The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide-co-glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium.
Methods:
NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 μm.
Results:
The drug loading efficiency of scaffolds was found to be higher than 84%, and about 90%–98% of NS was released at the end of 7 days with a fast drug release rate at the initial period of time and then in a slow and sustained manner. The corneal epithelial cells were isolated from New Zealand white rabbits. The obtained cells were seeded onto scaffolds and continued to increase during the time period of the study, indicating that the scaffolds might promote corneal epithelial cell proliferation without causing toxic effects for at least 10 days.
Conclusions:
The NS-loaded PLGA scaffolds exhibited a combination of controlled drug release and biomimetic properties that might be attractive for use in treatment of corneal damage both for controlled release and biomedical applications.
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References
1.
GhezziC.E., Rnjak-KovacinaJ., and KaplanD.L.Corneal tissue engineering: recent advances and future perspectives. Tissue Eng. Part B Rev. 21:278–287, 2015.
2.
NishidaK.Tissue engineering of the cornea. Cornea. 22:28–34, 2003.
3.
YangJ., YamatoM., KohnoC., et al.Cell sheet engineering: recreating tissues without biodegradable scaffolds. Biomaterials. 26:6415–6422, 2005.
4.
WangX., MajumdarS., MaG., et al.Chondroitin sulfate-based biocompatible crosslinker restores corneal mechanics and collagen alignment. Invest. Ophthalmol. Vis. Sci. 58:3887–3895, 2017.
5.
HallabN.J., BundyK.J., O'ConnorK., MosesR.L., and JacobsJ.J.Evaluation of metallic and polymeric biomaterial surface energy and surface roughness characterization for directed cell adhesion. Tissue Eng. 7:55–71, 2001.
6.
LiangW.H., KienitzB.L., PenickK.J., et al.Concentrated collagen-chondroitin sulfate scaffolds for tissue engineering applications. J. Biomed Mater. Res. A. 94A:1050–1060, 2010.
7.
MalafayaP.B., SilvaG.A., BaranE.T., and ReisR.L.Drug delivery therapies I—general trends and its importance on bone tissue engineering applications. Curr. Opin. Solid STM. 6:283–295, 2002.
8.
GomesM.E., and ReisR.L.Tissue engineering: key elements and some trends. Macromol. Biosci. 4:737–742, 2004.
9.
YangX.B., RoachH.I., ClarkeN.M.P., et al. Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification. Bone. 29:523–531, 2001.
10.
NojehdehianaH., MoztarzadehF., BaharvandH., NazarianH., and TahririM.Preparation and surface characterization of poly-L-lysine-coated PLGA microsphere scaffolds containing retinoic acid for nerve tissue engineering: in vitro study. Colloids Surf. B Biointerfaces. 73:23–29, 2009.
11.
DaviesN.H., SchmidtC., BezuidenhoutD., and ZillaP.Sustaining neovascularization of a scaffold through staged release of vascular endothelial growth factor-A and platelet-derived growth factor-BB. Tissue Eng. Part A. 18:26–34, 2012.
12.
JeongJ.H., ByunY., and ParkT.G.Synthesis and characterization of poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) biodegradable micelles. J. Biomater Sci. Polym. Ed. 14:1–11, 2003.
13.
AroninC.E.P., SefcikL.S., TholpadyS., et al.FTY720 Promotes local microvascular network formation and regeneration of cranial bone defects. Tissue Eng. Part A. 16:1801–1809, 2010.
14.
VishnubhotlaR., BharadwajS., SunS., MetlushkoV., and GloverS.Treatment with Y-27632, a ROCK inhibitor, increases the proinvasive nature of SW620 cells on 3D collagen type 1 matrix. Int. J. Biochem. Cell Biol. 2012:259142, 2012.
15.
AhujaM., DhakeA.S., SharmaS.K., and MajumdarD.K.Topical ocular delivery of NSAIDs. AAPS J. 10:229–241, 2008.
16.
Riazi-EsfahaniM., PeymanG., AydinE., et al.Prevention of corneal neovascularization: evaluation of various commercially available compounds in an experimental rat model. Cornea. 25:801–805, 2006.
17.
KimS.J., FlachA.J., and JampolL.M.Non-steroidal anti-inflammatory drugs in ophthalmology. Surv. Ophthalmol. 55:108–133, 2010.
18.
WhangK., GoldstickT.K., and HealyK.E.A biodegradable polymer scaffold for delivery of osteotropic factors. Biomaterials. 21:2545–2551, 2000.
19.
YaoJ., KoC.W., BaranovP.Y., et al.Enhanced differentiation and delivery of mouse retinal progenitor cells using a micropatterned biodegradable thin-film polycaprolactone scaffold. Tissue Eng. Part A. 21:1–12, 2015.
20.
ZhaoL., HeC., GaoY., et al.Preparation and cytocompatibility of PLGA scaffolds with controllable fiber morphology and diameter using electrospinning method. J. Biomed. Mater. Res B. 87:26–34, 2008.
21.
YuanY., ShiX., GanZ., and WangF.Modification of porous PLGA microspheres by poly-l-lysine for use as tissue engineering scaffolds. Colloids Surf. B Biointerfaces. 161:162–168, 2018.
22.
PatakangasJ., JingY., AsgharM.I., and LundP.D.Investigation of LiNiCuZn-oxide electrodes prepared by different methods: synthesis, characterization and properties for ceramic carbonate composite fuel cells. Int. J. Hydrogen Energ. 41:7609–7613, 2016.
23.
VlierbergheS.V., DubruelP., LippensE., et al.Toward modulating the architecture of hydrogel scaffolds: curtains versus channels. J. Mater. Sci. Mater. Med. 19:1459–1466, 2008.
24.
KayıranS., Bozdağ Pehlivan, S., Çelebier, M., and Ünlü, N. Determination of naproxen sodium from poly(lactide-co-glycolide) corneal scaffolds. Turk. J. Pharm. Sci., 7:57–68, 2010.
25.
RafatM., XeroudakiM., KoulikovskaM., et al.Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications. Biomaterials. 83:142–155, 2016.
26.
KimM.K., LeeJ.L., ShinK.S., et al.Isolation of putative corneal epithelial stem cells from cultured limbal tissue. Korean J. Ophthalmol. 20:55–61, 2006.
27.
JacobJ.T., RochefortJ.R., BiJ., and GebhardtB.M.Corneal epithelial cell growth over tethered-protein/peptide surface-modified hydrogels. J. Biomed. Mater. Res. B. 72:198–205, 2005.
28.
LekhanontK., ChoubtumL., ChuckR.S., et al.A serum- and feeder-free technique of culturing human corneal epithelial stem cells on amniotic membrane. Mol. Vis. 15:1294–1302, 2009.
29.
FrankeO., DurstK., MaierV., et al.Mechanical properties of hyaline and repair cartilage studied by nanoindentation. Acta Biomater. 3:873–881, 2007.
30.
International Standarts forBusiness, Government and SocietyISO 10993–5:2009, Biological evaluation of medical devices—Part 5: tests for in vitro cytotoxicity. www.iso.org/iso/catalogue_detail.htm?csnumber=36406 Accessed September24, 2019.
31.
UnyayarA., DemirbilekM., TurkogluM., et al.Evaluation of cytotoxic and mutagenic effects of coriolus versicolor and Funalia trogii extracts on mammalian cells. Drug Chem. Toxicol. 29:69–83, 2006.
32.
ParkH.K., LeeK.W., ChoiJ.S., and JooC.K.Mitomycin C-induced cell death in mouse lens epithelial lens. Ophthalmic Res. 34:213–219, 2002.
33.
KuoY.C., and KuI.N.Effects of gel concentration, human fibronectin, and cation supplement on the tissue-engineered cartilage. Biotechnol. Prog. 23:238–245, 2007.
34.
BolandE.D., EspyP.G., and BowlinG.L.Tissue engineering scaffolds. In: WnekG.E., BowlinG.L., eds. Encyclopedia of Biomaterials and Biomedical Engineering. Virginia: Richmond; 2004; p. 1633–1635.
35.
SchoofH., ApelJ., HeschelI., and RauG.Control of pore structure and size in freeze-dried collagen sponges. J. Biomed. Mater. Res. 58:352–357, 2001.
36.
HealyK.E., WhangK., and ThomasC.H.Method of Fabricating Emulsion Freeze-Dried Scaffold Bodies and Resulting Products. U.S. Patent No: 5723508, Evanston.
37.
ThomsonH.A., TreharneA.J., WalkerP., GrosselM.C., and LoteryA.J.Optimisation of polymer scaffolds for retinal pigment epithelium (RPE) cell transplantation. Br. J. Ophthalmol. 95:563–568, 2011.
38.
KimH., KimH.W., and SuhH.Sustained release of ascorbate-2-phosphate and dexamethasone from porous PLGA scaffolds for bone tissue engineering using mesenchymal stem cells. Biomaterials. 24:4671–4679, 2003.
39.
KuC.S., SathishkumarM., and MunS.P.Binding affinity of proanthocyanidin from waste Pinus radiata bark onto proline-rich bovine achilles tendon collagen type I. Chemosphere. 67:1618–1627, 2007.
40.
PengH., XiaoY., MaoX., et al.Amphiphilic triblock copolymers of methoxy-poly(ethyleneglycol)-b-poly(Llactide)-b-poly(L-lysine) for enhancement of osteoblast attachment and growth. Biomacromolecules. 10:95–104, 2009.
41.
CamposY., AlmirallA., FuentesG., et al.Tissue engineering: an alternative to repair cartilage. Tissue Eng. Part B Rev. 25:357–373, 2019.
42.
DuarteA.R.C., ManoJ.F., and ReisR.L.Dexamethasone-loaded scaffolds prepared by supercritical-assisted phase inversion. Acta Biomater. 5:2054–2062, 2009.
43.
YoonJ.J., and ParkT.G.Degradation behaviors of biodegradable macroporous scaffolds prepared by gas foaming of effervescent salts. J. Biomed. Mater. Res. 55:401–408, 2001.
44.
AbidZ., Dalskov MosgaardM., ManfroniG., et al.Investigation of mucoadhesion and degradation of PCL and PLGA microcontainers for oral drug delivery. Polymers. 11:1828, 2019.
45.
LiX.K., CaiS.X., LiuB., et al.Characteristics of PLGA-gelatin complex as potential artificial nerve scaffold. Colloids Surf. B Biointerfaces. 57:198–203, 2007.
46.
TezcanerA., and HicksD.In vitro characterization of micropatterned PLGA-PHBV8 blend films as temporary scaffolds for photoreceptor cells. J. Biomed. Mater. Res. A. 86:170–181, 2008.
47.
BarbantiS.H., SantosA.R., ZavagliaC.A., and DuekE.A.Porous and dense poly(L-lactic acid) and poly(D,L-lactic acid-co-glycolic acid) scaffolds: in vitro degradation in culture medium and osteoblasts culture. J. Mater. Sci. Mater. Med. 15:1315–1321, 2004.
48.
TesfamariamB.Bioresorbable vascular scaffolds: biodegradation, drug delivery and vascular remodeling. Pharmacol. Res. 107:163–171, 2016.
49.
ChewS.A., ArriagaM.A., and HinojosaV.A.Effects of surface area to volume ratio of PLGA scaffolds with different architectures on scaffold degradation characteristics and drug release kinetics. J. Biomed. Mater. Res. 104:1202–1211, 2016.
50.
RevesB.T., BumgardnerJ.D., ColeJ.A., YangY., and HaggardW.O.Lyophilization to improve drug delivery for chitosan-calcium phosphate bone scaffold construct: a preliminary investigation. J. Biomed. Mater. Res. 90:1–10, 2009.
51.
SandorM., EnscoreD., WestonP., and MathiowitzE.Effect of protein molecular weight on release from micron-sized PLGA microspheres. J. Control. Release, 76:297–311, 2001.
52.
KimK., LuuY.K., ChangC., et al.Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. J. Control. Release, 98:47–56, 2004.
53.
PrabaharanM., and JayakumarR.Chitosan-graft-β-cyclodextrin scaffolds with controlled drug release capability for tissue engineering applications. Int. J. Biol. Macromol. 44:320–325, 2009.
54.
ShinH.J., LeeC.H., ChoI.H., et al.Electrospun PLGA nanofiber scaffolds for articular cartilage reconstruction: mechanical stability, degradation and cellular responses under mechanical stimulation in vitro. J. Biomater. Sci. Polym. Ed. 17:103–119, 2006.
55.
DeshpandeP., McKeanR., BlackwoodK.A., et al.Using poly (lactide-co-glycolide) electrospun scaffolds to deliver cultured epithelial cells to the cornea. Regen. Med. 5:395–401, 2010.
56.
Tanifuji-TeraiN., TeraiK., HayashiY., ChikamaT., and KaoW.W.Expression of keratin 12 and maturation of corneal epithelium during development and postnatal growth. Invest. Ophthalmol. Vis. Sci. 47:545–551, 2006.
57.
HigaK., ShimmuraS., KatoN.et al. Proliferation and differentiation of transplantable rabbit epithelial sheets engineered with or without an amniotic membrane carrier. Invest. Ophthalmol. Vis. Sci. 48:597–604, 2007.
