhavdxt Words 4548 Pages 19
Projection based stereolithography process for 3D biomanufacturing of biomaterials.
Abstract
Stereolithography is highly versatile and precise process of solid free form additive manufacturing technique. Process requires biocompatible liquid photopolymer resin as a material which is one of the limitation of the process also. Curing liquid resin with a high intensity UV radiations at times causes over-curing which is highly undesirable.
In this project, behavior of different biomaterials have been observed under same condition and the results have been plotted and regression analysis for each has been done. The study of graphs and coefficient of determination of process with different materials shows how accurate the process is and it also helps ultimately to conclude the linear relationship between curing depth and exposure time. In any stereolithography case these curing depth and exposure time are chief governing parameters along with critical exposure and penetration depth.
1. Introduction
Stereolithography (also known as SL or SLA) builds parts layer-by-layer using a UV laser to solidify liquid photopolymer resins. It is commonly used to produce concept models, master patterns, large prototypes and investment casting patterns. [01]
This process is based on spatially controlled solidification of a liquid resin by photo-polymerization.
Stereolithography Apparatus which is also known as SLA is chiefly comprised of Ultraviolet laser device, tank full of photosensitive liquid resin and the computer which controls the motion of laser device.
Steps to manufacture object by stereolithography: - 1. A 3-D model of an object is designed in a CAD software and saved as a STL file. 2. The CAD software chops and slices the CAD model into series of thin parallel horizontal layers. 3. The sliced information is fed into processing unit of stereolithography apparatus. 4. Now control unit in setup directs the ultraviolet laser that scans and illuminates the top most layer of the photosensitive liquid and hardens it. The resin in the pattern is solidified to a defined depth, causing it to adhere to a support platform. 5. The supporting platform which supports the newly formed layer in liquid resin is lowered to the depth of one layer and a new layer of resin takes/recoats the position of previous layer. Depth of curing is slightly deeper than the height of the downwards motion of supporting platform. 6. This process is repeated layer by layer, hardening layer over layer until the part whole part is finished.
Once the last layer is cured the liquid resin is drained and the object is detached from the supporting platform. Now this pattern, once again the curing of object is done in UV light to improve the mechanical strength of the object. [02]
Melchels et al, Paper “A review on stereolithography and its applications in biomedical engineering” suggests that the setups are differentiated only in build orientation and in the method of illumination. [03]
According to build orientation of stereolithography apparatus: -
(a) Top Exposure setup
(b) Bottom Exposure setup
Fig. 1. Schematic of (a) Top Exposure and (b) Bottom Exposure. Picture credit: Yaghmaie et al. 2014.
In top exposure setup, the setup is supported by the platform which is dipped in the pool of the liquid resin. After top layer is polymerized and then the platform moves downwards to specified distance along with the attached top layer.
In bottom exposure, the photopolymer liquid resin is illuminated from the bottom of the setup and the top layer is attached to the supporting platform which moves up once the top layer is attached to it. As soon as it moves upwards the liquid resin takes its place and plain second layer of liquid resin is exposed to get projected. In this technique platform is not dipped inside the liquid resin vat.
Build orientation wise, as discussed you can observe that the bottom exposure approach is better than the top exposure because: - * The vat depth is independent of the object height. Less liquid resin is required in vat. * Recoating for the next layer is not required. * Illuminated layer is not exposed to the atmosphere, so oxygen inhibition is limited. * Saves waste of liquid resin in case multiple resin use. Resin can also be peppitted from the above.
Second differentiation can be done on the basis of method of illumination wise, in Mask Image Projection based Stereolithography (MIP-SL) apparatus,
(a) Scanning-based Stereolithography (b) Projection-based Stereolithography
Fig. 1. Schematic of (a) SSL and (b) PSL. Picture credit: (Yaghmaie et al.2014)
* In this technique, a digital mirror device (DMD), an array of several millions of small mirrors that can be independently turned to an on and off state and thus projects the two-dimensional pixel pattern image on the liquid resin that is cured at once than illuminating laser point to point and curing resin as in laser beam SLA. * Significant time reduction as whole layer is cured in one go than point-to-point projection. * Number of structures can be built simultaneously which helps in mass production. [04]
Recently a new technique that has come into existence is scanning-projection stereolithography (SPSL). In this method, DMD movers continuously over the area of the medium while the projected image is continuously updated.
Fig. 3. Schematic design of projection system while scanning a pattern. Picture Credit: Yaghmaie et al. 2014.
In SPSL technique, bottom exposure technique has been used for its advantage over the top exposure. The laser should move at right speed at which the resin should enough energy to polymerization. The slow displacement of laser will over cure the resin.
Biomaterial that are suitable for the stereolithography should possess two main qualities which are as follows:- 1. Material should be transparent polymer or oligomer which can polymerize into crosslinking polymer. 2. A photoinitiator that absorbs the photon and ultimately causes the polymerization. Two types are photoinitiator are available, 1- Radical photoinitiator and 2- Cationic photoinitiator. [04]
It should be noted that photosensitive resin should be in liquid state which can mix living cells and gets cured, acting as a building material for the live cells.
Stereolithography has multiple application in the field of biomanufacturing. It helps in production of scaffolds for tissue engineering applications. It helps Hearing-aid manufacturers to design lightweight products small enough not to be detected, comfortable, with rounded shapes to be close from the natural geometry of the ear canal. It can also manufacture the microfluidic components like micro needles for transdermal drug delivery. [12] It is used to produce surgical guides for the placement of dental implants, temporary crowns and bridges and resin models for lost was casting. [13]
2. Literature Review
Recently published paper by Farrokh Yaghmaie et al, 2014, “Scanning-projection based stereolithography” has discussed about the modification of stereolithography process by taking advantages of both the method of illumination techniques together and suggest a mathematical model for the above discussed SPSL technique. [04]
In SLA curing depth is determined by the energy of the light projected on the exposed liquid resin. So to control the depth of the cured surface, energy of the laser beam and the exposure time are the two important factors that should be taken into consideration. Kinetics of photopolymerization is mostly governed by the initiation step of photo-resin which is dependent upon exposure time and energy/intensity of the laser beam used. At a certain point to increase the mechanical strength, at times curing is done for long time but this overexposure results in curing of preceding layer which is highly undesirable. This effect can be controlled if penetration depth can be decreased, which can be done by increasing photo-initiator concentration or by adding dye in liquid resin. Non-reactive components will compete with the photo-initiators and which ultimately help in controlling the depth of penetration. Point to be noted that this will lead to increase in building/fabrication time of the object.
Mathematical Model
Beer Lambert’s law from optics gives the good idea mathematical model to calculate the total energy required. Maximum cure depth (Cd) of single spot light is
Cd= Dd * ln (Emax/Ec)
Where Dp is the light penetration depth and Ec is the effective critical exposure. Emax is the maximum energy exposure. Both Dp and Ec are resin parameters obtained via experimental procedure.
Assumption: - The mathematical modelling assumes uniform of the exposure from the source.
Fig. 4. The irradiance distribution of individual μ-mirror. Picture credit: Yaghmaie et al. 2014.
Energy exposed is the integral of the irradiance (I) over time. That is
E (mJ/cm2) = I (mW/cm2) * T (s)
Where T is the exposure time. For a single pass of a mirror, the energy received by a pixel on resin surface (E, mJ/cm2), depends on the number of active n-mirrors traversing over pixel (Nf), the irradiance reflected by each n-mirror (I, mW/cm2) and Tsps, which is single pixel shift time, the energy obtained is
E=I * Tsps * Nf
If Δ s= ρ, and scanning speed is Vs, then Tsps= ρ/Vs, thus
E= I * ρ * (Nf/Vs)
In practice I may vary along the DMD array and also on a pixel when frame is moving. In order to achieve the maximum energy reflected by an n-mirror (Emax), the maximum irradiance Imax is replaced,
Emax= Imax * ρ * (Nf/Vs)
More energy is received by the resin if the stage moves at slower speed. To do the production at fast rate, movement of laser should be faster. Tsps is limited by Fmax (the maximum frame rate of the DMD) and the Ec. Fmax is external factor so Ec is the limiting factor in our calculation.
So the convenient value of Vs for the required cured depth Cd is
Vs = Imax * ρ * (Nf/Ec) * exp(-Cd/Dp)
Cd and Ec can be found out by experiments of any material. The curing depth (Cd) is almost linearly proportional to the natural logarithm of exposure time.
Cd = Dp ln {(I * T)/ Ec} = A ln (T) + B, where A = Dp; and B = Dp ln (I/Ec).
Above equation shows that the curing depth (Cd) is the function of the exposure time (T).The graph is plotted and of Cd and T and the slope of the curve gives Dp. Ec is obtained from B (interception of working curve with the line Cd = 0).
Fig.5.Working curve of BEST PL-4151; experimental measurement (points); regression curve (solid line); semi logarithmic plot. Picture credit: Farrokh Yaghmaie et al, 2014.
Fig.5.Working curve of BEST PL-4151; experimental measurement (points); regression curve (solid line); semi logarithmic plot. Picture credit: Farrokh Yaghmaie et al, 2014.
Process Parameters:
Laser power (P): - From experimental observations, laser power is found to be approximately proportional to the curing degree of the prototype. When laser power is increased, the curing degree will be increased. This is due to the fact that, by using a high-power laser, the resin is exposed to high-intensity UV light which leads more cross-linking. At the same time, the depth and width of the laser-scanned line increase, thus, improving the curing degree of the prototypes.
*Critical exposure (Ec): - Ec is the critical exposure (mJ/cm2), meaning the minimum energy level required to transform the photopolymer from liquid to solid. *Depth of penetration (Dp): - Dp is the penetration depth of the light into the resin. Cure Depth (Cd ): - Cure depth is the distance to which the resin solidifies. Exposure Time (T): - Exposure time is the time in which UV radiation is irradiated on the surface of the resin solution. Scanning speed: - The scanning speed used affects the curing degree in the laser-curing process. When the laser scan is fast, the exposure energy in a unit area is less; thus, the curing degree will be low. Laser stability: - Fluctuations in the laser power will lead to different laser exposures, and thus, affect the curing degree of the prototype. Absorption rate of the materials: - Resins used in the SL process are photo-sensitive. When the wavelength of the radiation used is suitable for the resin, or the energy distribution is concentrative, the absorption rate will be high, resulting in large curing degree. [21]
Poor control over the cure depth will decrease the resolution of the scaffold because the overlong crosslinking time results in over-cure. Consequently, some voxels designed to remain uncrosslinked will polymerize, making the pore size and porosity lower than designed. Exposure times that are too short do not allow for proper crosslinking of the polymer layers, and the layer thickness may remain inadequate for successful scaffold fabrication. To ensure good attachment between subsequent layers, each layer should be crosslinked for a slightly longer time than required for the given layer thickness. [20]
* – Primary parameters
Further investigation done by Yaghmaie et al, in their next paper, ‘An analytical model for scanning-projection based stereolithography’, 2015, they showed how both process SPSL and PSL are not only different in setup wise but result wise too.
Comparison of PSL and SPSL techniques
1. Uniformity test for PSL and SPSL. (a) Sample of pattern used; (b) a part of produced layer by PSL and (c) a part of produced layer by SPSL.
[Picture credit: - Yaghmaie et al. 2014.] 3. Uniformity and resolution tests (a) original pattern (b); features generated by PSL and (c) features generated by SPSL.
[Picture credit: - Yaghmaie et al. 2014.]
3- Resolution and aspect ratio comparison tests for 15, 25, 35 and 45 pixels circles diameter. (a) Original pattern; (b) features generated by PSL and (c) features generated by SPSL.
[Picture credit: - Yaghmaie et al. 2014.]
4- Long patterns stitching test. A comparison between step-and-repeat PSL vs. SPSL (a) step-and-repeat PSL lines (under stitching); (b) step-and-repeat PSL lines (over stitching) and (c) SPSL lines.
[Picture credit: - Yaghmaie et al. 2014.]
Microstructure plays really important role in cell seeding, migration and nutrients transport during culture of scaffolds. If the structure is not porous enough it will not be able to transfer the nutrients that are required to support the life of active cells resulting in death of them in bulk. Many photo patterning approaches are being developed to fabricate properly porous microstructure.
Scaffolds properties influence cell-ECM interactions and dictate the mechanical properties and degradation behavior of a biomaterial. It is required that porous structures have enough surface area for the cells to attach and have pores big enough to transport the nutrients, vascularization and tissue in growth in the microstructure.
3 Materials and Methods
Most materials used for stereolithography are conventional epoxy resins, thermoplastic elastomers, and poly(ethyleneglycol) (PEG)-based hydrogels.
This project primarily focus on biomaterials and few of them are listed below along with their properties and functionalities: - 1- SL 7540- Formulated for next-generation durability, SL 7540 material from 3D Systems and Vantico creates parts with near-end-use plastic properties, right out of your stereolithography system. SL 7540 offers mechanical properties very similar to thermoplastics such as polypropylene. [19] The resin when fully cured, exhibits a great deal of elasticity and its physical properties are quite different from the more brittle bone material. Yet it is used as material to fabricate and understand functionality of bone structure. [20] 2- Cibatool XB 5170 and Cibatool XB 5170 + DBS 97/47- It’s a low volume shrinkage epoxy resin which has been found very useful in biomedicine field. [24] 3- Propylene fumarate- Almost all biopolymers have limited application in bone tissue engineering because of the lack of biodegradability or sufficient mechanical strength. One promising material to overcome these limitations is poly(propylene fumarate) (PPF), an unsaturated linear polyester that can be cross-linked though its carbon-carbon double bonds13 and can be degraded by simple hydrolysis of the ester bonds into nontoxic products. PPF has been used as an injectable material for making preformed scaffolds for bone tissue engineering applications. [22] 4- Polymer poly (propylene glycol) diacrylate (PPGDA) – PPGDA is highly used polymer to manufacture the tissue scaffold. Its properties are pretty similar to the desired properties of tissues. [23]
Method
A four-step experiment is carried out to plot the working curve at 395 nm wavelength. The procedure is defined as follows:
1. A 6 mm transparent PET cylinder is placed in a polymer container for easy handling of the cured layer (step 1). This is because Cd is usually less than 1 mm. Therefore, it is difficult to handle the produced layer without a carrier (the PET cylinder).
2. Enough resin (less than 3 mm height) is poured into the container. This layer is fully exposed using a circular pattern (step 2).
3. The PET cylinder with a solid layer is removed from the resin and is cleaned with Isopropyl Alcohol (IPA) for 5 min. The solid layer is then post cured for 4 min (step 3). [04]
4. The cured part thickness is measured using micro-meter (Step 4).
Picture credit: Yaghmaie et al. 2014.
It can be easily observed from the graphs and table the linear nature of our initial working equation.
Critical energy value affect the curing depth of the material but higher critical energy doesn’t mean that the material will be having less curing depth. – from the case Cibatool and Propylene fumerate.
Table above also shows the coefficient of determination (R2 ) which for every individual material is very close to 1, also indicates a perfect positive fit.
This can be interpreted from the R2 value that the dependent variable (Curing depth) can be predicted from the independent variable (Exposure time).
Conclusions
From the study it has been concluded that * Cure depth varies linearly with the exposure time. * Critical temperature and penetration depth are the deciding factor the cure depth. * Overcuring can be checked by maintaining proper scanning velocity. * SPSL produces better surface finish and more accurate results than PSL.
References
[01] Stratasys Direct Manufacturing. Stereolithography. Retrieved from <https://www.stratasysdirect.com/technologies/stereolithography/>
[02] Brain, Marshall. "How Stereolithography 3-D Layering Works" 05 October 2000. HowStuffWorks.com. <http://computer.howstuffworks.com/stereolith.htm> 06 October 2015.
[03] Ferry P.W. Melchels, Jan Feijen, Dirk W. Grijpma, Biomaterials 2010, “A review on stereolithography and its applications in biomedical engineering”, Volume 31, Issue 24, Pages 6121–6130.
[04] Mohammad Mahdi Emami,Farshad Barazandeh,Farrokh Yaghmaie 2014, “Scanning-projection based stereolithography”: Method and structure. Sensors and Actuators A: Physical, Elsevier, Volume 218, Pages116–124.
[05] Mohammad Mahdi Emami, Farshad Barazandeh, Farrokh Yaghmaie, 2015, “An analytical model for scanning-projection based stereolithography”, Journal of Materials Processing Technology, Volume 219, Pages 17–27.
[06] Lee HB, Khang G, Lee JH. 2003, Polymeric biomaterials. In: Park JB, Bronzino JD, editors. Biomaterials: principles and applications. Boca Raton, FL: CRC Press.
[07] Alexandros Selimis, Vladimir Mironov and Maria Farsari, 2014, Direct laser writing: Principles and materials for scaffold 3D printing, Microelectronic Engineering- Micro and Nanofabrication Breakthroughs for Electronics, MEMS and Life Sciences, 25 January 2015, Page 83-89.
[08] Laura Elomaa, Sandra Teixeira, Risto Hakala, Harri Korhonen, Dirk W. Grijpma, Jukka V. Seppälä, Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography.
[09] Robert Gauvin, Ying-Chieh Chen, Jin Woo Lee, Pranav Soman, Pinar Zorlutuna, Jason W. Nichol, Hojae Bae, Shaochen Chen, Ali Khademhosseini 2012, “Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography”; Biomaterials, Volume 33, Issue 15, Pages 3824–3834.
[10] Thomas Billiet, Mieke Vandenhaute, Jorg Schelfhout, Sandra Van Vlierberghe, Peter Dubruel, 2012, A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials, Volume 33, Issue 26, Pages 6020–6041
[11] Thomas Weiß, Gerhard Hildebrand, Ronald Schade and, Klaus Liefeith 2009, Two-Photon polymerization for microfabrication of three-dimensional scaffolds for tissue engineering application, Volume 9, Issue 5, pages 384–390.
[12] Amaud Bertsch, Sebastien Jiguet, Paul Bernhard, Philippe Renaud 2002, Microstereolithography: A Review. Materials Research Society Symposium Proceedings, Volume 758 Held in Boston, Massachusetts.
[13] Richard van Noort, The future of dental devices is digital, Dental Materials, 2012, Volume 28, Issue 1, Pages 3–12
[14] Pinar Zorlutuna, Jae Hyun Jeong, Hyunjoon Kong, Rashid Bashir, Stereolithography‐Based Hydrogel Microenvironments to Examine Cellular Interactions, Advanced Functional Materials, Volume 21, Issue 19, pages 3642–3651.
[15] Iwona Gibas and Helena Janik, Review: Synthetic Polymer Hydrogels for Biomedical Applications, Chemistry, Vol 4, No. 4, 2010.
[16] F.P. Melchels, A.M. Barradas, C.A. van Blitterswijk, J. de Boer, J. Feijen, D.W. Grijpma,
Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing, Acta Biomaterialia, 6 (11) (2010), pp. 4208–4217
[17] J. Zeltinger, J.K. Sherwood, D.A. Graham, R. Mueller, L.G. Griffith, Effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition, Tissue Eng, 7 (5) (2001), pp. 557–572
[18] L.E. Freed, F. Guilak, X.E. Guo, M.L. Gray, R. Tranquillo, J.W. Holmes, et al. Advanced tools for tissue engineering: scaffolds, bioreactors, and signaling. Tissue Eng, 12 (12) (2006), pp. 3285–3305
[19] Noshir Langrana, Madara Ogot, Art Henningsen, Ted Croitor, Jan Handeland, Juan Molina, Rapid Prototyping as a Method of Modeling the Mechanical Properties of Trabecular and Cortical Bone Structures, Mechanical Engineering, May 6th, 2002.
[20] Melchels FPW, Feijen J, Grijpma DW. A poly(d,l-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomaterials. 2009; 30:3801-3809.
[21] W.L. Wang, C.M. Cheah, J.Y.H. Fuh, L. Lu, Influence of process parameters on stereolithography part shrinkage, Materials & Design, Volume 17, Issue 4, 1996, Pages 205–213.
[22] Kee-Won Lee, Shanfeng Wang, Bradley C. Fox, Erik L. Ritman, Michael J. Yaszemski, and Lichun Lu, Poly(propylene fumarate) Bone Tissue Engineering Scaffold Fabrication Using Stereolithography : Effects of Resin Formulations and Laser Parameters, 2006.
[23] Philip Michael Lambert, Christopher B. Williams, Timothy E. Long, Lissett R. Bickford, Design and Fabrication of a Mask Projection Microstereolithography System for the Characterization and Processing of Novel Photopolymer Resins, Mechanical Engineering, 2014.
[24] SHIRLEY, Dianne, Beth, Ian, Malcolm, Ajay, Haridas, Martin, Russell, McALOON, Kevin, Thomas, SCHER, Herbert, Benson, US Patent- COLOUR CHANGING COMPOSITION AND COLOURING POLYMERIC ARTICLES MADE THEREFROM, 25.02.2004 Bulletin 2004/09, Application number: 99934915.2