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Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Research

Fabrication of electrospun poly(d,l lactide-co-glycolide)80/20 scaffolds loaded with diclofenac sodium for tissue engineering

Authors: Lila Nikkola, Tatjana Morton, Elizabeth R. Balmayor, Hanna Jukola, Ali Harlin, Heinz Redl, Martijn van Griensven, Nureddin Ashammakhi

Published in: European Journal of Medical Research | Issue 1/2015

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Abstract

Background

Adaptation of nanotechnology into materials science has also advanced tissue engineering research. Tissues are basically composed of nanoscale structures hence making nanofibrous materials closely resemble natural fibers. Adding a drug release function to such material may further advance their use in tissue repair.

Methods

In the current study, bioabsorbable poly(d,l lactide-co-glycolide)80/20 (PDLGA80/20) was dissolved in a mixture of acetone/dimethylformamide. Twenty percent of diclofenac sodium was added to the solution. Nanofibers were manufactured using electrospinning. The morphology of the obtained scaffolds was analyzed by scanning electron microscopy (SEM). The release of the diclofenac sodium was assessed by UV/Vis spectroscopy. Mouse fibroblasts (MC3T3) were seeded on the scaffolds, and the cell attachment was evaluated with fluorescent microscopy.

Results

The thickness of electrospun nanomats was about 1 mm. SEM analysis showed that polymeric nanofibers containing drug particles formed very interconnected porous nanostructures. The average diameter of the nanofibers was 500 nm. Drug release was measured by means of UV/Vis spectroscopy. After a high start peak, the release rate decreased considerably during 11 days and lasted about 60 days. During the evaluation of the release kinetics, a material degradation process was observed. MC3T3 cells attached to the diclofenac sodium-loaded scaffold.

Conclusions

The nanofibrous porous structure made of PDLGA polymer loaded with diclofenac sodium is feasible to develop, and it may help to improve biomaterial properties for controlled tissue repair and regeneration.
Literature
1.
go back to reference Ashammakhi N, Ndreu A, Piras A, Nikkola L, Sindelar T, Ylikauppila H, et al. Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering. J Nanosci Nanotechnol. 2006;6:2693–711.PubMedCrossRef Ashammakhi N, Ndreu A, Piras A, Nikkola L, Sindelar T, Ylikauppila H, et al. Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering. J Nanosci Nanotechnol. 2006;6:2693–711.PubMedCrossRef
2.
go back to reference Jahani H, Kaviani S, Hassanpour-Ezatti M, Soleimani M, Kaviani Z, Zonoubi Z. The effect of aligned and random electrospun fibrous scaffolds on rat mesenchymal stem cell proliferation. Cell J. 2012;14:31–8.PubMedCentralPubMed Jahani H, Kaviani S, Hassanpour-Ezatti M, Soleimani M, Kaviani Z, Zonoubi Z. The effect of aligned and random electrospun fibrous scaffolds on rat mesenchymal stem cell proliferation. Cell J. 2012;14:31–8.PubMedCentralPubMed
3.
go back to reference Parwe SP, Chaudhari PN, Mohite KK, Selukar BS, Nande SS, Garnaik B. Synthesis of ciprofloxacin-conjugated poly (l-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation. Int J Nanomedicine. 2014;9:1463–77.PubMedCentralPubMed Parwe SP, Chaudhari PN, Mohite KK, Selukar BS, Nande SS, Garnaik B. Synthesis of ciprofloxacin-conjugated poly (l-lactic acid) polymer for nanofiber fabrication and antibacterial evaluation. Int J Nanomedicine. 2014;9:1463–77.PubMedCentralPubMed
4.
go back to reference Boland ED, Telemeco TA, Simpson DG, Wnek GE, Bowlin GL. Utilizing acid pretreatment and electrospinning to improve biocompatibility of poly(glycolic acid) for tissue engineering. J Biomed Mater Res B Appl Biomater. 2004;71:144–52.PubMedCrossRef Boland ED, Telemeco TA, Simpson DG, Wnek GE, Bowlin GL. Utilizing acid pretreatment and electrospinning to improve biocompatibility of poly(glycolic acid) for tissue engineering. J Biomed Mater Res B Appl Biomater. 2004;71:144–52.PubMedCrossRef
5.
go back to reference Sequeira SJ, Soscia DA, Oztan B, Mosier AP, Jean-Gilles R, Gadre A, et al. The regulation of focal adhesion complex formation and salivary gland epithelial cell organization by nanofibrous PLGA scaffolds. Biomaterials. 2012;33:3175–86.PubMedCentralPubMedCrossRef Sequeira SJ, Soscia DA, Oztan B, Mosier AP, Jean-Gilles R, Gadre A, et al. The regulation of focal adhesion complex formation and salivary gland epithelial cell organization by nanofibrous PLGA scaffolds. Biomaterials. 2012;33:3175–86.PubMedCentralPubMedCrossRef
6.
go back to reference Esposito AR, Moda M, Cattani SM, de Santana GM, Barbieri JA, Munhoz MM, et al. PLDLA/PCL-T scaffold for meniscus tissue engineering. Biores Open Access. 2013;2:138–47.PubMedCentralPubMedCrossRef Esposito AR, Moda M, Cattani SM, de Santana GM, Barbieri JA, Munhoz MM, et al. PLDLA/PCL-T scaffold for meniscus tissue engineering. Biores Open Access. 2013;2:138–47.PubMedCentralPubMedCrossRef
7.
go back to reference Nikkola L, Seppala J, Harlin A, Ndreu A, Ashammakhi N. Electrospun multifunctional diclofenac sodium releasing nanoscaffold. J Nanosci Nanotechnol. 2006;6:3290–5.PubMedCrossRef Nikkola L, Seppala J, Harlin A, Ndreu A, Ashammakhi N. Electrospun multifunctional diclofenac sodium releasing nanoscaffold. J Nanosci Nanotechnol. 2006;6:3290–5.PubMedCrossRef
8.
go back to reference Perumcherry SR, Chennazhi KP, Nair SV, Menon D, Afeesh R. A novel method for the fabrication of fibrin-based electrospun nanofibrous scaffold for tissue-engineering applications. Tissue Eng Part C Methods. 2011;17:1121–30.PubMedCrossRef Perumcherry SR, Chennazhi KP, Nair SV, Menon D, Afeesh R. A novel method for the fabrication of fibrin-based electrospun nanofibrous scaffold for tissue-engineering applications. Tissue Eng Part C Methods. 2011;17:1121–30.PubMedCrossRef
9.
go back to reference Fiorani A, Gualandi C, Panseri S, Montesi M, Marcacci M, Focarete ML, et al. Comparative performance of collagen nanofibers electrospun from different solvents and stabilized by different crosslinkers. J Mater Sci Mater Med. 2014;25:2313–21.PubMedCrossRef Fiorani A, Gualandi C, Panseri S, Montesi M, Marcacci M, Focarete ML, et al. Comparative performance of collagen nanofibers electrospun from different solvents and stabilized by different crosslinkers. J Mater Sci Mater Med. 2014;25:2313–21.PubMedCrossRef
10.
go back to reference Kong LY, Ziegler GR. Quantitative relationship between electrospinning parameters and starch fiber diameter. Carbohyd Polym. 2013;92:1416–22.CrossRef Kong LY, Ziegler GR. Quantitative relationship between electrospinning parameters and starch fiber diameter. Carbohyd Polym. 2013;92:1416–22.CrossRef
11.
go back to reference Ignatova M, Manolova N, Rashkov I. Electrospun antibacterial chitosan-based fibers. Macromol Biosci. 2013;13:860–72.PubMedCrossRef Ignatova M, Manolova N, Rashkov I. Electrospun antibacterial chitosan-based fibers. Macromol Biosci. 2013;13:860–72.PubMedCrossRef
12.
go back to reference Sekiya N, Ichioka S, Terada D, Tsuchiya S, Kobayashi H. Efficacy of a poly glycolic acid (PGA)/collagen composite nanofibre scaffold on cell migration and neovascularisation in vivo skin defect model. J Plast Surg Hand Surg. 2013;47:498–502.PubMed Sekiya N, Ichioka S, Terada D, Tsuchiya S, Kobayashi H. Efficacy of a poly glycolic acid (PGA)/collagen composite nanofibre scaffold on cell migration and neovascularisation in vivo skin defect model. J Plast Surg Hand Surg. 2013;47:498–502.PubMed
13.
go back to reference da Silva MA, Crawford A, Mundy J, Martins A, Araujo JV, Hatton PV, et al. Evaluation of extracellular matrix formation in polycaprolactone and starch-compounded polycaprolactone nanofiber meshes when seeded with bovine articular chondrocytes. Tissue Eng Part A. 2009;15:377–85.PubMedCrossRef da Silva MA, Crawford A, Mundy J, Martins A, Araujo JV, Hatton PV, et al. Evaluation of extracellular matrix formation in polycaprolactone and starch-compounded polycaprolactone nanofiber meshes when seeded with bovine articular chondrocytes. Tissue Eng Part A. 2009;15:377–85.PubMedCrossRef
14.
go back to reference Li J, Fu R, Li L, Yang G, Ding S, Zhong Z, et al. Co-delivery of dexamethasone and green tea polyphenols using electrospun ultrafine fibers for effective treatment of keloid. Pharm Res. 2014;31:1632–43.PubMedCrossRef Li J, Fu R, Li L, Yang G, Ding S, Zhong Z, et al. Co-delivery of dexamethasone and green tea polyphenols using electrospun ultrafine fibers for effective treatment of keloid. Pharm Res. 2014;31:1632–43.PubMedCrossRef
15.
go back to reference Shen X, Xu Q, Xu S, Li J, Zhang N, Zhang L. Preparation and transdermal diffusion evaluation of the prazosin hydrochloride-loaded electrospun poly(vinyl alcohol) fiber mats. J Nanosci Nanotechnol. 2014;14:5258–65.PubMedCrossRef Shen X, Xu Q, Xu S, Li J, Zhang N, Zhang L. Preparation and transdermal diffusion evaluation of the prazosin hydrochloride-loaded electrospun poly(vinyl alcohol) fiber mats. J Nanosci Nanotechnol. 2014;14:5258–65.PubMedCrossRef
16.
go back to reference Kim K, Luu YK, Chang C, Fang D, Hsiao BS, Chu B, et al. Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J Control Release. 2004;98:47–56.PubMedCrossRef Kim K, Luu YK, Chang C, Fang D, Hsiao BS, Chu B, et al. Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J Control Release. 2004;98:47–56.PubMedCrossRef
17.
go back to reference Zupanc M, Kosjek T, Petkovsek M, Dular M, Kompare B, Sirok B, et al. Removal of pharmaceuticals from wastewater by biological processes, hydrodynamic cavitation and UV treatment. Ultrason Sonochem. 2013;20:1104–12.PubMedCrossRef Zupanc M, Kosjek T, Petkovsek M, Dular M, Kompare B, Sirok B, et al. Removal of pharmaceuticals from wastewater by biological processes, hydrodynamic cavitation and UV treatment. Ultrason Sonochem. 2013;20:1104–12.PubMedCrossRef
18.
go back to reference Ashammakhi N, Ndreu A, Yang Y, Ylikauppila H, Nikkola L, Hasirci V. Tissue engineering: a new take-off using nanofiber-based scaffolds. J Craniofac Surg. 2007;18:3–17.PubMedCrossRef Ashammakhi N, Ndreu A, Yang Y, Ylikauppila H, Nikkola L, Hasirci V. Tissue engineering: a new take-off using nanofiber-based scaffolds. J Craniofac Surg. 2007;18:3–17.PubMedCrossRef
19.
go back to reference Nakano A, Miki N, Hishida K, Hotta A. Solution parameters for the fabrication of thinner silicone fibers by electrospinning. Phys Rev E Stat Nonlin Soft Matter Phys. 2012;86:011801.PubMedCrossRef Nakano A, Miki N, Hishida K, Hotta A. Solution parameters for the fabrication of thinner silicone fibers by electrospinning. Phys Rev E Stat Nonlin Soft Matter Phys. 2012;86:011801.PubMedCrossRef
21.
go back to reference Choi JS, Lee SW, Jeong L, Bae SH, Min BC, Youk JH, et al. Effect of organosoluble salts on the nanofibrous structure of electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Int J Biol Macromol. 2004;34:249–56.PubMedCrossRef Choi JS, Lee SW, Jeong L, Bae SH, Min BC, Youk JH, et al. Effect of organosoluble salts on the nanofibrous structure of electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Int J Biol Macromol. 2004;34:249–56.PubMedCrossRef
22.
go back to reference Kumbar SG, Nukavarapu SP, James R, Nair LS, Laurencin CT. Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials. 2008;29:4100–7.PubMedCentralPubMedCrossRef Kumbar SG, Nukavarapu SP, James R, Nair LS, Laurencin CT. Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials. 2008;29:4100–7.PubMedCentralPubMedCrossRef
23.
go back to reference Viitanen P, Suokas E, Tormala P, Ashammakhi N. Release of diclofenac sodium from polylactide-co-glycolide 80/20 rods. J Mater Sci Mater Med. 2006;17:1267–74.PubMedCrossRef Viitanen P, Suokas E, Tormala P, Ashammakhi N. Release of diclofenac sodium from polylactide-co-glycolide 80/20 rods. J Mater Sci Mater Med. 2006;17:1267–74.PubMedCrossRef
24.
go back to reference Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1988;35:244–85.PubMedCrossRef Todd PA, Sorkin EM. Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1988;35:244–85.PubMedCrossRef
25.
go back to reference Nie H, Wang CH. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J Control Release. 2007;120:111–21.PubMedCrossRef Nie H, Wang CH. Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J Control Release. 2007;120:111–21.PubMedCrossRef
26.
go back to reference Xu X, Chen X, Xu X, Lu T, Wang X, Yang L, et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells. J Control Release. 2006;114:307–16.PubMedCrossRef Xu X, Chen X, Xu X, Lu T, Wang X, Yang L, et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor activity against glioma C6 cells. J Control Release. 2006;114:307–16.PubMedCrossRef
27.
go back to reference Chua KN, Tang YN, Quek CH, Ramakrishna S, Leong KW, Mao HQ. A dual-functional fibrous scaffold enhances P450 activity of cultured primary rat hepatocytes. Acta Biomater. 2007;3:643–50.PubMedCrossRef Chua KN, Tang YN, Quek CH, Ramakrishna S, Leong KW, Mao HQ. A dual-functional fibrous scaffold enhances P450 activity of cultured primary rat hepatocytes. Acta Biomater. 2007;3:643–50.PubMedCrossRef
28.
go back to reference Sun R, Gimbel HV, Liu S, Guo D, Hollenberg MD. Effect of diclofenac sodium and dexamethasone on cultured human Tenon’s capsule fibroblasts. Ophthalmic Surg Lasers. 1999;30:382–8.PubMed Sun R, Gimbel HV, Liu S, Guo D, Hollenberg MD. Effect of diclofenac sodium and dexamethasone on cultured human Tenon’s capsule fibroblasts. Ophthalmic Surg Lasers. 1999;30:382–8.PubMed
29.
go back to reference Hassanzadeh-Khayyat M, Lai EPC, Kollu K, Ormeci B. Degradation of diclofenac in molecularly imprinted polymer submicron particles by UV light irradiation and HCl acid treatment. J Water Resource Prot. 2011;3:643–54.CrossRef Hassanzadeh-Khayyat M, Lai EPC, Kollu K, Ormeci B. Degradation of diclofenac in molecularly imprinted polymer submicron particles by UV light irradiation and HCl acid treatment. J Water Resource Prot. 2011;3:643–54.CrossRef
30.
go back to reference Piras AM, Nikkola L, Chiellini F, Ashammakhi N, Chiellini E. Development of diclofenac sodium releasing bio-erodible polymeric nanomats. J Nanosci Nanotechnol. 2006;6:3310–20.PubMedCrossRef Piras AM, Nikkola L, Chiellini F, Ashammakhi N, Chiellini E. Development of diclofenac sodium releasing bio-erodible polymeric nanomats. J Nanosci Nanotechnol. 2006;6:3310–20.PubMedCrossRef
31.
go back to reference Ndreu A, Nikkola L, Ylikauppila H, Ashammakhi N, Hasirci V. Electrospun biodegradable nanofibrous mats for tissue engineering. Nanomedicine (Lond). 2008;3:45–60.PubMedCrossRef Ndreu A, Nikkola L, Ylikauppila H, Ashammakhi N, Hasirci V. Electrospun biodegradable nanofibrous mats for tissue engineering. Nanomedicine (Lond). 2008;3:45–60.PubMedCrossRef
Metadata
Title
Fabrication of electrospun poly(d,l lactide-co-glycolide)80/20 scaffolds loaded with diclofenac sodium for tissue engineering
Authors
Lila Nikkola
Tatjana Morton
Elizabeth R. Balmayor
Hanna Jukola
Ali Harlin
Heinz Redl
Martijn van Griensven
Nureddin Ashammakhi
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-015-0145-1

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