Andreas F. von Recum

Microtopography and Soft Tissue Response

Implants placed in soft tissue evoke a foreign body reaction. Polymeric implants having smooth surfaces, such as silicone rubber implants, develop a nonadherent fibrogranulous tissue capsule which contracts over time and stiffens. Conventional porous implants, such as those made from textiles, usually have pores larger than 20 microns and they become infiltrated with inflammatory tissue. The in vivo cell reaction to polymeric surfaces having pores smaller than 10 microns has not been investigated systematically. In this study the histocompatibility of materials having mean pore diameters from 0.4 to 10 microns was assessed. A material available with several different defined pore sizes Versapor filter material) was tested in vivo to determine relation between pore size and qualitative tissue response. Silicone-coated samples were also tested to determine the dependence of the observed tissue response on the implant surface chemistry. Results showed nonadherent, contracting capsules around implants having pore diameters smaller than 0.5 microns. Implants with pores ranging from 1.4 to 1.9 microns evoked thin, tightly adherent fibrous capsules without inflammatory cells. Porosities of 3.3 microns and larger became infiltrated with inflammatory tissue. Results indicate that the observed tissue response is predominantly dependent on implant surface topography and that variation in implant material may have little effect. It is concluded that a defined surface topography of 1 to 2 microns appears to allow direct fibroblast attachment to the surface independent of its chemical or electrochemical nature. Attached fibroblasts then produce a minimal connective tissue response to the implant and prevent or diminish the presence of inflammatory cells at the implant/tissue interface.

Influence of silicone (PDMS) surface texture on human skin fibroblast proliferation as determined by cell cycle analysis.

In vivo biocompatibility of soft-tissue implants is often hampered by development of capsules that eventually might contract and impair implant function. It has been shown that capsule formation can be significantly reduced by using materials with textured surface elements in the micron range. In this study the interaction of human fibroblasts with silicone surfaces was analyzed using cell cycle analysis. Silicone was textured with 2, 5, and 10 microns wide grooves (2MU, 5MU, 10MU, respectively) or kept smooth (SMT). Cell cycle analysis was performed after staining of cells with propidium iodide. Cells proliferated on the fibronectin-preadsorbed silicone, as demonstrated by increased coverage and occurrence of subpopulations in the S and G2/M phase of the cell cycle. Cells on SMT went faster into the S phase than cells on textured silicones. Cells on 10MU showed less proliferation than cells on 2MU and 5MU. Besides the basic percentages of cells in the different cycle phases, DNA profiles were also influenced by incubation time and texture, especially with respect to the presence of hypodiploid populations and asymmetry of the G0/G1 peak. Finally scatter characteristics were influenced. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay data did not reveal significant differences among the different samples. Fibronectin preadsorption of silicone only resulted in slightly higher MTT conversion. Cell cycle analysis proved to be a sensitive screening method for proliferation on the silicone surfaces and provided information beyond the normal G0/G1, S and G2/M subpopulations.

Surface Roughness, Porosity, and Texture as Modifiers of Cellular Adhesion

Substrate topography in the micrometer range is reviewed as a modifier of the response of cultured cells and of biocompatibility when implanted into tissues. Characterization methods for substrate topography are discussed, including scanning electron microscopy, profilometry, laser scanning, and confocal microscopy. Because of the current technical limitations in reproducing micron-level topographic details, only one method, ion-beam etching, has been found suitable for texturing substrates on nonplanar surfaces.

Macrophage response to microtextured silicone

Seven different silicone surface textures were tested for effect on macrophage spreading and metabolic activity in vitro. Variables of the textured arrays that could modify spreading were determined to be the size, spacing between, depth, density, and orientation of the individual surface events and the roughness of the surfaces. Cells were influenced by the size of the events and the roughness of the surfaces more than any other variables. Cell morphology data, surface area and perimeter, could be divided into discrete regions that correlated well with the size of the events. Cell dimensions on 5 microns textures were smallest while those on smooth silicone and glass surfaces were the largest. Surface texture events may be modifying contact guidance of the cells or interacting with specific transmembrane proteins to alter cell shape and function. The mitochondrial activity of cells attached to the textured silicones was determined by measuring the amount of reduced MTT directly through live cells. Cells on polystyrene (PS), 5VP and 8VP textures were metabolically more active than cells on the other textures. PMA was used to stimulate cells on the various textures. PMA-stimulated cells, on the smaller textures, 2VP, 5VP and 5CP, were less active than test cells that were not stimulated. The inability of PMA to stimulate these cells may be due to a structural alteration of protein kinase C. An hypothesis is introduced that includes a possible mechanism of how a micrometre-sized surface texture could modify cell function.

Species-related differences in percutaneous wound healing

Percutaneous devices permanently protrude through a surgically created defect in the skin. Usually they provide a connection for intracorporeal implants or organs with external devices. The skin penetration area presents unique medical problems. The interfacing tissue usually does not heal and seal to the implant but remains a focus of constant acute or chronic inflammation and eventually breaks down because of infection. This pathophysiological phenomenon has been studied previously with qualitative light microscopical methods. A large number of empirical studies have attempted to improve the implant-epidermal seal with various implant materials and designs. To allow systematic studies of the effect of biomaterials on implantepidermal interface phenomena, quantitative histological parameters were evaluated. Test implants were made from Dacron velour and placed in dogs, goats, and rabbits for various preselected periods to determine time- and species-related histopathological variations. Results showed that the degree of connective tissue “maturity” within the pores of the implant appears to be related to the concentration of giant cells and polymorphonuclear granulocytes (histocompatibility). The process of epidermal proliferation around porous percutaneous implants appears to follow certain fixed patterns under different conditions that are accompanied by expelling forces, resulting in an outward movement of the implant until it is completely extruded. The presence of microhematomas throughout the implantation period indicates that mechanical forces disrupt interfacial tissue bridges. The basic histological processes are qualitatively the same in the three animal species studied. However, there are quantitative differences with regard to epidermal migration rate and connective tissue maturation within the implant pores, which may explain the different failure modes and times observed among species. The study indicated that percutaneous healing may be directly related to histocompatibility of the implant material, mechanical interfacial forces, and epidermal proliferative patterns. The first two may eventually be controlled by selection of optimal implant materials and device configurations. The control of epidermal migration, however, will be the key to prolonging percutaneous implant life.

Surface characterization of microtextured silicone.

A set of microtextured silicone surfaces was manufactured using the technique of photolithography. The textures consist of a uniform array that imparts anisotropy to the surfaces. Processing the material required multiple steps which may have altered the surface characteristics. This project aimed to determine if a surface texture on implant grade silicone would affect the material characteristics. ESCA and contact angle studies revealed no measurable alteration of the surface chemistry or surface energy due to the texturing procedure or the presence of the texture. Both analytical techniques confirmed the material was silicone. The actual dimensions of the surface textures, size, spacing, depth and orientation of the textures were found to be close to the design values, using SEM and quantitative two- and three-dimensional profilometry. Standard 2D profilometry was not sufficient to characterize the surfaces, as a direct result of the uniformity of the arrays. A method of characterizing regular surface periodic structures is presented.

Intraocular Lens Implants: A Biocompatibility Review

The natural aging process of the eye inevitably leads to the formation of a cataract, resulting in an increasing loss of vision. A cataract is the clouding of the natural lens in the eye and represents a major physical impairment. Modern surgical techniques allow for removal of the clouded lens and replacement with a prosthetic intraocular lens. This article reviews the intraocular tissue response to the implant, which frequently leads to postoperative complications for the patient.

In vitro validation of a right ventricular thermodilution ejection fraction system

Right ventricular ejection fraction (RVEF) is used clinically as an index of right ventricular (RV) pump function. Clinical measurements of RVEF are complicated by the need for complex imaging equipment to compute RV volumes. Recently, the use of thermodilution (TD) methods have been suggested as a simplified means to measure RVEF (RVEFTD) in patients using rapid response thermistors. Validation, however, by comparison of RVEFTD and other methodsin vivo, is difficult. Accordingly, thermodilution derived EF measurements (EFTD) were compared to known values using anin vitro system, with known ejection fractions (EF) set from 17–78% and stroke rates varying independently from 50–100 strokes/min. EFTD was computed by fitting the downslope of the TD curve to a monoexponential function and computing the time constant of thermal decay. A significant correlation existed between EFTD and actual EF over the entire study (r=0.96, p<0.001). Bias analysis showed that the points were within a 95% confidence interval of ±12%. Multivariate analysis showed that stroke rate did not significantly affect TD measurements (r=0.03, p>0.7). This study demonstrates that TD accurately predicts EF using anin vitro system and appears to be independent of stroke rate. Thus, TD methods may provide an accurate, simple and reliable means to serially measure RVEF in the clinical setting.

An investigation of skin deformation around percutaneous devices

According to the literature one of the primary failure models of percutaneous devices (PDs) in soft tissue implantation sites is that of mechanically induced trauma along the implant/tissue interface. In order to avoid such avulsion, subcutaneous flanges have been incorporated into PD designs to provide a better distribution of stresses along the implant/tissue interface. Tissue necrosis and inflammation were then observed to be most pronounced around the rim of the subcutaneous flange. It was the goal of this study to develop and test PDs with subcutaneous flanges of varying stiffnesses in order to allow the flange to distribute stresses into the surrounding tissues more evenly, thereby reducing the likelihood of failure due to avulsion. PDs were tested with flanges of constant thickness or varying linearly, reducing toward the flange rim. They were evaluated using an in-vitro testing method which was designed to simulate the situation of an implanted PD subjected to external loading. The results indicated that the stiffness characteristics of the subcutaneous flange had a substantial effect on the behavior of the devices under loading. A PD having a radial stiffness decrease would improve the likelihood of implant survival in the clinical situation due to the reduction of mechanically induced trauma along the implant/tissue interface.

A Pioneer in Vascular Graft Development: Adam Wesolow, MD

Adam Wesolow, also known as Sigmund Adam Wesolowski, died on August 8. 1993. after a long illness. One of the pioneers of vascular graft development, he was a founding member of the Academy of Surgical Research and a member of the editorial board of this journal from its conception. A recent issue of the journal was devoted to his work and his influence on the field of surgical research. Adam was a personal friend of mine and of Phil Sawyer, the founding editor of this journal. He was, as well, a scientific mentor for many in thoracic and vascular surgical research and vascular graft development. He will be greatly missed.