Evaluation of titanium release from titanium alloy implants in patients with spinal instrumentation

ObjectiveThis study was performed to investigate the baseline serum titanium levels in patients with short-segment titanium alloy posterior instrumentation and to assess patient-, implant-, and surgery-related factors that might affect the serum titanium level.MethodTwo groups of patients were included in the study. The study group comprised 39 patients who had undergone short-segment posterior instrumentation from January 2013 to June 2016. The control group comprised 11 randomly selected patients who presented to the outpatient clinic with no history of orthopedic surgery. The serum titanium levels and inter-group differences were analyzed.ResultsThe mean serum titanium level was significantly higher in the study group than in the control group. No significant difference was observed between patients with different etiologies, implants used for fusion, numbers of instrumented segments, or postoperative durations.ConclusionThe serum titanium levels of patients with posterior lumbar spinal instrumentation are significantly higher than those of the normal population even after achievement of solid fusion. These levels are not affected by the use of transverse connectors, the use of cages, the operated segments, or the duration of implants.     

Mechanisms controlling protein release from lipidic implants: effects of PEG addition.

Different types of tristearin-based implants for controlled rh-interferon alpha-2a (IFN-alpha) release were prepared by compression and thoroughly characterised in vitro. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was added as a co-lyophilisation agent for protein stabilisation and different amounts of polyethylene glycol (PEG) as efficient protein release modifier. To get deeper insight into the underlying mass transport mechanisms, the release of IFN-alpha, HP-beta-CD and PEG into phosphate buffer pH 7.4 was monitored simultaneously and appropriate analytical solutions of Fick's second law of diffusion were fitted to the experimental results. Importantly, the addition of only 5-20% PEG to the lipidic implants significantly altered the resulting protein release rates and the relative importance of the underlying mass transport mechanisms. The release of IFN-alpha from PEG-free implants was purely diffusion controlled. In contrast, in PEG-containing devices other phenomena were also involved in the control of protein release: the IFN-alpha release rate remained about constant over prolonged periods of time and the total amounts of mobile IFN-alpha increased. Interestingly, the release of PEG itself as well as of HP-beta-CD from the implants remained purely diffusion controlled, irrespective of the amount of added PEG. Thus, different mass transport mechanisms govern the release of the drug, co-lyophilisation agent and release modifier out of the lipidic implants.     

Controlled release of anti-inflammatory agent alpha-MSH from neural implants.

Si-multi-electrode arrays implanted into brain tissue for long-term recording lose electrical connectivity due to the post-implantation inflammatory reaction. This inflammatory reaction creates a physical and electrical gap between the electrode and the surrounding neurons. In this study, novel nitrocellulose-based coatings were developed for the sustained delivery of the anti-inflammatory neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH). alpha-MSH was incorporated in micron-scale nitrocellulose coatings and slow, sustained release over 21 days was attained in vitro. The alpha-MSH released on day 21 was still bioactive, and successfully inhibited nitric oxide (NO) production by LPS-stimulated microglia. The amount of initial drug loading directly affected the release rate, with higher initial loading increasing the mass released but not the percent of drug released. The surface morphology and thickness of the coatings were examined by scanning electron microscopy (SEM) and profilometry. In addition, impedance measurement showed that the alpha-MSH loaded nitrocellulose coatings reduced the magnitude of electrode impedance at the biologically relevant frequency of 1 kHz. In conclusion, nitrocellulose-based, bioactive coatings that release anti-inflammatory agents without increasing the impedence of the electrode were successfully fabricated. These coatings have the potential to reduce inflammation at the electrode-brain interface in vivo, and facilitate long-term recordings from Si-multi-electrode arrays.     

Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.

Carbonated hydroxyapatite (CHA) coatings were applied onto titanium implants by using a biomimetic precipitation method. Different antibiotics were incorporated into the CHA coatings and their release and efficacy against bacteria growth were studied in vitro. The following antibiotics were used within this study: cephalothin, carbenicillin, amoxicillin, cefamandol, tobramycin, gentamicin and vancomycin. Increased concentrations of antibiotics in the coating solution led to a higher quantity of antibiotic incorporated into the CHA coating. Some antibiotics were better incorporated than others depending on their chemical structure. Antibiotics, containing carboxylic groups such as cephalothin, carbenicillin and cefamandol, were better incorporated than antibiotics lacking these groups. A bacterial inhibition test on Staphylococcus aureus bacteria showed inhibition of growth for all antibiotics that were released from the CHA coating. A release test was conducted in phosphate buffer saline PBS at pH 7.4 and 37 degrees C and showed that antibiotics containing carboxylic groups like cephalothin were slower released from the CHA coating than others. These results suggest that certain antibiotics are able to bind/chelate with calcium, resulting in a better incorporation into the CHA coating and a slower release. Antibiotics incorporated in CHA coatings on titanium implants might be used to prevent post-surgical infections and to promote bone-bonding of orthopedic devices.     

Predictability of drug release from cochlear implants

A simplified mathematical theory is presented allowing for in silico simulation of the effects of key parameters of miniaturized implants (size and composition) on the resulting drug release kinetics. Such devices offer a great potential, especially for local drug treatments, e.g. of the inner ear. However, the preparation and characterization of these systems is highly challenging, due to the small system dimensions. The presented mathematical theory is based on Fick's second law of diffusion. Importantly, theoretical predictions do not require the knowledge of many system-specific parameters: Only the "apparent" diffusion coefficient of the drug within the implant matrix is needed. This parameter can be easily determined via drug release measurements from thin, macroscopic films. The validity of the theoretical model predictions was evaluated by comparison with experimental results obtained with a cochlear implant. The latter consisted of miniaturized electrodes, which were embedded in a silicone matrix loaded with various amounts of dexamethasone. Importantly, independent experimental results confirmed the theoretical predictions. Thus, the presented simplified theory can help to significantly speed up the optimization of this type of controlled drug delivery systems, especially if long release periods are targeted (e.g., several months or years). Straightforward experiments with thin, macroscopic films and computer simulations can allow for rapid identification of optimal system design.     

纯钛金属种植体表面活性化的处理方法

检索pubmed数据库和中国期刊全文数据库文献,然后对资料进行整理,综述分析纯钛金属种植体表面活性化处理方法近年来国内外的进展.文献涉及钛种植体表面活性化处理方法主要有:酸蚀处理法、碱热处理法等化学处理方法,表面涂层、离子注入等物理方法,也有采用高能辐射技术,通过激发电离来调控钛氧化膜的性状,以及钛表面组织工程化等生物方法.目前报道的钛种植体表面改性的方法很多,但尚没有较公认的处理方法,为此探索一种最佳的化学表面骀活性化处理方法有着极其重要的科学意义.目前认为较简捷又行之有效的表面处理方法是化学处理法.     

Management of cranial and craniofacial bone defects with prefabricated individual titanium implants: follow-up and evaluation of 166 patients with 169 titanium implants from 1994 to 2000

Objective The TICC (Tomography, Image processing, CAD, CAM) processing chain developed at the Ruhr-University Bochum in Germany has already been established since several years for the reconstruction of large pre-existing posttraumatic skull defects with individual prefabricated implants made of pure titanium. So far, more than 500 titanium implants have been inserted with great success at more than 60 clinical centres worldwide. The aim of our study was to evaluate all implants inserted between 1994 and 2000. Materials and Methods The study describes the clinical experience with 166 patients receiving 169 skull implants between 1994 and 2000. All 169 implants were measured and categorized in the CAD system in terms of size and anatomical localization. The surgical and radiological reports of the patients were evaluated. Sixty patients operated at the university hospital in Bochum and nearby were clinically reviewed describing scars, position of the implants and cosmetic results. Questionnaires of 131 patients were analyzed regarding the postoperative quality of life distinctly. Results The study shows constantly good to excellent results intraoperatively as well as postoperatively regarding complications, fit of the implants and the clinical follow-up. In particular the enquiry of the patients shows that titanium skull implants improve quality of life. Conclusion High precision and easy handling as well as a low complication rate and the high contentedness of the patients make the individual titanium skull implants valuable for cranioplasty, especially in complicated applications with very large defects, multiple previous operations and additional irradiations. Even in these difficult cases predictable results are possible.     

Extended release of adenovirus from silica implants in vitro and in vivo

Despite promising preclinical results, the clinical benefits of cancer gene therapy have been modest heretofore. The main obstacle continues to be the level and persistence of gene delivery to sufficiently large areas of the tumor. One approach for overcoming this might entail extended local virus release. We studied the utility of silica gel monoliths for delivery of adenovirus to advanced orthotopic gastric and pancreatic cancer tumors. Initially, the biochemical properties of the silica-virus matrix were studied and nearly linear release as a function of time was detected. Virus stayed infective for weeks at +37 degrees C and months at +4 degrees C, which may facilitate storage and distribution. In vivo, extended release of functional replication deficient and also replication-competent, capsid-modified oncolytic viruses was seen. Treatment of mice with pancreatic cancer doubled their survival (P<0.001). Also, silica gel-based delivery slowed the development of antiadenovirus antibodies.     

In vitro and in vivo correlation of buserelin release from biodegradable implants using statistical moment analysis.

Here we investigated the possibility to develop different levels of correlation between in vitro drug release profiles and in vivo pharmacokinetic parameters for three Buserelin implant formulations. The in vitro and in vivo data were analyzed using model-independent and model-dependent methods. Since diffusion, dissolution and erosion effects influence drug release in most cases a simple kinetic model is unlikely to explain the overall in vivo release behavior. Thus the in vitro drug release curves were analyzed according to the theoretical models of Higuchi and Korsmeyer-Peppas. For the formulation with predominant diffusion controlled release level A IVIVC could be established (R2=0.986). Independent on drug release mechanism, a level B correlation between the mean in vitro dissolution time (MDT) and mean in vivo residence time (MRT) was obtained with a correlation coefficient of 0.983. Finally, level C correlation were observed when single in vitro parameters, e.g. T50% (time required to release 50% of drug in vitro) where compared with single in vivo parameters like AUC. This study suggests that a level B correlation could be achieved even when drug release occurs by a combination of diffusion and erosion processes. More sophisticated in vitro models mimicking drug release under in vivo conditions are clearly desirable for parenteral depot formulations.     

管状骨髓腔内骨整合式纯钛种植体与骨组织界面的整合状态

目的:自行设计管状骨髓腔内骨整合式纯钛螺旋状种植体组件,通过动物实验,观察种植体-骨组织界面的骨整合情况,为临床指缺损患者种植体式手指赝复体修复提供材料及依据。方法:实验于2005-08/12在第四军医大学西京医院整形外科实验室完成。采用国产纯钛制做螺旋形柱状种植体,根据成人正常掌骨和近节指骨及其髓腔的解剖学特点及临床应用的可行性,借鉴Bmnemark螺旋型种植体,自行开发研制纯钛种植体。选择新西兰大白兔10只,在麻醉显效后,胫骨髓腔内种植纯钛螺旋状种植体10枚,分别于术后2,4,8,12,16周各处死2只动物取材,X线摄片观察骨结合形成情况。结果:所有实验动物均进入结果分析,种植体无脱落。制备出掌指骨髓腔内骨整合式纯钛螺旋型种植体组件及配件。①X线观察结果:术后2周时,种植体与骨组织间可见到较明显透光间隙,种植体-骨界面未见骨小梁及新骨形成,术后4～6周,种植体与骨组织间透光间隙减小,可见种植体周围骨密度增高,种植体螺纹间新骨形成明显,术后8周,种植体与骨组织间已无明显透光间隙,均被高密度区替代,种植体周围骨密度增高,种植体螺纹间新骨形成明显,形成更完善的骨界面,界面骨成熟,术后12周与8周相比,变化不大。②大体及光镜观察结果:术后2周时,种植体与骨组织间为软组织界面,未见新骨生成;术后4～6周,种植体周围大量新生骨样组织形成;种植体周围及螺纹间新骨形成明显,形成骨性界面;术后12周与8周相比,骨性界面进一步形成。结论:该掌指骨髓腔内骨整合式纯钛螺旋状种植体组件,术后8周可以与周围骨组织形成完全骨结合。     

管状骨髓腔内骨整合式纯钛种植体与骨组织界面的整合状态

目的：自行设计管状骨髓腔内骨整合式纯钛螺旋状种植体组件，通过动物实验，观察种植体-骨组织界面的骨整合情况，为临床指缺损患者种植体式手指赝复体修复提供材料及依据。方法：实验于2005-08／12在第四军医大学西京医院整形外科实验室完成。采用国产纯钛制做螺旋形柱状种植体，根据成人正常掌骨和近节指骨及其髓腔的解剖学特点及临床应用的可行性，借鉴Bmnemark螺旋型种植体，自行开发研制纯钛种植体。选择新西兰大白兔10只，在麻醉显效后，胫骨髓腔内种植纯钛螺旋状种植体10枚，分别于术后2，4，8，12，16周各处死2只动物取材，X线摄片观察骨结合形成情况。结果：所有实验动物均进入结果分析，种植体无脱落。制备出掌指骨髓腔内骨整合式纯钛螺旋型种植体组件及配件。①X线观察结果：术后2周时，种植体与骨组织间可见到较明显透光间隙，种植体一骨界面未见骨小梁及新骨形成，术后4-6周，种植体与骨组织间透光间隙减小，可见种植体周围骨密度增高，种植体螺纹间新骨形成明显，术后8周，种植体与骨组织间已无明显透光间隙，均被高密度区替代，种植体周围骨密度增高，种植体螺纹间新骨形成明显，形成更完善的骨界面，界面骨成熟，术后12周与8周相比，变化不大。②大体及光镜观察结果：术后2周时，种植体与骨组织间为软组织界面，未见新骨生成；术后4—6周，种植体周围大量新生骨样组织形成；种植体周围及螺纹间新骨形成明显，形成骨性界面；术后12周与8周相比，骨性界面进一步形成。结论：该掌指骨髓腔内骨整合式纯钛螺旋状种植体组件，术后8周可以与周围骨组织形成完全骨结合。     

Properties of titanium dental implants produced by electro-discharge compaction

Highly porous dental implants of a cylindrical shape were fabricated from commercial grade titanium REP-atomized powders by EDC. They were intended to have the maximum porosity for maximum osseointegration, but to maintain the minimum mechanical properties functionally required. Two level full factorial experiments were conducted with respect to the sample weight, capacitance, input energy and electrode configuration. All samples were X-rayed prior to tests to ascertain the presence, extent and distribution of internal macroscopic voids. Torque and compression tests were conducted to evaluate the yield or ultimate strengths (34-90 cm N and 205-502 MPa, respectively). These results indicate that macroscopic void-free, highly porous implants can be fabricated.     

Effect of protein molecular weight on release from micron-sized PLGA microspheres.

This study investigates the effect of protein molecular weight on release kinetics from polymeric microspheres (1-3 microm). Proteins were encapsulated at high and low loadings in poly(lactic-co-glycolic acid) (PLGA) by a phase inversion technique. Mechanism of release from this type of microsphere appeared to be dependent on protein molecular weight for microspheres with low loadings (0.5-1.6%), while independent of protein molecular weight for microspheres with high loadings (4.8-6.9%). At low loadings, release of larger proteins was dependent on diffusion through pores for the duration of the study, while smaller proteins seemed to depend on diffusion through pores initially and on degradation at later times. Following an initial diffusion phase from low loaded microspheres, lysozyme and carbonic anhydrase, the two smallest proteins, exhibited lag phases with curtailed protein release followed by a phase of increased protein release between 4 and 8 weeks, a phenomenon not evident for larger proteins. It appears that by 8 weeks, PLGA had degraded enough to allow additional release of smaller proteins which were entrapped efficiently within the microspheres. Higher loaded microspheres, which have more interconnecting channels, did not exhibit the pronounced shift from diffusion-based to polymer degradation-based release seen with the lower loaded microspheres. Interestingly, microspheres encapsulating large proteins maintained sustained release rates for 56 days.     

Controlled release of a model protein from enzymatically degrading dextran microspheres.

Protein-loaded dextran microspheres were prepared by a water-in-water emulsion technique. With this technique, an aqueous solution of methacrylated dextran (dex-MA) is emulsified in an aqueous solution of poly(ethylene glycol) (PEG). Subsequently, the dispersed dex-MA phase is crosslinked by radical polymerization of the dextran-bound methacryloyl groups. This method renders microspheres with a hydrogel character of which the crosslink density can be controlled by the water content and the degree of substitution of the dex-MA (DS, the number of methacrylates per 100 glucopyranose residues). If an IgG solution was added to the dex-MA/PEG aqueous system prior to the polymerization reaction, the protein could be encapsulated in the dextran microspheres with a high yield (88-98%). The release of IgG was studied as a function of the water content, the DS and the degradation rate of the microspheres. The microspheres were rendered degradable by co-encapsulation of an endo-dextranase. Non-degrading microspheres mainly showed a burst release, which decreased with increasing crosslink density. By either a low water content (50%, w/w, or lower) or a high DS (DS 13), it was possible to reduce the burst release to about 10%, meaning that almost complete entrapment of the protein could be achieved. The release of IgG from degrading microspheres was predominantly dependent on the DS and the amount of encapsulated dextranase. No differences in release of IgG from microspheres with and without dextranase were observed at high DS (DS 13). This was ascribed to the inability of the enzyme to degrade these microspheres. On the other hand, the entrapped protein was completely released from enzymatically degrading microspheres with a DS 4. Moreover, the release rate of IgG was proportional to the degradation rate of these microspheres (depending on the amount of co-encapsulated dextranase). Interestingly, an almost zero-order release was observed from these microspheres for periods up to 30 days.     

纯钛种植体表面改性对骨结合的影响

背景：研究表明,对种植体表面进行化学、物理、生物化学等改性,可以显著提高种植体表面的生物学活性和骨结合强度。目的：综述并比较不同纯钛表面改性方法对骨结合的影响。方法：以“纯钛、种植体、种植、种植体表面、表面改性、生物活性、生物相容性、骨结合、研究进展”为中文关键词,以“pure titanium,implants,plant,the surface of the implant,surface modification,biological activity,biocompatibility,osseointegration,research progress”为英文关键词,用计算机检索CNKI数据库、万方数据库和PubMed数据库。结果与结论：钛具有稳定的化学性能、良好的生物相容性及较高的抗断裂强度,因而在种植修复中被广泛应用,但钛种植体是一种生物惰性材料,直接植入人体后的生物相容性和生物学活性较差,影响其与骨的结合。为提高种植体骨结合强度,目前最为有效的方法是对纯钛表面进行改性。大多数研究表明,经过改性后的种植体具有一定的骨诱导作用,可促使骨细胞在其表面黏附、增殖、分化及矿化。钛种植体经过物理、化学、生物化学等改性处理后,其表面形貌、化学成分、表面粗糙度及亲水性能等发生改变,从而提高了种植体的生物相容性和生物活性,促进了骨结合的发生。     

钛种植体表面改性的研究现状及应用进展

近年来,纯钛因其具有良好的生物相容性,而被应用于口腔种植领域,但其本身仍存在着许多问题.随着钛种植体广泛应用于临床,如何提高其种植的成功率引起了人们越来越多的关注.学者们研究了多种改善方法,其中钛种植体的表面处理对提高种植成功率起着重要作用,目前常用的表面处理方法主要包括:化学处理方法、物理方法,以及生物方法等,且不同处理方法都有其各自的优点.文章就目前国内外对钛种植体表面处理方法的研究现状及进展进行综述.     

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 2. Modulation of release rate.

Amphiphilic multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were used as matrix material for protein-loaded microspheres. The efficiency of lysozyme entrapment by a double emulsion method was found to depend on the swelling behavior of the polymers in water and decreased from 100% for polymers with a degree of swelling of less than 1.8 to 11% for PEG-PBT copolymers with a degree of swelling of 3.6. The particle size could be controlled by varying the concentration of the polymer solution used in the microsphere preparation. An increase in the polymer concentration resulted in a proportional increase in the particle size. The in vitro release profiles of the encapsulated model protein lysozyme could be precisely tailored by variation of the copolymer composition and the size of the microspheres. Both a slow continuous release of lysozyme, and a fast release which was completed within a few days could be obtained. The release behavior, attributed to a combination of diffusion and polymer degradation, could be described by a previously developed model.     

Characterization of crosslinked high amylose starch matrix implants. 2. In vivo release of ciprofloxacin.

The purpose of this study was to develop a crosslinked high amylose starch (CLHAS) matrix implant as a sustained antimicrobial delivery system for local prevention and/or treatment of osteomyelitis. Implants (200 mg) of CLHAS containing 2.5% (5 mg), 7.5% (15 mg), 15.0% (30 mg) and 20.0% (40 mg) of ciprofloxacin (CFX), were prepared by direct compression of dry blends. Rabbits were administered six 2.5, two 7.5, one 15.0 or one 20.0%-CFX implants along the femur between the quadriceps and biceps femoris muscles to determine systemic (serum) versus local (muscle and bone) CFX concentrations over 1 month. Blood samples were taken throughout the study for CFX assay. Muscle and femur were collected at 3, 7, 14, 21 and 28 days after implantation for host response evaluation and CFX assay. Residual polymer was explanted to determine the remaining dose of CFX. All animals remained healthy during the study. Local tissue reaction was mild and limited to the implantation site. Serum CFX concentrations remained low regardless of implant loading. Increased drug loading resulted in a higher and longer release of CFX in muscle and in bone. Local CFX concentrations were detected largely in excess of the MIC over 28 days with 20.0%-CFX implants. More residual CFX in polymer was detected over a longer period of time at high loading. These results strongly support the development of CLHAS implants for local antibacterial therapy.