β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼/左氧氟沙星缓释材料的成骨检测

背景：在聚乳酸-聚羟基乙酸中加入β-磷酸三钙可调控其降解速率和强度。 目的：观察β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼/左氧氟沙星缓释材料修复兔股骨髁骨缺损的效果。 方法：制作兔右股骨髁直径5 mm、长10 mm的圆柱形骨缺损模型,随机分3组,其中两组分别于骨缺损处植入β-磷酸三钙/聚乳酸-聚羟基乙酸材料和β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼/左氧氟沙星缓释材料,空白对照组不植入任何材料。通过影像学、大体标本、组织学检查评价骨缺损修复效果。 结果与结论：术后12周时,β-磷酸三钙/聚乳酸-聚羟基乙酸材料组和β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼/左氧氟沙星缓释材料组骨缺损都得到修复,两组新骨占缺损区面积差异无显著性意义(P > 0.05),空白对照组骨缺损未修复。表明β-磷酸三钙/聚乳酸-聚羟基乙酸/异烟肼/左氧氟沙星缓释材料可以很好修复兔股骨髁缺损。     

聚乳酸-羟基乙酸共聚物/硅酸钙三维多孔骨组织工程支架的构建与性能

BACKGROUND: Some disadvantages exsist in commonly used poly(lactic-co-glycolic acid) (PLGA) scaffolds, including acidic degradation products, suboptimal mechanical properties, low pore size, poor porosity and pore connectivity rate and uncontrollable shape. OBJECTIVE: To construct a scaffold with three-dimensional (3D) pores by adding calcium silicate to improve the properties of PLGA, and then detect its degradability, mechanical properties and biocompatibility. METHODS: PLGA/calcium silicate porous composite microspheres were prepared by the emulsion-solvent evaporation method, and PLGA 3D porous scaffold was established by 3D-Bioplotter, and then PLGA/calcium silicate composite porous scaffolds were constructed by combining the microspheres with the scaffold using low temperature fusion technology. The compositions, morphology and degradability of the PLGA/calcium silicate porous composite microspheres and PLGA microspheres, as well as the morphology, pore properties and compression strength of the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds were measured, respectively. Mouse bone marrow mesenchymal stem cells were respectively cultivated in the extracts of PLGA/calcium silicate porous composite microspheres and PLGA microspheres, and then were respectively seeded onto the PLGA 3D scaffolds and PLGA/calcium silicate composite porous scaffolds. Thereafter, the cell proliferation activity was detected at 1, 3 and 5 days. RESULTS AND CONCLUSION: Regular pores on the PLGA microspheres and internal cavities were formed, and the PH values of the degradation products were improved after adding calcium silicate. The fiber diameter, pore, porosity and average pore size of the composite porous scaffolds were all smaller than those of the PLGA scaffolds. The compression strength and elasticity modulus of the composite porous scaffolds were both higher than those of the PLGA scaffolds (P < 0.05). Bone marrow mesenchymal stem cells grew well in above microsphere extracts and scaffolds. These results indicate that PLGA/calcium silicate composite porous scaffolds exhibit good degradability in vitro, mechanical properties and biocompatibility.     

3D生物打印构建聚乳酸羟基乙酸/纳米羟基磷灰石支架骨形态发生蛋白2缓释复合体的实验研究

BACKGROUND: Tissue-engineered bone scaffold fabricated by 3D-bioprinting technique has good controllability in morphology and structure. However, construction of tissue-engineered bone/cell growth factor complex and time-dose effect of sustained-release factors are needed to be further researched.  OBJECTIVE: To fabricate a sustained-release composite of polylactic-co-glycolic acid (PLGA)/nano-hydroxyapatite (n-HA) scaffold carrying bone morphogenetic protein-2 (BMP-2) using 3D-bioprinting technique, and test the biological properties of the PLGA/n-HA scaffold carrying BMP-2 and the sustained-release properties, thereby to discuss its feasibility as the tissue-engineered bone scaffold composite.  METHODS: Temperature-sensitive chitosan hydrogel was prepared using chitosan and β-glycerophosphate to construct a sustained-release composite, chitosan nanoparticles carrying BMP-2 . 3D-bioprinting technique was utilized to fabricate the PLGA/n-HA scaffold carrying BMP-2. Biological features of the scaffold composite were tested, and time-dose effect of BMP-2 sustained-release was observed.  RESULTS AND CONCLUSION: The average pore size of the scaffold-cytokine composite was (431.31±18.40) μm, and the porosity was (73.64±1.82)%. The cumulative release rate of BMP-2 from the scaffold-cytokine composite that effectively controlled the burst release during 48 hours and 30 days were suitable for the physiological needs. In conclusion, the porosity, pore size, release property, degradation rate, and mechanical strength of the scaffold-cytokine composite all meet the biological requirements of tissue-engineered bone construction. 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

可注射聚富马酸丙二醇酯/β-磷酸三钙骨水泥的体外生物活性及其降解性

BACKGROUND: Poly(propylene fumarate) (PPF) can crosslink at room temperature, and β-tricalcium phosphate (β-TCP) has good biocompatibility, but PPF/β-TCP composite bone cement has not yet been systematically studied. OBJECTIVE: To prepare PPF/β-TCP composite bone cement and to explore its in vitro bioactivity and degradability. METHODS: β-TCP and PPF were respectively synthesized by liquid-phase precipitation and a two-step method, and PPF/β-TCP composite bone cement was prepared through mixing PPF with β-TCP. The    in vitro bioactivity of PPF/β-TCP was compared with the commercial poly(methyl methacrylate) (PMMA) through the ability of forming hydroxyapatite after immersed in simulated body fluid for 7 days. The in vitro degradability of PPF/β-TCP was studied via investigating the transformation of pH values, water uptake and mass loss, compressive strength and morphology at each time point. RESULTS AND CONCLUSION: There were hydroxyapatites formed on the PPF/β-TCP material, but none on the commercial PMMA material. The pH values of the PPF/β-TCP were stable in PBS for 63 days, indicating its degradation is moderate; the mass loss was up to 13.5% after 84 days. Scanning electron microscope displayed the degraded PPF/β-TCP surface, and its compressive strength was decreased gradually, which good for the integrity and sustainability of mechanical properties during degradation. These results suggest that PPF/β-TCP bone cement holds mineralization and degradability in vitro.     

磷酸钙材料在骨软骨缺损修复支架中的应用

背景：磷酸钙材料与天然骨矿物质相似,具有良好的生物活性、骨传导性和可降解性,在金属植入物涂层及骨缺损修复材料中已有大量研究与应用。 目的：综述不同物相磷酸钙材料的特点及在骨软骨支架中的应用。 方法：应用计算机检索PubMed数据库、中国学术期刊网络出版总库、维普数据库2000年1月至2015年2月的有关文章,中文检索词为“骨软骨,磷酸钙(包括羟基磷灰石、磷酸三钙、聚磷酸钙等),组织工程”,英文检索词为“osteochondral;calcium phosphate;tissue engineering”。 结果与结论：由于磷酸钙具有多种物相和晶型,通过不同工艺方法调控磷酸钙的结构尺寸可以得到丰富的材料体系,如羟基磷灰石、磷酸三钙、聚磷酸钙、无定形磷酸钙等,其生物学性能和力学性能均有所差异,其中以羟基磷灰石的应用最为广泛。将磷酸钙与其他材料复合制备多层的复合支架是骨软骨组织工程研究的一个趋势。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

N-乙酰半胱氨酸丝素微球复合磷酸钙骨水泥的制备及表征

BACKGROUND: Calcium phosphate bone cement has been applied to clinical surgery because of its good biocompatibility and osteoconduction. However poor mechanical properties and lack of osteoinductivity limit its wide application. OBJECTIVE: To develop calcium phosphate cement incorporated with N-acetylcysteine (NAC) loaded silk fibroin microspheres (SFM), which is a kind of new injectable bone graft material with slow-release function, and evaluate its physical and chemical properties and cell compatibility. METHODS: Empty SFMs were prepared with emulsion solvent evaporation to absorb NAC solution of different concentrations by NAC-SFM and the concentration of NAC at the maximum drug loading ratio was determined. Then, NAC-SFM was loaded into calcium phosphate bone cement to test the drug release properties in vitro. MC3T3-E1 osteoblasts were cultured on the surface of NAC-SFM calcium phosphate bone cement and cell attachment and growth were observed by scanning electron microscope. Additionally, MC3T3-E1 cells were cultured with three kinds of bone cement extracts (calcium phosphate cement, SFM-calcium phosphate cement, NAC-SFM-calcium phosphate cement, as well as cultured in the α-minimum essential medium containing a volume fraction of 10% fetal bovine serum and 1% penicillin-streptomycin double antibody as the control. MTS assay was used to evaluate cell proliferation. RESULTS AND CONCLUSION: Microspheres in the composite bone cement presented with smooth surface, same size, diffused distribution and no obvious destroy. Thus, the SFM could remain stable in the reaction process of the composite bone cement. The double slow release system which contained silk fibroin microspheres and calcium phosphate bone cement showed a significant decrease in the cumulative release percentage of NAC within the first 24 hours compared with the control group (P < 0.05). In the next 28 days, the release speed of NAC was significantly lower in the NAC-SFM-calcium phosphate cement group than the calcium phosphate cement group (P < 0.05). In addition, different extracts had no significant cytotoxicity to the growth of MC3TC-E1 cells. Thus, the NAC-SFM-calcium phosphate cement has good cytocompatibility, which provide a new insight into the development of bone repair biomaterials. 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

自固化磷酸钙人工骨Ⅱ型诱导成骨及修复腱骨界面损伤的生物力学分析

背景：自固化磷酸钙人工骨Ⅱ型与重组人骨形态发生蛋白均有一定的成骨诱导作用,存在修复腱骨界面损伤的可能。 目的：探讨自固化磷酸钙人工骨Ⅱ型的成骨诱导作用及修复腱骨界面损伤生物力学情况。 方法：35只成年健康的新西兰白兔,随机选取5只,处死后取双侧肩关节腱骨界面标本作为正常对照。剩余30只构建腱骨界面损伤模型后,随机等分为实验组和模型组,模型组不填塞任何药物,实验组填塞自固化磷酸钙人工骨Ⅱ型进行修复。 结果与结论：填塞自固化磷酸钙人工骨Ⅱ型后,兔损伤腱骨界面明显恢复,且随时间的延长,修复效果更佳,骨形态发生蛋白2表达水平也随之增加,损伤腱骨界面最大抗拉强度以及最大刚度明显增加。表明利用自固化磷酸钙人工骨Ⅱ型复合重组人骨形态发生蛋白对腱骨界面损伤进行修复具有良好的成骨诱导作用,可以促进损伤的修复。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Submucosal injection of poly(lactic-co-glycolic acid) microspheres in rabbit bladder as a potential treatment for urinary incontinence and vesicoureteral reflux: preliminary results

Endoscopic injection of bulking agents has been gaining attention as a therapy for urinary incontinence and vesicoureteral reflux because this therapy is simpler, less operation time-consuming and less painful than traditional surgical operations. The ideal bulking agent for the injection therapies must be easily injectable, biocompatible, volume-stable, non-antigenic and non-migratory. We evaluated poly(lactic-co-glycolic acid) (PLGA) microspheres as an injectable bulking agent for urologic injection therapies. To determine whether PLGA microspheres meet the requirements of an ideal bulking agent, PLGA microspheres were injected into the submucosal sites of a rabbit bladder wall. The microspheres were easily injectable. Two and five weeks post-implantation, histological examinations indicated that host cells from the surrounding bladder tissues migrated to the space between the injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted microspheres, but the inflammatory reaction diminished at 5 weeks. The hybrid tissue volume did not significantly decrease over time. There was no evidence of microsphere migration to the distant organs. Although long-term studies are needed to evaluate the therapeutic potential of this method, these preliminary results suggest the possibility of PLGA microspheres as a potentially useful injection material for urinary injection therapies.