Abstract
Bone morphogenetic protein 2 (BMP-2)-functionalized poly(l-lactide-co-ε-caprolactone) (PLCL) porous scaffolds have shown promising results in bone tissue regeneration studies. It is believed that even better results are achieved by hierarchical porous scaffolds and a designed sequential release of growth factors. We therefore synthesized (l-lactide-co-glycolide)-g-poly(ethylene glycol) (PLGA-g-PEG) oligomers which could be injected into PLCL porous scaffolds. They were synthesized by ring-opening polymerization and carefully characterized by nuclear magnetic resonance spectroscopy (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and size exclusion chromatography (SEC). The sol–gel transition temperature, pH, and functional life were determined and correlated with the molecular structure of PLGA-g-PEG. We found that low molecular weight PLGA-g-PEG was obtained and poly(l-lactide-co-glycolide-co-poly(ethylene glycol) methyl ether) (PLGA-MPEG) appeared to contribute to gelation. It was possible to design a system that formed a hydrogel within 1 min at 37 °C with a pH between 6 and 7 and with a functional life of around 1 month. These low molecular weight thermosensitive PLGA-g-PEG oligomers, which can be injected into PLCL scaffolds, appear promising for bone tissue engineering applications.
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References
Finne A, Albertsson A-C (2004) New functionalized polyesters to achieve controlled architectures. J Polym Sci Part A Polym Chem 42:444–452. doi:10.1002/pola.10805
Tyson T, Målberg S, Wåtz V et al (2011) Functional and highly porous scaffolds for biomedical applications. Macromol Biosci 11:1432–1442. doi:10.1002/mabi.201100166
Idris SB, Arvidson K, Plikk P et al (2010) Polyester copolymer scaffolds enhance expression of bone markers in osteoblast-like cells. J Biomed Mater Res A 94:631–639. doi:10.1002/jbm.a.32726
Dånmark S, Finne-Wistrand A, Wendel M et al (2010) Osteogenic differentiation by rat bone marrow stromal cells on customized biodegradable polymer scaffolds. J Bioact Compat Polym 25:207–223. doi:10.1177/0883911509358812
Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3–12. doi:10.1016/S0169-409X(01)00239-3
Slaughter BV, Khurshid SS, Fisher OZ et al (2009) Hydrogels in regenerative medicine. Adv Mater 21:3307–3329. doi:10.1002/adma.200802106
Ruel-Gariépy E, Leroux J-C (2004) In situ-forming hydrogels—review of temperature-sensitive systems. Eur J Pharm Biopharm 58:409–426. doi:10.1016/j.ejpb.2004.03.019
Chen G, Hoffman AS (1995) Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373:49–52. doi:10.1038/373049a0
Malmsten M, Lindman B (1992) Self-assembly in aqueous block copolymer solutions. Macromolecules 25:5440–5445. doi:10.1021/ma00046a049
Jeong B, Bae YH, Lee DS, Kim SW (1997) Biodegradable block copolymers as injectable drug-delivery systems. Nature 388:860–862
Jeong B, Bae YH, Kim SW (1999) Thermoreversible gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions. Macromolecules 32:7064–7069. doi:10.1021/ma9908999
Jeong B, Wang L-Q, Gutowska A (2001) Biodegradable thermoreversible gelling PLGA-g-PEG copolymers. Chem Commun 2001:1516–1517
Chung Y-M, Simmons KL, Gutowska A, Jeong B (2002) Sol-gel transition temperature of PLGA-g-PEG aqueous solutions. Biomacromolecules 3:511–516. doi:10.1021/bm0156431
Jeong B, Lee KM, Gutowska A, An YH (2002) Thermogelling biodegradable copolymer aqueous solutions for injectable protein delivery and tissue engineering. Biomacromolecules 3:865–868. doi:10.1021/bm025536m
Cho K, Kim C, Lee J, Park JK (1999) Synthesis and characterization of poly(ethylene glycol) grafted poly(l-lactide). Macromol Rapid Commun 20:598–601
Gilding DK, Reed AM (1979) Biodegradable polymers for use in surgery—polyglycolic/poly(actic acid) homo- and copolymers: 1. Polymer (Guildf) 20:1459–1464. doi:10.1016/0032-3861(79)90009-0
Jeong B, Windisch CF, Park MJ et al (2003) Phase transition of the PLGA-g-PEG copolymer aqueous solutions. J Phys Chem B 107:10032–10039. doi:10.1021/jp027339n
Lin G, Cosimbescu L, Karin NJ, Tarasevich BJ (2012) Injectable and thermosensitive PLGA-g-PEG hydrogels containing hydroxyapatite: preparation, characterization and in vitro release behavior. Biomed Mater 7:024107. doi:10.1088/1748-6041/7/2/024107
Dunn AS, Campbell PG, Marra KG (2001) The influence of polymer blend composition on the degradation of polymer/hydroxyapatite biomaterials. J Mater Sci Mater Med 12:673–677
Dånmark S, Finne-Wistrand A, Schander K et al (2011) In vitro and in vivo degradation profile of aliphatic polyesters subjected to electron beam sterilization. Acta Biomater 7:2035–2046
Zhou S, Zheng X, Yu X et al (2007) Hydrogen bonding interaction of poly(d,l-lactide)/hydroxyapatite nanocomposites. Chem Mater 19:247–253. doi:10.1021/cm0619398
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The authors gratefully acknowledge the financial support from KTH, Royal Institute of Technology.
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Fagerland, J., Finne-Wistrand, A. Mapping the synthesis and the impact of low molecular weight PLGA-g-PEG on sol–gel properties to design hierarchical porous scaffolds. J Polym Res 21, 337 (2014). https://doi.org/10.1007/s10965-013-0337-8
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DOI: https://doi.org/10.1007/s10965-013-0337-8