Study on structural optimum design of implantable drug delivery micro-system

In this paper, design, modeling, and simulation of a new type of controlled drug delivery system based on biodegradable polymers is report. The system consists of arrays of micro-chambers for drug storage to achieve linear release. The micro-chambers were fabricated with biodegradable polymer using the UV-LIGA technology and the controlled release process is the combined results of design of the micro-chambers and the biodegradable characteristics of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as improved efficiency, reduced side effect, on-spot delivery, and convenient therapy. Mathematical model has been developed for two kind of biodegradable polymer micro-system respectively, and numerical simulations were conducted to analyze the biodegradation and the controlled release process. The mathematical model can be used to optimize the structural design for controlled-release system with the desired release characteristics.     

基于Monte Carlo模型的微型PLGA给药系统建模及仿真

多腔体的微型可降解高分子聚合物PLGA药物缓释系统是一种新型植入式给药微器件,其载体结构是结合药物释放的要求和高分子聚合物生物降解特性进行设计并利用MEMS工艺制备.为了解微型给药系统实际释药的性能,需要对其进行建模和仿真研究.基于体溶蚀的Monte Carlo溶蚀模型,建立了具有多腔体的微型PLGA给药载体的释药模型,并对腔体结构为圆形的微型给药系统进行了释药过程仿真.仿真结果表明本文建立的微系统释药模型可以较为准确的描述微系统的释药过程,仿真模型对进一步开发微型PLGA给药系统有重要的参考价值.     

Modeling and simulation of drug delivery from a new type of biodegradable polymer micro-device

In this paper, modeling and simulation of a new type of controlled drug delivery micro-device based on biodegradable polymers is reported. The micro-device consists of micro-chambers arrays for drug storage to achieve linear release. The micro-chambers are fabricated with polyanhydrides (CPP-SA) using the UV-LIGA technology and the controlled release process are the combined results of the design of the micro-chambers and the biodegradable characteristics of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as larger loading volume than the matrices release systems, easier control for the release rate, etc. It is necessary to optimize the structure for the long-term and zero-order drug release. Based on the Monte Carlo erosion model, the drug release model is founded for the drug delivery system and using the new model, the drug release profiles from the delivery systems with different structures are simulated. The simulated results indicate that the effect of the drug delivery is dependent on the micro-structure of the delivery system and the simulated drug profiles of coaxial rings micro-cavity shape equal to zero-order released model approximatively. The simulated results are very important to the application research of the new biodegradable polymer micro-device.     

Numerical simulation of drug release from collagen matrices by enzymatic degradation

Biodegradable collagen matrices have become a promising alternative to synthetic polymers as drug delivery systems for sustained release. Previously, a mathematical model describing water penetration, matrix swelling and drug release by diffusion from dense collagen matrices was introduced and tested (cf. Radu et al. in J. Pharm. Sci. 91:964–972, 2002). However, enzymatic matrix degradation influences the drug release as well. Based on experimental studies (cf. Metzmacher in Enzymatic degradation and drug release behavior of dense collagen implants. Ph.D. thesis, LMU University of Munich, 2005), a mathematical model is presented here that describes drug release by collagenolytic matrix degradation. Existence and uniqueness of a solution of the model equations is reviewed. A mixed Raviart–Thomas finite element discretization for solving the coupled system of partial and ordinary differential equations is proposed and analyzed theoretically. The model is verified by a comparison of numerically calculated and experimentally measured data and, in particular, investigated by a parameter sensitivity study. For illustration, some concentration profiles of a two-dimensional simulation are shown.     

Silicon microneedle array with biodegradable tips for transdermal drug delivery

This paper presents the fabrication process, characterization results and basic functionality of silicon microneedle array with biodegradable tips for transdermal drug delivery. In order to avoid the main problems related to silicon microneedles; the breaking of the top part of the needles inside the skin, a simple solution can be the fabrication of microneedle array with biodegradable tips. A silicon microneedle array was fabricated by deep reactive ion etching (RIE), using the photoresist reflow effect and RIE notching effect. The biodegradable tips were successfully realized using the electrochemical anodization process that selectively generated porous silicon only on the top part of the skin. The porous tips can be degraded within a few weeks if some of them are broken inside the skin during the insertion and release process. The paper presents also the results of in vitro release of calcein with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without microneedle enhancer, the microneedle array had presented significant enhancement of drug release.     

Numerical modeling of a novel degradable drug delivery system with microholes

Based on UV-LIGA technology, a novel drug delivery microsystem is proposed to eliminate the time lag in initial drug release. With proper microholes in bonding membrane, the drug release rate can be controlled at a stable level in the whole release process. This microsystem is fabricated by degradable polymer and suitable for subcutaneous implants. As a significant parameter, the demarcation time of polymer absorption/erosion is estimated by comparing the experimental results of polymer erosion and in vitro release. By considering diffusion, swelling and erosion mechanisms simultaneously, a numerical drug releasing model is developed to investigate the effect of microholes on drug release and impact factors of linear drug releasing. The simulation results show that the microholes are beneficial to eliminate the time lag, and furthermore, the area of microholes and the initial drug loading have great impact on the release time and the linear drug release rate.     

Biodegradable polylactic acid microstructures for scaffold applications

In this research, we present a simple and cost effective soft lithographic process to fabricate polylactic acid (PLA) scaffolds for tissue engineering. In which, the negative photoresist JSR THB-120N was spun on a glass subtract followed by conventional UV lithographic processes to fabricate the master to cast the PDMS elastomeric mold. A thin poly(vinyl alcohol) (PVA) layer was used as a mode release such that the PLA scaffold can be easily peeled off. The PLA precursor solution was then cast onto the PDMS mold to form the PLA microstructures. After evaporating the solvent, the PLA microstructures can be easily peeled off from the PDMS mold. Experimental results show that the desired microvessels scaffold can be successfully transferred to the biodegradable polymer PLA. Encouraging progress in bovine endothelial cells seeding was observed.     

Rapidly in situ forming biodegradable hydrogels by combining alginate and hydroxyapatite nanocrystal

The in situ forming biodegradable polymer scaffolds are important biomaterials for tissue engineering and drug delivery.Hydrogels derived from natural proteins and polysaccharides are ideal tissue engineering scaffolds since they resemble the extracellular matrices of the tissue comprising various amino acids and sugar based macromolecules.This work presented an injectable system from partially oxidized alginate and hydroxyapatite(HAP) nanocrystal for tissue engineering and drug delivery applications.In sit...     

Post-buckling dynamic behavior of self-assembled 3D microstructures

The paper presents the snap-through phenomenon in the case of micro fabricated clamped-clamped buckled beam. This dynamic post-buckling behavior is likely to occur in 3D microstructures when they are subjected to large vibration amplitudes. The main difference between this work and previous studies is the MEMS specific beam dimension, especially the large initial deflection of the buckled beam that involves the inversion of the two first resonance frequencies. The mathematical development allows showing how the vibration amplitude of the supporting base affects the post-buckling dynamic behavior of the beam. For each frequency, the limit between the stable behavior and the snap-through behavior is evaluated. Moreover, the effect of environment is taken into account from the damping point of view. Samples are fabricated and the experiment is described. Measurements are compared to the theoretical approach and the results are in good agreement with the proposed model.     

A new process for fabricating tip-shaped polymer microstructure array with patterned metallic coatings

In this paper, we present a new process for fabricating tip-shaped polymer microstructure array coated by patterned metal layer. This new process involves three techniques including: micro-molding, patterned metal layer transfer, and electrochemical-based sacrificial layer. As we know, it is very difficult to remove the extra photoresist (PR) in the concave areas in traditional micro-fabrication technology, which hinders patterning metal layers on three-dimensional (3D) microstructures. The electrochemical-based sacrificial layer technique can effectively resolve this problem, which is verified by scanning electron microscopy (SEM) characterization. Comparative study between the 3D metal-coated polyimide microstructures fabricated with and without the electrochemical-based sacrificial layer step is also performed and SEM images proved the effect of the presented process. The applicability of the developed process is also demonstrated with the successful fabrication of a pyramid-shaped polyimide microelectrodes array for neural stimulation.     

基于晶格理论的聚合物溶液活度模型

根据Gibbs-Helmholtz热力学基本关系式,结合溶液晶格模型推导出适合聚合物体系的活度系数模型,该模型方程含有结合项、剩余项和自由体积项。将其与Entropic-FV(EFV)、UNIFAC-FV及UNIFAC模型,同时用于预测14个由PIB、PS和PPO等聚合物与苯、甲苯和丁烷等溶剂组成的聚合物-溶剂体系中溶剂的活度,并与实验数据进行比较,活度的平均偏差分别为3．98%、6．61%、4．92%、19．19%。计算结果显示该模型的预测精度高于其它3种常用的聚合物、溶剂体系的溶剂活度模型。     

Space–Time Signal Analysis and the 3D Shearlet Transform

In this work, we address the problem of analyzing video sequences by representing meaningful local space–time neighborhoods. We propose a mathematical model to describe relevant points as local singularities of a 3D signal, and we show that these local patterns can be nicely highlighted by the 3D shearlet transform, which is at the root of our work. Based on this mathematical framework, we derive an algorithm to represent space–time points which is very effective in analyzing video sequences. In particular, we show how points of the same nature have a very similar representation, allowing us to compute different space–time primitives for a video sequence in an unsupervised way.     

用VRML实现晶粒三维形貌仿真结果可视化

该文以连续形核模型和晶粒的细胞生长法为基础,提出一种“晶界多边形逐个拓扑,晶粒形貌逐个构建”的三维仿真算法;采用面向对象的方法,在VC++6.0中完成了晶粒的三维形貌仿真;结合VRML的技术特点,将仿真结果自动转换为场景文件,并在浏览器中实现交互式的三维可视化。实验表明,所建仿真模型较好地模拟了三维多晶体组织,因此可为多晶材料显微组织的研究提供一种三维数字化模型。     

需求可拆分车辆路径问题的禁忌搜索算法

为解决实际配送运输中的车辆路径问题（Vehicle Routing Problem,VRP）,通过改进传统的数学模型,解除每个客户需求只能由l辆车配送的约束,建立改进的可拆分车辆路径问题（Split Delivery VRP,SDVRP）数学模型,并利用禁忌搜索算法（Taboo Search Algorithm,TSA）进行求解．在TSA的设计中,根据SDVRP模型的特点对初始解、邻域搜索和解的评价等进行特殊处理．算例表明,该模型不仅可以解决VRP模型中不允许配送点需求量超出装载量的限制,而且通过相应配送点需求量的拆分和重新组合,可节省车辆数目、缩短路线长度、提高车辆装载率．     

Maskless writing of microfluidics: Rapid prototyping of 3D microfluidics using scratch on a polymer substrate

We present a new rapid prototyping method designed for simple fabrication of 3D microfluidics using a maskless direct writing technique on polymer substrates. The entire process is enabled by a commercial cutter plotter with 10 μm resolution precision and high speed. A CAD design of top and bottom microstructures is directly written on a polymer substrate using a cutter plotter after setting up the suitable force. The smallest channel width of 20 μm was obtained with the minimum force and 100 μm from the maximum. Also the written depth increased linearly with force from 30 to 130 μm. Several 3D microfluidic devices are demonstrated using a maskless writing technique. The entire fabrication process from CAD layout to a final 3D device can be completed in 30 min outside the clean room facilities.     

Microfabrication Technology of Biodegradable Polymers for Interconnecting Microstructures

A microtechnology for synthetic biodegradable polymers has been developed to fabricate three-dimensionally (3-D) shaped and microstructured multilayer constructs for biomedical applications. A unique micromolding method is proposed to create deep and interconnecting microstructures which facilitate cellular scale interconnection across the layers for cell-to-cell communication and the supply of nutrients and oxygen. A geometrical condition and molding setup for interconnecting microstructuring are described and demonstrated experimentally. Furthermore, various types of synthetic biodegradable polymers are explored and compared with regard to the behavior during the proposed process. Considering the thermal instability of synthetic biodegradable polymers, it is also confirmed that the proposed process does not affect the property of the polymers. Finally, microfabricated 3-D multilayer constructs is presented to demonstrate the feasibility of the technology as a unique scaffolding method     

Thermomechanical Model of an Impermeable Porous Medium with a Chemically Active Filler

A self-consistent mathematical model describing the thermomechanical behavior of an elastic medium, which contains voids filled with a chemically active substance, is considered. The behavior of the medium is described by thermomechanical equations. Processes in the pores are described by a lumped model which allows for energy release, chemical reactions, and conditions of phase equilibrium. The model makes it possible to take into account an arbitrary number of components, which can be in solid and three mobile phases (liquid gaseous, liquid hydrocarbon, and aqueous phases). The distribution of components between phases is obtained using a thermodynamically consistent technique under assumption that any mobile component can be present in any mobile phase. In order to describe the thermodynamic behavior of the components with allowance for phase transitions, cubic equations of state are used, which are rather common in engineering practice. An algorithm based on a combination of domain decomposition method and physical splitting approach is proposed for the numerical solution of the model system of equations.     

Biodegradable submicrometric sieves in PLLA fabricated by soft lithography

Sieves are membranes with a regular array of uniform pores that present low flow resistance. Because of such characteristics they are promising devices for filtration, separation of particles by size and drug delivery control systems. In this paper, we propose and demonstrated the use of a soft lithography process for fabrication of biodegradable sieves in PLLA (poly-l-lactide) with pores in the scale of hundred of nanometers. The fabrication process is suitable for mass production and submicrometric pore diameters can be fabricated with homogeneity of about 15%. The PLLA self sustained sieve can be integrated to PLLA capsules, compounding a drug delivery systems or implants.     

具有排列扫描特征的多态蠕虫传播模型

多数蠕虫传播模型都是基于简单的随机扫描,蠕虫形态相对固定。为此,研究排列扫描技术,结合自然生物的取食繁殖规则,提出一种多态蠕虫动态传播的数学模型。通过一系列相互独立的方程表现蠕虫的整体行为,计算传播过程中各类被感染蠕虫的数目。仿真实验结果表明,该模型能准确描述多态蠕虫的传播过程。     

群体机器人合作觅食任务数学模型的建立与分析

群体机器人系统的数学模型可以预测系统的群体行为,能够在设计系统硬件或开发仿真程序之前,分析个体特征对群体行为的影响,以指导个体控制策略的改进。本文提出群体机器人合作觅食任务的数学模型。该数学模型由微分比率方程组构成,能够描述合作觅食任务群体行为的动态特征。仿真实验表明,数学模型的预测结果与仿真实验数据可以较好的拟合。