Evaluation of Angiogenic Factor Release From Thermosensitive Poly N-Vinylcaprolactam -g-Collagen: In Vitro and In Vivo Studies

Evaluation of Angiogenic Factor Release From Thermosensitive Poly N-Vinylcaprolactam -g-Collagen: In Vitro and In Vivo Studies

I n this study, a thermosensitive poly N-vinylcaprolactam -g-collagen PNVCL-g-Col hybrid hydrogel was synthesized by conjugation using the NHS/EDC cross-linking system, and characterized. At first, the efficiency of in vitro sustained delivery of human vascular endothelial growth factor VEGF from the thermosensitive PNVCL-g-Col hydrogel modified with heparin, was evaluated for duration of ten days under in vitro physiological conditions 37oC, pH 7.4 . The results indicated that PNVCL-g-Col hydrogel preserved its stability and released ~90% of the loaded VEGF within this time period. In vitro study showed that PNVCL-g-Col was basically histocompatible. Then, the in vivo angiogenic activity of the VEGF-releasing PNVCL-g-Col was investigated using a subcutaneous rat model. In vivo study confirmed that angiogenic-factor-loaded PNVCL-g-Col had the capacity to induce neovascularization indicating that the in vivo bioactivity of the VEGF was preserved in the thermosensitive PNVCL-g-Col

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  • 1. Hoffman AS. Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation. Adv. Drug Deliv. Rev., 65, 10–16, 2013.
  • 2. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev., 64, 49–60, 2012.
  • 3. Peppas NA, Hilt JZ, Khademhosseini A. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater;18:1345–60, 2006.
  • 4. Jeong B, Kim SW, Bae YH. Rev. Thermosensitive Sol−Gel Reversible Hydrogels. Adv. Drug Delivery, 64 (Supplement), 154−162, 2012.
  • 5. Cortez-Lemus NA, Licea-Claverie A. Poly(Nvinylcaprolactam), a comprehensive review on a thermoresponsive polymer becoming popular. Prog Polym Sci 53,1, 2016.
  • 6. Ferraz CC, Varca GHCC, Ruiz J, Lopes PS, Mathor MB, Lugão AB, Bucio E. Radiation-grafting of thermo- and pH-responsive poly(N-vinylcaprolactam-coacrylic acid) onto silicone rubber and polypropylene films for biomedical purposes, Radiat. Phys. Chem. 97, 298–303, 2014.
  • 7. Gillette BM, Jensen JA, Tang B. In situ collagen assembly for integrating microfabricated threedimensional cell-seeded matrices. Nat. Mater. 7(8):636–640, 2008.
  • 8. Klouda L, Mikos AG. Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm. 68, 34–45, 2008.
  • 9. Lee SC, Kwon IK, Park K. Hydrogels for delivery of bioactive agents: A historical perspective. Adv Drug Deliv Rev; 65:17–20, 2013.
  • 10. Chu H, and Wang Y. Therapeutic angiogenesis: controlled delivery of angiogenic factors. Ther. Deliv. 3, 693–714, 2012.
  • 11. Gu C, Zheng R, Yang Z, Wen A, Wu H, Zhang H, Yi D. Novel glycidyl methacrylated dextran/ gelatin nanoparticles loaded with basic fibroblast growth factor: Formulation and characteristics. Drug Dev Ind Pharm;35: 1419–142, 2009.
  • 12. Prabaharan M, Grailer JJ, Steeber DA, Gong S. Stimuli-Responsive Chitosan-graft-Poly(Nvinylcaprolactam) as a Promising Material for Controlled Hydrophobic Drug Delivery. Macromol. Biosci., 8, 843–851, 2008.
  • 13. Liu J, Debuigne A, Detrembleur C, Jerome C. Poly(Nvinylcaprolactam): a thermoresponsive macromolecule with promising future in biomedical field. Adv Healthc Mater. 3, 1941– 68, 2014.
  • 14. Wu JY, Liu SQ, Heng PWS, Yang YY. Evaluating proteins release from, and their interactions with, thermosensitive poly (N-isopropylacrylamide) hydrogels. J Control Release. 102:361–372, 2005.
  • 15. Durkut S, Elçin YM. Synthesis and characterization of thermosensitive poly(N-vinylcaprolactam)-g-collagen. Artificial Cells, Nanomedicine, and Biotechnology, 45: 8, 1665-1674, 2017.
  • 16. Nortona LW, Tegnella E, Toporek SS, Reichert WM. In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings. Biomaterials 26 3285–3297, 2005.
  • 17. Elcin EA and Elcin MY. Localized Angiogenesis Induced by Human Vascular Endothelial Growth Factor-Activated PLGA Sponge. Tissue Engineering 12(4):959-6, 2006.
  • 18. Pike DB, Cai S, Pomraning KR, Firpo MA, Fisher RJ, Shu XZ, Prestwich GD, Peattie RA. Heparin-regulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF. Biomaterials Volume 27, Issue 30, October, Pages 5242-5251, 2006.
  • 19. Peattie RA, Rieke ER, Hewett EM, Fisher RJ, Shu XZ, Prestwich GD. Dual growth factor-induced angiogenesis in vivo using hyaluronan hydrogel implants. Biomaterials, 27 (2006), pp. 1868-1875, 2006.