داربست هیدروژلی شبکه‌ای‌شده با باریکه الکترون از پلیمرهای طبیعی و سنتزی: سنتر و مشخصه‌یابی

نوع مقاله : پژوهشی

نویسندگان

1 یزد، دانشگاه آزاد اسلامی، واحد یزد، گروه مهندسی پزشکی، کد پستی 8915813135

2 یزد، دانشگاه یزد، گروه مهندسی شیمی و پلیمر، کد پستی 8915818411

3 تهران، دانشگاه تربیت مدرس، دانشکده مهندسی شیمی، گروه مهندسی زیست‌پزشکی، صندوق پستی 111-14115

چکیده

فرضیه: در سال‌های اخیر، به‌دلیل تشابه مشخصه‌های داربست‌های هیدروژلی با ماتریس برون‌یاخته‌ای بافت‌های مختلف، توجه به تهیه و ارزیابی آن‌ها در مهندسی بافت رشد فزاینده‌ای داشته است. از میان روش‌های مختلف تهیه هیدروژل، استفاده از تابش یوننده دارای چند برتری است، زیرا به واکنشگرهای شیمیایی نیاز ندارد و محصول می‌تواند به شکل نهایی تابش‌دهی‌شده و هم‌زمان با شبکه‌ای‌شدن با تابش‌دهی سترون‌ شود. در این پژوهش، اصلاح شیمیایی با گلیسیدیل‌متاکریلات و آمیخته‌سازی فیزیکی با پلی(‌وینیل ‌الکل) برای تهیه داربست‌های هیدروژلی بر پایه پلی‌ساکاریدها، کتیرا و کربوکسی‌متیل‌ کیتوسان به‌کمک تابش باریکه الکترون، ارزیابی شد. 
روش‌ها: برای تهیه داربست هیدروژلی، ابتدا پلیمرهای طبیعی کتیرا و کربوکسی‌متیل‌ کیتوسان با گلیسیدیل‌متاکریلات عامل‌دار شدند و در ادامه محلول‌های آمیخته‌ای پلیمرهای اصلاح‌شده و پلی(‌وینیل ‌الکل)، در معرض باریکه الکترون قرار گرفتند. سپس شکل‌شناسی، محتوای ژل، رفتار تورمی، استحکام فشاری، خواص رئولوژیکی و زیست‌سازگاری هیدروژل‌ها بررسی شد.
یافته‌ها: کتیرای عامل‌دارشده با گلیسیدیل‌متاکریلات و کربوکسی‌متیل ‌کیتوسان در محلول آبی و در معرض باریکه الکترون شبکه‌ای شدند. آمیخته‌سازی پلی‌(وینیل ‌الکل) با پلیمرهای اصلاح‌شده، موجب تشکیل شبکه پلیمری درهم‌نفوذی با استحکام فشاری، مدول ذخیره و مقدار تورم افزایش‌یافته شد. محتوای ژل هیدروژل‌ها بسته به دُز تابش‌دهی و ترکیب‌درصد پلیمرها در  حدوده %65 تا %98 متغیر بود. در آزمون‌های استحکام فشاری و رئولوژی، هیدروژل‌ها رفتار گران‌روکشسان و خاصیت بازیابی کشسانی مناسبی نشان دادند. استحکام فشاری هیدروژل‌های تولیدشده از آمیخته‌ فیزیکی پلیمرها در محدوده  1414kPa-1200بود. زنده‌مانی یاخته‌های مزانشیمی انسانی تماس‌یافته با عصاره هیدروژل، پس از 24 و 72h  گرم‌خانه‌گذاری بیش‌تر از %85 بود. با توجه به این نتایج، هیدروژل‌های شبکه پلیمری درهم‌نفوذی تولیدشده در این مطالعه می‌توانند به‌عنوان گزینه امیدوارکننده برای ارزیابی بیشتر به‌ویژه مهندسی بافت غضروف پیشنهاد شوند. 

کلیدواژه‌ها


عنوان مقاله [English]

Electron Beam-Irradiated Crosslinked Hydrogel Scaffold form Natural and Synthetic Polymers: Synthesis and Characterization

نویسندگان [English]

  • Zeinab Aghelinejad 1
  • Moslem Tavakol 2
  • Mahboobeh Mahmoodi 1
  • Maryam Dehghan-Niri 3
1 Biomedical Engineering Faculty, Yazd Branch, Islamic Azad University, Postal Code 8915813135, Yazd, Iran
2 Department of Chemical and Polymer Engineering, Yazd University, Postal Code 8915818411, Yazd, Iran
3 Biomedical Engineering Division, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran
چکیده [English]

Hypothesis: Recently, preparation and investigation of hydrogel scaffolds in tissue engineering have gained increasing attentions owing to similarity of their characteristics to extracellular matrix of different tissues. Among different methods for hydrogel preparation, the use of ionizing radiation presents several advantages as it can occur without the need to add chemical agents and the final products can be irradiated to final form in the package, also simultaneously sterilized by irradiation during crosslinking. In this study, chemical modification with glycidylmethacrylate (GMA) as well as physical blending with poly(vinyl alcohol) (PVA) was investigated to prepare hydrogel scaffolds based on polysaccharides, gum tragacanth (GT) and carboxymethyl chitosan (NOCC) using electron beam irradiation.
Methods: For preparation of the hydrogels, first, GT and NOCC were functionalized with GMA. Afterwards, the blended solutions of these modified polymers and PVA were exposed to electron beam irradiation. Finally, the morphology, gel content, swelling behavior, compressive strength, rheological properties and biocompatibility of the hydrogels were investigated.
Findings: GMA-functionalized GT and NOCC in aqueous solution were crosslinked by electron beam irradiation. Blending of PVA with these modified polymers leads to the formation of an interpenetrating polymeric network (IPN) with enhanced compressive strength, storage modulus and swelling degree in comparison with the hydrogels prepared with unblended polymers. The gel content of the hydrogels varies between 65 to 98% as a function of polymer composition and irradiation dose. The hydrogels show viscoelastic behaviors in both compression and rheology analyses as well as excellent elastic recovery in cyclic compression analysis. The stress fracture of IPN hydrogels is found in the range of 1200-1414 kPa. The viability of MSCs, exposed to hydrogel extracts is above 85% after 24 and 72 h incubation. According to these results, the IPN hydrogels prepared in this study may be suggested as a promising candidate for further investigation, especially in cartilage tissue engineering. 

کلیدواژه‌ها [English]

  • "Gum tragacanth"
  • "Carboxymethyl chitosan"
  • "Poly(vinyl alcohol)"
  • "Electron beam irradiation"
  • "Hydrogel scaffolds"
  1. , Rodríguez Y., Correa H., Moreno A., and Carrizales L., Pilot Scale-up and Shelf Stability of Hydrogel Wound Dressings Obtained by Gamma Radiation, Rad. Phys. Chem., 81, 1249-1253, 2012.
  2. Choi J., Pant B., Lee C., Park M., Park S.-, and Kim H.-Y., Preparation and Characterization of Eggshell Membrane/PVA Hydrogel via Electron Beam Irradiation Technique, J. Ind. Eng. Chem., 47, 41-45, 2016.
  3. Tavakol M., Dehshiri S., and Vasheghani-Farahani E., Electron Beam Irradiation Crosslinked Hydrogels Based on Tyramine Conjugated Gum Tragacanth, Polym., 152, 504-509, 2016.
  4. Ajji Z., Mirjalili G., Alkhatab A., and Dada H., Use of Electron Beam for the Production of Hydrogel Dressings, Phys. Chem., 77, 200-202, 2008.
  5. Sahraei S.S., Kalhor N., and Sheykhhasan M., Application of Scaffolds in Cartilage Tissue Engineering: A Review Paper, Razi J. Med. Sci., 26, 42-55, 2019.
  6. Tavakol M., Vasheghani-Farahani E., Soleimani M., Hashemi-Najafabadi S., and Hajizadeh A., Preparation of an Enzyme Catalyzed In-Situ Forming Hydrogel Based on Chemically Modified Tragacanth for Cartilage Tissue Engineering, Molecul. Res., 32, 297-310, 2019.
  7. Dehghan-Niri M., Vasheghani-Farahani E., Eslaminejad M.B., Tavakol M., and Bagheri F., Preparation of Gum Tragacanth/Poly(vinyl alcohol)/Halloysite Hydrogel Using Electron Beam Irradiation with Potential for Bone Tissue Engineering, Polym., 305, 120548, 2023.
  8. Tavakol M. and Mohammadifar M.A., A Review on Gum Tragacanth and Its Biomedical Applications, J. Chem. Chem. Eng. (Persian), 36, 1-20, 2017.
  9. Tavakol M., Vasheghani-Farahani E., Soleimani M., Mohammadifar M.A., Hashemi-Najafabadi S., and Hafizi M., Synthesis and Characterization of an Enzyme Mediated In-Situ Forming Hydrogel Based on Gum Tragacanth for Biomedical Applications, J. Biotech., 12, 15811, 2013.
  10. Tavakol M., Vasheghani-Farahani E., Mohammadifar M.A., Soleimani M., and Hashemi-Najafabadi S., Synthesis and Characterization of an In-Situ Forming Hydrogel Using Tyramine Conjugated High Methoxyl Gum Tragacanth, Biomater. Appl., 30, 1016-1025, 2016.
  11. Fattahi A., Petrini P., Munarin F., Shokoohinia Y., Golozar M.A., Varshosaz J., and Tanzi M.C., Polysaccharides Derived from Tragacanth as Biocompatible Polymers and Gels, J. Appl. Polym. Sci., 129, 2092-2102, 2013.
  12. Haeri S.M.J., Sadeghi Y., Salehi M., Farahani R.M., and Mohsen N., Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells on Gum Tragacanth Hydrogel, Biologicals, 44, 123-128, 2016.
  13. Fayazzadeh E., Rahimpour S., Ahmadi S.M., Farzampour S., Anvari M.S., Boroumand M.A., and Ahmadi S.H., Acceleration of Skin Wound Healing with Tragacanth (Astragalus) Preparation: An Experimental Pilot Study in Rats, Acta Med. Iran., 52, 3-8, 2014.
  14. Cai K., Yao K., Li Z., Yang Z., and Li X., Rat Osteoblast Functions on the O-Carboxymethyl Chitosan-Modified Poly(D,L-lactic acid) Surface, Biomat. Sci. Polym. Ed., 12, 1303-1315, 2001.
  15. Fattahi R., Soleimani M., Khani M.-M., Rasouli M., and Hosseinzadeh S., A Three-Dimensional Structure with Osteoconductive Function Made of O-Carboxymethyl Chitosan Using Aspirin as a Cross-Linker, J. Polym. Mater. Poly. Biomater., 73, 1-17, 2023.
  16. Firoozi M., Entezam M., Masaeli E., Ejeian F., and Nasr-Esfahani M.H., Physical Modification Approaches to Enhance Cell Supporting Potential of Poly(vinyl alcohol)-Based Hydrogels, Appl. Polym. Sci., 139, 51485, 2022.
  17. Fang J., Li P., Lu X., Fang L., Lv X., and Ren F., A Strong, Tough, and Osteoconductive Hydroxyapatite Mineralized Polyacrylamide/Dextran Hydrogel for Bone Tissue Regeneration, Acta Biomater., 88, 503-513, 2019.
  18. Zhao L., Gwon H.-J., Lim Y.-M., Nho Y.-C., and Kim S.Y., Hyaluronic Acid/Chondroitin Sulfate-Based Hydrogel Prepared by Gamma Irradiation Technique, Polym., 102, 598-605, 2014.
  19. Yoshii F., Zhao L., Wach R.A., Nagasawa N., Mitomo H., and Kume T., Hydrogels of Polysaccharide Derivatives Crosslinked with Irradiation at Paste-Like Condition, Instrum. Meth. B., 208, 320-324, 2003.
  20. Stammen J.A., Williams S., Ku D.N., and Guldberg R.E., Mechanical Properties of a Novel PVA Hydrogel in Shear and Unconfined Compression, Biomaterials, 22, 799-806, 2001.
  21. Karvinen J., Koivisto J., Jönkkäri I., and Kellomäki M., The Production of Injectable Hydrazone Crosslinked Gellan Gum-Hyaluronan-Hydrogels with Tunable Mechanical and Physical Properties, Mech. Behav. Biomed. Mater., 71, 383-391, 2017.
  22. Kamiloglu S., Sari G., Ozdal T., and Capanoglu E., Guidelines for Cell Viability Assays, Food Frontiers, 1, 332-349, 2020.
  23. Reis A.V., Cavalcanti O.A., Rubira A.F., and Muniz E.C., Synthesis and Characterization of Hydrogels Formed from a Glycidyl Methacrylate Derivative of Galactomannan, J. Pharm., 267, 13-25, 2003.
  24. Rashid T.U., Shamsuddin S.M., Khan M.A., and Rahman M.M., Evaluation of Fat Binding Capacity of Gamma Irradiated Chitosan Extracted from Prawn Shell, Soft Mater., 12, 262-267, 2014.
  25. Khoylou F. and Naimian F., Radiation Synthesis of Superabsorbent Polyethylene Oxide/Tragacanth Hydrogel, Phys. Chem., 78, 195-198, 2009.
  26. Teimouri S., Abbasi S., and Sheikh N., Effects of Gamma Irradiation on Some Physicochemical and Rheological Properties of Persian Gum and Gum Tragacanth, Food Hydrocoll., 59, 9-16, 2016.
  27. Giammona G., Pitarresi G., Cavallaro G., and Spadaro G., New Biodegradable Hydrogels Based on an Acryloylated Polyaspartamide Cross-Linked by Gamma Irradiation, Biomater. Sci. Polym. Ed., 10, 969-987, 1999.
  28. Singh B., Varshney L., Francis S., and Rajneesh, Designing Tragacanth Gum Based Sterile Hydrogel by Radiation Method for Use in Drug Delivery and Wound Dressing Applications, J. Biol. Macromol., 88, 586-602, 2016.
  29. Dehghan-Niri M., Vasheghani-Farahani E., Eslaminejad M., Tavakol M., and Bagheri F., Physicomechanical, Rheological and In-Vitro Cytocompatibility Properties of the Electron Beam Irradiated Blend Hydrogels of Tyramine Conjugated Gum Tragacanth and Poly(vinyl alcohol), Sci. Eng. C, 114, 111073, 2020.
  30. Entezam M., Ehghaghiyan A., Sedeh N.N., Jafari S.H., and Khonakdar H.A., Physicomechanical and Antimicrobial Characteristics of Hydrogel Based on Poly(vinyl alcohol): Performance Improvement via Inclusion of Chitosan-Modified Nanoclay, Appl. Polym. Sci., 136, 47444, 2019.
  31. Stenhamre H., Nannmark U., Lindahl A., Gatenholm P., and Brittberg M., Influence of Pore Size on the Redifferentiation Potential of Human Articular Chondrocytes in Poly(urethane urea) Scaffolds, Tissue Eng. Regen. Med., 5, 578-88, 2011.
  32. Lien S.-M., Ko L.-Y., and Huang T.-J., Effect of Pore Size on ECM Secretion and Cell Growth in Gelatin Scaffold for Articular Cartilage Tissue Engineering, Acta Biomater., 5, 670-679, 2008.
  33. Matsiko A., Gleeson J., and O’Brien F., Scaffold Mean Pore Size Influences Mesenchymal Stem Cell Chondrogenic Differentiation and Matrix Deposition, Tissue Eng. A, 21, 3-14. 2014.
  34. Bahadoran M., Shamloo A., and Nokoorani Y.D., Development of a Polyvinyl Alcohol/Sodium Alginate Hydrogel-Based Scaffold Incorporating bFGF-Encapsulated Microspheres for Accelerated Wound Healing, Rep., 10, 7342, 2020.
  35. Lee K.Y. and Mooney D.J., Hydrogels for Tissue Engineering. Rev., 101, 1869-1880, 2001.
  36. Kumar A. and Han S.S., PVA-Based Hydrogels for Tissue Engineering: A Review, J. Polym. Mater. Polym. Biomater., 66, 159-182, 2017.
  37. Wan Ishak W.H., Rosli N.A., Ahmad I., Ramli S., and Mohd Amin M.C.I., Drug Delivery and In-Vitro Biocompatibility Studies of Gelatin-Nanocellulose Smart Hydrogels Cross-Linked with Gamma Radiation, Mater. Res. Technol., 15, 7145-7157, 2021.
  38. Vasheghani-Farahani E., Vera J.H., Cooper D.G., and Weber M.E., Swelling of Ionic Gels in Electrolyte Solutions, Ind. Eng. Chem. Res., 29, 554-560, 1990.
  39. Yoshida R., Okuyama Y., Sakai K., Okano T., and Sakurai Y., Sigmoidal Swelling Profiles for Temperature-Responsive
    Poly(N-isopropylacrylamide-co-butyl methacrylate) Hydrogels, J. Membr. Sci., 89, 267-277, 1994.