TY - JOUR
T1 - Sustained delivery of growth factors with high loading efficiency in a layer by layer assembly
AU - Damanik, Febriyani F. R.
AU - Brunelli, Marzia
AU - Pastorino, Laura
AU - Ruggiero, Carmelina
AU - van Blitterswijk, Clemens
AU - Rotmans, Joris
AU - Moroni, Lorenzo
N1 - Funding Information:
This research forms part of the Project P3.03 DialysisXS of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation. The financial contribution of the Nierstichting Nederland is gratefully acknowledged. This research project was also possible, thanks to the Dutch Province of Limburg.
Publisher Copyright:
© 2019 The Royal Society of Chemistry.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Layer by layer (LBL) assembly has garnered considerable interest due to its ability to generate multifunctional films with high tunability and versatility in terms of substrates and polyelectrolytes, allowing the option to use complex devices and drugs. Polyelectrolytes, such as growth factors (GFs), are essential, but costly, delicate, biological molecules that have been used in various tissue regeneration applications. For this reason, the controlled drug delivery of efficiently loaded GFs via LBL assembly (GF-LBL) can contribute to the establishment of cost-effective biologically triggered biomedical applications. We have developed an LBL method to load GFs (specifically, transforming growth factor beta 1, platelet-derived growth factor beta beta, and insulin growth factor 1), with up to 90% efficiency approximately, by gas plasma surface activation and tuning the pH to increase the ionic strength of polyelectrolytes. Poly(styrenesulfonate) (PSS) and poly(ethyleneimine) (PEI) have been used to provide the initial necessary charge for multilayer build-up. Heparin and dextran sulphate have been investigated as counter polyelectrolytes to enhance the activity of GFs by protecting their ligands, where heparin resulted in the highest achievable loading efficiency for all GFs. Oxygen gas plasma and acidic pH levels also resulted in a significant increase in GF loading efficiency. The three GFs were released by diffusion and erosion in a controlled manner over lengthy time scales and the bioactivity was maintained for up to 14 days. When tested as implants in vitro, GF-LBL constructs increased fibroblast proliferation, influenced cell morphology and migration, and enhanced myofibroblast differentiation, indicating that the biological functionalities of the GFs were preserved. In conclusion, this developed LBL assembly method can provide a simple drug delivery system, which may yield more effective applications for tissue regeneration as well as biomedical sciences at large.
AB - Layer by layer (LBL) assembly has garnered considerable interest due to its ability to generate multifunctional films with high tunability and versatility in terms of substrates and polyelectrolytes, allowing the option to use complex devices and drugs. Polyelectrolytes, such as growth factors (GFs), are essential, but costly, delicate, biological molecules that have been used in various tissue regeneration applications. For this reason, the controlled drug delivery of efficiently loaded GFs via LBL assembly (GF-LBL) can contribute to the establishment of cost-effective biologically triggered biomedical applications. We have developed an LBL method to load GFs (specifically, transforming growth factor beta 1, platelet-derived growth factor beta beta, and insulin growth factor 1), with up to 90% efficiency approximately, by gas plasma surface activation and tuning the pH to increase the ionic strength of polyelectrolytes. Poly(styrenesulfonate) (PSS) and poly(ethyleneimine) (PEI) have been used to provide the initial necessary charge for multilayer build-up. Heparin and dextran sulphate have been investigated as counter polyelectrolytes to enhance the activity of GFs by protecting their ligands, where heparin resulted in the highest achievable loading efficiency for all GFs. Oxygen gas plasma and acidic pH levels also resulted in a significant increase in GF loading efficiency. The three GFs were released by diffusion and erosion in a controlled manner over lengthy time scales and the bioactivity was maintained for up to 14 days. When tested as implants in vitro, GF-LBL constructs increased fibroblast proliferation, influenced cell morphology and migration, and enhanced myofibroblast differentiation, indicating that the biological functionalities of the GFs were preserved. In conclusion, this developed LBL assembly method can provide a simple drug delivery system, which may yield more effective applications for tissue regeneration as well as biomedical sciences at large.
KW - TRANSFORMING GROWTH-FACTOR-BETA-1
KW - POLYELECTROLYTE MULTILAYERS
KW - HEPARAN-SULFATE
KW - THIN-FILMS
KW - DEPOSITION
KW - SURFACE
KW - DIFFERENTIATION
KW - NANOPARTICLES
KW - FABRICATION
KW - ADSORPTION
U2 - 10.1039/c9bm00979e
DO - 10.1039/c9bm00979e
M3 - Article
C2 - 31713550
SN - 2047-4830
VL - 8
SP - 174
EP - 188
JO - Biomaterials Science
JF - Biomaterials Science
IS - 1
T2 - 29th Annual Conference of the European Society for Biomaterials (ESB)
Y2 - 9 September 2018 through 13 September 2018
ER -