In this study, polycaprolactone scaffolds fabricated by a salt-leaching process were loaded with biphasic calcium phosphate successfully to improve the osteoconductivity in bone regeneration. The surface of polycaprolactone/biphasic calcium phosphate scaffolds was aminolyzed by 1,6-hexamethylenediamine to introduce amino groups onto the surface, which was verified qualitatively by ninhyrin staining. Collagen was further immobilized on the aminolyzed porous polycaprolactone via N-ethyl-N′-(3-dimethylaminopropy) carbodiimide hydrochloride/hydroxy-2,5-dioxopyrolidine-3-sulfonic acid sodium cross-linking. The pore size of polycaprolactone/biphasic calcium phosphate-collagen scaffolds was 200–300 µm, which was suitable for bone in-growth. The X-ray photoelectron spectroscopy confirmed the coupling of collagen immobilized on the surface of polycaprolactone/biphasic calcium phosphate. In vitro results demonstrated that the spreading and viability of MC3T3-E1 cells were remarkably improved in the polycaprolactone/biphasic calcium phosphate-collagen scaffolds. The in vivo study was carried out by implanting the porous polycaprolactone, polycaprolactone/biphasic calcium phosphate, and polycaprolactone/biphasic calcium phosphate-collagen to the skulls of rats. Although the addition of biphasic calcium phosphate particles in the polycaprolactone scaffolds does not have a strong effect on the new bone formation, the immobilization of collagen on the polycaprolactone/biphasic calcium phosphate scaffolds significantly improved the bone regeneration even though the implantation time was short, 6 weeks. The present results provide more evidence that functionalizing polycaprolactone with biphasic calcium phosphate and collagen may be a feasible way to improve the osteoconduction in bone regeneration.
YavariSAAhmadiSMvan der StokJ. Effects of bio-functionalizing surface treatments on the mechanical behavior of open porous titanium biomaterials. J Mech Behav Biomed Mater2014; 36: 109–119.
2.
de MelAJellGStevensMM. Biofunctionalization of biomaterials for accelerated in situ endothelialization: a review. Biomacromolecules2008; 9: 2969–2979.
3.
SanghviABMillerKP-HBelcherAM. Biomaterials functionalization using a novel peptide that selectively binds to a conducting polymer. Nat Mater2005; 4: 496–502.
4.
MaiaFRBidarraSJGranjaPL. Functionalization of biomaterials with small osteoinductive moieties. Acta Biomater2013; 9: 8773–8789.
5.
PuleoDANanciA. Understanding and controlling the bone–implant interface. Biomaterials1999; 20: 2311–2321.
6.
SealBLOteroTCPanitchA. Polymeric biomaterials for tissue and organ regeneration. Mater Sci Eng R: Rep2001; 34: 147–230.
7.
ZhuYGaoCShenJ. Surface modification of polycaprolactone with poly(methacrylic acid) and gelatin covalent immobilization for promoting its cytocompatibility. Biomaterials2002; 23: 4889–4895.
8.
Ghasemi-MobarakehLPrabhakaranMPMorshedM. Bio-functionalized PCL nanofibrous scaffolds for nerve tissue engineering. Mater Sci Eng C2010; 30: 1129–1136.
9.
WuQYoshinoTSakabeH. Chemical modification of zein by bifunctional polycaprolactone (PCL). Polymer2003; 44: 3909–3919.
10.
ZhuYGaoCLiuX. Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cytocompatibility of human endothelial cells. Biomacromolecules2002; 3: 1312–1319.
11.
GoddardJMHotchkissJH. Polymer surface modification for the attachment of bioactive compounds. Prog Polym Sci2007; 32: 698–725.
12.
Roohani-EsfahaniS-INouri-KhorasaniSLuZ. The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite–PCL composites. Biomaterials2010; 31: 5498–5509.
13.
YangFWolkeJGCJansenJA. Biomimetic calcium phosphate coating on electrospun poly(ε-caprolactone) scaffolds for bone tissue engineering. Chem Eng J2008; 137: 154–161.
14.
TanPSTeohSH. Effect of stiffness of polycaprolactone (PCL) membrane on cell proliferation. Mater Sci Eng C2007; 27: 304–308.
15.
Dos SantosEAFarinaMSoaresGA. Chemical and topographical influence of hydroxyapatite and β-tricalcium phosphate surfaces on human osteoblastic cell behavior. J Biomed Mater Res Part A2009; 89: 510–520.
16.
EharaAOgataKImazatoS. Effects of α-TCP and TetCP on MC3T3-E1 proliferation, differentiation and mineralization. Biomaterials2003; 24: 831–836.
17.
HeWMaZYongT. Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its potential for endothelial cells growth. Biomaterials2005; 26: 7606–7615.
18.
PorterJRHensonAPopatKC. Biodegradable poly(3-caprolactone) nanowires for bone tissue engineering applications. Biomaterials2009; 30: 780–788.
19.
YangCRWangYJChenXF. Biomimetic fabrication of BCP/COL/HCA scaffolds for bone tissue engineering. Mater Lett2005; 59: 3635–3640.
20.
LeeB-TYounM-HPaulRK. In situ synthesis of spherical BCP nanopowders by microwave assisted process. Mater Chem Phys2007; 104: 249–253.
21.
LiuXSmithLAHuJ. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials2009; 30: 2252–2258.
22.
KimH-WSongJ-HKimH-E. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration. Adv Funct Mater2005; 15: 1988–1994.
23.
LinhNTBLeeK-HLeeB-T. Functional nanofiber mat of polyvinyl alcohol/gelatin containing nanoparticles of biphasic calcium phosphate for bone regeneration in rat calvaria defects. J Biomed Mater Res Part A2013; 101: 2412–2423.
24.
So-RaSNguyen-ThuyBLHun-MoY. In vitro and in vivo evaluation of electrospun PCL/PMMA fibrous scaffolds for bone regeneration. Sci Technol Adv Mater2013; 14: 015009.
25.
MattanaveeWSuwantongOPuthongS. Immobilization of biomolecules on the surface of electrospun polycaprolactone fibrous scaffolds for tissue engineering. ACS Appl Mater Interfaces2009; 1: 1076–1085.
26.
AroninCEPCooperJA JrSefcikLS. Osteogenic differentiation of dura mater stem cells cultured in vitro on three-dimensional porous scaffolds of poly(ε-caprolactone) fabricated via co-extrusion and gas foaming. Acta Biomater2008; 4: 1187–1197.
27.
NingCChengHZhuW. In vitro mineralization of surface-modified porous polycaprolactone scaffolds in simulated body fluid. Appl Surf Sci2008; 255: 429–431.
28.
WuFLiuCO'NeillB. Fabrication and properties of porous scaffold of magnesium phosphate/polycaprolactone biocomposite for bone tissue engineering. Appl Surf Sci2012; 258: 7589–7595.
29.
ZhaoJGuoLYYangXB. Preparation of bioactive porous HA/PCL composite scaffolds. Appl Surf Sci2008; 255(5): 2942–2946. Part 2.
30.
FrohberghMEKatsmanABottaGP. Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering. Biomaterials2012; 33: 9167–9178.
31.
KimY-HJyotiMASongH-Y. Immobilization of cross linked Col-I–OPN bone matrix protein on aminolysed PCL surfaces enhances initial biocompatibility of human adipogenic mesenchymal stem cells (hADMSC). Appl Surf Sci2014; 303: 97–106.
32.
TangYWSanterreJPLabowRS. Use of surface-modifying macromolecules to enhance the biostability of segmented polyurethanes. J Biomed Mater Res1997; 35: 371–381.
33.
VenugopalJRLowSChoonAT. Nanobioengineered electrospun composite nanofibers and osteoblasts for bone regeneration. Artif Organ2008; 32: 388–397.
34.
LinhNTBMinYKLeeB-T. Hybrid hydroxyapatite nanoparticles-loaded PCL/GE blend fibers for bone tissue engineering. J Biomater Sci Polym Ed2012; 24: 520–538.
35.
AnselmeK. Osteoblast adhesion on biomaterials. Biomaterials2000; 21: 667–681.
36.
WirthCComteVLagneauC. Nitinol surface roughness modulates in vitro cell response: a comparison between fibroblasts and osteoblasts. Mater Sci Eng C2005; 25: 51–60.
37.
PremVSChandraPS. Protein-Bioceramic interactions at the interface. In: Proteins at interfaces III state of the art, USA: American Chemical Society Symposium Series, 2012, pp. 55–76. .
38.
LourençoBMarchioliGSongW. Wettability influences cell behavior on superhydrophobic surfaces with different topographies. Biointerphases2012; 7: 1–11.
39.
MatsuuraTHosokawaROkamotoK. Diverse mechanisms of osteoblast spreading on hydroxyapatite and titanium. Biomaterials2000; 21: 1121–1127.
40.
LiLQianYJiangC. The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds. Biomaterials2012; 33: 3428–3445.
41.
Wojak-CwikIMHintzeVSchnabelrauchM. Poly(L-lactide-co-glycolide) scaffolds coated with collagen and glycosaminoglycans: impact on proliferation and osteogenic differentiation of human mesenchymal stem cells. J Biomed Mater Res Part A2013; 101: 3109–3122.
42.
StadlingerBPillingEMaiR. Effect of biological implant surface coatings on bone formation, applying collagen, proteoglycans, glycosaminoglycans and growth factors. J Mater Sci Mater Med2008; 19: 1043–1049.
43.
RentschCRentschBBreierA. Long-bone critical-size defects treated with tissue-engineered polycaprolactone-co-lactide scaffolds: a pilot study on rats. J Biomed Mater Res Part A2010; 95: 964–972.
44.
RammeltSHeckCBernhardtR. In vivo effects of coating loaded and unloaded Ti implants with collagen chondroitin sulfate, and hydroxyapatite in the sheep tibia. J Orthopaedic Res2007; 25: 1052–1061.
