While the beneficial effect of magnetic nanoparticle on the biological functions of calcium phosphate scaffolds has been well documented,little is known about the effect of magnetic nanoparticle on the in vivo performance of hydroxyapatite(HA)scaffolds.In this study,to further investigate the influence of magnetic hydroxyapatite(MHA)scaffolds on bone repair and the interactions between the magnetic scaffolds and the exterior magnetic field in vivo,we implanted the scaffolds into a beagle dog experimental model of femur transverse defect.Compared with traditional HA scaffolds,the MHA scaffolds could accelerate bone tissue regeneration in situ,especially in the first month.Moreover,it had a synergic effect between external magnetic fields and MHA scaffolds on bone repair in vivo.After 1 month,the bone density on MHA exposed to an external magnetic field was roughly 30%greater than that of HA,and only slightly less than the bone density observed on HA after 3 months.Overall,the results suggest the improvement of bone ingrowth is critical for HA scaffold with magnetic fields,which is significant for the early bone fixation and repair.
Novel poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGGE) micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers (PLGGE2000, PLGGE1100 and PLGGE500) were characterized by XRD, TG and DSC. The critical micelle concentrations (CMCs) of the amphiphilic copolymers were 1.04, 0.55 and 0.13 μg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were homogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the preparation of the micelles. Interestingly, extended cylindrical micelles were obtained using CHCl 3 as solvent. The micelles could trap doxorubicin (DOX) in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxicity against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM observation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.
In this study, the effects of forsterite and clinoenstatite powder extracts on the proliferation and osteogenic differentiation of rat adipose-derived stem cells (ASCs) were investigated and compared with the β-tricalcium phosphate (β-TCP) powder extracts. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and live-dead staining were performed to evaluate the viability and proliferation of rat ASCs. Osteogenic differentiation of rat ASCs were assayed by alkaline phosphatase (ALP) staining and ALP activity test. The expression of osteogenic marker genes (alkaline phosphatase (ALP), runt related transcription factor 2 (Runx2), collagen type Iα1 (Col1α1), secreted phosphoprotein1 (Spp1, osteopontin), integrin binding sialoprotein (Ibsp), bone gla protein (Bglap)) were detected by real-time polymerase chain reaction (PCR). The MTT assay and the live-dead staining showed that all the three ceramics possessed good cytocompatibility with rat ASCs. Furthermore, forsterite and clinoenstatite promoted the proliferation of rat ASCs compared with β-TCP. The results of the ALP activity test and the real-time PCR demonstrated that forsterite and clinoenstatite promoted the osteogenic differentiation of rat ASCs. These results suggested that forsterite and clinoenstatite are bioactive ceramics that may be used for preparation of bone tissue engineering (BTE) scaffolds.
An anti-tumor drug doxorubicin was encapsulated in micelles of poly(ethylene glycol)-b-poly(2,2-dihydroxyl- methyl propylene carbonate) (PEG-b-PDHPC) diblock copolymers. The morphololgy of both blank miceiles and drug loaded micelles was characterized by TEM. The in vitro drug release profiles of micelles were investigated, The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts. The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitr9 anti-tumor efficacies. The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs. The drug release rate of PEG45-b-PDHPC34 micelles was faster than that of mPEGt14-b-PDHPC26 micelles. Both of the two block copolymers were non-toxic. The confocal laser scanning microscopy a:ad flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells. The PEG45-b-PDHPC34 micelles exhibited higher anti-tumor activity comparing to mPEGxla-b-PDHPC26 micelles.
α-Cyclodextrin/poly(ethylene glycol)(α-CD/PEG) polyrotaxane nanoparticles were prepared via a self-assembly method. Anticancer drug methotrexate(MTX) was loaded in the nanoparticles. The interaction between MTX and polyrotaxane was investigated. The formation, morphology, drug release and in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles were studied. The results show that the MTX could be efficiently absorbed on the nanoparticles, and hydrogen bonds were formed between MTX andα-CDs. The typical channel-type stacking assembly style of polyrotaxane nanoparticles was changed after MTX was loaded. The mean diameter of drug loaded polyrotaxane nanoparticles were around 200 nm and the drug loading content was as high as about 20%. Drug release profiles show that most of the loaded MTX was released within 8 hours and the cumulated release rate was as high as 98%. The blank polyrotaxane nanoparticles were nontoxicity to cells. The in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles was higher than that of free MTX.
Amphiphilic dendritic poly(glutarnic acid)-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly(glutamic acid) as the macroinitiator in the ring-opening polymerization of NCA-Phe. The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly(glutamic acid) segments as shell. The biocompatibility of the micelles was studied. The release of the anticancer drug doxorubicin from the micelles was investigated in vitro. The results showed that the sustaining release of the drug could last for 60 h. The micellar drug release system was efficient in inhibiting the proliferation of HepG2 liver cancer cells, 75% cancer cells were killed under appropriate in vitro incubation.
Biodegradable poly(L-lactide-r-trimethene carbonate) copolymers (P(LLA-co-TMC)) with different compositions were synthesized. The degradation of the copolymers was carried out in phosphate buffer saline solutions (pH = 7.4) at 37℃. The compositions, structure and properties of the copolymers in degradation were characterized with IH-NMR, DSC, XRD, GPC, and SEM. The weight loss of the P(LLA-co-TMC) 50/50 was much faster than that of P(LLA-co-TMC) 85/15 and PLLA homopolymer. Interestingly, though the molecular weight of the compolymers decreased greatly during degradation, the compositions were rarely varied. After long time degradation, the PLLA segments were induced to crystallize in the P(LLA-co-TMC) 85/15 copolymer. The SEM observation of the surface and cross-section of P(LLA-co- TMC) 85/15 copolymer films found it was similar to the bulk degradation of PLLA homopolymer.