Inkjet Printing of Cyanoacrylate Adhesives

This article was downloaded by: [Infatrieve] On: 15MaICI1 2010 Access details: Access Details: [subscription number 780998633] Publisher Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37— 41 Mortimer Street, London W1T 3J'l-I, UK The Journal of Adhesion Publication details. including instructions for authors and subscription information: http://wwwjnformaworld.comlsmpp/title~content:t713453635 Inkjet Prl'.nting of Cyanoacrylate Adhesive Anand Doraiswamy «; Rene crombez “; weidian Shen D; Yuan-Shin Lee C, Roger J. Narayan A = Joint Department of Biomedical Engineering, University of North Carolina, chapel Hill, NC, USA l= Surface science and Nano—Tribology Laboratory, Eastern Michigan University, Ypsilanti, MI. USA I Edward P. Fitts Department of Industrial and Systems Engineering, North Carolina state University. Raleigh, NC, USA online publication date: 05 February 2010 To cite this Article Doraiswam , Anarld, Crornbez, Rene, Shen, Weidiarl, Lee, Yuan-Shirl and Narayarl, Roger J.(2010) 'Inkjet Printing of Cyanoacry ate Adhesive‘. The Journal of Adhesion, 86: 1. 1 — 9 To link to this Article: D01: 10.1080/00Z18460903é17651 URL‘ http://dx.doi.org/10.1080/00218460903417651 PLEASE SCROLL DOWN FOR ARTICLE Full terms and conditions of use: http://www.informaworld.com/terms-and-conditions-or-access.pdi This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Dnwnlnaded lay. linrnerievel At ll? 34 is March 2010 The Joitrllal ofAd7xeslull, 86:l—9, 2010 Copyright « Taylor at Francis Group, LLC ISSN 00214-1464 print/1.’i4.’i—.’i8Z3 online DO]: 10. 1080/LlLl2184$U9034 1765 1 Taylor& Francis Ynyimhluunii clan? lnkjet Printing of Cyanoacrylate Adhesive Anand Doraiswamyl, Rene Crombezz, Weidian Shenz, Yuan-Shin Lees, and Roger J. Narayanl ‘Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA 2Surface science and Nano—Tn'bology Laboratory, Eastern Michigan University, Ypsilanti, MI, USA “Edward P. Eitts Department of Industrial and systems Engineering, North Carolina State University, Raleigh, NC, USA In thls study, we have dcrhoastr-ated the asc of pwzuelcctrlc trthyct prtrltlllg fu fabrtcalc mttrroscale patterns n/"Vetl7tm(1" rrbatyl nyanoanrylate tissue adht» . Dptlcal microscopy, ctarrac farce mtcroscopy, rrortotrtdchtatiah, and a cell viability assay were used to erorrrrac the stractarol, mac/lunical, aha biologlcall pr-opcrttcs of mlcroscale cyaaoaorylatc patterns. The ublllty to mpldly fabricate rrrrcrosoalc put— terns ofmediml and veterinary ad/lestws will Mable reduced bond lines between tissues, imprrlued tissue inlegrlty, and reduced Zoxllrlly. We eaoislorr that plezn2l2c- trlc irthjet deposition c/‘cyartoacrylatcs arid other medical aolhesloes may be used to enhance wvund reprllr In rrllcmllasculm surgery, Keywords: Medical adhesives; Microfabncation; Piezoelectric inlget printing INTRODUCTION A current challenge in microvascular surgery involves closing of small blood vessels or end-to-end joining of blood vessels. The conventional technique for joining blood vessels involves the use of sutures. Conven- tional suturing techniques are generally considered to be successful; Received 19 January 2009; in nrial rorm 24 July 2009. One at a collection of papers honoring J. Herbert Waite, the recipient in February 2009 or The Aahesrorr Socwty An-arrl fur Excellcllce rrr Adhosroh Sclcncc, sponsored lry 3M. Address correspondence to Roger J. Narayan, Department of Biomedical Engineer mg, University or North Carolina, chapel Hill, NC 27599—7575, USA. E—mail' roger_narayan@unc.cdu Pnuxlneded Ry. lfnfacrieve‘ 2 A. Domiswamy el al. these techniques are associated with a 90-95% success rate. On the other hand, suturing techniques involve damage to the blood vessel endothelium, which is associated with several clinical complications, including foreign body reaction, platelet aggregation, distortion of the blood vessel, and ischemia of the blood vessel wall l1J. Endothelial lacerations can lead to the development of strictures at locations where blood vessels are being joined; these strictures may result in failure of grafted tissue [2]. In addition, suturing is a time consuming process; surgical delays associated with the suturing process may lead to tissue damage. An alternative joining technique that has gained support in recent years involves the use of adhesives, which hold tissue together for sev- eral weeks while tissue regrowth processes take place. It is thought that adhesives may be used to perform joining of blood vessels with easier tissue manipulation and fewer complications than conventional suturing techniques. For example, fibrin glue has previously been uti- lized for joining blood vessels [3,4]. The components obtained from pooled human plasma (fibrinogen, factor XIII, and thrombin) undergo various clinical virus safety, manufacturing, and pasteurization mea- sures. However, there are several safety issues that have limited the use of these materials, including the possibility of disease transmission and anaphylactic reaction. For example, concerns exist regarding the transmission of hepatitis viruses, human immunodeficiency virus, human T-cell lymphotropic virus-1, Parvovirus B19, bovine spongiform encephalopathy, and other pathogens from blood-derived materials. Several medical applications for N-butyl cyanoacrylate were demonstrated by Leonard and his colleagues at the Walter Reed Army Medical Center, including joining of tissues, joining of blood vessels, and hemostasis of wounds [5—7]. For example, Matsumoto et al. demonstrated that N-butyl cyanoacrylate is effective for hemostasis of kidney wounds and liver wounds, which enables shorter operating times and simpler surgeries than the conventional suture method [8—10l. Joining of tissues with N-butyl cyanoacrylate was also asso- ciated with less blood loss than the conventional suture method [11]. Recent work by Saba et al. suggests that N-butyl cyanoacrylate is a suitable alternative to conventional suturing for joining of blood vessels l12l. N-butyl cyanoacrylate may be suitable for use in micro- vascular surgery as it is currently used for embolization of arteriove- nous malformations as well as for treatment of bleeding associated with gastic varices [13,14]. We have recently demonstrated that piezoelectric inkjet printing is a non-contact and non-destructive tech- nique for patterning many biological materials. In our previous work, piezoelectric jetting was used to develop microscale patterns of several Pnuxlneded Ry. lfnfacrieve‘ Imp; Prmling of Uyanoacrylolc Arllwsiup 3 biological materials, including streptavidin protein, sinapinic acid, deoxyribonucleic acid, marine mussel adhesive protein, multiwalled carbon nanotube/DNA hybrid materials, and monofunctional acrylate esters l15—17l. Fourier transform infrared spectroscopy studies of inkjetted and dropcast marine mussel adhesive protein, n-butyl cya- noacrylate, and 2-octyl cyanoacrylate demonstrated similar peak intensity values, which suggests that piezoelectric inkjet printing does not significantly alter the structure of these materials [16,17]. In this study, piezoelectric ink-jet technology was used to investigate piezo- electric inkjetting of Vetbond" b-butyl cyanoacrylate tissue adhesive. The patterned materials were examined using optical microscopy, atomic force microscopy, nanoindentation, and a cell viability assay. We envision that piezoelectric inkjet deposition of cyanoacrylate adhe- sives may be used to enhance wound repair in microvascular surgery. For example, piezoelectric inkjet printing may enable processing of adhesive patterns in closed chest coronary artery bypass graft surgery and in other surgeries that involve limited surgical access [14]. MATERIALS AND METHODS Vetbond" tissue adhesive (3M, St. Paul, MN, USA) contains n-butyl cyanoacrylate (>98"u), hydroquinone (~:*v am Paurlasded ay ll"far~ieve Imp; Prmtiitg of Cyanoacrylatc Ad/irsiue .=. (3—[4,5-dimethyl-2-thiazol]-2,5-diphenyl-2H-tetrazolium bromide) [19]. HAAE-1 cells were seeded in well culture plates (~5000 cells/well) containing equal amounts of inkjetted Vetbond tissue adhesive (n:4). Cells growing on empty wells with plain media were used as controls. At 24 hours, the cells were exposed to media (control) and assayed. The cells were incubated in a MTT medium (0.5mg/mL) for 4 hours, the tetrazolium metabolized within the mitochondria was extracted, and the absorbance was quantified. The absorbance was determined spectrophotometrically at 2. 550nm in an ELISA plate reader (Multiskan RC Labsystems, Helsinki, Finland). RESULTS AND DISCUSSION Vetbond tissue adhesive was successfully deposited into microscale patterns using the piezoelectric inkjet printer. Figure 2 shows an optical micrograph of a Vetbond tissue adhesive dot array pattern on a silicon wafer. Inkjetting of Vetbond tissue adhesive in dot array patterns on silicon (111) revealed ~56;im features; spacing between drops was maintained at ~266iim. The uniformity of pattern size and pattern spacing suggests reproducible positioning of material is provided by piezoelectric inkjet printing (Fig. 2). The Vetbond tissue FIGURE 2 Optical micrograph ofVetbond n-butyl cyanoacrylate tissue adhe- sive inkjetted into an array pattern on a silicon substrate. Reprinted from I17| with permission. Downloaded By. llnfntrievel At 1|? :4 15 March 2010 s A. Doroiswamy 2! 211. FIGURE 3 2.8 X 2.8 pm topographic image of Vetbond n-butyl cyanoacrylate tissue adhesive inkjetted on a silicon substrate. (left) Z-scale of 400 nm and (right) phase image are shown. adhesive produced reproducible features in commercial as-prepared form. This result indicates that piezoelectric inkjet printing may be directly used with conventional cyanoacrylate adhesives. Figure 3 contains atomic force micrographs of Vetbond tissue adhesive inkjetted in a thin film on a silicon (111) wafer. The micrographs revealed the presence of randomly oriented 2-3 pm globular struc- tures. The average surface roughness (S3) over the 20-um scan-range was shown to be 0,117iim; a root mean square (Sq) of 0.180 iim was observed. Figure 4(a) contains the average modulus of Vetbond tissue adhesive up to an indentation depth of 500 nm. Figure 4(b) contains the average hardness of Vetbond tissue adhesive up to an indentation depth of 500 nm. The elastic modulus values for inkjetted Vetbond tis- sue adhesive are significantly higher than Young's modulus values for 2-hydroxyethyl methacrylate and methacrylic acid obtained by micro- indentation testing (50-60 kPa) or by tensile testing (255 kPa) [20,21]. Differences in mechanical property values for these materials may result from differences in composition and viscoelastic behavior of the polymer. Figure 5 contains a graph illustrating MTT viability of HAAE-1 vascular endothelial cells for Vetbond tissue adhesive and media (control). Vetbond tissue adhesive showed lower viability than the control material. Chen et al. demonstrated that methoxypropyl cyanoacrylate and N-butyl cyanoacrylate exhibit cytotoxicity toward cultured bovine corneal epithelial cells, corneal endothelial cells, and Downloaded lay. Iinfntrievel 2.: 10 :4 15 March 2010 Inhjel Prmlinp of Cyanoacrylate Adhesive 7 Modulus ts Indclllallon Depth 35 _ 3 A: Z 5 ‘f W Hll}mm:m....iIHl 3 K I ' * ’ i ’ :3 I5 2 I 0.5 0 0 I {)0 200 300 400 50“ (300 Imlcniailon I)cp|h (nm) (a) 0 1 Ilordllcss V5 linieunrnrii Dtplli ms E; 0.3 )3 9. ms h Em lm'"’“1|I-.......ri.... . . UJI5 0 I.) I0" 200 30" 400 SI)“ GUI) Iridcnidiion Dcpili (rim) (Ia) FIGURE 4 (a) Modulus vs. indentation depth of Vetbond n-butyl cyanoacry- late tissue adhesive. (b) Hardness vs. indentation depth of Vetbond n-butyl cyanoacrylate tissue adhesive. Data represented as mean i standard deviation. keratinocytes [22]. The toxicity of cyanoacrylate adhesives is attribu- ted to the spontaneous degradation of this material into formaldehyde and cyanoacetate compounds; in particular, the release of formalde- hyde may contribute to in vitru and in viva cell toxicity [23,24]. In vitro kinetics studies by Leonard et al. demonstrated that N-butyl cyanoa- crylate undergoes hydrolytic degradation at a relatively slow rate, which facilitates metabolism of cyanoacrylate degradation products by the surrounding tissues [25]. The degradation rate and toxicity of cyanoacrylate polymers can be reduced by increasing the length of the alkyl chain [26]. Inkjet printing and other novel micropatterning techniques may simultaneously improve the accuracy of cynaoacrylate Downloaded lay. Iinfntrievel 2.: 10 :4 is March 2010 s A. Doroiswamy 2! 211. I20- I00 80 to 40 HAAE-I Percentage Viah ty :0 0 . Vetbond Media FIGURE 5 M'1'I‘ viability of HAAE-1 vascular endothelial cells on Vetbond n-butyl cyanoacrylate tissue adhesive and media (control). Data represented as mean 1 standard deviation. use, reduce the amount of cyanoacrylate used in surgery, and decrease cytotoxicity [27]. CONCLUSIONS Current methods for applying adhesives during microvascular surgery are considered to be rudimentary. We have demonstrated piezoelectric ink-jetting as a powerful, non-contact, and non-destructive technique for rapid prototyping of surgical sealants and biological adhesives for future clinical applications. Only sufficient material to form a seal will be introduced to the lesion site. As a result, toxicity may be mini- mized, bond lines between tissues may be reduced, and improved bond strengths may be realized. Piezoelectric jetting may overcome many of the problems associated with conventional tissue bonding materials and methods. We envision that this technique may be used to improve wound repair in microvascular surgery as well as in ophthalmic and orthopedic surgery. REFERENCES |1| Chow, s. P., Mtcmsurg. 4, 5-9 (1933). [2] Green,A R , MiIIing,M A, P., and Green,A. R. T., Br. .1. Plastic slug as, 435445 (1985). Downloaded By. Ilnfncxievel At 10 34 is March 2010 Inkjez Prmlinp of Cyanoacrylate Adhesive 9 [31 Wadstrom, J. and Wik, 0., Scand. (1993) [4] Han, s. K., Kim, s. W., and Kim, w. K., Microsurg. 13, 30&311 (1995). [51 ousterhout, D. K, Johnston, E, H, and Leonard, F‘, .1, Surg. Res. 10, 213-219 (1970). [61 Bhaskar, s. N., Frisch, J., Margetis, P. M., and Leonard, F, Ural Sltrg., Oral Med, Oral Path. 22, 526-535 (1966). [7] Collins, .1. A., James, R. M., Levitsky, s. A., Brandenburg, c. E., Anderson, R. W., Leonard, F, and I-Iardaway, R, M, Surg. 65, 260-263 (1969), [81 Matsumoto, M. '1', Pani, K. c., Hardaway, R. M., Leonard, 17, and I-Ieisterkamp, c. A., Arch. Surg. 94, 157-139 (1967). [91 Matsumoto, T., Hardaway, R. M., Heisterkamp, c. A., Pani, K. c., Leonard, F, and Margetis, P. M., Arch. Surg, 94, 855-860 (1967). [101 Matsumoto, T., Pani, K. (1., Hardaway, R. M., Leonard, r, Jenning, P. 13., and Heisterkamp, c. A., Arch. Surg. 94, 392-395 (1967). [11] Matsumoto, T., Fani, K. c., Hardaway, R. M., Jennings, P. 13, Teschan, P. 13, and Leonard, F, Arrh. Surg. 94, 355491 (1967). [121 Saba, 13., Yilmaz, M., Yavuz, H., Noyan, s., Avci, 13., Ercan, A., Ozkan, H., and Cengiz, M Eur. Surg. Res. 99, 239-244 (2007). 1131 Velat, G. J. Reavey-Cantwell, J. Sistrom, c , Smullen, D., Fautheree, G. L., Whiting, J., Lewis, s. B, Mericle, R. A, Firment, c. s., and Hon, B. L., Neurusurg, ea, ONS75—ONS82 (2008) [14] Bastiaaansc, J., Borst, C., van dcr Helm, Y. J. M, Lon, K. H. 11., and Grucndcman, P F, Amt. Tlmmc. Sing. 70, 1354-1355 (2000), See PMID 11051903. 1151 Sumerel, J., Lewis, J., Doraiswamy, A, Deravi, L. 1-‘, Sewell, s, L., Gerdon, A. E, Wright, D. W., and Narayan, R. J., Biotcchnol. .1. 1, 97t"»9s7 (2006). See D01 10.1002/hiot.200600123. [16] Dora1swamy,A., Dunaway, '1'. M., Wilker, J J., and Narayan, R, J,J. Biomed Mater. Res, 3 16712312 (2005), [171 Doraiswamy, A, Sumerel, J., Wllker, J, and Narayan, R, J., Inkjet printing of biomedical adhesives, in Biosurfuces and Bmtnterfocex, M. Firestone, J. Schmidt, and N Malmstadt (Eds.) (Mater. Res. Soc. symp. Proc. 95013, Warrendale, PA, 2007), 0950-D12—05. See http://www.mrs.org/s_mrs/sec_subscribe.asp'?—CID=B85& I')ID=198043&nctio etail. [15] Wilson, D. J., Chcnery, D. H., Btiwring, H. K, Wilson, K., Turner, R., Maughan, .1, West, P. J., and Ansell, c. w. G.,J. Biomuter. Sci. PolymerEdn. 16, 449-472 (2005). See 1101 1163/156B56205370200. [191 Mossman, T., J Immunol. Math. 65, 55-63 (1983). [201 Lee, 5. J., Bnurnc, G. R., Chen, x, Sawyer, w. o., and Sartintiranont, M, Acta Biomaler. 4, 1560-1563 (2005). 1211 Enns, J. B, P702. 1996 54:1) Artnu. Tech. Cam’. 3, 2552-2556 (1995). [22] Chen, W. L., Lin, c. '1‘, I-Isieh, c. Y., Tu, 1. 1-1, Chen, w. Y. W., and Ho, F. R, Cornea 26, 122tL1234 (2007). [23] Leggat, P. A smith, D. R., and Kedjarune U., ANZ J. Surg. 77, 209-213 (2007). 1241 Toriumi, D. M. and 0'Cvi'ady, K, Otolalyngol. Clm. N. Am. 27, 203-209 (1994). See PMID 5159422, [251 Leonard, F, Kulkarni, R. K., Brandes, G., Nelson, J., and Cameron, J. J., J. Appl. Polymer Sol. 10, 259-272 (1966). I261 Mueller, R. H, Lherm, c., Herbert, J, and Cuuvreur, P,,B)omI1tzrials 11, 590-595 (1990). See D01 10.1016/0142-9612(90)90o54-4. [271 Wessels, 1. F. and McNeill, J. 1., Ophthalmic sure. 20, 211-214 (1999). See PMID 5159422. . Plast. Recnnstr. Sltrg. Hand Surg. 27, 257-261