Original Article
Characterization of poly(L-glutamic acid)-grafted hyaluronan as a novel candidate medicine and biomedical device for intra-articular injection
Kazuaki Muramatsu,
Yuya Tajima,
Rin Kaneko,
Yuta Yanagita,
Hiroyuki Hirai,
Nana Hiura,
Corresponding Author
Kazuaki Muramatsu
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Correspondence to: Kazuaki Muramatsu; e-mail: [email protected]Search for more papers by this authorYuya Tajima
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorRin Kaneko
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorYuta Yanagita
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorHiroyuki Hirai
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorNana Hiura
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorKazuaki Muramatsu,
Yuya Tajima,
Rin Kaneko,
Yuta Yanagita,
Hiroyuki Hirai,
Nana Hiura,
Corresponding Author
Kazuaki Muramatsu
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Correspondence to: Kazuaki Muramatsu; e-mail: [email protected]Search for more papers by this authorYuya Tajima
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorRin Kaneko
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorYuta Yanagita
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorHiroyuki Hirai
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorNana Hiura
Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University, Ishizaka, Hatoyama-cho, Hiki-gun, Saitama, 350-0394 Japan
Search for more papers by this authorAbstract
A novel hyaluronan (HA) derivative, poly(L-glutamic acid)-grafted hyaluronan (PGA-g-HA), was synthesized to improve the durability of conventional HA products for intra-articular injection. The purpose of this study was to investigate the characteristics of the novel HA derivative in terms of viscoelasticity, degradation behavior, non-immunogenicity, and bioactivity using preliminary in vitro and in vivo experiments. The storage modulus (G′) and loss modulus (G″) of PGA-g-HA were similar to those of HA80 (approximately 8.0 × 105 Da) rather than those of original HA200 (approximately 2.0 × 106 Da). PGA-g-HA showed strong resistance against hyaluronidase hydrolysis compared to unmodified HA200. The immunogenicity resulting from grafting PGA to HA200 was not detected in bone marrow derived dendritic cells. The anti-inflammatory activity of PGA-g-HA was confirmed in IL-1β-stimulated chondrocytes. In addition, compared to unmodified HA200, the intra-articular injection of PGA-g-HA produced greater chondroprotective effects on a monoiodoacetic acid-induced model of rat knee osteoarthritis at two weeks after a single treatment. Therefore, PGA-g-HA is expected to be a promising medicine and biomedical device for intra-articular injection. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3006–3016, 2017.
REFERENCES
- 1Weissman B, Meyer K. The structure of hyalobiuronic acid and of hyaluronic acid from umbilical cord. J Am Chem Soc 1954; 76: 1753–1757.
- 2Kawasaki K, Ochi M, Uchio Y, Adachi N, Matsusaki M. Hyaluronic acid enhances proliferation and chondroitin sulfate synthesis in cultured chondrocytes embedded in collagen gels. J Cell Physiol 1999; 179: 142–148.
10.1002/(SICI)1097-4652(199905)179:2<142::AID-JCP4>3.0.CO;2-Q CAS PubMed Web of Science® Google Scholar
- 3Andhare RA, Takahashi N, Knudson W, Knudson CB. Hyaluronan promotes the chondrocyte response to BMP-7. Osteoarthritis Cartilage 2009; 17: 906–916.
- 4Yatabe T, Mochizuki S, Takizawa M, Chijiiwa M, Okada A, Kimura T, Fujita Y, Matsumoto H, Toyama Y, Okada Y. Hyaluronan inhibits expression of ADAMTS4 (Aggrecanase-1) in human osteoarthritic chondrocytes. Ann Rheum Dis 2009; 68: 1051–1058.
- 5Hashizume M, Mihara M. High molecular weight hyaluronic acid inhibits IL-6-induced MMP production from human chondrocytes by up-regulating the ERK inhibitor, MKP-1. Biochem Biophys Res Commun 2010; 403: 184–189.
- 6Julovi SM, Ito H, Nishitani K, Jackson CJ, Nakamura T. Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. J Orthop Res 2011; 29: 258–264.
- 7Kataoka Y, Ariyoshi W, Okinaga T, Kaneuji T, Mitsugi S, Takahashi T, Nishihara T. Mechanisms involved in suppression of ADAMTS4 expression in synoviocytes by high molecular weight hyaluronic acid. Biochem Biophys Res Commun 2013; 432: 580–585.
- 8Ichimaru S, Nakagawa S, Arai Y, Kishida T, Shin-Ya M, Honjo K, Tsuchida S, Inoue H, Fujiwara H, Shimomura S, Mazda O, Kubo T. Hypoxia potentiates anabolic effects of exogenous hyaluronic acid in rat articular cartilage. Int J Mol Sci 2016; 17: E1013.
- 9Harada M, Uzuki M, Ishiguro N, Iwadate K, Sawai T. Mechanism of the protective effect of high molecular weight hyaluronic acid against cartilage degeneration. Clin Rheumatol 2015; 27: 51–63.
- 10Campo GM, Avenoso A, Campo S, D'Ascola A, Traina P, Rugolo CA, Calatroni A. Differential effect of molecular mass hyaluronan on lipopolysaccharide-induced damage in chondrocytes. Innate Immunity 2010; 16: 48–63.
- 11Sato H, Takahashi T, Ide H, Fukushima T, Tabata N, Sekine F, Kobayashi K, Negishi M, Niwa Y. Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Arthritis Rheum 1988; 31: 63–71.
- 12Stafford CT, Niedermeier W, Holley HI, Pigman W. Studies on the concentration and intrinsic viscosity of hyaluronic acid in synovial fluids of patients with rheumatic diseases. Ann Rheum Dis 1964; 23: 152–157.
- 13Dahl LB, Dahl LMS, Engstrom-Laurent A, Granath K. Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 1985; 44: 817–822.
- 14Watterson JR, Esdaile JM. Viscosupplementation: Therapeutic mechanisms and clinical potential in osteoarthritis of the knee. J Am Acad Orthop Surg 2000; 8: 277–284.
- 15 American Academy of Orthopaedic Surgery. We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee. OrthoGuidelines, Treatments of osteoarthritis of the knee (2nd edition), http://www.orthoguidelines.org/guideline-detail?id=1214, May 18, 2013.
- 16Richette P, Chevalier X, Ea HK, Eymard F, Henrotin Y, Ornetti P, Sellam J, Cucherat M, Marty M. Hyaluronan for knee osteoarthritis: an updated meta-analysis of trials with low risk of bias. RMD Open 2015; 1: e000071.
- 17Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum 2016; 45: S28–S33.
- 18Necas J, Bartosikova L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan): a review. Vet Med 2008; 53: 397–411.
- 19Gigante A, Callegari L. The role of intra-articular hyaluronan (Sinovial) in the treatment of osteoarthritis. Rheumatol Int 2011; 31: 427–444.
- 20Chareancholvanich K, Pornrattanamaneewong C, Narkbunnam R. Increased cartilage volume after injection of hyaluronic acid in osteoarthritis knee patients who underwent high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 2014; 22: 1415–1423.
- 21Ayhan E, Kesmezacar H, Akgun I. Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. Would J Orthop 2014; 5: 351–361.
- 22Roos J, Epaulard O, Juvin R, Chen C, Pavese P, Brion JP. Acute pseudoseptic arthritis after intraarticular sodium hyaluronan. Joint Bone Spine 2004; 71: 352–354.
- 23Stern R. Hyaluronan catabolism: a new metabolic pathway. Eur J Cell Biol 2004; 83: 317–325.
- 24Elmorsy S, Funakoshi T, Sasazawa F, Todoh M, Tadano S, Iwasaki N. Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model. Osteoarthritis Cartilage 2014; 22: 121–127.
- 25Ghosh P, Guidolin D. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: Are the effects molecular weight dependent? Semin Arthrit Rheum 2002; 32: 10–37.
- 26Schiavinato A, Finesso M, Cortivo R, Abatangelo G. Comparison of the effects of intra-articular injections of hyaluronan and its chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee joints. Clin Exp Rheumatol 2002; 20: 445–454.
- 27Michou L, Job-Deslandre C, de Pinieux G, Kahan A. Granulomatous synovitis after intraarticular Hyaln GF-20. A report of two ceases. Joint Bone Spine 2004; 71: 438–440.
- 28Marino AA, Waddell DD, Kolomytkin OV, Pruett S, Sadasivan KK, Albright JA. Assessment of immunologic mechanisms for flare reactions to Synvisc. Clin Orthop Relat Res 2006; 442: 187–194.
- 29Finelli I, Chiessi E, Galesso D, Renier D, Paradossi G. Gel-like structure of a hexadecyl derivative of hyaluronic acid for the treatment of osteoarthritis. Macromol Biosci 2009; 9: 646–653.
- 30Finelli I, Chiessi E, Galesso D, Renier D, Paradossi G. A new viscosupplement based on partially hydrophobic hyaluronic acid: A comparative study. Biorheology 2011; 48: 263–275.
- 31Smith MM, Russell AK, Schiavinato A, Little CB. A hexadecylamide derivative of hyaluronan (HYMOVIS) has superior beneficial effects on human osteoarthritic chondrocytes and synoviocytes than unmodified hyaluronan. J Inflamm 2013; 10: 26.
- 32Pavan M, Galesso D, Menon G, Renier R, Guarise C. Hyaluronan derivatives: Alkyl chain length boosts viscoelastic behavior to depolymerization. Carbohydr Polym 2013; 97: 321–326.
- 33Oliviero F, Scanu A, Ramonda R, Frallonardo P, Sfriso P, Dayer JM, Punzi L. IL-1β and IL-8 are scavenged by the hexadecylamide derivative of hyaluronic acid: A new mechanism. J Biomed Mater Res Part A 2015; 103A: 2823–2829.
- 34Antunes JC, Tsaryk R, Goncalves RM, Pereira CL, Landes C, Brochhausen C, Ghanaati S, Barbosa MA, Kirkpatrick CJ. Poly(γ-glutamic acid) as an exogenous promoter of chondrogenic differentiation of human mesenchymal stem/stromal cells. Tissue Eng Part A 2015; 21: 1869–1885.
- 35Grauer O, Wohlleben G, Seubert S, Weishaupt A, Kampgen E, Gold R. Analysis of maturation states of rat bone-marrow-derived dendritic cells using an improved culture technique. Histochem Cell Biol 2002; 117: 351–362.
- 36Nicolas A, Cathelin D, Larmonier N, Fraszczak J, Puig PE, Bouchot A, Bateman A, Solary E, Bonnotte B. Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. J Immunol 2007; 179: 812–818.
- 37O'Flynn L, Treacy O, Ryan AE, Morcos M, Cregg M, Gerlach J, Joshi L, Nosov M, Ritter T. Donor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu. Mol Ther 2013; 21: 2102–2112.
- 38Muramatsu K, Ide M, Miyawaki F. Biological evaluation of tissue-engineered cartilage using thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan. J Biomat Nanobiotech 2012; 3: 1–9.
- 39Kobayashi K, Imaizumi R, Sumichika H, Tanaka H, Goda M, Fukunari A, Komatsu H. Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats. J Vet Med Sci 2003; 65: 1195–1199.
- 40van Buul CM, Siebelt M, Leijs MJC, Bos PK, Waarsing JH, Kops N, Weinans H, Verhaar JAV, Bernsen MR, van Osch GJVM. Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis. J Orthop Res 2014; 32: 1167–1174.
- 41Moilanen LJ, Hamalainen M, Nummenmaa E, Ilmarinen P, Vuolteenaho K, Nieminen RM, Lehtimaki L, Moilanen E. Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice – potential role of TRPA1 in osteoarthritis. Osteoarthritis Cartilage 2015; 23: 2017–2026.
- 42Haxaire K, Marechal Y, Milas M, Rinaudo M. Hydration of polysaccharide hyaluronan observed by IR spectrometry. I. Preliminary experiments and band assignments. Biopolymers (Biospectroscopy) 2003; 72: 10–20.
- 43Bezakova Z, Hermannova M, Drimalova E, Malovikova A, Ebringerova A, Velebny V. Effect of microwave irradiation on the molecular and structural properties of hyaluronan. Carbohydr Polym 2008; 73: 640–646.
- 44Fuente M, Seijo B, Alonso MJ. Novel hyaluronan-based nanocarriers for transmucosal delivery of macromolecules. Macromol Biosci 2008; 8: 441–450.
- 45Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2006; 2: CD005321.
- 46Frizziero A, Maffulli N, Masiero S, Frizziero L. Six-months pain relief and functional recovery after intra-articular injections with hyaluronic acid (mw 500–730 KDa) in trapeziometacarpal osteoarthritis. Muscles Ligaments Tendons J 2014; 4: 256–261.
- 47Pavelka K, Uebelhart D. Efficacy evaluation of highly purified intra-articular hyaluronic acid (SinovialⓇ) vs hylan G-F20 (SynviscⓇ) in the treatment of symptomatic knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non-inferiority study. Osteoarthritis Cartilage 2011; 19: 1294–1300.
- 48Mihara M, Higo S, Uchiyama Y, Tanabe K, Saito K. Different effects of high molecular weight sodium hyaluronate and NSAID on the progression of the cartilage degeneration in rabbit OA model. Osteoarthritis Cartilage 2007; 15: 543–549.
- 49Dasa V, Dekoven M, Sun K, Allan S, Sooyeol L. Clinical and cost outcomes from different hyaluronic acid treatments in patients with knee osteoarthritis from a US health plan claims database. Drugs Context 2016; 5: 212296.
- 50Kikuchi T, Yamada H, Shimmei M. Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis. Osteoarthritis Cartilage 1996; 4: 99–110.
- 51Kwiecinski JJ, Dorosz SG, Ludwig TE, Abubacker S, Cowman MK, Schmidt TA. The effect of molecular weight on hyalronan's cartilage boundary lubricating ability — alone and in combination with proteoglycan 4. Osteoarthritis Cartilage 2011; 19: 1356–1362.
- 52Gloria A, Borzacchiello A, Causa F, Ambrosio L. Rheological characterization of hyaluronic acid derivatives as injectable materials toward nucleus pulposus regeneration. J Biomater Appl 2012; 26: 745–759.
- 53Scott JE, Cummings C, Brass A, Chen Y. Secondary and tertiary structures of hyaluronan in aqueous solution, investigated by rotary shadowing-electron microscopy and computer simulation. Hyaluronan is a very efficient network-forming polymer. Biochem J 1991; 274: 699–705.
- 54Scott JE, Heatley F. Hyaluronan forms specific stable tertiary structures in aqueous solution: A 13C NMR study. Proc Natl Acad Sci USA 1999; 96: 4850–4855.
- 55Muramatsu K. Manufacturing method of modified hyaluronic acids and/or its salts. Japanese Patent, JP2016–141697A.
- 56Umeda T, Miyoshi T, Onuki Y, Manabw T, Komatsu S, Hayashi T, Matsumura G. A retention test after dingle intra-articular administration of high molecular weight sodium hyaluronate (NRD101) into the rabbit knee. Jpn Pharmacol Ther 1994; 22: S779–S785.
- 57Hsieh CS, Heimberger AB, Gold JS, O'Garr A. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an αβ T-cell-receptor transgenic system. Proc Natl Acad Sci USA 1992; 89: 6065–6069.
- 58Germann T, Gately MK, Schoenhaut DS, Lohoff M, Mattner F, Fischer S, Jin SC, Schmitt E, Rude E. Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells. Eur J Immunol 1993; 23: 1762–1770.
- 59de Jong EC, Smits HH, Kapsenberg ML. Dendritic cell-mediated T cell polarization. Springer Semin Immuno 2005; 26: 289–307.
- 60Levings MK, Sangregorio R, Galbiati F, Squadrone S, de WaalMalefyt R, Roncarolo MG. IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 2001; 166: 5530–5539.
- 61Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001; 2: 261–268.
- 62Park J, Babensee JE. Differential function effects of biomaterials on dendritic cell maturation. Acta Biomaterialia 2012; 8: 3606–3617.
- 63Peach RJ, Hollenbaugh D, Stamenkovic I, Aruffo A. Identification of hyaluronic acid binding sites in extracellular domain of CD44. J Cell Biol 1993; 122: 257–264.
- 64Bajorath J, Greenfield B, Munro SB, Day AJ, Aruffo A. Identification of CD44 residues important for hyaluronan binding and delineation of the binding site. J Biol Chem 1998; 273: 338–343.
- 65Sung MH, Park C, Choi JC, Uyama H, Park SL. Hyaluronidase inhibitor containing poly-gamma glutamic acid as an effective component. United States Patent, US8916141B2.
- 66Benazzo F, Perticarini L, Padolino A, Castelli A, Gifuni P, Lovato M, Manzini C, Giordan N. A multi-center, open label, long-term follow-up study to evaluate the benefits of a new viscoelastic hydrogel (HymovisR) in the treatment of knee osteoarthritis. Eur Rev Med Pharmacol Sci 2016; 20: 959–968.
- 67Yoshioka K, Yasuda Y, Kisukeda T, Nodera R, Tanaka Y, Miyamoto K. Pharmacological effects of novel cross-linked hyaluronate, Gel-200, in experimental animal models of osteoarthritis and human cell lines. Osteoarthritis Cartilage 2014; 22: 879–887.
- 68Ishikawa M, Yoshioka K, Urano K, Tanaka Y, Hatanaka T, Nii A. Biocompatibility of cross-linked hyaluronate (Gel-200) for the treatment of knee osteoarthritis. Osteoarthritis Cartilage 2014; 22: 1902–1909.
Citing Literature
