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Biomedical subjects

G A Ksander

Publications and source records attributed to G A Ksander.

At least 19 recordsLinked to original sources
PubMed1992

Tissue compatibility of collagen-silicone composites in a rat subcutaneous model.

Collagen-silicone composites were fabricated and tested for biocompatibility by subcutaneous implantation in rats. The silicone component consisted of addition cure or condensation cure sheets. The collagen component was either (a) a sponge layer 2 mm thick, (b) a thin film 12-20 microns thick, or (c) residual collagen bonded to or incorporated in the silicone rubber. Collagen sponges were mechanically bonded to silicone sheets, and collagen thin films and residual collagen were physically and chemically attached to epoxy-derivatized silicone sheets. Analysis of implanted samples showed that reduced capsule formation occurred around collagen sponge-silicone, compared to control silicone sheets. Only where the underlying silicone sheet, or interpenetrating silicone, was exposed to the tissue, did limited capsule formation occur. In contrast, thin capsule developed completely around silicone coated with a thin collagen film and around silicone bonded to residual collagen. Sponge-silicone composites and control silicone sheets were free of acute and chronic inflammation, except for occasional foreign body giant cells in sponge adjacent to silicone. Silicone coated with micron-thick collagen films exhibited some inflammation, but residual collagen-silicone did not. This study suggests that, to prevent capsule formation, a collagen coat must be of minimum thickness and surface coverage sufficient to prevent any contact between silicone and tissue.

Animals↗
PubMed1992

Skin distribution and differential expression of transforming growth factor beta 1 and beta 2.

Transforming growth factor beta (TGF-beta) 1 and 2 have both become increasingly important in cutaneous biology, but their expression and distribution in human skin are not entirely clear. In this report, normal forearm skin from four volunteers was investigated for TGF-beta 1 and beta 2 immunostaining with antibodies that detect preferentially either cell- or matrix-associated forms of these peptides. Marked cell-associated TGF-beta 1 was found in the dermis, particularly around blood vessels and ducts; cellular TGF-beta 2 immunostaining was less prominent, and was predominantly around blood vessels. Neither TGF-beta 1 nor -beta 2 could be detected in the epidermis or epithelial structures, and the dermal matrix contained minimally detectable amounts of the two isoforms. In all cases, dermal matrix and cells contained greater amounts of TGF-beta 1 than TGF-beta 2. Previous studies have shown that both TGF-beta 1 and -beta 2 can induce dramatic increases in extracellular matrix, and both peptides have been implicated in the pathogenesis of fibrosis. We therefore investigated TGF-beta 1 and -beta 2 immunostaining in involved forearm skin of four patients with systemic sclerosis. Compared to normal skin, fibrotic specimens showed increased amounts of matrix and epidermal TGF-beta 1, but not TGF-beta 2. We conclude that TGF-beta 1 and -beta 2 expression in human skin is differentially regulated, and that their distribution is varied and complex.

Adult↗
PubMed1991

Differences in the biological activities of transforming growth factor-beta and platelet-derived growth factor in vivo.

Transforming growth factor-beta 1 (TGF-beta 1 and recombinant platelet-derived growth factor-BB (rPDGF-BB) promoted an extensive, dose-dependent development of fibrous connective tissue when continuously delivered for 8 days by mini-osmotic pumps implanted subcutaneously in adult guinea pigs. Biochemical analyses demonstrated that TGF-beta 1 and rPDGF-BB stimulated dose-dependent increases in the dry weight, and protein, DNA, collagen, and glycosaminoglycan (GAG) contents of the fibrous connective tissue capsule that enveloped the pumps. The GAG/DNA mass ratio was markedly elevated by TGF-beta 1, but the collagen/DNA, protein/DNA, and collagen/protein ratios were not significantly increased. In contrast, rPDGF-BB generally decreased these mass ratios. Histological analyses suggested that this was due to the fact that rPDGF-BB induced a very cellular response with a marked influx of neutrophils and fibroblasts. TGF-beta 1 induced significantly less cellular response, which consisted primarily fibroblasts and macrophages. These results indicated that rPDGF-BB and TGF-beta 1 induced connective tissue deposition in vivo in a dose-dependent fashion, although the cellular nature of the responses as well as the structural composition of the extracellular matrices were clearly distinguishable between the two growth factors.

Animals↗
PubMed1990

The effect of platelet releasate on wound healing in animal models.

The alpha granules of platelets contain growth factors that are important in wound healing. We found that a major effect of thrombin-induced human platelet releasates in animal models of wound healing is to enhance the development of granulation tissue and new connective tissue matrix. These studies provide further evidence that platelet-derived protein factors may be useful in treating full-thickness dermal wounds by increasing the rate of granulation tissue formation.

Animals↗
PubMed1990

Inhibition of connective tissue formation in dermal wounds covered with synthetic, moisture vapor-permeable dressings and its reversal by transforming growth factor-beta.

An investigation of synthetic, adherent, moisture vapor-permeable dressings (SAM) on dermal wounds healing by secondary intent has yielded the novel observation that SAM dressings severely inhibited the deposition of granulation tissue and subsequent collagenous tissue when compared with air-exposed wounds in mouse and guinea pig systems. Repair tissue was quantitated histomorphometrically in full-thickness wounds covered with SAM or left air-exposed for periods up to 3 weeks. Early in healing, mouse wounds left open to the atmosphere formed a scab which overlay a large volume of granulation tissue derived from two sources, one lateral, and the other deep and centrally located. In contrast, SAM-covered wounds contained only a small amount of granulation tissue which was derived solely from lateral sources. Granulation tissue was replaced by fibrous connective tissue over time, and this was always less in SAM-covered wounds. Deposition of large amounts of connective tissue in air-exposed wounds was associated with significant polymorphonuclear and mononuclear cell infiltrates, while the lack of granulation tissue formation in SAM-covered sites was associated with reduced inflammation. Dressing-induced inhibition of connective tissue could be partially reversed by treatment with transforming growth factor-beta form 1 or 2. Deposition of granulation tissue in large lenticular wounds in guinea pig skin, but not in 6-mm punch wounds, was also inhibited when the wounds were covered with SAM, and the morphology of air-exposed and SAM-covered wounds was similar to that in mice. SAM-covered wounds in mice and guinea pigs may be useful as models of chronic non-healing wounds.

Animals↗
PubMed1990

A novel polyclonal antibody (CL-B1/29) for immunolocalization of transforming growth factor-beta 2 (TGF-beta 2) in adult mouse.

A polyclonal antibody (CL-B1/29) raised against a synthetic peptide with an amino acid sequence identical to the first 29 N-terminal residues of bovine bone-derived transforming growth factor-beta 2 (TGF-beta 2) was characterized and used for immunolocalization of TGF-beta 2 in adult mice. Reduced staining of immunoblots and tissue after absorption of the antiserum with the immunizing peptide or with TGF-beta 2 but not with purified TGF-beta 1 demonstrated that the reagent is specific for TGF-beta 2, with little or no crossreactivity with TGF-beta 1. The immunolocalization of TGF-beta 2 was investigated in formalin-fixed, paraffin-embedded cultured cells and murine tissue. Specimens pre-digested with testicular hyaluronidase demonstrated immunostaining predominantly of extracellular connective tissue matrix, whereas specimens pre-digested with pronase E demonstrated primarily cytoplasmic staining. Immunoreactivity was widely distributed in connective tissue, muscle, adsorptive and secretory epithelia, especially of endocrine tissue, and neural tissue of adult mice.

Animals↗
PubMed1990

Transforming growth factors-beta 1 and beta 2 induce synthesis and accumulation of hyaluronate and chondroitin sulfate in vivo.

Subcutaneous implantation in rats of partially purified transforming growth factor-beta (TGF-beta) derived from bovine bone induced extensive development of connective tissue with associated edema. Subcutaneous injection of pure TGF-beta 1 or TGF-beta 2 also induced connective tissue deposition in mice and guinea pigs. Sustained release of TGF-beta 1 from mini-osmotic pumps implanted subcutaneously in mature guinea pigs promoted connective tissue deposition that encapsulated the pumps. Biochemical analyses of the connective tissue capsule demonstrated that TGF-beta 1 induced a dose-dependent accumulation of glycosaminoglycans (GAGs). The GAG/DNA ratio also increased as a function of the rate of TGF-beta 1 released, suggesting that the factor increased production of GAGs per cell. Cellulose acetate gel electrophoresis of the GAGs and hydrolysis with specific glycosidases revealed that the majority of GAGs consisted of hyaluronate and chondroitin sulfate. These results demonstrate that TGF-beta 1 and TGF-beta 2 stimulate the production of not only collagenous extracellular matrix components, but also dramatically increase the in vivo synthesis of hyaluronate and chondroitin sulfate.

Animals↗
PubMed1990

Exogenous transforming growth factor-beta 2 enhances connective tissue formation and wound strength in guinea pig dermal wounds healing by secondary intent.

The presence of transforming growth factor-beta (TGF-beta) at the site of acute injury, its ability to attract inflammatory and connective tissue cells, and its stimulatory effect on the deposition of connective tissue matrix combine to suggest that it may play a key role in the response to injury. The effect of exogenous TGF-beta form 2 on dermal wounds healing by secondary intent was investigated using a sponge composed of collagen and heparin as a delivery vehicle. Longitudinal lenticular-shaped wounds on the dorsum of adult guinea pigs were treated at the time of wounding with delivery vehicle containing 0.5, 1, or 5 micrograms of purified, bovine bone-derived TGF-beta 2, and were compared with wounds that received vehicle only or were untreated. At days 8 and 14 the amount of connective tissue in the wounds and the extent of epithelialization were determined by histomorphometric methods, and wound breaking strength was determined. At day 8, but not at day 14, wounds treated with 1 or 5 micrograms of TGF-beta 2 contained a significantly higher proportion of connective tissue than did wounds treated with vehicle only, and they also exhibited higher wound strength. No effect on wound size or re-epithelialization was detected. The observations provide evidence that a single treatment with exogenous TGF-beta 2 delivered in collagen/heparin sponge vehicle can accelerate repair in guinea pig dermal wounds allowed to heal by secondary intent.

Animals↗
PubMed1988

Collagen coatings reduce the incidence of capsule contracture around soft silicone rubber implants in animals.

Silicone rubber miniprostheses known to be associated with a high rate of experimental capsule contracture were implanted subcutaneously in rats. Prostheses were coated either with 2 layers of collagen cross-linked with formaldehyde or with 1 layer of collagen cross-linked with glutaraldehyde. Noncoated prostheses were implanted as controls. Contracture was defined as grossly observable distortion of the implant mounds from round to avoid. Capsules were examined histologically at explant at 255 days. In the control group with no coating present capsules formed very early in 100% of the implants. The group with a 2-layer, formaldehyde-treated collagen coat demonstrated the greatest total surface area covered with coating, the least degree of capsule formation, the lowest rate of contracture (7%), and the longest onset. The group with a single layer of collagen treated with glutaraldehyde showed an intermediate coverage of coating, an intermediate degree of capsule formation, an intermediate contracture rate (50%), and an intermediate time of onset. These observations confirm earlier results by showing a correlation between intact collagen coating and absence of capsule formation, and also further demonstrate a significant reduction in the rate of capsule contracture for collagen-coated implants.

Animals↗
PubMed1986

A concentration gradient of bacteria within wound tissues and scab.

This investigation was designed to evaluate the effect of a synthetic moisture vapor permeable dressing on the size of the bacterial population of superficial wounds. Split-thickness donor sites were created in pig skin and were treated with a synthetic occlusive dressing (Tegaderm), with fine mesh gauze, or with nothing. All wounds became spontaneously infected with a variety of bacteria, predominantly with Staphylococcus epidermidis. The population of the Tegaderm wounds was always greater than that of the untreated controls, while that of the gauze treated wounds was equal to or less than that of the controls. Tegaderm dressed wounds healed more quickly than did the others. A gradient in the concentration of bacteria within the wounds was seen, with a very high concentration in the scab (10(8) cells/g), an intermediate concentration (10(6) cells/g) in the dermal layer, and the lowest concentration (10(4) cells/g) in the hypodermal level of the wound tissue. Such a gradient has not previously been reported. No evidence was seen that the level of infection declined over time for any of the dressings. Apparent bacterial clearing in earlier investigations may be due to the progressive loss of superficial wound tissues with the corresponding exclusion of the high concentration of bacteria within these layers from the tissue sampled.

Animals↗
PubMed1985

Reduced capsule formation around soft silicone rubber prostheses coated with solid collagen.

Silicone rubber miniprostheses were coated with solid collagen formed from a fibrillar collagen suspension (Zyderm collagen implant) and then implanted subcutaneously in rats. There was a reduced amount of capsule formation around the coated prostheses, whereas the uncoated control implants all became surrounded by normal capsule. At the interface between the collagen coating and the surrounding tissue, no capsule formation was seen. At the interface between the prosthesis and the collagen coating, no capsule or only slight, locally limited, capsule formation was seen. Furthermore, capsule associated with coated implants was measurably thinner than that around control implants. When capsule appeared around coated implants, it was frequently associated with defects in the continuity of the coating. Host cells, fibroblasts, and round cells progressively invaded the coatings from the periphery inward, frequently along defects in the coating. The difference between coated and control implants became less pronounced between 60 and 120 days after implantation, as the amount of intact coating decreased. This work supports the hypotheses that the collagen coatings, while intact, prevent capsule formation, that the coatings produced by the present method are imperfect and are broken down with time, and that the disappearance of the coatings results in subsequent capsule formation. These hypotheses permit the deduction that development of better, more persistent coatings will permit indefinitely prolonged inhibition of capsule formation.

Animals↗
PubMed1985

The incidence of experimental contracture varies with the source of the prosthesis.

Nominally equivalent gel-filled miniprostheses supplied by three different manufacturers were placed subcutaneously in rats under identical conditions in a double-blind comparison. The incidence of experimental contracture, defined by grossly visibly asymmetrical distortion of the implant, was 0, 9, and 91 percent for the different manufacturers, consistent with previous observations. Differences among the different implants with respect to the density of the fibrillar capsule structure, the cellularity, and the amount of extruded gel did not correlate with the incidence of contracture. Contracture rate was inversely proportional to the relative degree of filling of the prostheses, as reflected in deviations from the nominal hemispherical shape, and to the viscosity of the gel filling. For implants of the same type, the incidence of contracture was higher when the prosthesis was underfilled. Contracted capsules were more fibrous and contained more cells with microfilament bundles. It is concluded that the physical and geometric properties of silicone implants are critical in the expression of contracture and that these properties vary significantly among prosthesis manufacturers.

Animals↗
PubMed1979

Effects of diffused soluble steroid on capsules around experimental breast prostheses in rats.

Saline-filled miniprostheses were implanted beneath the dorsal panniculus carnosus of rats. The control prostheses contained only saline, while the experimental prostheses contained soluble methylprednisolone sodium succinate. At 10-day intervals the in situ compressibility of the tissue mound around the implants was measured mechanically. At 60 and 120 days, the control mounds were harder than those around the steroid prostheses, and the control prostheses were surrounded by a thicker capsular membrane. The control capsules contained more non-collagenous protein than the steroid modified capsules. We suggest that this non-collagenous protein may be related to the proteopolysaccharide cement which binds the fibers of immature scar together--and that the effect of our steroid treatment was to reduce this proteopolysaccharide component of the capsule membrane and thereby cause its dissolution.

Amino Acids↗
PubMed1978

A microarchitectural model of regional variations in hypodermal mobility in porcine and human skin.

In this paper, we focus on the hypodermal component of the integument and its functional contribution to properties of skin mobility. A specially designed mechanical apparatus was used to measure hypodermal extensibility in vivo of 6-mm "island" punches at selected anatomical sites in anesthetized pigs. Representative regional hypodermal force displacement curves were found to differ statistically in magnitude of acceleration, slope, and extensions at breaking point. A vertically oriented "lattice network" of hypodermal fibrous elements arranged in geometric subunits is consistently seen in sample specimens. Microarchitectural differences in network configuration, geometric unit size, fat infiltration, and intrinsic collagen fiber length can be correlated directly to the biomechanical data. These findings are corroborated by light microscopy, scanning electron microscopy, and quantitative hydroxyproline concentrations. A similar network is confirmed in human cadaver biopsies. Clinically, our data suggest that skin mobility is at least partially allowed by unfolding and stretching of the hypodermal vertical collagen network, and that regional variations in fibrous network architecture satisfy specific functional requisites (e.g., joint mobility, skin stabilization), as well as serving as an expansile retractile reservoir for the deposition and absorption of fat.

Adipose Tissue↗
PubMed1978

Study of encapsulation of silicone rubber implants in animals. A foreign-body reaction.

It has long been known that the formation of a fibrous capsule around an implant is a general phenomenon in nature, an inevitable result of the tissue defense mechanism called the foreign body reaction. We have investigated this reaction in animals and find it consists of a series of interrelated processes in which the final result may vary, depending on the susceptibility of the foreign material to phagocytosis, incorporation by giant cells, or isolation by fibrosis. This susceptibility depends, in turn, on the physical and chemical properties of the implant. The process of capsule formation, as well as the structure of the final capsule, is similar in animal models and in humans--so that investigations of human encapsulation may be done in animals. The cause of abnormal induration around human breast implants is still unknown, and the question of whether normal induration in the animal model can be used to elucidate abnormal clinical induration depends on further investigation of both phenomena.

Animals↗
PubMed1978

Effects of local instillation of triamcinolone on the capsules around silicone bag-gel prostheses in animals.

"Soft" silicone bag-gel miniprostheses were implanted in 103 rats. The experimental animals had periprosthetic instillations of zero, 0.2, or 2 mg of triamcinolone acetonide at implantation. The compressibility, the architecture, and the chemical composition of the surrounding tissues were observed at 10 and at 120 days. The compressibility was also measured by mechanical means at 10 day intervals. At 120 days all capsules were similar. All the capsules gradually became firmer with time after the implantation. After 60 days, the steroid-treated capsules were very slightly more compressible (softer) than the controls. This slight difference in compressibility could not be correlated with the other changes in the capsule properties we examined. It is suggested that the structure of these capsules may be similar to that of immature scar, and that it is kept in this condition by the continued stimulus of the foreign implant.

Animals↗
PubMed1978

Experimental effects on surrounding fibrous capsule formation from placing steroid in a silicone bag-gel prosthesis before implantation.

Soft-gel miniprostheses of silicone were implanted subcutaneously into 75 male rats. Groups of prostheses were preinjected with saline, a commercial form of triamcinolone acetonide, or a suspension of crystalline triamcinolone acetonide. The softness of the prosthesis mound later was measured objectively, and the capsules surrounding the implants were analyzed by histology, SEM, and chemistry, at various intervals up to 120 days after implantation. The control implants developed a normal laminar capsule. With an incidence increasing up to 100 percent at 120 days, the steroid-treated implants were surrounded by capsules lacking an inner membrane. The inner membrane of the laminar capsule had a high protein content (relative to normal tissue) and a relatively reduced collagen content, while the diffuse capsule resulting from the TA treatment had a high protein content and a high collagen content (about the same as normal tissue). No differences were found in the softness of the mounds of the implanted prostheses. The effect of the TA treatment was explained on the basis of its collagenolytic effect, which could gradually erode the normal capsule membrane. Capsule firmness could not be related to the architecture or the protein or collagen content in our findings. We hypothesize that normal capsule firmness may be related to the amount and kind of interconnection between the loose outer zone of connective tissue and the surrounding tissue.

Animals↗