Doku Mühendisliğinde Kitozanın Kullanım Alanları

Doku mühendisliği günümüzde ve gelecekte tıbbın en önemli tedavi stratejisini oluşturacaktır. Günümüzde rejeneratif tıpta süregelen araştırmaların çoğu doku mühendisliğinde biyomateryallerle oluşturulan destek ve yapı malzemesinin scaffold geliştirilmesi üzerinedir. Bir biyomateryal olan kitozanın doğal bir polimer olması, gözenkli bir yapıya sahip oluşu, kimyasal modifikasyonlara uygunluğu, jel formunda kullanılabilirlik özelliği, biyouyumlu olması ve metabolitlerinin toksik olmaması; doku mühendisliğinde ilgi odağı olmuştur. Kitin ve kitozan türevi bileşiklerin, biyomateryal olarak çok çeşitli alanlarda kullanıldığı bilinmektedir. Kitozan türevlerinin hücre uyumlu oluşu ve lizozimler tarafından yıkılabilmesi bu alanda kullanımını oldukça arttırmaktadır. Yapılan çalışmalarda kitozanın in vitro kültür ortamlarında dokuların büyüme hızı ve doku tabakalanması üzerine olumlu bir etkisi olduğu gösterilmiştir. Kitozanın, dokuların matriks içeriğinde bulunan glikozaminoglikanlara benzerliği nedeniyle bağ dokusu tamirinde ve organogeneziste oldukça uygun bir biyomateryal olduğu belirtilmektedir. In vivo çalışmalarda da kitozanın deri fibroblastlarında sayısal bir artışa neden olduğu gösterilmiştir. Kitozanın membran formu değişik doku kültürlerinde hücre tutunması ve hücreye penetrasyonu üzerine olumlu bir etkiye sahiptir. Kitozanın doku mühendisliğindeki önemli derecedeki mitojenik aktivitesinin yüksek oranda deasetile olabilmesine bağlanmaktadır. Organik bir biyomateryal olan kitozanın güncelliğini önemli derecede koruması kuvvetli ölçüde şartlara gore değiştirilebilen formuna dayanmaktadır

Application Fields of Chitosan In Tissue Engineering

Tissue engineering will provide the most therapeutical strategy of medicine currently and in future. Most of the current investigations concerning regenerative medicine involves development of supporting and structural materials scaffold . Chitosan, as a biomaterial, is a focus of interest in tissue engineering by presenting the following features such as being a natural polymer, having a porous structure, being reliable to chemical modifications, easy-to-use in gel form, being biocompatible, and crating non-toxic metabolites. Derivatives of chitin and chitosan are widely used as biomaterials in many fields. Being cell friendly and easy-to-be degraded by lysosomal activity results in its wide usage in bioengineering. Investigations pointed out its positive effect on tissue growth and tissue layering rates. Possesing a similarity to glycosaminoglycans in tissue matrix, chitosan is defined as a highly suitable biomaterial in connective tissue regenation and organogenesis. In vivo studies represented its effects on increasing number of skin fibroblasts. Membranous form of chitosan has a positive impact on the cellular attachment and penetration. Considerable mitogenic activity of chitosan in tissue engineering is related to its high degree of deacetylisation. Chitosan, as an organic biomaterial, is strongly preserving its current importance strongly based on its flexibility according to different conditions

Keywords:

chitosan tissue engineering, polymer,

PDF

___

Kim In-Yong, Seog-Jin Seo, Hyun-Seuk Moon, Mi-Kyong Yoo, In-Young Park,Bom-Chol. Kim, Chong-Su Cho: Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv, 2008; 26: 1-21.

Uslu B, Arbak S, Biltekin B, Denir S, Özbaş-Turan S, Akbuğa J, Bilir A. Farklı Kitozan Formlarının Fibroblast Hücre Aktivitesi Üzerine Proliferatif Etkisinin İn vitro Karşılaştırması, Marmara Üniversitesi Tıp Fakültesi Uzmanlık Tezi, 2008.

Wang YC, Lin MC: Fabrication of novel porous PGA-chitosan hybrid matrix for tissue engineering. Biomaterials, 2003; 24:1047-1057.

Çakar N. Primer Hücre Kültürü: Temel Hücre Kültürü Teknikleri Kursu Kitapçığı. Hacettepe Üniversitesi yayınları, 2006.

Kaş H S: Chitosan properties, preparations and application to microparticulate systems. J Microencapsul, 1997; 14: 689-711.

Güvercin M. Kitozanın yumuşak doku iyileşmesindeki etkisinin deneysel olarak incelenmesi ve hücre kültürü ile değerlendirilmesi, Doktora Tezi. Marmara Üniversitesi Diş Hekimliği Fakültesi Yayınları, 2004.

Vårum KM, Ottİy MH, Smidsrİd O: Acid hydrolysis of chitosans. Carbohyd Polym, 2001; 46: 89-98.

Okuyama K, Noguchi K, Kanenari M, Egawa T, Osawa K, Ogawa K: Structural diversity of chitosan and its complexes. Carbohyd Polym, 2000; 41: 237-247.

Bhatia SC, Ravi NA: Mossbauer Study of the interaction of chitosan and d-glucosamine with iron and relevance to other metalloenzymes. Biomacromolecules, 2003; 4: 723-727.

Şenel S, Mc Clure S J: Potential applications of chitosan in veterinary medicine. Advanced Drug Delivery Reviews, 2004; 56,10: 1467- 1480.

Kiyozumi T, Kanatani Y, Ishihara M, Saitoh D, Shimizu J, Yura H, Suzuki S, Okada Y, Kikuchi M: The effect of chitosan hydrogel containing DMEM/F medium on full-thickness skin defects after deep dermal burn. Burns, 2007; 33: 642-648.

Ding SJ: Biodegradation behavior of chitosan /calcium phosphate composites. Journal of Non-Crystalline Solids, 2007; 353: 24-25, 2367-2373.

Wafa IAF, Tao J, Gehan EB, Cato TL: Synthesis, characterization of chitosans and fabrication of sintered chitosan microspherematrices for bone tissue engineering. Acta Biomaterialia, 2007; 4: 503-514.

Cheng M, Deng J: Study on physical properties and nerve cell affinity of composite films from chitosan and gelatin solutions. Biomaterials, 2003; 24: 2871-2880.

Khor E, Lim LY: Implantable aplications of chitin and chitosan. Biomaterials, 2003; 24: 2339-2349.

Koide SS: Chitin-Chitosan: properties, benefits and risks. Nutrition Research, 1998; 18: 1091-1101.

Kurita K: Chemistry and application of chitin and chitosan. Polym Deg Stab, 1998; 59: 117-120.

Singla A K, Chawla M: Chitosan: some pharmaceutical and biological aspects – an update. J Pharm Pharmacol, 2001; 53: 1047-1067.

Chen M, Deng J: Study on physical properties and nerve cell affinity of composite films from chitosan and gelatin solutions. Biomaterials, 1998; 24: 2871-2880.

Kurita K: Chemistry and application of chitin and chitosan. Polym Deg Stab, 2001; 59: 117-120.

Akbuğa J, Aral C, Özbaş-Turan S, Kabasakal L, Keyer-Uysal M: Transfection efficiency of chitosan microspheres: effect of DNA topology. STP Pharm Sci, 2003; 13: 99-103.

Shigemasa Y, Minami S: Applications of chitin and chitosan for biomaterials. Biotechnol. Genet Eng Rev, 1998; 13: 383-420.

Akbuğa JA Biopolymer: Chitosan. Int J Pharm Adv, 1995; 1: 3-18.

Wang X, Ye J, Chen L, Wang Y: Microstructure and properties of a calcium phosphate cement tissue engineering scaffold modified with collagen and chitosan. Engineering Materials, 2007; 983-986.

Muzarelli R, Conti F, Ferrara P: Biological activity of chitosan: ultrastructural study. Biomaterials, 1988; 9: 247-252.

Yao F, Chen W, Wang H, Liu H, Yao K, Sun P, Lin H: A study on cytocompatible poly (chitosan-g-L-lactic acid). Polymer, 2003; 44: 6435-6441.

Wan Y, Wu H, Wen D: Porous-conductive chitosan scaffolds for tissue engineering: preperation and characterization. Macromol Biosci, 2004; 16: 882-890.

Stone CA, Wright H, Clarke T, Powell R, Devaraj V S: Healing skin graft donor sites dressed with chitosan. British Journal of Plastic Surgery, 2000; 53: 601-606.

Graeme IH, Dettmar PW, Goddard PA, Hampsor FC, Michael D, Edward J Wood: The effect of chitin and chitosan on the proliferation of human fibroblasts and keratinocytes in vitro. Biomaterials, 2001; 22: 2959-2966.

Poon YF, Zhu YB, Shen JY, Siu Choon Ng, Mary B, Chan-Park: Cytocompatible hydrogels based on photocrosslinkable methacrylated O-Carboxymethylchitosan with tunable charge: synthesis and characterization. Advanced Functional Materials, 2007; 17 (13): 2139-2150.

Shen JY, Pan XY, Lim CH, Chan-Park, Zhu X, Beuerman RW: Synthesis, Characterization, Photocuring Characteristics, In Vitro Degradation and Biocompatibility of Biodegradable Liquid Photocurable PCLLGA Copolymers. Biomacromolecules, 2007; (2): 376-385.

Fathke C, Wilson L, Hutter J, Kapoor V, Smith A, Hocking A, Isik F: Contribution of bone marrow derived cells to skin, collagen deposition and wound repair. Stem Cells, 2004; 22, 5: 812-822.

Mayumi M, Yuichi K, Yoko W, Kozue K: Laminin-1 peptide –conjugated chitosan membrans as a novel approach for cell engineering. The FASEB Journal, 2003; 17: 875-877.

Ueno H, Yamada H, Tanaka W, Kaba N, Matsuura M, Okumura M, Kadosawa T, Fujinaga T: Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials, 1999; 20: 1407-1414.

Illum L: Chitosan and its use as a pharmaceutical excipient. Pharm Res, 1998; 15: 1326-1331

Langer R: New methods of drug delivery. Science, 1990; 249: 1527-1533Cui W, Kim D H, Imamura M, Hyon SH, Inoue K: Tissue –engineered pancreatic islets, culturing rat islets in the chitosan sponge. Cell Transplant, 2001; 5: 499-502.

Khor E, Lim LY: Implantable aplications of chitin and chitosan. Biomaterials, 2003; 24: 2339-2349.

Shu XZ, Zhu KJ: Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm, 2002; 233: 217-225

Yin J , Song Z, Kun L, Zheng Y, Yan Y, Qiong L, Shifeng Y, Xuesi C. Buildup of L-b-L Multilayer Film Based on PGA and Chitosan for Biologically Active Coating. Macromolecular Bioscience 2009; 9: 268-278

Dureja H, Tiwary AK, Gupta S: Stimulation of skin permeability in chitosan membranes. Int J Pharm, 2001; 213: 193-198.

Thanou M, Verhoef JC, Junginger H E: Chitosan and its derivatives as intestinal absorption enhancers. Adv Drug Del Rev, 2001; 50: 91-101.

Mumper RJ, Wang JJ, Claspell JM, Rolland AP: Novel polymer condensing carriers for gene delivery. Proc. Int. Symp Control Rel Bioact Mater, 1995; 22: 178-179.

Aral C, Özbaş-Turan S, Kabasakal L, Keyer-Uysal M, Akbuğa J: Studies of effective factors of plasmid DNA-loaded chitosan microspheres I. plasmid size, chitosan concentration and plasmid addition techniques. STP Pharm Sci, 2000; 10: 83-88.

Kiyozumi T, Kanatani Y, Ishihara M, Saitoh D, Shimizu J, Yura H, Suzuki S, Okada Y, Kikuchi M: The effect of chitosan hydrogel containing DMEM/F medium on full-thickness skin defects after deep dermal burn. Burns, 2007; 33: 642-648.

Kong J, Qiang AO, XI J, Zang L, Gong YZ, Zhang X, Nan M: Proliferation and Differentiation of MC 3T3-E1 Cells Cultured on Nanohydroxyapatite/ chitosan Composite Scaffolds. Chinese Journal of Biotechnology, 2001; 23: 262-267.

Mori T, Okumora M, Matsuura M, Ueno K: Effects of chitin and its derivates on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials, 1997; 18: 947-951.

Malette WG, Quigley H, Gaines RD: Chitosan : A new hemostatic. Annals. Thorac Surg, 1983; 36; 55-58.

Wafa IAF, Tao J, Gehan EB, Cato TL: Synthesis, characterization of chitosans and fabrication of sintered chitosan microspherematrices for bone tissue engineering. Acta Biomaterialia, 2007; 4: 503-514.

Payne JM, Cobb CM, Rapley JW: Migration of human gingival fibroblasts over guided tissue regeneration barrier materials. J. Periodontology, 1996; 67: 236-244.

Chuang WY, Young TH, Yao CH: Properties of the poly (vinyl alcohol) / chitosan blend and its effect on the culture of fibroblast in vitro. Biomaterials, 1999; 20: 1479-1487.

Germershaus O, Mao S, Sitterberg J, Bakowsky U, Kissel T: Gene delivery using chitosan, trimethyl chitosan or polyethylenglycol-graft-trimethyl chitosan block copolymers: Establishment of structure-activity relationships in vitro. J Control Release 2008; 125:145-154.

Zahraoui C, Sharrock P: Influence of sterilization on injecktable bone biomaterials. Bone, 1999; 25(2): 63-65.

Yan YH, Cui J, Chan-Park MB, Wang X, Wu QY: Systematic studies of covalent functionalization of carbon nanotubes via argon plasma-assisted UV grafting. Nanotechnology, 2007; 11: 115-712.

Zhu Y, Mary B, Chan-Park MB: Density quantification of collagen grafted onto biodegradable polyester: its application to esophageal smooth muscle cell. Annal Biochem, 2007; 363: 119-127.