کاربرد پلی‌استرهای آلیفاتیک زیست‌تخریب‌پذیر در مهندسی بافت

نوع مقاله : مروری

نویسندگان

شیراز، دانشگاه شیراز، دانشکده علوم، بخش شیمی،‌ کد پستی ۸۴۳۳۴-۷۱۹۴۶

چکیده

مهم‌ترین چالش در انواع مهندسی بافت، طراحی داربست‌ها با خواص فیزیکی، مکانیکی و زیستی مشابه با ماتریس برون‌سلولی (ECM) بافت هدف است. در حالت ایده­‌آل تکثیر مناسب سلول­‌ هم‌زمان با تخریب داربست و در نهایت بازسازی و ایجاد بافت مدنظر درون داربست اتفاق می‌افتد. استفاده از پلیمرهای زیست‌­تخریب­‌پذیر یا ترکیبی از این پلیمرها و سرامیک، فلزات یا کربن به ایجاد داربست‌ها با خواص مدنظر منجر می‌­شود. تاکنون پلیمرهای طبیعی و سنتزی مختلفی بدین منظور پیشنهاد شده‌­اند که پلی‌استرهای آلیفاتیک زیست­‌تخریب‌­پذیر و زیست‌­سازگار به‌­دلیل داشتن خواص قابل پیش‌­بینی و تنظیم‌پذیر، یکی از بهترین ماتریس‌های پلیمری در طراحی داربست­‌های استفاده‌شده در مهندسی بافت شناخته شده‌اند. به‌دلیل خواص منحصر به‌فرد این پلیمرها، تعداد پژوهش‌های انجام‌شده روی آن‌ها با هدف کاربرد در مهندسی بافت در حال افزایش است و بنابراین بررسی مروری اهداف و چالش­‌های پیش‌رو ضروری به‌نظر می­‌رسد. بر این اساس، هدف مقاله حاضر معرفی و بررسی پژوهش‌های انجام‌شده درباره پلی­‌استرهای آلیفاتیک زیست­‌تخریب­‌پذیر پرکاربرد شامل پلی­(لاکتیک ­اسید) (PLA)، پلی(گلیکولیک ­اسید) (PGA)، پلی­(لاکتیک-co-گلیکولیک اسید) (PLGA)، پلی­‌کاپرولاکتون (PCL) و خانواده پلی‌­استرهای میکروبی پلی­‌هیدروکسی­‌آلکانوآت­‌ها (PHA) به­‌ویژه پلی‌­هیدروکسی ­بوتیرات (PHB) و کوپلیمر پلی(3-هیدروکسی بوتیرات-3coهیدروکسی والرات) (PHBV) است. در این مقاله به‌­طور ویژه روش­‌های سنتز، خواص ساختاری، فیزیکی، مکانیکی و زیستی این پلیمرها بررسی می‌شود و با ارزیابی روش‌­های متنوع اصلاح فیزیکی و شیمیایی گزارش­‌شده در مقاله‌های پژوهشی سال­‌های اخیر، به چگونگی غلبه بر چالش طراحی داربست مشابه با ECM پاسخ داده می‌شود. همچنین، درباره کاربرد این پلی­‌استرها در مهندسی انواع بافت سخت و نرم از جمله استخوان، غضروف، رباط، تاندون، ماهیچه، طحال، قرنیه و پوست بحث می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

Biodegradable Aliphatic Polyesters for Application in Tissue Engineering

نویسندگان [English]

  • Amir-Reza Arvaneh
  • Mehdi Sadat-Shojai
Department of Chemistry, College of Sciences, Shiraz University, Postal Code 71946-84334, Shiraz, Iran
چکیده [English]

Designing scaffolds with physical, mechanical, and biological properties like those of the extracellular matrix (ECM) of the target tissue, is the most critical challenge in tissue engineering. Ideally, proper cell proliferation can simultaneously occur with the degradation of the scaffold to finally restore and create the desired tissue within the scaffold. The use of biodegradable polymers or a combination of these polymers and ceramics, metals or carbon leads to the fabrication of scaffolds with the required properties. Thus far, different natural and synthetic polymers have been proposed for this purpose, of which aliphatic biodegradable and biocompatible polyesters as a result of their predictable and adjustable properties have been known as one of the best polymeric matrices in designing scaffolds used in tissue engineering. Due to the unique properties of these polymers, the number of research works performed on them for application in tissue engineering is increasing and therefore it is necessary to review the goals and challenges ahead. Accordingly, the present work has attempted to re-examine studies performed on widely used biodegradable aliphatic polyesters including poly(lactic acid)(PLA), poly(glycolic acid)(PGA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and the family of microbial polyesters of the polyhydroxyalkanoates (PHA), especially poly(hydroxybutyrate) (PHB) as well as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) copolymer. This article specially focuses on the synthetic techniques and structural, physical, mechanical, and biological properties of these polymers to overcome the challenging task of designing ECM-like scaffolds by evaluating the various physical and chemical modification methods reported in recent research papers. The present study also reviews and discusses the application of these polyesters in soft and hard tissue engineering, such as bone, cartilage, ligament, tendon, muscle, spleen, cornea, and skin.

کلیدواژه‌ها [English]

  • Polyester
  • biodegradable
  • tissue engineering
  • extracellular matrix
  • biocompatible
  1. References

    1. Meyer U., Meyer T., Handschel J., and Wiesmann H.P. (Eds.), Fundamentals of Tissue Engineering and Regenerative Medicine, Springer Science and Business Media, Berlin, 1, 5-12, 2009.
    2. Sadat-Shojai M., Hydroxyapatite: Inorganic Nanoparticles of Bone (Properties, Applications, and Preparation Methodologies) (Persian), Iranian Student Book Agency, Tehran, 2010.
    3. Sharp P.A. and Langer R., Promoting Convergence in Biomedical Science,Science333, 527-527, 2011.
    4. Ratner B.D., Biomaterials: Been There, Done That, and Evolving into the Future, Rev. Biomed. Eng.,21, 171-191, 2019.
    5. Los M.J., Hudecki A., and Wiechec E., Stem Cells and Biomaterials for Regenerative Medicine, Academic, 85-98, 2018.
    6. Vert M., Doi Y., Hellwich K.H., Hess M., Hodge P., Kubisa P., Rinaudo M., and Schué F., Terminology for Biorelated Polymers and Applications (IUPAC Recommendations 2012), Pure Appl. Chem., 84, 377-410, 2012.
    7. Dutta R.C., Dutta A.K., and Basu B., Engineering Implants for Fractured Bones, Metals to Tissue Constructs, Mater. Eng. Appl., 1, 9-13, 2017.
    8. Skalak R. and Fox C.F., Tissue Engineering, Alan R. Liss, New York, 211-216, 1988.
    9. Florea D.A., Andronescu E., and Grumezescu A.M., Innovative Biomaterials in Bone Tissue Engineering, Int., 1, 2-12, 2019.
    10. Sadat-Shojai M., Khorasani M.T., Jamshidi A., and Irani S., Nano-hydroxyapatite Reinforced Polyhydroxybutyrate Composites: A Comprehensive Study on the Structural and In Vitro Biological Properties, Sci. Eng. C,33, 2776-2787, 2013.
    11. Sadat-Shojai M., Calcium Phosphate Reinforced Polyester Nanocomposites for Bone Regeneration Applications, Depan D. (Ed.), Biodegradable Polymeric Nanocomposites: Advances in Biomedical Applications, Taylor and Francis (CRC), USA, 1-34, 2015.
    12. Chen Q., Liang S., and Thouas G.A., Elastomeric Biomaterials for Tissue Engineering, Polym. Sci., 38, 584-671, 2013.
    13. Saini M., Singh Y., Arora P., Arora V., and Jain K., Implant Biomaterials: A Comprehensive Review, World J. Clin. Cases, 3, 52, 2015.
    14. Manavitehrani I., Fathi A., Badr H., Daly S., Shirazi A.N., and Dehghani F., Biomedical Applications of Biodegradable Polyesters,Polymers, 8, 20, 2016.
    15. Alexis F., Factors Affecting The Degradation and DrugRelease Mechanism of Poly (Lactic Acid) and Poly [(Lactic Acid)-co-(Glycolic Acid)], Int., 54, 36-46, 2005.
    16. Jiang S., Wang M., and He J., A Review of Biomimetic Scaffolds for Bone Regeneration: Towards A Cell-Free Strategy, Transl. Med., 6, e10206, 2020.
    17. John R.P., Nampoothiri K.M., and Pandey A., Fermentative Production of Lactic Acid from Biomass: An Overview on Process Developments and Future Perspectives, Microbiol. Biotechnol., 74, 524-534, 2007.
    18. Jiménez A., Peltzer M.A., and Ruseckaite R.R. (Eds.), Poly (Lactic Acid) Science and Technology: Processing, Properties, Additives and Applications, Royal Society of Chemistry, UK, 3-66, 2015.
    19. Martin D.P. and Williams S.F., Medical Applications of Poly-4-hydroxybutyrate: A Strong Flexible Absorbable Biomaterial, Eng. J., 16, 97-105, 2003.
    20. Ebnesajjad, Handbook of Biopolymers and Biodegradable Plastics: Properties, Processing and Applications, William Andrew, New York, 2012.
    21. Farahini T.D., Entezami A.A., Mobedi H., Abtahi M., and Palashi M., Ring-Opening Bulk-Melt Polymerization of Poly(L-Lactide), J. Polym. Sci. Technol. (Persian),4, 241-248, 2003.
    22. Fukushima K. and Kimura Y., An Efficient Solid-State Polycondensation Method for Synthesizing Stereocomplexed Poly (Lactic Acid) s with High Molecular Weight, Polym. Sci. A Polym. Chem., 46, 3714-3722, 2008.
    23. Martin O. and Avérous L., Poly(lactic acid): Plasticization and Properties of Biodegradable Multiphase Systems, Polymer, 42, 6209-6219, 2001.
    24. Wang Q., Bao Y., Ahire J., and Chao Y., Co-encapsulation of Biodegradable Nanoparticles with Silicon Quantum Dots and Quercetin for Monitored Delivery, Healthc. Mater., 2, 459-466, 2013.
    25. Mi H.Y., Salick M.R., Jing X., Jacques B.R., Crone W.C., Peng X.F., and Turng L.S., Characterization of Thermoplastic Polyurethane/Polylactic Acid (TPU/PLA) Tissue Engineering Scaffolds Fabricated by Microcellular Injection Molding, Sci. Eng. C, 33, 4767-4776, 2013.
    26. Kouya T., Tada S.I., Minbu H., Nakajima Y., Horimizu M., Kawase T., Lloyd D.R., and Tanaka T., Microporous Membranes of PLLA/PCL Blends for Periosteal Tissue Scaffold, Lett., 95, 103-106, 2013.
    27. Serra T., Ortiz-Hernandez M., Engel E., Planell J.A., and Navarro M., Relevance of PEG in PLA-Based Blends for Tissue Engineering 3D-Printed Scaffolds, Sci. Eng. C, 38, 55-62, 2014.
    28. Davachi S.M., Kaffashi B., Zamanian A., Torabinejad B., and Ziaeirad Z., Investigating Composite Systems Based on Polylactide and Polylactide/Triclosan Nanoparticles for Tissue Engineering and Medical Applications, Sci. Eng. C, 58, 294-309, 2016.
    29. Tanase C.E. and Spiridon I., PLA/Chitosan/Keratin Composites for Biomedical Applications, Sci. Eng. C, 40, 242-247, 2014.
    30. Han X., Wang D., Chen X., Lin H., and Qu F., One-Pot Synthesis of Macro-Mesoporous Bioactive Glasses/Polylactic Acid for Bone Tissue Engineering, Sci. Eng. C, 43, 367-374, 2014.
    31. Bolay N.L, Santran V., Dechambre G., Combes C., Drouet C., Lamure A., and Rey C., Production, by Co-grinding in a Media Mill, of Porous Biodegradable Polylactic Acid-Apatite Composite Materials for Bone Tissue Engineering, Powder Technol., 190, 89-94, 2009.
    32. Shen W., Zhang G., Li Y., and Fan G., Effects of the Glycerophosphate-Polylactic Copolymer Formation on Electrospun Fibers, Surf. Sci, 443, 236-243, 2018.
    33. Cai X., Tong H., Shen X., Chen W., Yan J., and Hu J., Preparation and Characterization of Homogeneous Chitosan-Polylactic Acid/Hydroxyapatite Nanocomposite for Bone Tissue Engineering and Evaluation of Its Mechanical Properties, Acta Biomater., 5, 2693-2703, 2009.
    34. Charles-Harris M., Valle S.D., Hentges E., Bleuet P., Lacroix D., and Planell J.A., Mechanical and Structural Characterisation of Completely Degradable Polylactic Acid/Calcium Phosphate Glass Scaffolds, Biomaterials, 28, 4429-4438, 2007.
    35. Lanao R.P.F., Jonker A.M., Wolke J.G., Jansen J.A., Hest J.C.V., and Leeuwenburgh S.C., Physicochemical Properties and Applications of Poly(lactic-co-glycolic acid) for Use in Bone Regeneration, Tissue Eng. Part B: Rev., 19, 380-390, 2013.
    36. Dong Y., Marshall J., Haroosh H.J., Mohammadzadehmoghadam S., Liu D., Qi X., and Lau K.T., Polylactic Acid (PLA)/Halloysite Nanotube (HNT) Composite Mats: Influence of HNT Content and Modification, Part A: Appl. S., 76, 28-36, 2015.
    37. Ranjbar-Mohammadi M., Shaki H., and Kargozar S., Fabrication of Nanofibrous Hybrid Scaffolds from Polylactic Acid-Graphene and Gelatin for Application in Bone Tissue Engineering, J. Polym. Sci. Technol. (Persian), 6, 565-576, 2019.
    38. Fu S. and Zhang P., Surface Modification of Polylactic Acid (PLA) and Polyglycolic Acid (PGA) Monofilaments via the Cold Plasma Method for Acupoint Catgut-Embedding Therapy Applications, Res. J., 89, 3839-3849, 2019.
    39. Sadat-Shojai M., Khorasani M.T., Dinpanah-Khoshdargi E., and Jamshidi A., Synthesis Methods for Nanosized Hydroxyapatite with Diverse Structures, Acta Biomater., 9, 7591-7621, 2013.
    40. Sadat-Shojai M. and Moghaddas H., How Geometry, Size, and Surface Properties of Tailor-Made Particles Control the Efficiency of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Hydroxyapatite Nanocomposites, Appl. Polym. Sci., 137, 49810, 2020.
    41. Persson M., Lorite G.S., Kokkonen H.E., Cho S.W., Lehenkari P.P., Skrifvars M., and Tuukkanen J., Effect of Bioactive Extruded PLA/HA Composite Films on Focal Adhesion Formation of Preosteoblastic Cells, Colloid Surface B, 121, 409-416, 2014.
    42. Hu Y., Liu Y., Qi X., Liu P., Fan Z., and Li S., Novel Bioresorbable Hydrogels Prepared from Chitosan-graft-Polylactide Copolymers, Int., 61, 74-81, 2012.
    43. Dehghani F., Fathi A., Mithieux S.M., and Weiss A.S., Formation of Bone, US Pattent Application US16/932,625 (WO/2017/035595A1, 2017.), 2020.
    44. Yang F., Murugan R., Wang S., and Ramakrishna S., Electrospinning of Nano/Micro Scale Poly(L-lactic acid) Aligned Fibers and Their Potential in Neural Tissue Engineering, Biomaterials, 26, 2603-2610, 2005.
    45. Woo K.M., Jun J.H., Chen V.J., Seo J., Baek J.H., Ryoo H.M., Kim G.S., Somerman M.J., and Ma P.X., Nano-Fibrous Scaffolding Promotes Osteoblast Differentiation and Biomineralization, Biomaterials, 28, 335-343, 2007.
    46. Zong X., Bien H., Chung C.Y., Yin L., Fang D., Hsiao B.S., Chu B. and Entcheva E., Electrospun Fine-Textured Scaffolds for Heart Tissue Constructs, Biomaterials, 26, 5330-5338, 2005.
    47. VazM., Tuijl S.V., Bouten C.V.C., and Baaijens F.P.T., Design of Scaffolds for Blood Vessel Tissue Engineering Using a Multi-Layering Electrospinning Technique, Acta Biomater., 1, 575-582, 2005.
    48. Jem K.J. and Tan B., The Development and Challenges of Poly(lactic acid) and Poly(glycolic acid), Ind. Eng. Polym. Res., 3, 60-70, 2020.
    49. Jamshidian M., Tehrany E.A., Imran M., Jacquot M., and Desobry S., Poly(lactic acid): Production, Applications, Nanocomposites, and Release Studies, Rev. Food Sci. F, 9, 552-571, 2010.
    50. Biomaterials, Artificial Organs and Tissue Engineering, Hench L.L and Jones J.R. (Eds.), Woodhead, UK, 1, 37-58, 97-106, 201-215, 2005.
    51. Gentile P., Chiono V., Carmagnola I., and Hatton P.V., An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-based Biomaterials for Bone Tissue Engineering, J. Mol. Sci., 15, 3640-3659, 2014.
    52. Lin X., Wang W., Zhang W., Zhang Z., Zhou , Cao Y., and Liu W., Hyaluronic Acid Coating Enhances Biocompatibility of Nonwoven PGA Scaffold and Cartilage Formation, Tissue Eng. Part C: Methods, 23, 86-97, 2017.
    53. Toosi S., Naderi-Meshkin H., Kalalinia F., HosseinKhani H., Heirani-Tabasi A., Havakhah S., Nekooei S., Jafarian A.H., Rezaie F., Peivandi M.T., and Mesgarani H., Bone Defect Healing Is Induced by Collagen Sponge/Polyglycolic Acid, Mater. Sci. Mater. Med., 30, 1-10, 2019.
    54. Allaf R.M., Rivero I.V., and Ivanov N., Fabrication of Co-continuous Poly(ε-caprolactone)/Polyglycolide Blend Scaffolds for Tissue Engineering, J. Appl. Polym. Sci., 132, 2015.
    55. Kim B.N., Ko Y.G., Yeo T., Kim E.J., Kwon O.K., and Kwon O.H., Guided Regeneration of Rabbit Calvarial Defects Using Silk Fibroin Nanofiber-Poly (glycolic acid) Hybrid Scaffolds, ACS Biomater. Sci. Eng., 5, 5266-5272, 2019.
    56. Fujimaki H., Uchida K., Inoue G., Matsushita O., Nemoto N., Miyagi M., Inage K., Takano S., Orita S., Ohtori S., and Tanaka K., Polyglycolic Acid-Collagen Tube Combined with Collagen-Binding Basic Fibroblast Growth Factor Accelerates Gait Recovery in a Rat Sciatic Nerve Critical-Size Defect Model, Biomed. Mater. Res. B Appl. Biomater., 108, 326-332, 2020.
    57. Dehnavi N., Parivar K., Goodarzi V., Salimi A., and Nourani M.R., Systematically Engineered Electrospun Conduit Based on PGA/Collagen/Bioglass Nanocomposites: The Evaluation of Morphological, Mechanical, and Bio-properties, Adv. Technol., 30, 2192-2206, 2019.
    58. Song Y., Ren M., Wu Y., Li , Song C., Wang F., and Huang Y., The Effect of Different Surface Treatment Methods on the Physical, Chemical and Biological Performances of a PGA Scaffold, RSC Adv., 9, 20174-20184, 2019.
    59. Díez-Pascual A.M. and Díez-Vicente A.L., Multifunctional Poly(glycolic acid-co-propylene fumarate) Electrospun Fibers Reinforced with Graphene Oxide and Hydroxyapatite Nanorods, Mater. Chem. B, 5, 4084-4096, 2017.
    60. Fujita M., Kinoshita Y., Sato E., Maeda H., Ozono S., Negishi H., Kawase T., Hiraoka Y., Takamoto T., Tabata Y., and Kameyama Y., Proliferation and Differentiation of Rat Bone Marrow Stromal Cells on Poly(glycolic acid)–Collagen Sponge, Tissue Eng., 11, 1346-1355, 2005.
    61. Mikos A.G., Bao Y., Cima L.G., Ingber D.E., Vacanti J.P., and Langer R., Preparation of Poly(glycolic acid) Bonded Fiber Structures for Cell Attachment and Transplantation, Biomed. Mater. Res., 27, 183-189, 1993.
    62. Cima L.G., Ingber D.E., Vacanti J.P., and Langer R., Hepatocyte Culture on Biodegradable Polymeric Substrates, Bioeng, 38, 145-158, 1991.
    63. Moon S.I., Lee C.W., Taniguchi I., Miyamoto M., and Kimura Y., Melt/Solid Polycondensation of L-Lactic Acid: An Alternative Route to Poly(L-lactic acid) with High Molecular Weight, Polymer, 42, 5059-5062, 2001.
    64. Takahashi K., Taniguchi I., Miyamoto M., and Kimura Y., Melt/Solid Polycondensation of Glycolic Acid to Obtain High-Molecular-Weight Poly(glycolic acid), Polymer, 41, 8725-8728, 2000.
    65. Kricheldorf H.R., Boettcher C., and Tönnes K.U., Polylactones: 23. Polymerization of Racemic and Mesod, l-Lactide with Various Organotin Catalysts-Stereochemical Aspects, Polymer, 33, 2817-2824, 1992.
    66. Kowalski A., Duda A., and Penczek S., Mechanism of Cyclic Ester Polymerization Initiated with Tin (II) Octoate. 2. Macromolecules Fitted with Tin (II) Alkoxide Species Observed Directly in MALDI-TOF Spectra, Macromolecules, 33, 689-695, 2000.
    67. Duval C., Nouvel C., and Six J.L., Is Bismuth Subsalicylate an Effective Nontoxic Catalyst for Plga Synthesis?, Polym. Sci. A Polym. Chem., 52, 1130-1138, 2014.
    68. Makadia H.K. and Siegel S.J., Polylactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier, Polymers, 3, 1377-1397, 2011.
    69. Engineer C., Parikh J., and Raval A., Review on Hydrolytic Degradation Behavior of Biodegradable Polymers from Controlled Drug Delivery System, Trends Biomater Artif Organs, 25, 2011.
    70. Samantaray P.K., Little A., Haddleton D.M., McNally T., Tan B., Sun Z., Huang W., Ji Y., and Wan C., Poly(glycolic acid) (PGA): A Versatile Building Block Expanding High Performance and Sustainable Bioplastic Applications,Green Chem., 22, 4055-4081, 2020.
    71. Huang W., Shi X., Ren L., Du C., and Wang Y., PHBV Microspheres-PLGA Matrix Composite Scaffold for Bone Tissue Engineering, Biomaterials, 31, 4278-4285, 2010.
    72. Meng Z.X., Wang Y.S., Ma C., Zheng W., Li L., and Zheng Y.F., Electrospinning of PLGA/Gelatin Randomly-Oriented and Aligned Nanofibers as Potential Scaffold in Tissue Engineering, Sci. Eng. C, 30, 1204-1210, 2010.
    73. Qian J., Xu W., Yong X., Jin X., and Zhang W., Fabrication and In Vitro Biocompatibility of Biomorphic PLGA/nHA Composite Scaffolds for Bone Tissue Engineering, Sci. Eng. C, 36, 95-101, 2014.
    74. Mehrasa M., Asadollahi M.A., Ghaedi K., Salehi H., and Arpanaei A., Electrospun Aligned PLGA and PLGA/Gelatin Nanofibers Embedded with Silica Nanoparticles for Tissue Engineering, J. Biol. Macromol., 79, 687-695, 2015.
    75. Wan Y., Qu X., Lu J., Zhu C., Wan L., Yang J., Bei J., and Wang S., Characterization of Surface Property of Poly(lactide-co-glycolide) After Oxygen Plasma Treatment, Biomaterials, 25, 4777-4783, 2004.
    76. Liu P., Sun L., Liu P., Yu W., Zhang Q., Zhang W., Ma J., Liu P., and Shen J., Surface Modification of Porous PLGA Scaffolds with Plasma for Preventing Dimensional Shrinkage and Promoting Scaffold-Cell/Tissue Interactions, Mater. Chem. B, 6, 7605-7613, 2018.
    77. Qu X., Cui W., Yang F., Min C., Shen H., Bei J., and Wang S., The Effect of Oxygen Plasma Pretreatment and Incubation in Modified Simulated Body Fluids on the Formation of Bone-Like Apatite on Poly(lactide-co-Glycolide)(70/30), Biomaterials, 28, 9-18, 2007.
    78. Yang X., Li Y., He W., Huang Q., Zhang R., and Feng Q., Hydroxyapatite/Collagen Coating on PLGA Electrospun Fibers for Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells, Biomed. Mater. Res. A, 106, 2863-2870, 2018.
    79. Babilotte J., Martin B., Guduric V., Bareille R., Agniel R., Roques S., Héroguez V., Dussauze M., Gaudon M., Nihouannen D.L., and Catros S., Development and Characterization of A PLGA-HA Composite Material to Fabricate 3D-Printed Scaffolds for Bone Tissue Engineering, Sci. Eng. C, 118, 111334, 2021.
    80. Salehi R., Aghazadeh M., Rashidi M.R., Samadi N., Salehi S., Davaran S., and Samiei M., Bioengineering of Dental Pulp Stem Cells in a Microporous PNIPAAm-PLGA Scaffold, J. Polym. Mater. Polym. Biomater., 63, 767-776, 2014.
    81. Choi S.H. and Park T.G., Synthesis and Characterization of Elastic PLGA/PCL/PLGA Tri-Block Copolymers, Biomater. Sci., Polym. Ed., 13, 1163-1173, 2002.
    82. Hajzamani D., Shokrollahi P., Najmoddin N., and Shokrolahi F., Effect of Engineered PLGA-Gelatin-Chitosan/PLGA-Gelatin/PLGA-Gelatin-Graphene Three-Layer Scaffold on Adhesion/Proliferation of HUVECs, Adv. Technol, 31, 1896-1910, 2020.
    83. Qian K., Li B., Zhu W., Zhao J., and Liu Y., Preliminary Evaluates of Silica/β-TCP/PLGA Microspheres for Dentin Regeneration In Vivo, Appl. Ceram., 119, 357-363, 2020.
    84. Dai W., Kawazoe N., Lin X., Dong J., and Chen G., The Influence of Structural Design of PLGA/Collagen Hybrid Scaffolds in Cartilage Tissue Engineering, Biomaterials, 31, 2141-2152, 2010.
    85. Nojehdehian H., Moztarzadeh F., Baharvand H., Nazarian H., and Tahriri M., Preparation and Surface Characterization of Poly-L-Lysine-Coated PLGA Microsphere Scaffolds Containing Retinoic Acid for Nerve Tissue Engineering: In Vitro Study, Colloid Surface B, 73, 23-29, 2009.
    86. Khatib M.E., Mauro A., Wyrwa R., Mattia M.D., Turriani M., Giacinto O.D., Kretzschmar B., Seemann T., Valbonetti L., Berardinelli P., and Schnabelrauch M., Fabrication and Plasma Surface Activation of Aligned Electrospun PLGA Fiber Fleeces with Improved Adhesion and Infiltration of Amniotic Epithelial Stem Cells Maintaining Their Teno-Inductive Potential, Molecules, 25, 3176, 2020.
    87. Nair L.S. and Laurencin C.T., Biodegradable Polymers as Biomaterials, Polym. Sci., 32, 762-798, 2007.
    88. Hayashi T., Biodegradable Polymers for Biomedical Uses, Polym. Sci., 19, 663-702, 1994.
    89. Coulembier O., Degée P., Hedrick J.L., and Dubois P., From Controlled Ring-Opening Polymerization to Biodegradable Aliphatic Polyester: Especially Poly(β-malic acid) Derivatives, Polym. Sci., 31, 723-747, 2006.
    90. Engelberg I. and Kohn J., Physico-Mechanical Properties of Degradable Polymers Used in Medical Applications: A Comparative Study, Biomaterials, 12, 292-304, 1991.
    91. Woodruff M.A. and Hutmacher D.W., The Return of A Forgotten Polymer-Polycaprolactone in the 21st Century, Polym. Sci., 35, 1217-1256, 2010.
    92. Díaz E., Sandonis I., and Valle M.B., In Vitro Degradation of Poly(caprolactone)/nHA Composites. Nanomater., 2014, 1-8, 2014.
    93. Gan Z., Liang Q., Zhang J., and Jing X., Enzymatic Degradation of Poly(ε-caprolactone) Film in Phosphate Buffer Solution Containing Lipases, Degrad. Stab, 56, 209-213, 1997.
    94. Kim M. and Kim G.H., Electrohydrodynamic Direct Printing of PCL/Collagen Fibrous Scaffolds with a Core/Shell Structure for Tissue Engineering Applications, Eng. J., 279, 317-326, 2015.
    95. Sadat-Shojai M. and Ghadiri-Ghalenazeri S., A Modular Strategy for Fabrication of Responsive Nanocomposites Using Functionalized Oligocaprolactones and Hydroxyapatite Nanoparticles, New J. Chem., 44, 20155-20166, 2020.
    96. Pan L., Pei X., He R., Wan Q., and Wang J., Multiwall Carbon Nanotubes/Polycaprolactone Composites for Bone Tissue Engineering Application, Colloid Surface B, 93, 226-234, 2012.
    97. Dziadek M., Menaszek E., Zagrajczuk B., Pawlik J., and Cholewa-Kowalska K., New Generation Poly (ε-caprolactone)/Gel-Derived Bioactive Glass Composites for Bone Tissue Engineering: Part I. Material Properties, Sci. Eng. C, 56, 9-21, 2015.
    98. Zhao X., Lui Y.S., Choo C.K.C., Sow W.T., Huang C.L., Ng K.W., Tan L.P., and Loo J.S.C., Calcium Phosphate Coated Keratin-PCL Scaffolds for Potential Bone Tissue Regeneration, Sci. Eng. C, 49, 746-753, 2015.
    99. Hassan M.I. and Sultana N., Characterization, Drug Loading and Antibacterial Activity of Nanohydroxyapatite/Polycaprolactone (nHA/PCL) Electrospun Membrane, 3 Biotech., 7, 249, 2017.
    • Coimbra P., Santos P., Alves P., Miguel S.P., Carvalho M.P., Sá K.D.D., Correia I.J., and Ferreira P., Coaxial Electrospun PCL/Gelatin-MA Fibers As Scaffolds for Vascular Tissue Engineering, Colloid Surface B, 159, 7-15, 2017.
    1. Min S.K., Jung S.M., Kim S.H., Kim C.R., and Shin H.S., Implications of The Oxygenated Electrospun Poly(ɛ-caprolactone) Nanofiber for the Astrocytes Activities, Biomed. Mater. Res. B: Appl. Biomater., 101, 1267-1274, 2013.
    2. Gomes S., Rodrigues G., Martins G., Henriques C., and Silva J.C., Evaluation of Nanofibrous Scaffolds Obtained from Blends of Chitosan, Gelatin and Polycaprolactone for Skin Tissue Engineering, J. Biol. Macromol., 102, 1174-1185, 2017.
    3. Liu W., Feng Z., Ou-Yang W., Pan X., Wang X., Huang P., Zhang C., Kong D., and Wang W., 3D Printing of Implantable Elastic PLCL Copolymer Scaffolds, Soft Matter., 16, 2141-2148, 2020.
    4. Mary S.A. and Dev V.R.G., Electrospun Herbal Nanofibrous Wound Dressings for Skin Tissue Engineering, Text. Inst., 106, 886-895, 2015.
    5. Wang S., Lu L., Gruetzmacher J.A., Currier B.L., and Yaszemski M.J., A Biodegradable and Cross-Linkable Multiblock Copolymer Consisting of Poly(propylene fumarate) and Poly(ε-caprolactone): Synthesis, Characterization, and Physical Properties, Macromolecules, 38, 7358-7370, 2005.
    6. Touré A.B., Mele E., and Christie J.K., Multi-layer Scaffolds of Poly(caprolactone), Poly(glycerol sebacate) and Bioactive Glasses Manufactured by Combined 3D Printing and Electrospinning, Nanomaterials, 10, 626, 2020.
    7. Hooshmand-Ardakani A., Talaei-Khozani T., Sadat-Shojai M., Bahmanpour S., and Zarei-fard N., In Vitro Characterization of Multilamellar Fibers with Uniaxially Oriented Electrospun Type I Collagen Scaffolds, Mater. Sci. Eng., 2020, 1-13, 2020.
    • Khang G.,Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine,Taylor and Francis Group, Boca Raton, 13, 135-136, 2012.
    • Fu S., Ni P., Wang B., Chu B., Zheng L., Luo F., Luo J., and Qian Z., Injectable and Thermo-Sensitive PEG-PCL-PEG Copolymer/Collagen/n-HA Hydrogel Composite for Guided Bone Regeneration, Biomaterials, 33, 4801-4809, 2012.
    1. Li Z. and Tan B.H., Towards the Development of Polycaprolactone Based Amphiphilic Block Copolymers: Molecular Design, Self-Assembly and Biomedical Applications, Sci. Eng. C, 45, 620-634, 2014.
    2. Ranjha N.M., Mudassir J., and Majeed S., Synthesis and Characterization of Polycaprolactone/Acrylic Acid (PCL/AA) Hydrogel for Controlled Drug Delivery, Mater. Sci., 34, 1537-1547, 2011.
    3. Sudesh K., Abe H., and Doi Y., Synthesis, Structure and Properties of Polyhydroxyalkanoates: Biological Polyesters, Polym. Sci., 25, 1503-1555, 2000.
    4. Bassas M., Rodríguez E., Llorens J., and Manresa A., Poly(3-hydroxyalkanoate) Produced from Pseudomonas Aeruginosa 42A2(NCBIM 40045): Effect of Fatty Acid Nature as Nutrient, Non. Cryst. Solids, 352, 2259-2263, 2006.
    5. Dai Y., Lambert L., Yuan Z., and Keller J., Characterisation of Polyhydroxyalkanoate Copolymers with Controllable Four-Monomer Composition, Biotechnol., 134, 137-145, 2008.
    6. Kaur L., Khajuria R., Parihar L., and Singh G.D., Polyhydroxyalkanoates: Biosynthesis to Commercial Production-A Review, Microbiol. Biotechnol. Food. Sci., 2019, 1098-1106, 2019.
    7. Rodriguez-Contreras A., Recent Advances in the Use of Polyhydroyalkanoates in Biomedicine, Bioengineering, 6, 82, 2019.
    8. Kouhi M., Fathi M., Prabhakaran M.P., Shamanian M., and Ramakrishna S., Enhanced Proliferation and Mineralization of Human Fetal Osteoblast Cells on PHBV-Bredigite Nanofibrous Scaffolds, Today Proc., 5, 15702-15709, 2018.
    9. Dong Y., Liao S., Ngiam M., Chan C.K., and Ramakrishna S., Degradation Behaviors of Electrospun Resorbable Polyester Nanofibers, Tissue Eng. Part B: Rev., 15, 333-351, 2009.
    10. Butt F.I., Muhammad N., Hamid A., Moniruzzaman M., and Sharif F., Recent Progress in the Utilization of Biosynthesized Polyhydroxyalkanoates for Biomedical Applications-Review, J. Biol. Macromol., 120, 1294-1305, 2018.
    11. He J., Chen S., and Yu Z., Determination of Poly-β-Hydroxybutyric Acid in Bacillus Thuringiensis by Capillary Zone Electrophoresis with Indirect Ultraviolet Absorbance Detection, Chromatogr. A, 973, 197-202, 2020.
    12. Dahl S.R., Olsen K.M., and Strand D.H., Determination of Gamma-Hydroxybutyrate (GHB), Beta-Hydroxybutyrate (BHB), Pregabalin, 1, 4-Butane-Diol (1, 4BD) and Gamma-Butyrolactone (GBL) in Whole Blood and Urine Samples by UPLC–MSMS, Chromatogr. B, 885, 37-42, 2012.
    13. Xiao X.Q., Zhao Y., and Chen G.Q., The Effect of 3-Hydroxybutyrate and Its Derivatives on the Growth of Glial Cells, Biomaterials, 28, 3608-3616, 2007.
    14. Mochizuki M. and Hirami M., Structural Effects on the Biodegradation of Aliphatic Polyesters, Adv. Technol., 8, 203-209, 1997.
    15. Tokiwa Y. and Calabia B.P., Review Degradation of Microbial Polyesters, Lett., 26, 1181-1189, 2004.
    16. Wang Y.W., Wu Q., and Chen G.Q., Gelatin Blending Improves the Performance of Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Films for BiomedicalApplication, Biomacromolecules, 6, 566-571, 2005.
    17. Liu H., Pancholi M., Iii J.S., and Raghavan D., Influence of Hydroxyvalerate Composition of Polyhydroxy Butyrate Valerate (PHBV) Copolymer on Bone Cell Viability and In Vitro Degradation, Appl. Polym. Sci., 116, 3225-3231, 2010.
    18. Doi Y., Kanesawa Y., Kunioka M., and Saito T., Biodegradation of Microbial Copolyesters: Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and Poly(3-hydroxybutyrate-co-4-hydroxybutyrate), Macromolecules, 23, 26-31, 1990.
    19. Eldsäter C., Karlsson S., and Albertsson A.C., Effect of Abiotic Factors on The Degradation of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in Simulated and Natural Composting Environments, Degrad. Stab, 64, 177-183, 1999.
    20. Abe H., Doi Y., Aoki H., and Akehata T., Solid-State Structures and Enzymatic Degradabilities for Melt-Crystallized Films of Copolymers of (R)-3-Hydroxybutyric Acid with Different Hydroxyalkanoic Acids, Macromolecules, 31, 1791-1797, 1998.
    21. Abe H. and Doi Y., Side-Chain Effect of Second Monomer Units on Crystalline Morphology, Thermal Properties, and Enzymatic Degradability for Random Copolyesters of (R)-3-Hydroxybutyric Acid with (R)-3-Hydroxyalkanoic Acids, Biomacromolecules, 3, 133-138, 2002.
    22. Shishatskaya E.I., Khlusov I.A., and Volova T.G., A Hybrid PHB-Hydroxyapatite Composite for Biomedical Application: Production, In Vitro and In Vivo Investigation, Biomater. Sci. Polym. Ed., 17, 481-498, 2006.
    23. Sadat-Shojai M., Electrospun Polyhydroxybutyrate/Hydroxyapatite Nanohybrids: Microstructure and Bone Cell Response, Mater. Sci. Technol., 32, 1013-1020, 2016.
    24. Salvatore L., Carofiglio V.E., Stufano P., Bonfrate V., Calò E., Scarlino S., Nitti P., Centrone D., Cascione M., Leporatti S., and Sannino A., Potential of Electrospun Poly(3-hydroxybutyrate)/Collagen Blends for Tissue Engineering Applications, Healthcare Eng, 2018, 1-13, 2018.
    25. Meischel M., Eichler J., Martinelli E., Karr U., Weigel J., Schmöller G., Tschegg E.K., Fischerauer S., Weinberg A.M., and Stanzl-Tschegg S.E., Adhesive Strength of Bone-Implant Interfaces and In-Vivo Degradation of PHB Composites for Load-Bearing Applications, Mech. Behav.Biomed.Mater.,53, 104-118, 2016.
    26. Culenova M., Birova I., Alexy P., Galfyova P., Nicodemou A., Moncmanova B., Plavec R., Tomanova K., Mencik P., Ziaran S., and Danisovic L., In Vitro Characterization of Poly(lactic acid)/Poly(hydroxybutyrate)/Thermoplastic Starch Blends for Tissue Engineering Application,Cell Transplant, 30, 1-12, 2021.
    27. Misra S.K., Ansari T.I., Valappil S.P., Mohn D., Philip S.E., Stark W.J., Roy I., Knowles J.C., Salih V., and Boccaccini A.R., Poly(3-hydroxybutyrate) Multifunctional Composite Scaffolds for Tissue Engineering Applications, Biomaterials, 31, 2806-2815, 2010.
    28. Sadat-Shojai M., Khorasani M.T., and Jamshidi A., A New Strategy for Fabrication of Bone Scaffolds Using Electrospun Nano-HAp/PHB Fibers and Protein Hydrogels, Eng. J., 289, 38-47, 2016.
    29. Sadat-Shojai M., Controlled Pattern of Cell Growth in Modulated Protein Nanocomplexes: Regulating Cells Spreading in Three Dimensions, Today, 21, 686-688, 2018.
    30. P., Voinova V.V., Kuznetsova E.S., Zharkova I.I., Makhina T.K., Myshkina V.L., Chesnokova D.V., Kudryashova K.S., Feofanov A.V., ShaitanK.V., and Bonartseva G.A., BSA Adsorption on Porous Scaffolds Prepared from BioPEGylated Poly(3-hydroxybutyrate), Appl. Biochem. Microbiol, 54, 379-386, 2018.
    31. Chernozem R.V., Guselnikova O., Surmeneva M.A., Postnikov P.S., Abalymov A.A., Parakhonskiy B.V., Roo N.D., Depla D., Skirtach A.G., and Surmenev R.A., Diazonium Chemistry Surface Treatment of Piezoelectric Polyhydroxybutyrate Scaffolds for Enhanced Osteoblastic Cell Growth, Mater. Today, 20, 100758, 2020.
    32. Chan S.Y., Chan B.Q.Y., Liu Z., Parikh B.H., Zhang K., Lin Q., Su X., Kai D., Choo W.S., Young D.J., and LohX.J., Electrospun Pectin-Polyhydroxybutyrate Nanofibers for Retinal Tissue Engineering, ACS Omega, 2, 8959-8968, 2017.
    33. Zamanifard M., Khorasani M.T., Daliri M., and Parvazinia M., Preparation and Modeling of Electrospun Polyhydroxybutyrate/Polyaniline Composite Scaffold Modified by Plasma and Printed by an Inkjet Method and Its Cellular Study, Biomater. Sci. Polym. Ed., 31, 1515-1537, 2020.
    34. Li H.Y., Li H., Wang B.J., Gu Q., Jiang Z.Q., and Wu X.D., Synthesis and Properties of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Chitin Nanocrystals Composite Scaffolds for Tissue Engineering, Chem. Lett., 25, 1635-1638, 2014.
    35. Paşcu E.I., Stokes J., and McGuinness G.B., Electrospun Composites of PHBV, Silk Fibroin and Nano-Hydroxyapatite for Bone Tissue Engineering, Sci. Eng. C, 33, 4905-4916, 2013.
    36. Wu J., Sun J., and Liu J., Evaluation of PHBV/Calcium Silicate Composite Scaffolds for Cartilage Tissue Engineering, Surf. Sci., 317, 278-283, 2014.
    37. Zhang S., Prabhakaran M.P., Qin X., and Ramakrishna S., Biocomposite Scaffolds for Bone Regeneration: Role of Chitosan and Hydroxyapatite within Poly-3-hydroxybutyrate-co-3-hydroxyvalerate on Mechanical Properties and In Vitro Evaluation, Mech. Behav. Biomed.Mater., 51, 88-98, 2015.
    38. Pramanik N., Dutta K., Basu R.K., and Kundu P.P., Aromatic Π-conjugated Curcumin on Surface Modified Polyaniline/Polyhydroxyalkanoate Based 3D Porous Scaffolds for Tissue Engineering Applications, ACS Biomater. Sci. Eng., 2, 2365-2377, 2016.
    39. Unalan I., Colpankan O., Albayrak A.Z., Gorgun C., and Urkmez A.S., Biocompatibility of Plasma-Treated Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanofiber Mats Modified by Silk Fibroin for Bone Tissue Regeneration, Sci. Eng. C, 68, 842-850, 2016.
    40. Sadat-Shojai M. and Moghaddas H., Modulated Composite Nanofibers with Enhanced Structural Stability for Promotion of Hard Tissue Healing, Iran J. Sci. Technol. Trans. A: Sci., 45, 529-537, 2021.
    41. Liu H., Huang J., Zhou Z., Hu Y., Li Y., Zou P., and Dai Y., Surface Modification of PHBV Tissue Engineering Nanofibrous Scaffolds with Hyaluronic Acid, Hunan Univ. Nat. Sci., 44, 87-95, 2017.
    42. Antonova L.V., Silnikov V.N., Khanova M.Y., Koroleva L.S., Serpokrilova I.Y., Velikanova E.A., Matveeva V.G., Senokosova E.A., Mironov A.V., Krivkina E.O., and Kudryavtseva Y.A., Adhesion, Proliferation and Viability of Human Umbilical Vein Endothelial Cells Cultured on the Surface of Biodegradable Non-Woven Matrices Modified with RGD Peptides, Transplantol. Iskusstv. Organov., 21, 142-152, 2019.
    43. Baradaran-Rafii A., Biazar E., and Heidari-Keshel S., Cellular Response of Limbal Stem Cells on PHBV/Gelatin Nanofibrous Scaffold for Ocular Epithelial Regeneration, J. Polym. Mater., 64, 879-887, 2015.
    44. Wang Y., Ke Y., Ren L., Wu G., and Chen X., Photografting Polymerization of Polyacrylamide on Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Films. II. Wettability and Crystallization Behaviors of Poly(3-hydroxybutyrate-co-3-Hydroxyvalerate)-graft-Polyacrylamide Films, Appl. Polym. Sci., 107, 3765-3772, 2008.
    45. Kouhi M., Reddy V.J., and Ramakrishna S., GPTMS-Modified Bredigite/PHBV Nanofibrous Bone Scaffolds with Enhanced Mechanical and Biological Properties, Biochem. Biotechnol., 188, 357-368, 2019.
    46. Mukheem A., HossainM., Shahabuddin S., Muthoosamy K., Manickam S., Sudesh K., Saidur R., Sridewi N., and Campus N.M., Bioplastic Polyhydroxyalkanoate (PHA): Recent Advances in Modification and Medical Applications, Org., 1-37, 2018.