Objective To review the latest researches of synthetic biodegradable polymers for bone repair and reconstruction, to predict the progress of bone substitute materials and bone tissue engineering scaffolds in future. Methods The l iterature concerning synthetic biodegradable polymers as bone substitute materials or bone tissue engineering scaffolds was collected and discussed. Results Al i phatic polyester, polyanhydride, polyurethane and poly (amino acids) were the most extensively studied synthetic biodegradable polymers as bone substitutes and the scaffolds. Each polymer was of good biological safety and biocompatibil ity, and the degradation products were nontoxic to human body. The mechanical properties and degradation rate of the polymers could be adjusted by the type or number of the monomers anddifferent synthetic methods. Therefore, the polymers with suitable mechanical strength and degradation rate could be produced according to the different requirements for bone grafting. Prel iminary studies in vivo showed their favorable capacity for bone repair. Conclusion The synthetic biodegradable polymers, especially the copolymers, composite materials and those carrying bone growth factors are expected to be the most promising and ideal biomaterials for bone repair and reconstruction.
【Abstract】 Objective To evaluate the biocompatibil ity of the sheep BMSCs cultured on the surface of photografting modified copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate(PHBV). Methods BMSCs were isolated from bone marrow of the posterior il iac crest of a 6-month old sheep by whole marrow adherent culture method. The 3rd passage BMSCs were seeded onto modified PHBV and conventional PHBV films, or three-dimension scaffolds. Cell-adhesion rates were calculated by hemocytometer at 1, 2 and 6 hours after seeded. Cell morphology was examined by scanning electron microscope when the BMSCs were cultured for 3 days, 1 week and 3 weeks. Cell cycle was analyzed by flow cytometry at 5 days after seeded. The content of protein in BMSCs was determined by BCA assay and the content of DNA was quantified by Hoechst 33258 assay at 4, 8 and 12 days after seeded. Results At 1 hour after seeded, cell-adhesion rate on modified PHBV films (52.7% ± 6.0%) was significantlyhigher than that of conventional PHBV films (37.5% ± 5.3%) (P lt; 0.05); At 2 and 6 hours after seeded, cell-adhesion rate of modified PHBV films was similar to that of PHBV films (P gt; 0.05). The surface of modified PHBV film was rougher. In the early culture stage, more cells adhered to modified PHBV and the cells displayed much greater spreading morphology. Furthermore, ECM on modified PHBV were richer. There were no significant differences between the trial team and the control on the cell cycle and the content of DNA and protein of BMSCs (P gt; 0.05). Conclusion Photografting modification on PHBV can promote BMSCs’ adhesion and enhance their biocompatibil ity.
OBJECTIVE: To investigate the selection and manufacture of ideal extracellular matrix materials in bone tissue engineering. METHODS: The recent literatures about biodegradable polymers served as culture scaffolds of osteoblasts were widely reviewed, the advantages and disadvantages of biodegradable synthetic polymers and natural polymers were analysed. RESULTS: The ideal extracellular matrix material in bone tissue engineering should be made up of inorganic materials, synthetic polymers and natural polymers, which possesses morphological structure of three-dimensional foam with self-mediated drug slow delivery system of bone growth factors. CONCLUSION: The design and manufacture of combined extracellular matrix materials in bone tissue engineering is a very important and urgent challenge.
ObjectiveTo prepare curcumin loaded monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolicacid) (mPEG-PLGA) nanopaticles (CUR-NPs), investigate the effect of curcumin (CUR) and CUR-NPs on reversing corticosteroid resistance induced by cigarette smoke extract (CSE), and compare biological function between CUR and CUR-NPs in macrophages RAW264.7. MethodsmPEG-PLGA nanoparticles loaded with CUR were prepared via emulsion solvent evaporation.In lipopolysaccharide (LPS) stimulated macrophages RAW264.7, budesonide (BUD) was used to treat macrophages RAW264.7.In LPS and CSE stimulated macrophages RAW264.7, BUD (10-10-10-5 mol/L), CUR(10-10-10-5 mol/L), CUR(10-7 mol/L)+BUD(10-9-10-5 mol/L), CUR(10-9-10-5 mol/L)+BUD(10-7 mol/L), and CUR-NPs(10-9-10-5 mol/L)+BUD(10-7 mol/L) were respectively used to treat macrophages RAW264.7 activated.The level of IL-8 in cell culture supernatant was measured by ELISA.In CSE stimulated macrophages RAW264.7, CUR(10-7 and 10-6 mol/L) and CUR-NPs(10-7 and 10-6 mol/L) were used to treat macrophages RAW264.7.The mRNA level of HDAC2 was measured by real-time PCR, the protein level of HDAC2 was measured by Western blot.Cellular uptake of CUR and CUR-NPs in macrophages RAW264.7 was determined by cellular fluorescence intensity observed and detected by laser confocal microscopy imaging. ResultsThe morphology of CUR-NPs was spherical and the mean particle size was (356.4±146.6)nm.Compared with LPS stimulation, co-stimulation of LPS and CSE led to a significant decrease in the maximum inhibitory rate of BUD on IL-8 (P < 0.05) and a significant increase in the 50% inhibitory concentration (IC50) of BUD on IL-8 (P < 0.05).When using LPS+CSE to stimulate, compared with BUD (10-10-10-5 mol/L) group, the maximum inhibitory rate of BUD in CUR (10-7 mol/L)+BUD (10-9-10-5 mol/L) group on IL-8 was significantly higher (P < 0.05) and the IC50 of BUD decreased significantly (P < 0.05).When using LPS+CSE to stimulate, CUR and CUR-NPs in 10-9, 10-8 and 10-7 mol/L concentration, the inhibitory rate of CUR-NPs+BUD (10-7 mol/L) on IL-8 was significantly higher than that of CUR+BUD (10-7 mol/L) (P < 0.05). CSE stimulation induced a significant decrease in the mRNA and protein expression of HDAC2. Compared with CSE group, the mRNA and protein levels of HDAC2 of CUR(10-7 and 10-6 mol/L) group and CUR-NPs(10-7 and 10-6 mol/L) group were significantly higher (P < 0.05).In 10-7 mol/L concentration, the mRNA and protein levels of HDAC2 in CUR-NPs group were significantly higher than those in CUR group.In 10-7 mol/L concentration, cellular uptake of CUR in CUR-NPs was significantly higher than the native CUR. ConclusionsCUR and CUR-NPs can reverse the corticosteroid resistance induced by CSE.CUR-NPs can improve the cellular uptake of CUR.In the case of low concentration, CUR-NPs have more biological activity than CUR.
ObjectiveTo evaluate the combination of lipopolysaccharide-amine nanopolymersomes (LNPs), as a gene vector, with target gene and the transfection in bone marrow mesenchymal stem cells (BMSCs) so as to provide a preliminary experiment basis for combination treatment of bone defect with gene therapy mediated by LNPs and stem cells. MethodsPlasmid of bone morphogenetic protein 2 (pBMP-2)-loaded LNPs (pLNPs) were prepared. The binding ability of pLNPs to pBMP-2 was evaluated by a gel retardation experiment with different ratios of nitrogen to phosphorus elements (N/P). The morphology of pLNPs (N/P=60) was observed under transmission electron microscope (TEM) and atomic force microscope (AFM). The size and Zeta potential were measured by dynamic light scattering (DLS). The resistance of pLNPs against DNase I degradation over time was explored. The viability of BMSCs, transfection efficiency, and expression of target protein were investigated after transfection by pLNPs in vitro. ResultsAt N/P≥1.5, pLNPs could completely retard pBMP-2; at N/P of 60, pLNPs was uniform vesicular shape under AFM; TEM observation demonstrated that pLNPs were spherical nano-vesicles with the diameter of (72.07±11.03) nm, DLS observation showed that the size of pLNPs was (123±6) nm and Zeta potential was 20 mV; pLNPs could completely resist DNase I degradation within 4 hours, and such protection capacity to pBMP-2 decreased slightly at 6 hours. The cell survival rate first increased and then decreased with the increase of N/P, and reached the maximum value at N/P of 45; the cytotoxicity was in grade I at N/P≤90, which meant no toxicity for in vivo experiment. While the transfection efficiency of pLNPs increased with the increase of N/P, and reached the maximum value at N/P of 60. So it is comprehensively determined that the best N/P was 60. At 4 days, transfected BMSCs expressed BMP-2 continuously at a relatively high level at N/P of 60. ConclusionLNPs can compress pBMP-2 effectively to form the nanovesicles complex, which protects the target gene against enzymolysis. LNPs has higher transfection efficiency and produces more amount of protein than polyethylenimine 25k and Lipofectamine 2000.
Objective To investigate the ability of gene-loaded lipopolysaccharide-amine nanopolymersomes (LNPs) in inducing osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by in vitro gene transfection, where LNPs were used as a non-viral cationic carrier, and their properties were optimized during synthesis. Methods LNPs were synthesized by a graft-copolymerization method, and the effects of different pH environments during synthesis on physicochemical properties of LNPs and LNPs/plasmid of bone morphogenetic protein 2-green fluorescent protein (pBMP-2-GFP) complexes were explored. Then, optimized LNPs with maximum transfection efficiency and safe cytotoxicity in rat BMSCs were identified by cytotoxicity and transfection experiments in vitro. Thereafter, the optimized LNPs were used to mediate pBMP-2-GFP to transfect rat BMSCs, and the influences of LNPs/pBMP-2-GFP on osteogenic differentiation of BMSCs were evaluated by monitoring the cell morphology, concentration of BMP-2 protein, activity of alkaline phosphatase (ALP), and the formation of calcium nodules. Results The nitrogen content, particle size, and zeta potential of LNPs synthesized at pH 8.5 were lower than those of the other pH groups, with the lowest cytotoxicity (96.5%±1.4%) and the highest transfection efficiency (98.8%±0.1%). After transfection treatment, within the first 4 days, BMSCs treated by LNPs/pBMP-2-GFP expressed BMP-2 protein significantly higher than that treated by Lipofectamine2000 (Lipo)/pBMP-2-GFP, polyethylenimine 25K/pBMP-2-GFP, and the blank (non-treated). At 14 days after transfection, ALP activity in BMSCs treated by LNPs/pBMP-2-GFP was higher than that treated by Lipo/pBMP-2-GFP and the blank, comparable to that induced by osteogenic medium; with alizarin red staining, visible calcium nodules were found in BMSCs treated by LNPs/pBMP-2-GFP or osteogenic medium, but absent in BMSCs treated by Lipo/pBMP-2-GFP or the blank with apoptosis. At 21 days after transfection, transparent massive nodules were discovered in BMSCs treated by LNPs/pBMP-2-GFP, and BMSCs exhibited the morphologic features of osteoblasts. Conclusion LNPs synthesized at pH 8.5 has optimal transfection efficiency and cytotoxicity, they can efficiently mediate pBMP-2-GFP to transfect BMSCs, and successfully induce their directional osteogenic differentiation, whose inducing effect is comparable to the osteogenic medium. The results suggest that gene transfection mediated by LNPs may be a convenient and effective strategy in inducing directional differentiation of stem cells.
As one of the stimulus-response polymeric intelligent materials, shape memory polymers have been widely applied in biomedicine due to their better biocompatibility, higher controllability, stronger deformation restorability and biodegradability compared with shape memory alloys and shape memory ceramics. This review will introduce the structural principles of shape memory polymers and summarize their applications in the treatment of vascular diseases, especially in endovascular therapy. At the same time, the related technical problems and the future of shape memory polymers are prospected. With the continuous development of processing technology and materials, it can be predicted that shape memory polymers will be more widely used in the medical field.
Traditional bone repair materials, such as titanium, polyetheretherketone, and calcium phosphate, exhibit limitations, including poor biocompatibility and incongruent mechanical properties. In contrast, ceramic-polymer composite materials combine the robust mechanical strength of ceramics with the flexibility of polymers, resulting in enhanced biocompatibility and mechanical performance. In recent years, researchers worldwide have conducted extensive studies to develop innovative composite materials and manufacturing processes, with the aim of enhancing the bone repair capabilities of implants. This article provides a comprehensive overview of the advancements in ceramic-polymer composite materials, as well as in 3D printing and surface modification techniques for composite materials, with the objective of offering valuable insights to improve and facilitate the clinical application of ceramic-polymer composite materials in the future.