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Biomedical subjects

A Hiltner

Publications and source records attributed to A Hiltner.

At least 37 records · Page 2Linked to original sources

Infrared spectral analysis of extractables from poly(etherurethane urea) (PEUU) elastomers.

Poly(etherurethane urea) (PEUU) elastomers when employed as biomedical devices may be susceptible to extraction upon implantation. Four PEUU elastomers containing a single PEUU formulation, but varying in terms of their additives, were subjected to an in vitro extraction procedure. The additives in the PEUUs were Methacrol 2138 F at 5 wt% and Santowhite powder at 1 wt% levels. Only 1-2 wt% of the PEUUs was extractable with methanol. Fourier transform infrared spectroscopy (FT-IR) furnished qualitative and quantitative information on the extractables. The extractables consisted of a PEUU component that on the average was richer in soft segment than the bulk PEUU, and the two additives, Methacrol 2138 F and Santowhite powder.

Biocompatible Materials↗

Theoretical analysis on cell size distribution and kinetics of foreign-body giant cell formation in vivo on polyurethane elastomers.

The nature of in vivo leukocyte adhesion and foreign-body giant cell (FBGC) formation on polyurethanes was studied through theoretical and statistical analyses in terms of cell size distribution, density changes, and kinetics of FBGC formation. The results showed that the size distribution of FBGCs followed a "most probable" distribution. During FBGC formation, the densities of FBGCs changed with time. At an early stage, the number of FBGCs increased with time to a maximum at the expense of macrophages. As more FBGCs were formed and less macrophages were present, the fusion of FBGCs among themselves became significant. This, in turn, caused a gradual decrease of FBGC density with time. The rate of FBGC formation was characterized by a rate constant that represented certain characteristics of cell fusion and FBGC formation and the density of initial FBGC-forming macrophages that were a small fraction of leukocytes adhering to the surface. The direct correlations of surface cracking and pitting and adherent FBGCs demonstrated the influence of phagocytic actions of FBGCs on the biostability of implanted polyurethanes. While the cracking was thought to be caused by oxidative degradation facilitated by oxygen ion/radical release of FBGCs, the pitting appeared to result from the Methacrol 2138F aggregates diffusing out of the polymer in an acidic microenvironment under FBGCs, which in turn could be enhanced by the surface degradation and cell phagocytosis. The added Santowhite powder in polyurethane had a significant influence on FBGC formation: It reduced FBGC density and rate of FBGC formation by reducing leukocyte adhesion and the number of macrophages participating in FBGC formation.

Amines↗

Effect of some additives on the biostability of a poly(etherurethane) elastomer.

Four materials based on a single poly-(etherurethane) (PEU) prepared from MDI and PTMEG but differing in additives were studied in the cage implant system. The two additives studied were Santowhite powder at the 1% level and Methacrol 2138F 5%. Methacrol 2138F appeared to be immiscible with the base PEU and was dispersed in discrete domains about 0.5-micron in size. The retrieved PEU specimens were also cleaned and examined in the optical and scanning electron microscopes, and the size and density of adherent foreign body giant cells (FBGCs) were measured at implantation times up to 10 weeks. Methacrol 2138F had no effect on the density, coverage or size distribution of adherent FBGCs, but leaching of Methacrol 2138F was considered to be responsible for extensive pitting of the PEU surface. On the other hand, Santowhite powder appeared to inhibit formation of FBGCs, and while surface cracking and flaking were observed as early as 3 weeks postimplantation on some PEUs, the Santowhite powder effectively inhibited surface cracking and flaking up to the longest implantation time studied.

Amines↗

Cellular interactions with biomaterials: in vivo cracking of pre-stressed Pellethane 2363-80A.

The phenomenon of stress cracking of Pellethane 2363-80A (PEU) was investigated using the cage implant system. A cytotoxic polyvinylchloride (PVC) and a silicone rubber containing an anti-inflammatory steroid were used to create inflammatory environments in which the biostability of the pre-stressed PEU was tested. These coimplants provided alternative in vivo environments to study in vivo polymer interactions. The inflammatory responses to the implanted cages were monitored by analyzing the exudates aspirated from the cages at different implantation times over 21 days. The pre-stressed PEU specimens were retrieved after 5, 10, and 15 weeks postimplantation and examined by optical microscopy (OM) and scanning electron microscopy (SEM). The results support the conclusion that in vivo cracking of stressed (strained) Pellethane 80A is related to cell-polymer interactions. Severe cracking or rupture of the implanted PEU specimens was observed as early as 5 weeks postimplantation. Molecular chain degradation of the implanted specimens was evident from molecular weight measurements. Neither surface cracking nor degradation of macromolecules was found on the pre-stressed PEU specimens with the added cytotoxic PVC implanted over 15 weeks. No cracking was observed on the pre-stressed specimens in the presence of steroid silicone rubber, even after 10 weeks implantation.

Animals↗

In vivo leucocyte interactions on Pellethane surfaces.

In vivo leucocyte interactions of three Pellethane materials of varying hardness were qualitatively and quantitatively characterized using a cage implant system over a 21 d implantation period. Scanning electron microscopy (SEM) and cytochemical staining were utilized to observe the cellular events occurring at the leucocyte-biomaterial interface. Many of the quantitative assays performed, the intracellular alkaline phosphatase activity of exudate leucocytes, the intracellular acid phosphatase activity of adherent leucocytes, the density of adherent leucocytes and the foreign body giant cell network formation tendencies of adherent leucocytes, suggest increased cellular activation with increased Pellethane hardness. Qualitative SEM evaluation of Pellethane surfaces revealed a variety of cellular activities. These included macrophage adherence, cytoplasmic spreading and macrophage-macrophage membrane fusions to form foreign body giant cells. The foreign body giant cells exhibited nuclear reorganization and, when compared with adherent macrophages, they displayed an enhanced ability to fuse to neighbouring leucocytes, increased spreading of membrane processes over the polymer surface, the presence of large cytoplasmic vacuoles, and a lengthened duration of enzymatic activity. Contact angle analysis showed the Pellethane surfaces to be hydrophobic and of low hysteresis. The critical surface tension and the dispersive component of the total surface tension were found to increase with Pellethane hardness.

Alkaline Phosphatase↗

Hierarchical structure of the intervertebral disc.

Optical microscope techniques are used to characterize the hierarchical structure of the collagenous components of the human intervertebral disc. In the anterior annulus fibrosus, the thickness of lamellae increases abruptly 2 mm inward from the edge of the disc, dividing the annulus into peripheral and transitional regions. Lamellae in the lateral and posterior aspects of the disc have a broad distribution of lamellar thicknesses throughout the annulus. In alternating lamellae, fibers are inclined with respect to the vertical axis of the spine in a layup structure. From the edge of the disc inward to the nucleus, this interlamellar angle decreases from +62 to +45 degrees. Within lamellae, the collagen fibers exhibit a planar crimped morphology. The plane of the waveform is inclined with respect to the vertical axis by the interlamellar angle. From the edge of the disc inward, the crimp angle increases from 20 to 45 degrees and the crimp period decreases from 26 to 20 um. A hierarchical model of the intervertebral disc has been developed that incorporates these morphological gradients.

Adult↗

Hierarchical structure in polymeric materials.

The diversity of monomers available for synthesis of high polymers makes it possible to prepare a wide variety of long-chain macromolecular compounds. It is instructive to consider a hierarchical organization of structure in polymers at four successive levels--the molecular, nano-, micro-, and macrolevels--and to examine how interactions at and between these various levels of structure have important and often quite specific influences. Examples are drawn from semicrystalline polymers with flexible chains, liquid-crystalline polymers composed of rigid macromolecules, and amorphous polymers. Structural hierarchies in biocomposite systems are also discussed, particularly in soft connective tissues such as tendon and intervertebral disk.

Animals↗

Biodegradation of a polyurethane in vitro.

This study examines the effect of in vitro exposure to enzymes on the performance properties of Biomer, a segmented polyetherurethane used in a number of blood-contacting devices such as catheters, heart assist pumps, and chambers for artificial hearts. The ultrathin samples were treated with two proteolytic enzymes, papain and urease, for periods of 1-6 months at 37 degrees C. The treated Biomer samples were subjected to chemical and physical analysis. Effects of biodegradation by the enzymes were assessed by fatigue tests, gel permeation chromatography (GPC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis. Papain was found to be more effective in degrading the polymer than urease. Mechanisms for enzymic degradation are proposed.

Biodegradation, Environmental↗

In vivo leucocyte interactions with the NHLBI-DTB primary reference materials: polyethylene and silica-free polydimethylsiloxane.

In vivo leucocyte interactions with the NHLBI-DTB primary reference materials, low density polyethylene (LDPE) and silica-free polydimethylsiloxane (PDMS), were qualitatively and quantitatively characterized using a cage implant system over a 21 d implantation period. Scanning electron microscopy (SEM) and cytochemical staining procedures were utilized to observe the cellular events occurring at the leucocyte/biomaterial interface. The results showed that more cells adhered to the PDMS surface than the LDPE surface at days 4 and 7. The differential analysis revealed that mononuclear cells, presumably macrophages, preferentially adhered to both polymer surfaces. By day 21, there were more very large (greater than 20 nuclei per cell) foreign body giant cells (FBGCs) present on the PDMS surface than the LDPE surface. The phagocytic capabilities of the adhered cells, including the FBGCs, decreased to a greater extent on the PDMS surface, corresponding to the earlier and more extensive spreading of these cells observed in the morphological analysis.

Alkaline Phosphatase↗

The effects of an enhanced inflammatory reaction on the surface properties of cast Biomer.

The ability of a biomaterial to withstand the rigors of the harsh biologic environment is an important consideration when considering a material for long-term biomedical applications. Using a cage implant system, the effects of an intense inflammatory reaction on cast Biomer have been investigated. The inflammatory response to cast Biomer was greatly increased by coimplanting Biomer films with a cytotoxic poly(vinyl chloride) (PVC) in rats for a period of 21 days. Cast Biomer films were characterized by weight, advancing contact angle with water in air, attenuated total reflectance infrared spectroscopy and scanning electron microscopy (SEM). The analyses were performed before any treatment, after autoclaving and sonication, and after 21 days implantation with the cytotoxic (PVC) in rats. The results of the study indicated that cast Biomer does not undergo significant chemical degradation when subjected to the effects of an intense inflammatory reaction for 21 days. Implantation does, however, lead to rearrangement that results in a more polar and hydrophilic surface, suggesting that the polymer adapts to the hydrophilic environment of the inflammatory exudate.

Animals↗

In vivo biocompatibility studies. I. The cage implant system and a biodegradable hydrogel.

A cage implant system has been utilized to examine the in vivo biocompatibility of a biodegradable hydrogel, poly(2-hydroxy-ethyl-L-glutamine) (PHEG). This system permits the quantitative determination of the components of the inflammatory exudate which surrounds the implanted polymer within the cage system. This system permits the serial examination of exudate components without sacrificing the animal. In addition, this system allows the subsequent removal of the polymer for surface and mechanical studies. Following implantation of the biodegradable hydrogel, quantitative and differential white cell counts of the exudates were determined over a 21-day period. In addition, concomitant extracellular enzyme analyses for alkaline phosphatase, acid phosphatase, prostatic acid phosphatase, leucine amino-peptidase, and Cathepsin B1 were determined. Corresponding control samples from exudates of the cage implant without the polymer were also determined. The two-tailed Student's t-test for unpaired samples was used to statistically compare the control and implanted polymer values for these respective analyses at the various time periods. A comparison of the cellular response for the control system and the PHEG system did not show statistically significant differences during the first 7 days following implantation. The acute inflammatory response, polymorphonuclear leukocyte predominant, was followed by a mild chronic inflammatory response, macrophage and lymphocyte predominant, and during this time period, 8-14 days, macrophages were present in significantly larger numbers for the PHEG system when compared to the control values. Enzymic analysis of the exudates revealed statistically significant differences between control and PHEG values at time intervals where no differences were noted in cell density or population. These results are discussed in terms of cell-polymer interactions leading to cellular activation and enhanced enzyme exocytosis by the inflammatory cells. Stress-strain measurements on implanted PHEG samples showed that significant in vivo degradation had occurred during the acute inflammatory phase of the response, i.e., the first 7 days.

Acid Phosphatase↗

Organization of collagen fibers in the intestine.

The characteristic extinction pattern which is observed when the submucosa is viewed in the optical polarizing microscope has been analyzed in terms of the configuration and orientation of the 4 micron diameter collagen fibers. It is shown that the observed polarization effects are produced by periodic variations in orientation of fully birefringent fibers. The fiber configuration required to produce the observed polarization effects is a tilted wave configuration with a crimp period of approximately 20 micron. In the model, the tilted waveform fibers are crimped in register and form parallel arrays. The arrays are oriented in layers at approximately +30 degrees and -30 degrees to the longitudinal direction and are mirror images of each other. Analysis of the extinction pattern shows that the model satisfactorily accounts for the observed polarization effects at several different angles of the crossed polaroids. The calculated strain necessary to straighten the wavy fibers of the model correlates well with the observed strain to uncrimp the collagen fibers in the intestine. This suggests that the initial response to stress is gradual uncrimping of the collagen fibers, and concurrently, a decrease in the angle between biaxially oriented fibers, rather than extension of the straight fibers.

Animals↗

Ultrastructural properties of collagen fibrils in rat intestine.

Collagen fibers (bundles of fibrils) of rat small intestine as observed by Nomarski differential interference contrast microscopy were densely packed in parallel undulating arrays. At the electron microscopical level the diameters of intestinal collagen fibrils increased gradually from 50 nm at three weeks of age to 80 nm at 12 months of age. At each age the fibril diameters were fairly uniform in size. At three weeks or six months of age collagen fibrils from stretched, salted samples were somewhat larger in diameter (12-16%) than those from unstretched, unsalted samples. A biaxial orientation existed between bundles of collagen fibrils at angles that varied from 32 degrees to 81 degrees with a mean of 60 degrees. Thus, intestinal collagen at the fibril level is aligned at varying angles to the longitudinal and circular directions of the intestine.

Aging↗

Organization of collagen fibers in rat tail tendon at the optical microscope level.

The collagen fibers of tendon have a wavy configuration which is important for the mechanical function of the tissue. An investigation into the organization of collagen fibers in rat tail tendon at the level of the light microscope has led us to propose a new model for the basic tendon unit. This unit, which is termed the fascicle, is usually triangular in cross-section and 150 to 300 microns in diameter. The fibrous entities which comprise the fascicle take the planar waveform configuration seen in the polarized transmission microscope and in longitudinal histology sections. The plane of the waveform is parallel to the long side of the fascicle and adjacent planes are arranged with the waveform in registry. Other structural features observed in the microscope can be produced by defects in this ordered arrangement. Thus slip parallel to the plane of the waveform can produce the crimp reversal observed in through-focus photomicrographs. The ridges and valleys which characterize the surface of the fascicle result from out-of-plane crimping. The surface topology is probably important in maintaining registry between neighboring fascicles.

Animals↗

Scanning electron microscopy of collagen fibers in intestine.

Collagen fibers of rat intestine were observed with and without mechanical stress in the scanning electron microscope. Observations were correlated with the previous results obtained by optical polarized microscopy to provide further insight into the organization and morphology of intestinal collagen. Larger fibers, approximately 4 micrometers in diameter, are densely packed in parallel undulating arrays. The initial response to stress is straightening of the original fibers. The extended fibers are biaxially oriented at +30 degrees and -30 degrees to the longitudinal direction. These large fibers appear as assemblies of subfibers. At higher magnifications, the larger fibers appear to be enmeshed in a network of small randomly oriented fibers approximately 0.2 micrometer in diameter. Study of the effect of age on fiber morphology showed that the length of the large fiber undulations increases during maturation but remains constant during aging. The diameters of large and small fibers appear not to change with age, but more of the 4 micrometers fibers are loosely associated into larger fibers which can be observed at both the optical microscope and scanning electron microscope levels. A hierarchical organization of intestinal collagen is proposed.

Aging↗

Biodegradation of a poly(alpha-amino acid) hydrogel. I. In vivo.

A new hydrogel material has been prepared by crosslinking a hydrophilic, nonionic poly(amino acid), poly(2-hydroxyethyl-L-glutamine). The material properties of the hydrogel can be controlled by variation in the crosslink density, and the swelling ratio was found to be a sensitive and convenient method for measuring the extent of in vivo biodegradation of implanted specimens. Degradation of the material was observed only during the first 2 weeks of subcutaneous implantation in rats, and is attributed to hydrolysis by proteolytic enzymes released during the acute and chronic stages of the normal inflammatory response.

Animals↗