Polycaprolactone (PCL) electrospun scaffolds have been widely investigated for cartilage repair application. However, their hydrophobicity and small pore size has been known to prevent cell attachment, proliferation and migration. Here, PCL was blended with gelatin (GEL) combining the favorable biological properties of GEL with the good mechanical performance of the former. Also, polyethylene glycol (PEG) particles were introduced during the electrospinning of the polymers blend by simultaneous electrospraying. These particles were subsequently removed resulting in fibrous scaffolds with enlarged pore size. PCL, GEL and PEG scaffolds formulations were developed and extensively structural and biologically characterized. GEL incorporation on the PCL scaffolds led to a considerably improved cell attachment and proliferation. A substantial pore size and interconnectivity increase was obtained, allowing cell infiltration through the porogenic scaffolds. All together these results suggest that this combined approach may provide a potentially clinically viable strategy for cartilage regeneration.
JohnstoneBAliniMCucchiariniM, et al.
Tissue engineering for articular cartilage repair – the state of the art. Eur Cell Mater2013;
25: 248–267.
2.
Camarero-EspinosaSRothen-RutishauserBFosterEJ, et al.
Articular cartilage: from formation to tissue engineering. Biomater Sci2016;
4: 734–767.
3.
ArmientoARStoddartMJAliniM, et al.
Biomaterials for articular cartilage tissue engineering: learning from biology. Acta Biomater2018;
65: 1–20.
4.
O’BrienFJ.Biomaterials & scaffolds for tissue engineering. Mater Today2011;
14: 88–95.
5.
Ghasemi-MobarakehLPrabhakaranMPMorshedM, et al.
Electrospun poly(ε-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials2008;
29: 4532–4539.
6.
ZhengRDuanHXueJ, et al.
The influence of Gelatin/PCL ratio and 3-D construct shape of electrospun membranes on cartilage regeneration. Biomaterials2014;
35: 152–164.
7.
KishanAPCosgriff-HernandezEM.Recent advancements in electrospinning design for tissue engineering applications: a review. J Biomed Mater Res A2017;
105A: 2892–2905.
8.
HornerCBLowKNamJ.Electrospun scaffolds for cartilage regeneration. In: HLiu (ed.) Nanocomposites for musculoskeletal tissue regeneration.
Amsterdam:
Elsevier, pp.213–240.
9.
McCullenSDAutefageHCallananA, et al.
Anisotropic fibrous scaffolds for articular cartilage regeneration. Tissue Eng Part A2012;
18: 2073–2083.
10.
SteeleJAMMcCullenSDCallananA, et al.
Combinatorial scaffold morphologies for zonal articular cartilage engineering. Acta Biomater2014;
10: 2065–2075.
11.
DamanikFFRSpadoliniGRotmansJ, et al.
Biological activity of human mesenchymal stromal cells on polymeric electrospun scaffolds. Biomater Sci2019;
7: 1088–1100.
12.
GautamSDindaAKMishraNC.Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method. Mater Sci Eng C Mater Biol Appl2013;
33: 1228–1235.
13.
YaoRHeJMengG, et al.
Electrospun PCL/Gelatin composite fibrous scaffolds: mechanical properties and cellular responses. J Biomater Sci Polym Ed2016;
27: 824–838.
14.
BhattaraiNLiZGunnJ, et al.
Natural-synthetic polyblend nanofibers for biomedical applications. Adv Mater2009;
21: 2792–2797.
15.
PowellHMBoyceST.Engineered human skin fabricated using electrospun collagen-PCL blends: morphogenesis and mechanical properties. Tissue Eng Part A2009;
15: 2177–2187.
16.
AldanaAAAbrahamGA.Current advances in electrospun gelatin-based scaffolds for tissue engineering applications. Int J Pharm2017;
523: 441–453.
17.
ZhangYOuyangHChweeTL, et al.
Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J Biomed Mater Res Part B Appl Biomater2005;
72: 156–165.
18.
StrobelHACalamariELBeliveauA, et al.
Fabrication and characterization of electrospun polycaprolactone and gelatin composite cuffs for tissue engineered blood vessels. J Biomed Mater Res Part B Appl Biomater2018;
106: 817–826.
19.
Alvarez-PerezMAGuarinoVCirilloV, et al.
Influence of gelatin cues in PCL electrospun membranes on nerve outgrowth. Biomacromolecules2010;
11: 2238–2246.
20.
FuWLiuZHuR, et al.
Electrospun gelatin/PCL and collagen/PLCL scaffolds for vascular tissue engineering. Int J Nanomedicine2014;
9: 2335–2344.
21.
KeRYiWTaoS, et al.
Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes. Mater Sci Eng C2017;
78: 324–332.
22.
XueJFengBZhengR, et al.
Engineering ear-shaped cartilage using electrospun fibrous membranes of gelatin/polycaprolactone. Biomaterials2013;
34: 2624–2631.
23.
HeXFengBHuangC, et al.
Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering. Int J Nanomedicine2015;
10: 2089–2099.
24.
Rnjak-KovacinaJWeissAS.Increasing the pore size of electrospun scaffolds. Tissue Eng Part B Rev2011;
17: 365–372.
25.
HunzikerEBQuinnTMHäuselmannHJ.Quantitative structural organization of normal adult human articular cartilage. Osteoarthr Cartil2002;
10: 564–572.
26.
BakerBMShahRPSilversteinAM, et al.
Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation. Proc Natl Acad Sci USA2012;
109: 14176–14181.
27.
PhamQPSharmaUMikosAG.Electrospun poly (epsilon-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: Characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules2006;
7: 2796–2805.
28.
FormicaFAÖztürkEHessSC, et al.
A bioinspired ultraporous nanofiber-hydrogel mimic of the cartilage extracellular matrix. Adv Healthc Mater2016;
5: 3129–3138.
29.
WrightLDAndricTFreemanJW.Utilizing NaCl to increase the porosity of electrospun materials. Mater Sci Eng C2011;
31: 30–36.
30.
BakerBMGeeAOMetterRB, et al.
The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials2008;
29: 2348–2358.
31.
WangKZhuMLiT, et al.
Improvement of cell infiltration in electrospun polycaprolactone scaffolds for the construction of vascular grafts. J Biomed Nanotechnol2014;
10: 1588–1511.
32.
ChongEJPhanTTLimIJ, et al.
Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution. Acta Biomater2007;
3: 321–330.
33.
RoseJBSidneyLEPatientJ, et al.
In vitro evaluation of electrospun blends of gelatin and PCL for application as a partial thickness corneal graft. J Biomed Mater Res A2019;
107: 828–838.
34.
LiJMakA.Hydraulic permeability of polyglycolic acid scaffolds as a function of biomaterial degradation. J Biomater Appl2005;
19: 253–266.
35.
OliverWCPharrGM.An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res1992;
7: 1564–1583.
36.
Gil-CastellOBadiaJDRibes-GreusA.Tailored electrospun nanofibrous polycaprolactone/gelatin scaffolds into an acid hydrolytic solvent system. Eur Polym J2018;
101: 273–281.
37.
SkotakMRagusaJGonzalezD, et al.
Improved cellular infiltration into nanofibrous electrospun cross-linked gelatin scaffolds templated with micrometer sized polyethylene glycol fibers. Biomed Mater2011;
6: 055012.
ErenciaMCanoFTorneroJA, et al.
Preparation of electrospun nanofibers from solutions of different gelatin types using a benign solvent mixture composed of water/PBS/ethanol. Polym Adv Technol2016;
27: 382–392.
41.
Ratajska-GadomskaBGadomskiW.Influence of confinement on solvation of ethanol in water studied by Raman spectroscopy. J Chem Phys2010;
133: 234505.
42.
MunjHRLannuttiJJTomaskoDL.Understanding drug release from PCL/gelatin electrospun blends. J Biomater Appl2017;
31: 933–949.
43.
LittleCJBawolinNKChenX.Mechanical properties of natural cartilage and tissue-engineered constructs. Tissue Eng Part B Rev2011;
17: 213–227.
44.
TripathiAMeloJS.Preparation of a sponge-like biocomposite agarose-chitosan scaffold with primary hepatocytes for establishing an in vitro 3D liver tissue model. RSC Adv2015;
5: 30701–30710.
45.
JeongCGZhangHHollisterSJ.Three-dimensional poly(1,8-octanediol-co-citrate) scaffold pore shape and permeability effects on sub-cutaneous in vivo chondrogenesis using primary chondrocytes. Acta Biomater2011;
7: 505–514.
46.
ChoDChenSJeongY, et al.
Surface hydro-properties of electrospun fiber mats. Fibers Polym2015;
16: 1578–1586.
47.
ElzeinTNasser-EddineMDelaiteC, et al.
FTIR study of polycaprolactone chain organization at interfaces. J Colloid Interface Sci2004;
273: 381–387.
48.
LimYCJohnsonJFeiZ, et al.
Micropatterning and characterization of electrospun poly(ε-caprolactone)/gelatin nanofiber tissue scaffolds by femtosecond laser ablation for tissue engineering applications. Biotechnol Bioeng2011;
108: 116–126.
49.
MohammadzadehmoghadamSDongY.Fabrication and characterization of electrospun silk fibroin/gelatin scaffolds crosslinked with glutaraldehyde vapor. Front Mater2019;
6: 1–12.
50.
DulnikJDenisPSajkiewiczP, et al.
Biodegradation of bicomponent PCL/gelatin and PCL/collagen nanofibers electrospun from alternative solvent system. Polym Degrad Stab2016;
130: 10–21.
51.
ChiengBIbrahimNYunusW, et al.
Poly(lactic acid)/poly(ethylene glycol) polymer nanocomposites: effects of graphene nanoplatelets. Polymers (Basel)2013;
6: 93–104.
52.
ChenCLiuKWangH, et al.
Morphology and performances of electrospun polyethylene glycol/poly (DL-lactide) phase change ultrafine fibers for thermal energy storage. Sol Energy Mater Sol Cells2013;
117: 372–381.
53.
PramanikSAtaollahiFPingguan-MurphyB, et al.
In vitro study of surface modified poly(ethylene glycol)-impregnated sintered bovine bone scaffolds on human fibroblast cells. Sci Rep2015;
5: 9806–9811.
54.
ZhouQZhangHZhouY, et al.
Alkali-mediated miscibility of gelatin/polycaprolactone for electrospinning homogeneous composite nanofibers for tissue scaffolding. Macromol Biosci2017;
17: 1–10.
55.
WongSCBajiALengS.Effect of fiber diameter on tensile properties of electrospun poly(ε-caprolactone). Polymer (Guildf)2008;
49: 4713–4722.
56.
GongMChiCYeJ, et al.
Icariin-loaded electrospun PCL/gelatin nanofiber membrane as potential artificial periosteum. Colloids Surf B Biointerfaces2018;
170: 201–209.
57.
WangJYuanBHanR.Modulus of elasticity of randomly and aligned polymeric scaffolds with fiber size dependency. J Mech Behav Biomed Mater2018;
77: 314–320.
58.
BellucciGSeedhomBB.Mechanical behaviour of articular cartilage under tensile cyclic load. Rheumatology (Oxford)2001;
40: 1337–1345.
59.
BoiMMarchioriGBerniM, et al.
Nanoindentation: an advanced procedure to investigate osteochondral engineered tissues. J Mech Behav Biomed Mater2019;
96: 79–87.
60.
JungJWLeeHHongJM, et al.
A new method of fabricating a blend scaffold using an indirect three-dimensional printing technique. Biofabrication2015;
7: 045003.
61.
StolzMGottardiRRaiteriR, et al.
Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol2009;
4: 186–192.
62.
AntonsJMarascioMGMNohavaJ, et al.
Zone-dependent mechanical properties of human articular cartilage obtained by indentation measurements. J Mater Sci Mater Med2018; 29: 57.
63.
DivietoCSassiMP.A first approach to evaluate the cell dose in highly porous scaffolds by using a nondestructive metabolic method. Futur Sci OA2015;
1: FSO58.
64.
FengBTuHYuanH, et al.
Acetic-acid-mediated miscibility toward electrospinning homogeneous composite nanofibers of GT/PCL. Biomacromolecules2012;
13: 3917–3925.
65.
WangKXuMZhuM, et al.
Creation of macropores in electrospun silk fibroin scaffolds using sacrificial PEO-microparticles to enhance cellular infiltration. J Biomed Mater Res A2013;
101: 3474–3481.
66.
FeeTSurianarayananSDownsC, et al.
Nanofiber alignment regulates NIH3T3 cell orientation and cytoskeletal gene expression on electrospun PCL+gelatin nanofibers. PLoS One2016;
11: e0154806.
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