Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer

Rapid prototyping (RP) is a molding technique that builds a three-dimensional (3D) model from computer-aided design (CAD) data. We fabricated new tailor-made bone implants (TIs) from α-tricalcium phosphate powder using an RP ink-jet printer based on computed tomography (CT) data, and evaluated their safety and efficacy. CT data of the skulls of seven beagle dogs were obtained and converted to CAD data, and bone defects were virtually made in the skull bilaterally. TIs were designed to fit the defects and were fabricated using the 3D ink-jet printer with six horizontal cylindrical holes running through the implants, designed for possible facilitation of vascular invasion and bone regeneration. As a control, hydroxyapatite implants (HIs) were cut manually from porous hydroxyapatite blocks. Then, craniectomy was performed to create real skull defects, and TIs and HIs were implanted. After implantation, CT was performed regularly, and the animals were euthanized at 24 weeks. No major side effects were observed. CT analysis showed narrowing of the cylindrical holes; bony bridging between the implants and the temporal bone was observed only for TIs. Histological analysis revealed substantial new bone formation inside the cylindrical holes in the TIs, while mainly connective tissues invaded the porous structures in HIs. Bone marrow was observed only in TIs. Osteoclasts were seen to resorb regenerated bone from inside the cylindrical holes and to invade and probably resorb the TIs. These data suggest that TIs are a safe and effective bone substitute, possessing osteoconductivity comparable with that of HIs.     

Preparation of starch macrocellular foam for increasing the dissolution rate of poorly water-soluble drugs

Starch macrocellular foam (SMF), a novel natural bio-matrix material, was prepared by the hard template method in order to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Nitrendipine (NDP) was chosen as a model drug and was loaded into SMF by the solvent evaporation method. SMF and the loaded SMF samples (NDP-SMF) were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy. In vitro drug release studies showed that SMF significantly increased the dissolution rate of NDP. In vivo studies showed that the NDP-SMF tablets clearly increased the oral bioavailability of NDP in comparison with the reference commercial tablets. All the results obtained demonstrated that SMF was a promising carrier for the oral delivery of poor water-soluble drugs.     

新型可降解泪道支架的制备及其生物降解性和生物相容性评估

背景 泪道探通术联合泪道支架植入是治疗泪道阻塞性疾病的主要方法,传统的非降解材料泪道支架存在需二次手术取出及并发症较多的缺点,基于可降解生物高分子材料的泪道支架及其应用是相关领域的研究热点. 目的 采用高分子可降解生物材料构建可降解泪道支架,并观察其植入兔泪道后的生物降解性和生物相容性.方法 与华中科技大学化学研究院共同研制左旋聚乳酸:聚己内酯+15％聚乙二醇中空管状可降解材料的泪道支架.采用计算机随机数字分配法将3～4月龄清洁级日本大耳兔32只随机分为术后1、4、8和16周组,将泪道支架植入实验兔左眼泪道,分别于相应时间点取出植入的泪道支架进行称量和观察,评价各组泪道支架的形状,并计算支架的失重率;采用泪道内窥镜检查各组兔术眼泪道黏膜的术后反应情况;分别于上述时间点处死各组实验兔,制备泪道黏膜组织标本,分别采用苏木精-伊红染色于光学显微镜下行组织病理学检查及激光扫描电子显微镜下行黏膜表面的超微结构观察. 结果 制作的可降解泪道支架为光滑、柔韧的亲水乳白色中空管道,术后1周组术眼取出的泪道支架完整,术后4周组可见泪道支架管口劈裂,术后16周组泪道支架断裂成不连续的碎片.术后1、4、8和16周组支架失重率分别为(13.44±6.59)％、(23.96±6.33)％、(55.08±6.55)％和(78.00±8.74)％,其中术后16周组泪道支架失重率最高,与术后8周组比较差异有统计学意义(q=4.27,P＜0.05),而术后1周组与术后4周组间差异无统计学意义(q=1.71,P＞0.05).泪道内窥镜检查可见术后4周组、术后8周组术眼黏膜水肿、充血和轻度增生,术后16周组术眼黏膜表现接近正常.组织病理学检查显示,术后1、4、8周组术眼泪道固有层大量炎性细胞浸润,术后16周组术眼泪道黏膜固有层仅见少量炎性细胞.激光扫描电子显微镜检查显示,术后8周组术眼泪道黏膜表面有不同程度的皱褶,表面微绒毛数量减少,排列紊乱,术后16周组术眼泪道黏膜上皮细胞表面微绒毛长度和数量增加,黏膜基底结构完整.各组兔眼均未见术后并发症. 结论 可降解泪道支架植入兔眼后对泪道黏膜的刺激性小,损伤轻微,具有较好的生物可降解性、生物相容性及生物力学特性.     

Novel zinc alloys for biodegradable surgical staples

BACKGROUND The development of biodegradable surgical staples is desirable as non-biodegradable Ti alloy staples reside in the human body long after wound healing, which can cause allergic/foreign-body reactions, adhesion, or other adverse effects. In order to develop a biodegradable alloy suitable for the fabrication of surgical staples, we hypothesized that Zn, a known biodegradable metal, could be alloyed with various elements to improve the mechanical properties while retaining biodegradability and biocompatibility. Considering their biocompatibility, Mg, Ca, Mn, and Cu were selected as candidate alloying elements, alongside Ti, the main material of clinically available surgical staples.AIM To investigate the in vitro mechanical properties and degradation behavior and in vivo safety and feasibility of biodegradable Zn alloy staples.METHODS Tensile and bending tests were conducted to evaluate the mechanical properties of binary Zn alloys with 0.1–6 wt.% Mg, Ca, Mn, Cu, or Ti. Based on the results,three promising Zn alloy compositions were devised for staple applications(wt.%): Zn-1.0Cu-0.2Mn-0.1Ti(Zn alloy 1), Zn-1.0Mn-0.1Ti(Zn alloy 2), and Zn-1.0Cu-0.1Ti(Zn alloy 3). Immersion tests were performed at 37℃ for 4 wk using fed-state simulated intestinal fluid(Fe SSIF) and Hank’s balanced salt solution(HBSS). The corrosion rate was estimated from the weight loss of staples during immersion. Nine rabbits were subjected to gastric resection using each Zn alloy staple, and a clinically available Ti staple was used for another group of nine rabbits. Three in each group were sacrificed at 1, 4, and 12 wk post-operation.RESULTS Additions of ≤1 wt.% Mn or Cu and 0.1 wt.% Ti improved the yield strength without excessive deterioration of elongation or bendability. Immersion tests revealed no gas evolution or staple fracture in any of the Zn alloy staples. The corrosion rates of Zn alloy staples 1, 2, and 3 were 0.02 mm/year in HBSS and 0.12, 0.11, and 0.13 mm/year, respectively, in Fe SSIF. These degradation times are sufficient for wound healing. The degradation rate is notably increased under low pH conditions. Scanning electron microscopy and energy dispersive spectrometry surface analyses of the staples after immersion indicated that the component elements eluted as ions in Fe SSIF, whereas corrosion products were produced in HBSS, inhibiting Zn dissolution. In the animal study, none of the Zn alloy staples caused technical failure, and all rabbits survived without complications. Histopathological analysis revealed no severe inflammatory reaction around the Zn alloy staples.CONCLUSION Staples made of Zn-1.0Cu-0.2Mn-0.1Ti, Zn-1.0Mn-0.1Ti, and Zn-1.0Cu-0.1Ti exhibit acceptable in vitro mechanical properties, proper degradation behavior,and in vivo safety and feasibility. They are promising candidates for biodegradable staples.     

透明质酸交联、酯化衍生物的制备及医学应用进展

透明质酸(Hyaluronan，HA)作为滑液和细胞外基质中一种丰富的糖氨聚糖成分，具有良好的生物相容性和生物降解性。然而，由于天然HA机械性能低，必须经化学修饰作用提高其化学和机械性能，才能作为生物材料广泛使用。本文综述了近年来对HA材料的交联、酯化两种重要化学修饰方法的研究成果，并介绍了这两大类HA衍生物作为新一类生物材料在组织工程、创伤愈合、手术防粘连、粘性补充物和药物释放等方面的应用情况和发展前景。     

Immersion behavior of gelatin-containing calcium phosphate cement

Calcium phosphate cements (CPCs) have many favorable properties that support their clinical use as bone defect repair. However, it is difficult to deliver to the required site and hard to compact adequately due to inherently low ductility of ceramics. The aim of this study focused on the effect of the gelatin content on properties of CPCs. The diametral tensile strength, morphology, and weight loss of gelatin cements were evaluated after immersion in physiological solution, in addition to setting time. The results indicated that the setting time significantly increased with increasing gelatin amount. The 2 wt.% gelatin could make CPCs attain the maximum strength value of 2.1 MPa at 15-day immersion, while 1.6 MPa for the cement without gelatin. It is concluded that the presence of gelatin improved mechanical properties of CPCs; in particular, 2 wt.% gelatin. CPCs containing 2 wt.% gelatin hardened in an acceptable time recommended for clinical applications.     

PLA-PEG嵌段共聚物在药物释放系统中的应用

介绍PLA-PEG嵌段共聚物的合成和性质,综述其作为胶束、微球、纳米粒等的载体在药物释放系统中的应用。聚乳酸-聚乙二醇嵌段共聚物因具备良好的生物可降解性和相容性而得到广泛应用。     

Preparation of a bioactive and degradable poly(epsilon -caprolactone)/silica hybrid through a sol-gel method

A bioactive and degradable poly(epsilon -caprolactone)/silica hybrid was synthesized for the application as a bone substitute. Triethoxysilane end capped polyepsilon -caprolactone) was prepared by the reaction with alpha,omega-hydroxyl poly(epsilon -caprolactone) and 3-isocyanatopropyl triethoxysilane using 1,4-diazabicyclo[2,2,2,]octane as a catalyst. It was then co-condensed with tetraethyl orthosilicate and calcium nitrate tetrahydrate via a sol-gel method. The bioactivity of the poly(epsilon -caprolactone)/silica hybrid was assessed using simulated body fluid and low crystalline apatite was successfully formed on its surface after soaking for 1 week at 36.5 degrees C. Its biodegradability was evaluated in the phosphate buffered saline and the degradability was mostly come from the poly(epsilon -caprolactone) phase in the hybrid. It means that this hybrid is likely to be applicable to a bioactive and degradable bone substitute.     

不同组分壳聚糖温敏凝胶材料理化性能评价

目的:评价不同组分壳聚糖温敏凝胶材料的理化性能。方法:先对壳聚糖粉高温高压消毒,然后壳聚糖溶液(0.1mol/L)和β-甘油磷酸钠(β-GP)溶液(1.83 mol/L)分别按照体积比9∶1和7∶1两种配比组分制备壳聚糖温敏凝胶。通过粘度变化、凝胶时间、溶胀率、降解率、微观结构等观察指标比较2种凝胶的性能差异。结果:凝胶时间9∶1组为(6.1±0.68)min,7∶1组为(4.98±0.5)min(P<0.05);初始粘度9∶1组为(9.95±0.40)Paos,7∶1组为(9.90±0.36)Paos(P>0.05),终粘度9∶1组为(50.05±1.06)Paos,7∶1组为(45.25±0.69)Paos(P<0.05);溶胀率9∶1组为(16.6±0.8)%,7∶1组为(16.9±0.7)%(P>0.05);含溶菌酶组的降解率(%)明显高于不含酶组(P<0.05),加酶组和不加酶组7∶1组降解均快于9∶1组(P<0.05)。扫描电镜结果显示9∶1组平均孔径为(1.01±0.62)μm,7∶1组的平均孔径为(0.79±0.44)μm(P>0.05)。结论:9∶1配比的壳聚糖温敏凝胶理化性能优于7∶1比例组。     

Biodegradation of Complex Bacteria on Phenolic Derivatives in River Water

Objective To isolate, incubate, and identify 4-chlorophenol-degrading complex bacteria, determine the tolerance of these bacteria to phenolic derivatives and study their synergetic metabolism as well as the aboriginal microbes and co-metabolic degradation of mixed chlorophenols in river water. Methods Microbial community of complex bacteria was identified by plate culture observation techniques and Gram stain method. Bacterial growth inhibition test was used to determine the tolerance of complex bacteria to toxicants. Biodegradability of phenolic derivatives was determined by adding 4-chlorophenol-degrading bacteria in river water. Results The complex bacteria were identified as Mycopiana, Alcaligenes, Pseudomonas, and Flavobacterium. The domesticated complex bacteria were more tolerant to phenolic derivatives than the aboriginal bacteria from Qinhuai River. The biodegradability of chlorophenols, dihydroxybenzenes and nitrophenols under various aquatic conditions was determined and compared. The complex bacteria exhibited a higher metabolic efficiency on chemicals than the aboriginal microbes, and the final removal rate of phenolic derivatives was increased at least by 55% when the complex bacteria were added into river water. The metabolic relationship between dominant mixed bacteria and river bacteria was studied. Conclusion The complex bacteria domesticated by 4-chlorophenol can grow and be metabolized to take other chlorophenols, dihydroxybenzenes and nitrophenols as the sole carbon and energy source. There is a synergetic metabolism of most compounds between the aboriginal microbes in river water and the domesticated complex bacteria, 4- chlorophenol-degrading bacteria can co-metabolize various chlorophenols in fiver water.