Abstract
With the advent of inexpensive and highly accurate 3D printing devices, a tremendous flurry of research activity has been unleashed into new resorbable, polymeric materials that can be printed using three approaches: hydrogels for bioprinting and bioplotting, sintered polymer powders, and solid cured (photocrosslinked) resins. Additionally, there is a race to understand the role of extracellular matrix components and cell signalling molecules and to fashion ways to incorporate these materials into resorbable implants. These chimeric materials along with microfluidic devices to study organs or create labs on chips, are all receiving intense attention despite the limited number of polymer systems that can accommodate the biofabrication processes necessary to render these constructs. Perhaps most telling is the limited number of photo-crosslinkable, resorbable polymers and fabrication additives (e.g., photoinitiators, solvents, dyes, dispersants, emulsifiers, or bioactive molecules such as micro-RNAs, peptides, proteins, exosomes, micelles, or ceramic crystals) available to create resins that have been validated as biocompatible. Advances are needed to manipulate 4D properties of 3D printed scaffolds such as pre-implantation cell culture, mechanical properties, resorption kinetics, drug delivery, scaffold surface functionalization, cell attachment, cell proliferation, cell maturation, or tissue remodelling; all of which are necessary for regenerative medicine applications along with expanding the small set of materials in clinical use. This manuscript presents a review of the foundation of the most common photopolymerizable resins for solidcured scaffolds and medical devices, namely, polyethylene glycol (PEG), poly(D, L-lactide) (PDLLA), poly-ε-caprolactone (PCL), and poly(propylene fumarate) (PPF), along with methodological advances for 3D Printing tissue engineered implants (e.g., via stereolithography [SLA], continuous Digital Light Processing [cDLP], and Liquid Crystal Display [LCD]).
Keywords: Additive manufacturing (3D printing), biocompatibility, crosslinker, co-crosslinker, cytotoxicity, Digital Light Processing (DLP), Digital Micromirror Device (DMD), dispersant, emulsifier, fabrication additive, light attenuator, Liquid Crystal Display (LCD), mask projection, photocrosslinking, photoinitiator, regenerative medicine, stereolithography, tissue engineering.
Graphical Abstract
[1]
Pereira RF, Bártolo PJ. 3D photo-fabrication for tissue engineering and drug delivery. Eng 2015; 1(1): 90-112.
[2]
Melchels FPW, Domingos MAN, Klein TJ, et al. Additive manufacturing of tissues and organs. Prog Polym Sci 2012; 37(8): 1079-104.
[3]
Bártolo PJ, Chua CK, Almeida HA, Chou SM, Lim ASC. Biomanufacturing for tissue engineering: Present and future trends. Virtual Phys Prototyp 2009; 4(4): 203-16.
[4]
Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials 2000; 21(24): 2529-43.
[5]
Pereira RF, Bártolo PJ. Recent advances in additive biomanufacturing. Comprehensive Materials Proc 2014; 10: 265-81.
[8]
Crivello JV, Reichmanis E. Photopolymer materials and processes for advanced technologies. Chem Mater 2014; 26(1): 533-48.
[9]
Fouassier JP, Lalevée J. Photoinitiators for Polymer Synthesis: Scope, Reactivity and Efficiency. John Wiley & Sons 2012.
[10]
Fouassier J, Allonas X, Burget D. Photopolymerization reactions under visible lights: Principle, mechanisms and examples of applications. Prog Org Coat 2003; 47(1): 16-36.
[11]
Armentrout PB. Reactions of scandium oxide (ScO+), titanium oxide (TiO+) and vanadyl (VO+) with deuterium: M+-OH bond energies and effects of spin conservation. J Phys Chem 1993; 97(3): 544-52.
[13]
Cooke MN, Fisher JP, Dean D, Rimnac C, Mikos AG. Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth. J Biomed Mater Res 2003; 64B(2): 65-9.
[14]
Beke S, Anjum F, Ceseracciu L, et al. Rapid fabrication of rigid biodegradable scaffolds by excimer laser mask projection technique: A comparison between 248 and 308 nm. Laser Phys 2013; 23(3)
[15]
Bártolo PJ. Stereolithography: Materials. Processes and Applications 2011. ISBN 978-0-387-92904-0.
[16]
Bennett J. Measuring UV curing parameters of commercial photopolymers used in additive manufacturing. Addit Manuf 2017; 18: 203-12.
[17]
Mott EJ, Busso M, Luo X, et al. Digital micromirror device (DMD)-based 3D printing of poly(propylene fumarate) scaffolds. Mater Sci Eng C 2016; 61: 301-11.
[18]
Lee JH, Prud’homme RK, Aksay IA. Cure depth in photopolymerization: Experiments and theory. J Mater Res 2001; 16(12): 3536-44.
[19]
Ullett JS, Schultz JW, Chartoff RP. Novel liquid crystal resins for stereolithography-processing parameters and mechanical analysis. Rapid Prototyping J 2003; 6(1): 8-17.
[20]
Tille C, Bens A, Seitz H. Processing characteristics and mechanical properties of a novel stereolithographic resin system for engineering and biomedicine, in virtual modelling and rapid manufacturing - advanced research in virtual and rapid prototyping. CRC 2005; pp. 311-5.
[21]
Arcaute K, Mann BK, Wicker RN. Stereolithography of three-dimensional bioactive poly (ethylene glycol) constructs with encapsulated cells. Ann Biomed Eng 2006; 34(9): 1429-41.
[22]
Cotti E, Scungio P, Dettori C, Ennas G. Comparison of the degree of conversion of resin based endodontic sealers using the DSC technique. Eur J Dent 2001; 5(2): 131-8.
[23]
Cheah CM, Fuh YJH, Nee AYC, et al. Characteristics of photopolymeric material used in rapid prototypes: Part II. Mechanical properties at post-cured state. J Mater Process Technol 1997; 67(1-3): 46-9.
[24]
Lin AC, Liang SR, Jeng JY, et al. Study of curing characteristics of photopolymer used in solid laser diode plotter rapid prototyping system. Plast Rubber Compos 2002; 31(4): 177-85.
[25]
Salmoria JV, Ahrens CH, Beal VE, Pires ATN, Soldi V. Evaluation of post-curing and laser manufacturing parameters on the properties of SOMOS 7110 photosensitive resin used in stereolithography. Mater Des 2009; 30(3): 758-63.
[26]
Dai Z, Ronholm J, Tian Y, Sethi B, Cao X. Sterilization techniques for biodegradable scaffolds in tissue engineering applications. J Tissue Eng 2016; 7: 204173141664881.
[27]
Wang MO, Etheridge JM, Thompson JA, et al. Evaluation of the in vitro Cytotoxicity of Bacteriocin. Biomacromol 2013; pp. 1321-9.
[28]
Guerra AJ, Cano P, Rabionet M, Puig T. Effects of different sterilization processes on the properties of a novel 3D ‐ printed polycaprolactone stent. Pol Adv Manufacturing 2018; pp. 1-9.
[29]
Barry JJA, Evseev AV, Markov MA, et al. In vitro study of hydroxyapatite-based photocurable polymer composites prepared by laser stereolithography and supercritical fluid extraction. Acta Biomater 2008; 4(6): 1603-10.
[30]
Quadrani P, Pasini A, Mattioli-Belmonte M, et al. High-resolution 3D scaffold model for engineered tissue fabrication using a rapid prototyping technique. Med Biol Eng Comput 2005; 43(2): 196-9.
[31]
Mapili G, Lu Y, Chen S, Roy K. Laser-layered microfabrication of spatially patterned functionalized tissue-engineering scaffolds. J Biomed Mater Res-Part B Appl Biomater 2005; 75(2): 414-24.
[32]
Lu Y, Mapili G, Suhali G, Chen S, Roy K. A digital micro-mirror device-based system for the microfabrication of complex, spatially patterned tissue engineering scaffolds. J Biomed Mater Res-Part A 2006; 77(2): 396-405.
[33]
Lee KW, Wang S, Fox BC, et al. Poly (propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: Effects of resin formulations and laser parameters. Biomacromol 2007; 8(40): 1077-84.
[34]
Lee SJ, Kang HW, Park JK, et al. Application of microstereolithography in the development of three-dimensional cartilage regeneration scaffolds. Biomed Microdevices 2008; 10(2): 233-41.
[35]
Lan PX, Lee JW, Seol YJ, Cho DW. Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. J Mater Sci Mater Med 2009; 20(1): 271-9.
[36]
Qiu Y, Zhang N, Kang Q, An Y, Wen X. Chemically modified light-curable chitosans with enhanced potential for bone tissue repair. J Biomed Mater Res-Part A 2009; 89(3): 772-9.
[37]
Melchels FPW, Feijen J, Grijpma DW. A poly(d,l-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomat 2009; 30(23-24): 3801-9.
[38]
Arcaute K, Mann BK, Wicker RB. Fabrication of off-the-shelf multilumen poly(Ethylene glycol) nerve guidance conduits using stereolithographyxs. Tissue Eng Part C Methods 2010; 17(1): 27-38.
[39]
Bian W, Li D, Lian Q, et al. Design and fabrication of a novel porous implant with pre-set channels based on ceramic stereolithography for vascular implantation. Biofabrication 2011; 3(3): 034103.
[40]
Blanquer SBG, Sharifi S, Grijpma DW. Development of poly (trimethylene carbonate) network implants for annulus fibrosus tissue engineering. J Appl Biomater Funct Mater 2012; 10(3): 177-84.
[41]
Madaghiele M, Marotta F, Demitri C, et al. Development of semi- and grafted interpenetrating polymer networks based on poly (Ethylene glycol) diacrylate and collagen. J Appl Biomater Funct Mater 2014; 12(3): 183-92.
[42]
Li YX, Li CL, Huang MJ. Effect of pH on the holographic properties of Al2O3 nanoparticle dispersed acrylate photopolymer. Int J Mod Phys B 2014; 28(11): 1450076.
[43]
Farkas B, Romano I, Ceseracciu L, et al. Four-order stiffness variation of laser-fabricated photopolymer biodegradable scaffolds by laser parameter modulation. Mater Sci Eng C 2015; 55: 14-21.
[44]
Elomaa I, Teixeira S, Hakala R, et al. Preparation of poly(ε-caprolactone)-based tissue engineering scaffolds by stereolithography. Acta Biomater 2011; 7(11): 3850-6.
[45]
Ronca A, Ambrosio L, Grijpma DW. Design of porous three-dimensional PDLLA/nano-hap composite scaffolds using stereolithography. J Appl Biomater Funct Mater 2012; 10(3): 249-58.
[46]
Dean D, Wallace J, Siblani A, et al. Continuous digital light processing (cDLP): Highly accurate additive manufacturing of tissue engineered bone scaffolds. Virtual Phys Prototyp 2012; 7(1): 13-24.
[47]
Grogan SP, Chung PH, Soman P, et al. Digital micromirror device projection printing system for meniscus tissue engineering. Acta Biomater 2013; 9(7): 7218-26.
[48]
Lin H, Zhang D, Alexander PG, et al. Application of visible light-based projection stereolithography for live cell-scaffold fabrication with designed architecture. Biomaterials 2013; 34(2): 331-9.
[49]
Bajaj P, Marchwiany D, Duarte C, Bashir R. Patterned three-dimensional encapsulation of embryonic stem cells using dielectrophoresis and stereolithography. Adv Healthc Mater 2013; 2(3): 450-8.
[50]
Schüller-Ravoo S, Zant E, Feijen J, Grijpma DW. Preparation of a Designed Poly(trimethylene carbonate) Microvascular Network by Stereolithography. Adv Healthc Mater 2014; 3(12): 2004-11.
[51]
Chiu SH, Wicaksono ST, Chen KT, Chen CY, Pong SH. Mechanical and thermal properties of photopolymer/CB (carbon black) nanocomposite for rapid prototyping. Rapid Prototyping J 2015; 21(3): 262-9.
[52]
Ronca A, Ronca S, Forte G, et al. Synthesis and characterization of divinyl-fumarate poly-ε-caprolactone for scaffolds with controlled architectures. J Tissue Eng Regen Med 2018; 12(1): e523-31.
[53]
Jiang C-P, Meizinta T. Development of LCD-based additive manufacturing system for biomedical application in ACM. Int Conf Proc Series. 2016; 7: 13-15.
[54]
Society of Manufacturing Engineers (SME) Medical Additive Manufacturing 3D Printing Annual Report 2018 (SME) 2018.http://www.sme.org/uploadedFiles/Medical_Additive_Manufacturing/2018-SME-Medical-AM3DP-Annual-Report.pdf
[55]
Pereira RF, Bártolo PJ. Photopolymerizable hydrogels in regenerative medicine and drug delivery 2014.
[http://dx.doi.org/10.4155/EBO.13.650]
[http://dx.doi.org/10.4155/EBO.13.650]
[56]
Kharkar PM, Kiick KL, Kloxin AM. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem Soc Rev 2013; 42(17): 7335-72.
[57]
Nguyen MK, Alsberg E. Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine. Prog Polym Sci 2014; 39(7): 1235-65.
[58]
Yang J-A, Yeom J, Hwang BW, Hoffman AS, Hahn SK. In situ-forming injectable hydrogels for regenerative medicine. Prog Polym Sci 2014; 39(12): 1973-86.
[59]
Annabi N, Tamayol A, Uquillas JA, et al. 25th anniversary article: Rational design and applications of hydrogels in regenerative medicine. Adv Mater 2014; 26(1): 85-124.
[60]
Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 2005; 23(1): 47-55.
[61]
Deforest CA, Polizzotti BD, Anseth KS. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat Mater 2009; 8(8): 659-64.
[62]
Fertier L, Koleilat H, Stemmelen M, et al. The use of renewable feedstock in UV-curable materials-A new age for polymers and green chemistry. Prog Polym Sci 2013; 38(6): 932-62.
[63]
Mistry AS, Cheng SH, Yeh T, et al. Fabrication and in vitro degradation of porous fumarate-based polymer/alumoxane nanocomposite scaffolds for bone tissue engineering. J Biomed Mater Res-Part A 2009; 89(1): 68-79.
[64]
Nguyen KT, West JL. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 2002; 23(22): 4307-14.
[65]
Shih H, Lin C-C. Visible-light-mediated thiol-ene hydrogelation using eosin-Y as the only photoinitiator. Macromol Rapid Commun 2013; 34(3): 269-73.
[66]
Knowlton S, Yenilmez B, Anand S, Tasoglu S. Photocrosslinking-based bioprinting: Examining crosslinking schemes. Bioprinting 2017; 5: 10-8.
[67]
De Gruijl FR, Van Kranen HJ, Mullenders LH. UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. J Photochem Photobiol B Biol 2001; 63(1-3): 19-27.
[68]
Nanda K, McCrory DC, Myers ER, et al. Accuracy of the papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: A systematic review. Ann Intern Med 2000; 132(10): 810-9.
[69]
Kulms D, Zeise E, Pöppelmann B, Schwarz T. DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene 2002; 21(38): 5844-51.
[70]
Smith S, Maclean M, MacGregor SJ, Anderson JG, Grant MH. Exposure of 3T3 mouse fibroblasts and collagen to high intensity blue light. IFMBE Proc 2009; 23: 1352-5.
[71]
Lim KS, Schon BS, Mekhileri NV, et al. New visible-light photoinitiating system for improved print fidelity in gelatin-based bioinks. ACS Biomater Sci Eng 2016; 2(10): 1752-62.
[72]
Rouillard AD, Berglund CM, Lee JY, et al. Methods for photocrosslinking alginate hydrogel scaffolds with high cell viability. Tissue Eng Part C Methods 2011; 17(2): 173-9.
[73]
Billiet T, Gevaert E, De Schryver T, Cornelissen M, Dubruel P. The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability. Biomaterials 2014; 35(1): 49-62.
[74]
Li Z, Torgersen J, Ajami A, et al. Initiation efficiency and cytotoxicity of novel water-soluble two-photon photoinitiators for direct 3D microfabrication of hydrogels. RSC Advances 2013; 3(36): 15939-46.
[75]
Hu J, Hou Y, Park H, et al. Visible light crosslinkable chitosan hydrogels for tissue engineering. Acta Biomater 2012; 8(5): 1730-8.
[76]
Manaia EB, Kaminski RCK, Corrêa MA, Chiavacci LA. Inorganic UV filters. Braz J Pharm Sci 2013; 49(2): 201-9.
[77]
Serpone N, Dondi D, Albini A. Inorganic and organic UV filters: Their role and efficacy in sunscreens and suncare products. Inorg Chim Acta 2007; 360(3): 794-802.
[78]
Amara S, Ben-Slama I, Mrad I, et al. Acute exposure to zinc oxide nanoparticles does not affect the cognitive capacity and neurotransmitters levels in adult rats. Nanotoxicol 2014; 89(SUPPL)1: 208-15.
[79]
Cho W-S, Kang B-C, Lee JK, et al. Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration. Part Fibre Toxicol 2013; 10: 9.
[80]
Shrivastava R, Raza S, Yadav A, Kushwaha P, Flora SJS. Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain. Drug Chem Toxicol 2014; 37(3): 336-47.
[81]
Deng X, Luan Q, Chen W, et al. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology 2009; 20(11): 115101.
[82]
Yin Y, Lin Q, Sun H, et al. Cytotoxic effects of ZnO hierarchical architectures on RSC96 Schwann cells Nanoscale Res Lett 2012; 7(1-8): 439.
[83]
Hu Q, Guo F, Zhao F, Fu Z. Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. Chemosphere 2017; 173: 373-9.
[84]
Chiang H-M, Xia Q, Zou X, et al. Nanoscale ZnO induces cytotoxicity and DNA Damage in human cell lines and rat primary neuronal cells. J Nanosci Nanotechnol 2012; 12(3): 2126-35.
[85]
Yang H, Zhu S, Pan N. Studying the mechanisms of titanium dioxide as ultraviolet-blocking additive for films and fabrics by an improved scheme. J Appl Polym Sci 2004; 92(5): 3201-10.
[86]
Popov AP, Priezzhev AV, Lademann J, Myllylä R. TiO2 nanoparticles as an effective UV-B radiation skin-protective compound in sunscreens. J Phys D Appl Phys 2005; 38(15): 2564-70.
[87]
Wallace J, Wang MQ, Thompson P, et al. Validating continuous digital light processing (cDLP) additive manufacturing accuracy and tissue engineering utility of a dye-initiator package. Biofabrication 2014; 69(1): 015003.
[88]
Ruszkiewicz JA, Pinkas A, Ferrer B, et al. Neurotoxic effect of active ingredients in sunscreen products, a contemporary review. Toxicol Rep 2017; 4: 245-59.
[89]
Chiu S-H, Wu DC. Preparation and physical properties of photopolymer/SiO2 nanocomposite for rapid prototyping system. J Appl Polym Sci 2008; 107(6): 3529-34.
[90]
Chen W, Inoue Y, Ishihara K. Preparation of photoreactive phospholipid polymer nanoparticles to immobilize and release protein by photoirradiation. Colloids Surf B Biointerfaces 2015; 135: 365-70.
[91]
Sasa N, Sato A, Yamaoka T. Use of functional microgels with vinyl groups to accelerate photopolymerization reaction. Polym Adv Technol 1994; 5(6): 297-308.
[92]
Hench LL, Splinter RJ, Allen WC, Greenlee TK. Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Mater Res 1971; 5(6): 117-41.
[93]
Zhao X. Introduction to bioactive materials in medicine. Bioact Mater Med Des Appl 2011; pp. 1-13.
[94]
Rodriguez CA, Lara-padilla H, Dean D. Bioceramics for musculoskeletal regenerative medicine: Materials and manufacturing process compatibility for synthetic bone grafts and medical devices. 3D Printing and Biofabrication 2018; 1-33.
[95]
Skoog SA, Goering PL, Narayan RJ. Stereolithography in tissue engineering. J Mater Sci Mater Med 2014; 25(3): 845-6.
[96]
Lian Q, Yang F, Xin H, Li D. Oxygen-controlled bottom-up mask-projection stereolithography for ceramic 3D printing. Ceram Int 2017; 43(17): 14956-61.
[97]
Levy RA, Chu TM, Halloran JW, Feinberg SE, Hollister S. CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant. Am J Neuroradiol 1997; 18(8): 1522-5.
[98]
Trombetta R, Inzana JA, Schwarz EM, Kates SL, Awad HA. 3D printing of calcium phosphate ceramics for bone tissue engineering and drug delivery. Ann Biomed Eng 2017; 45(1): 23-44.
[99]
Gmeiner R, Mitteramskogler G, Stampfl J, Boccaccini AR. Stereolithographic ceramic manufacturing of high strength bioactive glass. Int J Appl Ceram Technol 2015; 12(1): 38-45.
[100]
Raman R, Bashir R. Chapter 6–Stereolithographic 3D Bioprinting for Biomedical Applications. Elsevier Inc. 2015.
[101]
Farsari M, Filippidis G, Drakakis TS, et al. Three-dimensional biomolecule patterning. Appl Surf Sci 2007; 253(19): 8115-8.
[102]
Jacobs PF. Rapid prototyping & manufacturing: Fundamentals of stereolithography. Society of Manufacturing Engineers 1992.
[103]
Wallace J, Wang MO, Thompson P, et al. Validating continuous digital light processing (cDLP) additive manufacturing accuracy and tissue engineering utility of a dye-initiator package. Biofabrication 2014; 6(1): 015003.
[104]
Rodriguez CA, Lara-Padilla H, Dean D. Bioceramics for musculoskeletal regenerative medicine: Materials and manufacturing process compatibility for synthetic bone grafts and medical devices. In: Ovsianikov A., Yoo J., Mironov V. (eds) 3D Printing and Biofabrication. Reference Series in Biomedical Engineering. Springer, Cham 2018.
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