3D multi-agent models for protein release from PLGA spherical particles with complex inner morphologies

In order to better understand and predict the release of proteins from bioerodible micro- or nanospheres, it is important to know the influences of different initial factors on the release mechanisms. Often though it is difficult to assess what exactly is at the origin of a certain dissolution profile. We propose here a new class of fine-grained multi-agent models built to incorporate increasing complexity, permitting the exploration of the role of different parameters, especially that of the internal morphology of the spheres, in the exhibited release profile. This approach, based on Monte-Carlo (MC) and Cellular Automata (CA) techniques, has permitted the testing of various assumptions and hypotheses about several experimental systems of nanospheres encapsulating proteins. Results have confirmed that this modelling approach has increased the resolution over the complexity involved, opening promising perspectives for future developments, especially complementing in vitro experimentation

Influence of porosity and fibre diameter on the degradation of chitosan fibre-mesh scaffolds and cell adhesion

The state of the art approaches for tailoring the degradation of chitosan scaffolds are based on altering the chemical structure of the polymer. Nevertheless, such alterations may lead to changes in other properties of scaffolds, such as the ability to promote cell adhesion. The aim of this study was to investigate the influence of physical parameters such as porosity and fibre diameter on the degradation of chitosan fibre-mesh scaffolds, as a possible way of tailoring the degradation of such scaffolds. Four sets of scaffolds with distinct fibre diameter and porosity were produced and their response to degradation and cell adhesion was studied. The degradation study was carried out at 37"C in a lysozyme solution for five weeks. The extent of degradation was expressed as percentage of weight loss of the dried scaffolds after lysozyme treatment. Cell adhesion was assessed by Confocal Microscopy. The results have shown that the scaffolds with higher porosity degrade faster and that, within the same range of porosity, the fibres with smaller diameter degrade slightly faster. Furthermore, the morphological differences between the scaffolds did not affect the degree of cell adhesion, and the cells were observed throughout the thickness of all four types of scaffold

4D Numerical Analysis of Scaffolds: A New Approach

A large range of biodegradable polymers are used to produce scaffoldsfor tissue engineering, which temporarily replace the biomechanical functions ofa biologic tissue while it progressively regenerates its capacities. However, the mechanicalbehavior of biodegradable materials during its degradation, which is an importantaspect of the scaffold design, is still an unexplored subject. For a biodegradablescaffold, performance will decrease along its degradation, ideally in accordanceto the regeneration of the biologic tissue, avoiding the stress shielding effect or thepremature rupture. In this chapter, a new numerical approach to predict the mechanicalbehavior of complex 3D scaffolds during degradation time (the 4th dimension)is presented. The degradation of mechanical properties should ideally be compatibleto the tissue regeneration. With this new approach, an iterative process of optimizationis possible to achieve an ideal solution in terms of mechanical behavior anddegradation time. The scaffold can therefore be pre-validated in terms of functionalcompatibility. An example of application of this approach is demonstrated at the endof this chapter

Modeling of Polymer Erosion

The erosion of bioerodible polymers depends on many factors including the polymer chain length, bond cleavage velocity, swellability, crystallinity, and water diffusivity in the polymer matrix. This multitude of parameters makes modeling of erosion difficult. Only a few models exist that describe morphological changes of polymers during erosion qualitatively. In the present approach the polymer matrix was represented as the sum of small individual polymer matrix parts. The factors that determine erosion were combined, and the erosion of each matrix piece was regarded as a random event. Once such a matrix piece had come into contact with water, an individual life expectation was assigned to it using Monte Carlo techniques. The proposed model can describe complicated phenomena such as changes in polymer matrix microstructure, movement of erosion fronts, creation of pores, and weight loss during erosion, yet it is simple and easy to use. For quantitative evaluations the model was fit to experimental data for weight loss and erosion front movement. The so obtained model constants proved to be useful for the prediction of independent parameters like the porosity of polymer matrices during erosion. This modeling approach may help broaden the understanding of the role of polymer erosion when considering bioerodible polymers in applications such as controlled drug delivery or tissue engineering

The Influence of Microstructure and Monomer Properties on the Erosion Mechanism of a Class of Polyanhydrides

The erosion of three different polyanhydrides consisting of sebacic acid (SA) and 1,3-bis(p-carboxyphenoxy) propane (CPP) was investigated. Melt cast polymer matrices were prepared from the homopolymer p(SA) and two copolymers, p(CPP-SA) 20 : 80 and p(CPP-SA) 50 : 50. Particular attention was paid to the influence of the polymer matrix microstructure and of the monomers on erosion. Using polarized light microscopy we found that p(SA) and p(CPP-SA) 20 : 80 matrices consist of spherulites. SEM investigations showed that their crystalline parts are more resistant to erosion than their amorphous areas. The matrices erode into highly porous devices, whose porosity is detectable by mercury porosimetry. Using wide-angle x-ray diffractometry we found that monomers crystallize inside the pores. DSC investigations showed a maximum of crystallized SA after 2-6 days and a continuous increase of CPP, which stays in the devices for weeks. We conclude that the microstructure and the monomer properties are the two main factors which determine the erosion of these polymers. The obtained data on changes in porosity, crystallinity, polymer matrix thickness, erosion front velocities, crystalline monomer content, and monomer release provides the basis for quantitatively describing the erosion process

Drug delivery from bioerodible polymers: systemic and intravenous administration

The recent progress in understanding the erosion of biodegradable polymers and the manufacturing of controlled release devices for proteins and peptides is reported. The erosion mechanism of poly(anhydrides) was investigated as an example of biodegradable polymers and the erosion behavior is modeled mathematically. The results provide useful information on the microstructure and chemical environment inside these polymers during erosion. It is shown how they might affect the stability and the release of proteins. Concomitantly proteins were processed in controlled release devices. Special attention was paid to the stability of the biomolecules during the manufacturing of dosage forms. Furthermore, the development of a new type of biodegradable nanosphere as a future dosage form is shown