Abstract
Biocompatibility is important to assure a mild body reaction to an implanted device and its long-term stability and functionality. In diabetes research, subcutaneously implanted glucose monitoring systems need biocompatible surfaces for long-term application. The biocompatibility of poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (MPC), a material similar to the phospholipid layer of a cell membrane, was compared in vivo with the biocompatibility of polyurethane (PU), polyvinyl alcohol (PVA), and cuprophane (CUP). Needle-type glucose sensors and hollow-fiber probes used for microdialysis were coated with these four different biomaterials and implanted subcutaneously in 18 rats and 7 healthy volunteers. At set intervals, the implants and, in the case of the rats, also the surrounding tissue were removed and characterized by light and electron microscopy. MPC-coated sensors and hollow-fiber probes showed smooth and thin deposits in flat layers, whereas the surface deposits on PU- and PVA-coated sensors and those on CUP hollow-fiber probes appeared as rough, irregular, and dense attachments of aggregated cells and protein. This study confirmed results from earlier in vitro tests by showing the biocompatibility and reliability of MPC. Even though the amount of protein and cells attached to the MPC surface was not as low as expected from in vitro experiments, the biocompatibility and long-term stability of the implanted devices were superior to those of PU, PVA, and CUP.
Similar content being viewed by others
References
Shichiri M, Kishikawa H, Sakakida M, Kajiwara K, Hashiguchi Y, Nishida K, Uemura T, Konno Y, Ichinose K. Artificial endocrine pancreas and optimal blood glucose regulation in diabetic patients —from bedside-type to wearable-type. Diabetes Res Clini Pract 1994;24:S251-S259
Shichiri M, Sakakida M, Nishida K, Shimoda S, Konno Y, Miyata T. Wearable-type artificial endocrine pancreas and optimal blood glucose regulation in diabetic patients. Diabet Rec Int 1995;4:10–14
Shichiri M, Kawamori R, Yamasaki Y, Hakui N, Abe H. Wearable artificial endocrine pancreas with needle-type glucose sensor. Lancet 1982;2:1129–1131
Hashiguchi Y, Sakakida M, Nishida K, Uemura T, Kajiwara K, Shichiri M. Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Diabet Care 1994;17:387–396
Woodward SC, Salthouse TN. The tissue response to implants and its evaluation by light microscopy. In: Von Recum AF (ed) Handbook of biomaterials evaluation. New York: Macmillan, 1986;364–378
Ishihara K. Novel polymeric material for obtaining blood-compatible surfaces. Trends Polym Sci 1997;5:401–407
Ishihara K, Shibata N, Tanaka S, Iwasaki Y, Kurosaki T, Nakabayashi N. Improved blood compatibility of segmented polyurethane by polymeric additives having phospholipid polar group. II. Dispersion state of the polymeric additive and protein adsorption on the surface. J Biomed Mater Res 1996;32:401–408
Zhang S, Benmakroha Y, Rolfe P, Tanaka S, Ishihara K. Development of a haemocompatible pO2 sensor with phospholipid-based copolymer membrane. Biosensors Bioelectronics 1996;11:1019–1029
Yu J, Lamba NMK, Courtney JM, Whateley TL, Gaylor JDS, Lowe GDO, Ishihara K, Nakabayashi N. Polymeric biomaterials: influence of phosphorylcholine polar groups on protein adsorption and complement activation. Int J Artif Organs 1994;17:499–504
Nishida K, Sakakida M, Ichinose K, Uemura T, Uehara M, Kajiwara K, Miyata T, Shichiri M, Ishihara K, Nakabayashi N. Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate. Med Prog Technol 1995;21:91–103
Ishihara K, Miyazaki H, Kurosaki T, Nakabayashi N. Improvement of blood compatibility on cellulose dialysis membrane. III. Synthesis and performance of water-soluble cellulose grafted with phospholipid polymer as coating material on cellulose dialysis membrane. J Biomed Mater Res 1995;29:181–188
Ishihara K, Nakabayashi N. Hemocompatible cellulose dialysis membranes modified with phospholipid polymers. Artif Organs 1995;19:1215–1221
Ishihara K, Ueda T, Nakabayashi N. Preparation of phospholipid polymers and their properties as polymer hydrogel membranes. Polym J 1990;22:355–360
Shichiri M, Sakakida M, Nishida K, Shimoda S. Enhanced, simplified glucose sensors long-term clinical application of wearable artificial endocrine pancreas. Artif Organs 1998;22:32–42
Karnovsky MJ. A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol 1965;27: 137A-138A
Ishihara K, Tanaka S, Furukawa N, Kurita K, Nakabayashi N. Improved blood compatibility of segmented polyurethane by polymeric additives having phospholipid polar groups. I. Molecular design of polymeric additives and their function. J Biomed Mater Res 1996;32:391–399
DeFife KM, Yun JK, Azeez A, Stack S, Ishihara K, Nakabayashi N, Colton E, Anderson JM. Adhesion and cytokine production by monocytes on poly(2-methacryloyloxyethyl phosphorylcholineco-alkyl methacrylate)-coated polymers. J Biomed Mater Res 1995;29:431–439
Ueda T, Oshida H, Kurita K, Ishihara K, Nakabayashi N. Preparation of 2-methacryloyloxyethyl phosphorylcholine copolymers with alkyl methacrylates and their blood compatibility. Polym J 1992;24:1259–1269
Ishihara K. Blood compatible polymers. In: Tsuruta T, Hayashi T, Ishihara K, Kataoka K, Kimura Y (eds) Biomedical applications of polymeric materials. Boca Raton: CRC, 1993;89–115
Ishihara K, Fukumoto K, Miyazaki H, Nakabayashi N. Improvement of hemocompatibility on a cellulose dialysis membrane with a novel biomedical polymer having a phospholipid polar group. Artif Organs 1994;18:559–564
Reach G, Wilson GS. Can continuous glucose monitoring be used for the treatment of diabetes? Anal Chem 1992;64:381A-386A
Mirzadeh H, Katbab AA, Khorasani M T, Burford E, Gorgin E, Golestani A. Cell attachment to laser-induced Aam- and HEMA-grafted ethylene-propylene rubber as biomaterial: in vivo study. Biomaterials 1995;16:641–648
Iwasaki Y, Mikami A, Kurita K, Yui N, Ishihara K, Nakabayashi N. Reduction of surface-induced platelet activation on phospholipid polymer. J Biomed Mater Res 1997;36:508–515
Shichiri M, Fukushima H, Yamaguchi K, Kawamori R, Yamasaki Y, Ueda N, Kamada T. Membrane design for extending the longlife of an implantable glucose sensor. Diabet Nutr Metab 1989;2:309–313
Burczak K, Gamian E, Kochman A. Long-term in vivo performance and biocompability of poly(vinyl alcohol) hydrogel macrocapsules for hybrid-type artificial pancreas. Biomaterials 1996;17:2351–2356
Williams DF. Biomaterials and biocompatibility. Med Progr Technol 1976;4:31–42
Reach G, Wilson GS. Can continuous glucose monitoring be used for the treatment of diabetes? Anal Chem 1992;64:381–386
Hall B, Bird RR, Kojima M, Chapman D. Biomembranes as models for polymer surfaces. V. Thrombelastographic studies of polymeric lipids and polyesters. Biomaterials 1989;10:219–224
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nowak, T., Nishida, K., Shimoda, S. et al. Biocompatibility of MPC: in vivo evaluation for clinical application. J Artif Organs 3, 39–46 (2000). https://doi.org/10.1007/BF02479925
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02479925