The composite of poly-lactic-co-glycolic acid (PLGA) and calcium phosphate cements (CPC) are currently widely used in bone tissue engineering. However, the properties and biocompatibility of the alendronate-loaded PLGA/CPC (APC) porous scaffolds have not been characterized. APC scaffolds were prepared by a solid/oil/water emulsion solvent evaporation method. The morphology, porosity, and mechanical strength of the scaffolds were characterized. Bone marrow mesenchymal stem cells (BMSCs) from rabbit were cultured, expanded and seeded on the scaffolds, and the cell morphology, adhesion, proliferation, cell cycle and osteogenic differentiation of BMSCs were determined. The results showed that the APC scaffolds had a porosity of 67.43 ± 4.2% and pore size of 213 ± 95 µm. The compressive strength for APC was 5.79 ± 1.21 MPa, which was close to human cancellous bone. The scanning electron microscopy, cell counting kit-8 assay, flow cytometry and ALP activity revealed that the APC scaffolds had osteogenic potential on the BMSCs in vitro and exhibited excellent biocompatibility with engineered bone tissue. APC scaffolds exhibited excellent biocompatibility and osteogenesis potential and can potentially be used for bone tissue engineering.
ZhuXEiblOScheidelerLGeis-GerstorferJ. Characterization of nano hydroxyapatite/collagen surfaces and cellular behaviors. J Biomed Mater Res A2006; 79: 114–27.
2.
HolzwarthJMMaPX. Biomimetic nanofibrous scaffolds for bone tissue engineering. Biomaterials2011; 32: 9622–9.
3.
LalwaniGHensleeAMFarshidBLinLKasperFKQinYXMikosAGSitharamanB. Two-dimensional nanostructure-reinforced biodegradable polymeric nanocomposites for bone tissue engineering. Biomacromolecules2013; 14: 900–9.
4.
ConstantzBRIsonICFulmerMTPoserRDSmithSTVanWagonerMRossJGoldsteinSAJupiterJBRosenthalDI. Skeletal repair by in situ formation of the mineral phase of bone. Science1995; 267: 1796–8.
5.
SatoMAslaniASambitoMAKalkhoranNMSlamovichEBWebsterTJ. Nanocrystalline hydroxyapatite/titania coatings on titanium improves osteoblast adhesion. J Biomed Mater Res A2008; 84: 265–72.
6.
VorndranEGeffersMEwaldALemmMNiesBGbureckU. Ready-to-use injectable calcium phosphate bone cement paste as drug carrier. Acta Biomater2013; 9: 9558–67.
7.
BohnerMGbureckUBarraletJE. Technological issues for the development of more efficient calcium phosphate bone cements: a critical assessment. Biomaterials2005; 26: 6423–9.
8.
RuhePQBoermanOCRusselFGSpauwenPHMikosAGJansenJA. Controlled release of rhBMP-2 loaded poly (dl-lactic-co-glycolic acid)/calcium phosphate cement composites in vivo. J Control Release2005; 106: 162–71.
9.
BoneHG1HoskingDDevogelaerJPTucciJREmkeyRDToninoRPRodriguez-PortalesJADownsRWGuptaJSantoraACLibermanUA. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med2004; 350: 1189–99.
10.
RussellRWattsNBEbetinoFHRogersMJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int2008; 19: 733–59.
11.
ThamakeSIRautSLRanjanAPGryczynskiZVishwanathaJK. Surface functionalization of PLGA nanoparticles by non-covalent insertion of a homo-bifunctional spacer for active targeting in cancer therapy. Nanotechnology2011; 22: 035101–035101.
12.
ThamakeSIRautSLGryczynskiZRanjanAPVishwanathaJK. Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer. Biomaterials2012; 33: 7164–73.
13.
KuljaninJJankovićINedeljkovićJPrstojevićDMarinkovićV. Spectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe (III) ions. J Pharm Biomed Anal2002; 28: 1215–20.
14.
GinebraMPTraykovaTPlanellJA. Calcium phosphate cements: Competitive drug carriers for the musculoskeletal system?Biomaterials2006; 27: 2171–7.
15.
YasudaMMasadaKTakeuchiE. Treatment of enchondroma of the hand with injectable calcium phosphate bone cement. J Hand Surg Am2006; 31: 98–102.
16.
YuLLiYZhaoKTangYChengZChenJZangYWuJKongLLiuSLeiWWuZ. A Novel Injectable Calcium Phosphate Cement-Bioactive Glass Composite for Bone Regeneration. PloS One2013; 8: e62570–e62570.
YuanHLiYde BruijnJDde GrootKZhangX. Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials2000; 21: 1283–1283.
19.
JulienMKhairounILeGerosRZDelplaceSPiletPWeissPDaculsiGBoulerJMGuicheuxJ. Physico-chemical–mechanical and in vitro biological properties of calcium phosphate cements with doped amorphous calcium phosphates. Biomaterials2007; 28: 956–65.
20.
HongCYLinSKKokSHWongMYHongYC. Histologic reactions to a newly developed calcium phosphate cement implanted in the periapical and periodontal tissues. J Formos Med Assoc1990; 89: 297–297.
21.
BohnerMGbureckUBarraletJE. Technological issues for the development of more efficient calcium phosphate bone cements: a critical assessment. Biomaterials2005; 26: 6423–9.
22.
RuhePQHedbergELPadronNTSpauwenPHJansenJAMikosAG. Biocompatibility and degradation of poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composites. J Biomed Mater Res A2005; 74: 533–533.
23.
LinkDPvan den DolderJvan den BeuckenJJCuijpersVMWolkeJGMikosAGJansenJA. Evaluation of the biocompatibility of calcium phosphate cement/PLGA microparticle composites. J Biomed Mater Res A2008; 87: 760–760.
24.
van de WateringFCvan den BeuckenJJWalboomersXFJansenJA. Calcium phosphate/poly (d, l-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect. Clin Oral Implants Res2012; 23: 151–9.
25.
BoseSRoyMBandyopadhyayA. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol2012; 30: 546–54.
26.
NathSDSonSSadiasaAMinYKLeeBT. Preparation and characterization of PLGA microspheres by the electrospraying method for delivering simvastatin for bone regeneration. Int J Pharm2013; 443: 87–94.
27.
FisherJERogersMJHalasyJMLuckmanSPHughesDEMasarachiaPJWesolowskiGRussellRGRodanGAReszkaAA. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A1999; 96: 133–8.
28.
ContePFGuarneriV. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist2004; 9: 28–37.
29.
CremersSCPillaiGCPapapoulosSE. Pharmacokinetics/pharmacodynamics of bisphosphonates: use for optimisation of intermittent therapy for osteoporosis. Clin Pharmacokinet2005; 44: 551–70.
30.
BodyJJDielIBellR. Profiling the safety and tolerability of bisphosphonates. Semin Oncol2004; 31: 73–8.
31.
MiglioratiCASiegelMAEltingLS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol2006; 7: 508–14.
32.
von KnochFJaquieryCKowalskyMSchaerenSAlabreCMartinIRubashHEShanbhagAS. Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials2005; 26: 6941–9.
33.
KlawitterJJHulbertSF. Application of porous ceramics for the attachment of load bearing internal orthopedic applications. J Biomed Mater Res1971; 5: 161–229.
34.
MistryASMikosAG. Tissue engineering strategies for bone regeneration. Adv Biochem Eng Biotechnol2005; 94: 1–22.
35.
GoshimaJGoldbergVMCaplanAI. The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed in vivo in calcium phosphate ceramic blocks. Clin Orthop Relat Res1991; 262: 298–311.
36.
NadeSArmstrongLMcCartneyEBaggaleyB. Osteogenesis after bone and bone marrow transplantation: the ability of ceramic materials to sustain osteogenesis from transplanted bone marrow cells: preliminary studies. Clin Orthop Relat Res1983; 181: 255–63.
