Development of a double-layer electrospun patch as a potential prenatal treatment for myelomeningocele.

Myelomeningocele (MMC) is a congenital defect of the spine characterised by meningeal and spinal cord protrusion through the open vertebral arches. This defect causes progressive prenatal damage of the spinal cord, leading to lifelong handicap. Although mid-trimester surgical repair may reduce part of the handicap, an earlier and less invasive approach would further improve the prognosis, possibly minimising maternal and foetal risks. Several studies have proposed an alternative approach to surgical repair by covering the defect with a patch and protecting the exposed neural tissue. Our study aims to elaborate on a waterproof and biodegradable bioactive patch for MMC prenatal foetal repair. We developed a double-layer patch that can provide a waterproof coverage for the spinal cord, with a bioactive side, conducive to cell proliferation, and an antiadhesive side to avoid its attachment to the medulla.

Parametric sensitivity analysis applied to a specific one-dimensional internal bone remodelling problem.

The relative importance of the various parameters in inducing bone mass loss and osteoclastic perforations is still controversial. Therefore, there is a significant motivation to better understand the parameters behind such dynamic response, and great interest to carry out a parametric sensitivity study as it can provide useful information. As an application, the widely-accepted bone remodelling equation [M.G. Mullender, R. Huiskes, H. Weinans, A physiological approach to the simulation of bone remodeling as self organizational control process, J. Biomech. 27 (1994) 1389.] is investigated using the "n units" model [M. Zidi, S. Ramtani, Bone remodeling theory applied to the study of n unit-elements model, J Biomech. 32 (1999) 743.]. This analysis pointed out that the power in the modulus density relationship p and the power to which density is raised in normalizing the energy stimulus q, known as strongly implicated in the stability condition of the remodelling process, were also stated as insensitive parameters in the bone loss area.

Buckling of adaptive elastic bone-plate: theoretical and numerical investigation.

During day-to-day activities, many bones in the axial and appendicular skeleton are subjected to repetitive, cyclic loading that often results directly in an increased risk of bone fracture. In clinical orthopedics, trabecular fatigue fractures are observed as compressive stress fractures in the proximal femur, vertebrae, calcaneus and tibia, that are often preceded by buckling and bending of microstructural elements (Müller et al. in J Biomechanics 31:150 1998; Gibson in J Biomechanics 18:317-328 1985; Gibson and Ashby in Cellular solids 1997; Lotz et al. in Osteoporos Int 5:252-261 1995; Carter and Hayes in Science 194:1174-1176 1976). However, the relative importance of bone density and architecture in the etiology of these fractures are poorly understood and consequently not investigated from a biomechanical point of view. In the present contribution, an attempt is made to formulate a bone-plate buckling theory using Cowin's concepts of adaptive elasticity (Cowin and Hegedus in J Elast 6:313-325 1976; Hegedus and Cowin J Elast 6:337-352 1976). In particular, the buckling problem of a Kirchhoff-Love bone plate is investigated numerically by using the finite difference method and an iterative solving approach (Chen in Comput Methods Appl Mech Eng 167:91-99 1998; Hildebland in Introduction to numerical analysis 1974; Richtmyer and Morton in Difference methods for initial-value problems 1967).

Mechanical modelling of cell/ECM and cell/cell interactions during the contraction of a fibroblast-populated collagen microsphere: theory and model simulation.

The cell-derived forces generated during wound healing may be beneficial in reducing the wound size by contraction, but are also detrimental because of the high mechanical stresses in and around the scar that can cause pain, disfigurement and loss of tissue function. The fibroblasts seeded collagen matrix is regarded as an in vitro model for this process and as a suitable way to study these mechanical aspects which are poorly understood. It is proposed here, to improve the continuum theory of Murray-Oster by assuming that more than one control system may be operative in wound contraction regulation. In particular, it is suggested that the wound contraction mechanism is not exclusively due to cell/ECM interaction forces but rather that both ECM/cell and the cell/cell interactions operate together in such process.

Computer simulation of an adaptive damage-bone remodeling law applied to three unit-bone bars structure.

It is well admitted that the mechanical loading plays an important role in the growth and maintenance of our skeleton, and that microdamage (i.e.: microcracks) occurs naturally when the bone is overloaded during day-to-day activities. It is also argued, from experimental and theoretical viewpoint, that the cells which built and rebuilt the skeleton are sensitive for both strain and microdamage. The recent damage-bone remodeling theory is employed here to study the mechanical response of the three unit-bone bars that simulate bone trabeculae in the form of truss. It is shown that under constant load, such a structure exhibit inhomogeneous strain and it's response to external applied load depends strongly upon the manner in which the microdamage is distributed.

Damaged-bone adaptation under steady homogeneous stress.

In this work an extension of the adaptive-elasticity theory is proposed in order to include the contribution of bone microdamage as a stimulus. Some aspects of damaged-bone tissue adaptation, brought about by a change of the daily loading history, are investigated. In particular, under the assumption of a small strain approximation and isothermal conditions, the solution of the remodeling rate equation for steady homogeneous stress is discussed and the damage effect upon the remodeling time constant is shown. The result is both theoretical and numerical, based on a recent theory of internal damaged-bone remodeling (Ramtani, S., and Zidi, M., 1999, "Damaged-Bone Remodeling Theory: Thermodynamical Approach, " Mechanics Research Communications, Vol. 26, pp. 701-708. Ramtani, S., and Zidi, M., 2001, "A Theoretical Model of the Effect of Continum Damage on a Bone Adaption Model," Journal of Biomechanics, Vol. 34, pp. 471-479) and motivated by the works of Cowin, S. C., and Hegedus, D. M., 1976, "Bone Remodeling I: Theory and Adaptive Elasticity," Journal of Elasticity, Vol. 6, pp. 471-479 and Hegedus, D. H., and Cowin, S. C., 1976, "Bone Remodeling II: Small Strain Adaptive Elasticity," Journal of Elasticity, Vol. 6, pp. 337-352.

Remodeled-matrix contraction by fibroblasts: numerical investigations.

It is well known that the fibroblast-collagen-matrix contraction model is a unique way to study mechanical interactions that regulate wound contraction of connective tissue cells. This contraction, due to cell traction, plays important roles in wound healing and pathological contractures. A continuum model initially used for the study of mesenchymal morphogenesis is revisited and numerically investigated by assuming that the extracellular matrix has adaptive-elastic properties. The set of non-linear partial differential equations is solved numerically by a finite difference method and the obtained results are discussed.

A theoretical model of the effect of continuum damage on a bone adaptation model.

Throughout life, bone is continuously turning over by the well-regulated processes of bone formation and resorption. Everyday activities damage bone, and this damage is normally repaired in a continuous remodelling process. When an imbalance in this remodelling process occurs, bones may become more susceptible to fracture. This paper is devoted to a theoretical modelling of the competition between damage and internal remodelling in bones. The general theory of adaptive damaged-elastic materials proposed here as a model for the physiological process of damaged-bone remodelling follows the general framework of continuum thermodynamics where new damaged-bone remodelling law and associated thermodynamical restrictions are stated, and specialized to the case of small strain in isothermal processes. An attempt is also made to derive: (a) the damage force (adaptive damage energy release rate ) which controls the microcracks propagation and arrest, and (b) the damage rule by introducing damage thresholds and loading/unloading conditions.

Stability analysis and finite element simulation of bone remodeling model.

Bone remodeling is widely viewed as a dynamic process--maintaining bone structure through a balance between the opposed activities of osteoblast and osteoclast cells--in which the stability problem is often pointed out. By an analytical approach, we present a bone remodeling model applied to n unit-elements in order to analyze the stationary states and the condition of their stability. In addition, this theory has been simulated in a computer model using the Finite Element Method (FEM) to show a relationship between the bone remodeling process and the stability analysis.

Bone remodeling theory applied to the study of n unit-elements model.

The aim of this paper is to illustrate the application of mathematical tools for the analysis of non-linear dynamical systems to the study of global stability of one kind of bone remodeling scheme applied to n unit-elements model. The particular aspects analyzed here are the stationary states related to this theory and a condition of their stability. The non-linear equations governing the remodeling process are solved by finite-difference method and the well-known results on the heterogeneous spatial organizations have been retrieved and confirm the analytical study. This kind of remodeling theory is useful for investigating the effects of physiological parameters on the development, maintenance, and adaptation of bone under mechanical loading.