Poloxamer-based hydrogels hardening at body core temperature as carriers for cell based therapies: in vitro and in vivo analysis

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• 作者：Elias Volkmer (1)
  Uta Leicht (1)
  Martina Moritz (1)
  Christina Schwarz (1)
  Hinrich Wiese (2)
  Stefan Milz (3)
  Philipp Matthias (4)
  Winfried Schloegl (4)
  Wolfgang Friess (4)
  Michael Goettlinger (5)
  Peter Augat (5)
  Matthias Schieker (1) (6)
  
• 刊名：Journal of Materials Science Materials in Medicine
• 出版年：2013
• 出版时间：September 2013
• 年：2013
• 卷：24
• 期：9
• 页码：2223-2234
• 全文大小：3252KB
• 参考文献：1. AI Caplan. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2001;213(2):341-.
  2. Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem cell biology. Cell. 1997;88(3):287-8. CrossRef
  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143-. CrossRef
  4. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-8. CrossRef
  5. Docheva D, Popov C, Mutschler W, Schieker M. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med. 2001;11(1):21-8. CrossRef
  6. Kassam M. Stem cells: potential therapy for age-related diseases. Ann N Y Acad Sci. 2006;1067:436-2. CrossRef
  7. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med. 2000;6(11):1282-. CrossRef
  8. Schieker M, Seitz S, Gulkan H, Nentwich M, Horvath G, Regauer M, et al. Tissue engineering of bone. Integration and migration of human mesenchymal stem cells in colonized constructs in a murine model. Orthopade. 2004;33(12):1354-0. CrossRef
  9. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38(Suppl 4):S3-. CrossRef
  10. Drosse I, Volkmer E, Capanna R, De Biase P, Mutschler W, Schieker M. Tissue engineering for bone defect healing: an update on a multi-component approach. Injury. 2008;39(Suppl2):S9-0. CrossRef
  11. Schieker M, Heiss C, Mutschler W. Bone substitutes. Unfallchirurg. 2008;111(8):613-19; quiz 20.
  12. Vacanti CA. History of tissue engineering and a glimpse into its future. Tissue Eng. 2006;12(5):1137-2. CrossRef
  13. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101(7):1869-9. CrossRef
  14. Fedorovich NE, Alblas J, de Wijn JR, Hennink WE, Verbout AJ, Dhert WJ. Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. Tissue Eng. 2007;13(8):1905-5. CrossRef
  15. Cohn D, Sosnik A, inventors; Responsive biomedical composites. 2005.
  16. Park D, Wu W, Wang Y. A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer. Biomaterials. 2011;32(3):777-6. CrossRef
  17. Nguyen MK, Lee DS. Injectable biodegradable hydrogels. Macromol Biosci. 2010;10(6):563-9. CrossRef
  18. Liao HT, Chen CT, Chen JP. Osteogenic differentiation and ectopic bone formation of canine bone marrow-derived mesenchymal stem cells in injectable thermo-responsive polymer hydrogel. Tissue Eng Part C Methods. 2011;17(11):1139-9. CrossRef
  19. Cohn D, Lando G, Sosnik A, Garty S, Levi A. PEO–PPO–PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers. Biomaterials. 2006;27(9):1718-7. CrossRef
  20. Alexandridis P, Holzwarth JF, Hatton TA. Micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers in aqueous solutions: thermodynamics of copolymer association. Macromolecules. 1994;27(9):2414-5. CrossRef
  21. Boker W, Yin Z, Drosse I, Haasters F, Rossmann O, Wierer M, et al. Introducing a single-cell-derived human mesenchymal stem cell line expressing hTERT after lentiviral gene transfer. J Cell Mol Med. 2008;12(4):1347-9. CrossRef
  22. Haasters F, Prall WC, Anz D, Bourquin C, Pautke C, Endres S, et al. Morphological and immunocytochemical characteristics indicate the yield of early progenitors and represent a quality control for human mesenchymal stem cell culturing. J Anat. 2009;214(5):759-7. CrossRef
  23. Polzer H, Volkmer E, Saller MM, Prall WC, Haasters F, Drosse I, et al. Long-term detection of fluorescently labeled human mesenchymal stem cell in vitro and in vivo by semi-automated microscopy. Tissue Eng Part C Methods. 2012;18(2):156-5.
  24. Cespi M, Bonacucina G, Casettari L, Mencarelli G, Palmieri GF. Poloxamer thermogel systems as medium for crystallization. Pharm Res. 2012;29(3):818-6.
  25. Antunes FE, Gentile L, Rossi CO, Tavano L, Ranieri GA. Gels of pluronic F127 and nonionic surfactants from rheological characterization to controller drug permeation. Colloid Surf B Interfaces. 2011;87(1):42-. CrossRef
  26. Song MJ, Lee DS, Ahn JH, Kim DJ, Kimi SC. Dielectric behaviour during sol–gel transition of PEO–PPO–PEO triblock copolymers aqueous solution. Polym Bull. 2000;43:497-04. CrossRef
  27. Schwaz C, Leicht U, Drosse I, Ulrich V, Luibl V, Schieker M, et al. Characterization of adipose-derived equine and canine mesenchymal stem cells after incubation in agarose-hydrogel. Vet Res Commun. 2011;35(8):487-9. CrossRef
  28. Watanabe J, Kashii M, Hirao M, Oka K, Sugamoto K, Yoshikawa H, et al. Quick-forming hydroxyapatite/agarose gel composites induce bone regeneration. J Biomed Mater Res A. 2007;83(3):845-2.
  29. Sakai S, Hashimoto I, Kawakami K. Synthesis of an agarose-gelatin conjugate for use as a tissue engineering scaffold. J Biosci Bioeng. 2007;103(1):22-. CrossRef
  30. Nuss KM, Auer JA, Boos A, von Rechenberg B. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones. BMC Musculoskelet Disord. 2006;7:67. CrossRef
  
• 作者单位：Elias Volkmer (1)
  Uta Leicht (1)
  Martina Moritz (1)
  Christina Schwarz (1)
  Hinrich Wiese (2)
  Stefan Milz (3)
  Philipp Matthias (4)
  Winfried Schloegl (4)
  Wolfgang Friess (4)
  Michael Goettlinger (5)
  Peter Augat (5)
  Matthias Schieker (1) (6)
  
  1. Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Nussbaumstr. 20, 80336, Munich, Germany
  2. PolyMaterials AG, Innovapark 20, 87600, Kaufbeuren, Germany
  3. Anatomische Anstalt, Ludwig-Maximilians-University, Pettenkoferstr. 11, 80336, Munich, Germany
  4. Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University, Butenandtstr. 5, 81377, Munich, Germany
  5. Institute of Biomechanics, Trauma Center Murnau, Prof.-Küntscher-Str. 8, 82418, Murnau, Germany
  6. LivImplant GmbH, Truhenseeweg 8, 82319, Starnberg, Germany
  

文摘

Cell-based regenerative therapies for bone defects usually employ bone precursor cells seeded on solid scaffolds. Thermosensitive hydrogels that harden at body core temperature are promising alternative cell carriers as they are applicable minimally invasively. We modified Pluronic? P123 with different chain extenders and assessed rheology and biocompatibility of the resulting hydrogels. The best candidate was tested in a rat’s femoral defect model. All gels hardened above 25?°C with butane-diisocyanate-hydrogels (BDI-gels) displaying the highest storage moduli. BDI-gels showed the most favourable biocompatibility and did not affect cellular adipogenic or osteogenic differentiation in vitro. Implantation of BDI-hydrogel into femoral defects did not impede bone healing in vivo as evidenced by μCT and histological analysis. We conclude that thermosensitive BDI-gels are promising alternative cell carriers. The gels harden upon injection in vivo without interfering with bone metabolism. Further experiments will assess the gels-capacity to effectively transport living cells into bone defects.