Evaluation of the biocompatibility of silicone gel implants - histomorphometric study

Breast implants are medical devices that are used to augment breast size or to reconstruct the breast following mastectomy or to correct a congenital abnormality. Breast implants consist of a silicone outer shell and a filler (most commonly silicone gel or saline). Approximately 5 to 10 million women worldwide have breast implants. Histomorphometric study to evaluate the biological tissue compatibility of silicone implants suitable for plastic surgery and the adverse effects and risks of this material. Thirty Wistar white rats received subcutaneous implants and the revestiment of silicone gel Silimed ®®, and randomized into six groups of five animals each, according to the type of implanted material and the time of sacrifice. Eight areas of 60.11mm2 corresponding to the obtained surgical pieces were analyzed, counting mesenchymal cells, eosinophils, and foreign body giant cells, observing an acceptable biocompatibility in all implants, for subsequent statistical analysis by Tukey test. Silicone gel showed inflammation slightly greater than for other groups, with tissue reactions varying from light to moderate, whose result was the formation of a fibrous capsule around the material, recognized by the organism as a foreign body. Despite frequent local complications and adverse outcomes, this research showed that the silicone and top layer presented an acceptable chronic inflammatory reaction, which did not significantly differ from the control group. In general, it is possible to affirm that silicone gel had acceptable levels of biocompatibility, confirmed the rare presence of foreign body giant cells, and when of the rupture, formed a fibrous capsule around the material, separating the material of the organism. © AVICENA 2013.

Avaliação da biocompatibilidade de implantes de silicone gel em subcutâneo de ratos: estudo histomorfométrico

Objective: Histomorphometric study to evaluate the biological tissue compatibility of silicone implants suitable for plastic surgery. Methods: Thirty Wistar white rats received subcutaneous implants ande the revestiment of silicone gel Silimed, and randomized into six groups of five animals each, according to the type of implanted material and the time of sacrifice. Eight areas of 60.11 mm2 corresponding to the obtained surgical pieces were analyzed, counting mesenchymal cells, eosinophils, and foreign body giant cells, observing an acceptable biocompatibility in all implants, for subsequent statistical analysis by Tukey test. Results: Silicone gel showed inflammation slightly greater than for other groups, with tissue reactions varying from light to moderate, whose result was the formation of a fibrous capsule around the material, recognized by the organism as a foreign body. Conclusion: In general, it is possible to affirm that silicone gel had acceptable levels of biocompatibility, confirmed the rare presence of foreign body giant cells, and when of the rupture, formed a fibrous capsule around the material, separating the material of the organism.

Reinforced hydrogels for silicone copolymer delivery for scar remediation

Hypertrophic scars are formed by collagen overproduction in wounded areas and often occur in victims of severe burns. There are several methods for hypertrophic scar remediation and silicone gel therapy is one of the more successful methods. Research by others has shown that the activity of these gels may be due to migration of amphiphilic silicone oligomers from the gel and into the dermis, down-regulating production of collagen by fibroblasts. Normal silicone oil (PDMS) does not produce the same effect on fibroblasts. The main purpose of this project is the introduction of a particular amphiphilic silicone rake copolymer into an appropriate network which can absorb and release the silicone copolymer on the scarred area. Hydrogels are polymeric crosslinked networks which can swell in water or a drug solution, and gradually release the drug when applied to the skin. The application of gel enhances the effectiveness of the therapy, reduces the period of treatment and can be comfortable for patients to use. Polyethylene glycol (PEG) based networks have been applied in this research, because the amphiphilic silicone rake copolymer to be used as a therapy has polyethylene oxide (PEO) as a side chain. These PEO side chains have very similar chemical structure to a PEG gel chain so enhancing both the compatibility and the diffusion of the amphiphilic silicone rake copolymer into and out of the gel. Synthesis of PEG-based networks has been performed by two methods: in situ silsesquioxane formation as crosslink with a sol-gel reaction under different conditions and UV curing. PEG networks have low mechanical properties which is a fundamental limitation of the polymer backbone. For mechanical properties enhancement, composite networks were synthesized using nano-silica with different surface modification. The chemical structure of in situ silsesquioxane in the dry network has been examined by Solid State NMR, Differential Scanning Calorimetry (DSC) and swelling measurements in water. Mechanical properties of dry networks were tested by Dynamic Mechanical Thermal Analysis (DMTA) to determine modulus and interfacial interaction between silica and the network. In this way a family of self-reinforced networks has been produced that have been shown to absorb and deliver the active amphiphilic silicone- PEO rake copolymer.

Pre-clinical evaluation of amphiphilic silicone oligomers for scar remediation

The formation of hypertrophic scars is a frequent outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS; Perkins et al., 1983). Although widely used, knowledge regarding SGS and their mechanism of action on hypertrophic scars is limited. Furthermore, SGS require consistent application for at least twelve hours a day for up to twelve consecutive months, beginning as soon as wound reepithelialisation has occurred. Preliminary research at QUT has shown that some species of silicone present in SGS have the ability to permeate into collagen gel skin mimetics upon exposure. An analogue of these species, GP226, was found to decrease both collagen synthesis and the total amount of collagen present following exposure to cultures of cells derived from hypertrophic scars. This silicone of interest was a crude mixture of silicone species, which resolved into five fractions of different molecular weight. These five fractions were found to have differing effects on collagen synthesis and cell viability following exposure to fibroblasts derived from hypertrophic scars (HSF), keloid scars (KF) and normal skin (nHSF and nKF). The research performed herein continues to further assess the potential of GP226 and its fractions for scar remediation by determining in more detail its effects on HSF, KF, nHSF, nKF and human keratinocytes (HK) in terms of cell viability and proliferation at various time points. Through these studies it was revealed that Fraction IV was the most active fraction as it induced a reduction in cell viability and proliferation most similar to that observed with GP226. Cells undergoing apoptosis were also detected in HSF cultures exposed to GP226 and Fraction IV using the Tunel assay (Roche). These investigations were difficult to pursue further as the fractionation process used for GP226 was labour-intensive and time inefficient. Therefore a number of silicones with similar structure to Fraction IV were synthesised and screened for their effect following application to HSF and nHSF. PDMS7-g-PEG7, a silicone-PEG copolymer of low molecular weight and low hydrophilic-lipophilic balance factor, was found to be the most effective at reducing cell proliferation and inducing apoptosis in cultures of HSF, nHSF and HK. Further studies investigated gene expression through microarray and superarray techniques and demonstrated that many genes are differentially expressed in HSF following treatment with GP226, Fraction IV and PDMS7-g-PEG7. In brief, it was demonstrated that genes for TGFβ1 and TNF are not differentially regulated while genes for AIFM2, IL8, NSMAF, SMAD7, TRAF3 and IGF2R show increased expression (>1.8 fold change) following treatment with PDMS7-g-PEG7. In addition, genes for αSMA, TRAF2, COL1A1 and COL3A1 have decreased expression (>-1.8 fold change) following treatment with GP226, Fraction IV and PDMS7-g-PEG7. The data obtained suggest that many different pathways related to apoptosis and collagen synthesis are affected in HSF following exposure to PDMS7-g-PEG7. The significance is that silicone-PEG copolymers, such as GP226, Fraction IV and PDMS7-g-PEG7, could potentially be a non-invasive substitute to apoptosis-inducing chemical agents that are currently used as scar treatments. It is anticipated that these findings will ultimately contribute to the development of a novel scar therapy with faster action and improved outcomes for patients suffering from hypertrophic scars.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Avaliação da biocompatibilidade de vários elastômeros de silicone implantados no tecido subcutâneo de ratos: estudo histológico e histomorfométrico

Pós-graduação em Odontologia - FOA

Segurança biológica de implantes mamários de silicone: interrelação entre processos esterilizantes e biocompatibilidade

Os implantes mamários de silicone têm sido empregados, tanto nas cirurgias de aumento das mamas, quanto na reconstrução do tecido mamário após mastectomia. A segurança biológica dos implantes de silicone merece estudo relacionado aos processos de esterilização empregados, pois podem constituir-se em fator de comprometimento da estrutura química do polímero e, conseqüentemente, da biocompatibilidade. Este estudo consistiu na avaliação da biocompatibilidade de implantes mamários de silicone após terem sido submetidos aos processos de esterilização por calor seco, radiação gama e óxido de etileno. O parâmetro avaliado foi a viabilidade celular, empregando o método de difusão em agar e de captura do vermelho neutro. As amostras compreenderam implantes de silicone gel lisos, texturizados e revestidos com poliuretano e implantes texturizados pré-cheios com solução salina. Também foi realizado o teste de endotoxinas bacterianas pelo método do LAL e determinação da taxa de migração do gel de silicone (teste de bleed). Os três métodos de esterilização mostraram-se igualmente eficientes pela comprovação da condição de esterilidade dos implantes através de metodologia descrita na Farmacopéia Americana 27 edição. Os níveis de endotoxinas bacterianas dos implantes, também atenderam aos requisitos dos compêndios oficiais. Na avaliação da biocompatibilidade todos os implantes, independente dos processos de esterilização utilizados, apresentaram ausência de citotoxicidade. Os resultados do teste de bleed mostraram uma maior taxa de migração de gel para os implantes de superfície lisa em comparação com os implantes de superfície texturizada e revestida com poliuretano, quando esterilizados por calor seco. Ao comparar a taxa de migração do gel para os implantes de superfície lisa esterilizados por calor seco e óxido de etileno, obteve-se uma maior taxa de migração para aqueles implantes esterilizados por óxido de etileno. As diferentes avaliações realizadas neste estudo abrangeram aspectos biológicos, químicos e físicos relevantes para garantir um produto de boa qualidade e que, por assegurar a manutenção da característica de biocompatibilidade, resulta na segurança biológica deste tipo de implante.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

The effect of amphiphilic siloxane oligomers on fibroblast and keratinocyte proliferation and apoptosis

The formation of hypertrophic scars is a frequent medical outcome of wound repair and often requires further therapy with treatments such as Silicone Gel Sheets (SGS) or apoptosis-inducing agents, including bleomycin. Although widely used, knowledge regarding SGS and their mode of action is limited. Preliminary research has shown that small amounts of amphiphilic silicone present in SGS have the ability to move into skin during treatment. We demonstrate herein that a commercially available analogue of these amphiphilic siloxane species, the rake copolymer GP226, decreases collagen synthesis upon exposure to cultures of fibroblasts derived from hypertrophic scars (HSF). By size exclusion chromatography, GP226 was found to be a mixture of siloxane species, containing five fractions of different molecular weight. By studies of collagen production, cell viability and proliferation, it was revealed that a low molecular weight fraction (fraction IV) was the most active, reducing the number of viable cells present following treatment and thereby reducing collagen production as a result. Upon exposure of fraction IV to human keratinocytes, viability and proliferation was also significantly affected. HSF undergoing apoptosis after application of fraction IV were also detected via real-time microscopy and by using the TUNEL assay. Taken together, these data suggests that these amphiphilic siloxanes could be potential non-invasive substitutes to apoptotic-inducing chemical agents that are currently used as scar treatments.

Development of biomimetic squid-inspired suckers

Biomechanical properties of squid suckers were studied to provide inspiration for the development of sucker artefacts for a robotic octopus. Mechanical support of the rings found inside squid suckers was studied by bending tests. Tensile tests were carried out to study the maximum possible sucking force produced by squid suckers based on the strength of sucker stalks, normalized by the sucking areas. The squid suckers were also directly tested to obtain sucking forces by a special testing arrangement. Inspired by the squid suckers, three types of sucker artefacts were developed for the arm skin of an octopus inspired robot. The first sucker artefact made of knitted nylon sheet reinforced silicone rubber has the same shape as the squid suckers. Like real squid suckers, this type of artefact also has a stalk that is connected to the arm skin and a ring to give radial support.The second design is a straight cylindrical structure with uniform wall thickness made of silicone rubber. One end of the cylinder is directly connected to the arm skin and the other end is open. The final design of the sucker has a cylindrical base and a concave meniscus top. The meniscus was formed naturally using the surface tension of silicone gel, which leads to a higher level of the liquid around the edge of a container. The wall thickness decreases towards the tip of the sucker opening. Sucking forces of all three types of sucker artefacts were measured. Advantages and isadvantages of each sucker type were discussed. The final design of suckers has been implemented to the arm skin prototypes.

Headspace solid-phase microextraction with novel sol-gel permethylated-beta-cyclodextrin/hydroxyl-termination silicone oil fiber for determination of polybrominated diphenyl ethers by gas chromatography-mass spectrometry in soil

A simple, sensitive, and accurate method for determination of polybrominated diphenyl ethers (PBDEs) in soil has been developed based on headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). Permethylated-beta-cyclodextrin/hydroxyl-termination silicone oil (PM-beta-CD/OH-TSO) fiber was first prepared by sol-gel technology and employed in SPME procedure. By exploiting the superiorities of sot-gel coating technique and the advantages of the high hydrophobic doughnut-shaped cavity of PM-beta-CD, the novel fiber showed desirable operational stability and extraction ability. After optimization on extraction conditions like water addition, extraction temperature, extraction time, salts effect, and solvents addition, the method was validated in soil samples, achieving good linearity (r>0.999), precision (R.S.D. < 10%), accuracy (recovery>78%), and detection limits (S/N =3) raging from 13.0 to 78.3 pg/g. (c) 2007 Published by Elsevier B.V.

Avaliação volumétrica e funcional do músculo glúteo máximo submetido a gluteoplastia de aumento com implantes de silicone

A operação para aumento de glúteos com implantes teve início no fim da década de 1960, entretanto a técnica intramuscular, considerada padrão atualmente, foi descrita cerca de 30 anos depois. Cirurgiões e pacientes apresentam crescente interesse na realização do aumento de glúteos haja vista que sua frequência apresenta aumento nos últimos anos. A utilização de implantes intramusculares que superam o volume do músculo em mais de cinquenta por cento configura uma situação nova que deve ser estudada. O tecido muscular estriado esquelético apresenta grande suscetibilidade para atrofia secundariamente à compressão, e sendo o glúteo máximo um músculo importante na manutenção da postura ereta, deambulação, corrida e salto, é necessário pesquisar possíveis alterações musculares decorrentes da operação. O objetivo deste estudo é avaliar o volume e força do músculo glúteo máximo ao longo de 12 meses após a introdução de implantes intramusculares, o posicionamento destes implantes no interior da musculatura e mudanças antropométricas obtidas com a operação. Foram selecionadas 48 mulheres, 24 candidatas a gluteoplastia de aumento com implantes compuseram o grupo de estudo e 24 candidatas a mamoplastia de aumento compuseram o grupo controle de acordo com os critérios de inclusão e exclusão. As pacientes foram avaliadas em quatro momentos diferentes: pré-operatório e após três, seis e 12 meses da operação. Em todas as etapas foi realizada avaliação clínica nutricional, tomografia computadorizada com reconstrução 3D e teste isocinético. Todas as pacientes permaneceram afastadas de atividades físicas durante três meses após a operação. Foram utilizados implantes glúteos em gel coesivo de base oval e superfície lisa com volumes de 350 cm3 e 400 cm3. O nível de significância estatística foi mantido em 5%. As pacientes candidatas a gluteoplastia apresentaram valores da relação entre as medidas da cintura e do quadril maiores que aquelas do grupo controle. A operação de aumento glúteo com implantes demonstrou eficácia na melhora desta relação. Os implantes apresentaram posição obliqua com inclinação semelhante à das fibras musculares após três meses da operação, independente da posição em que foram inseridos. As pacientes do grupo de estudo apresentaram atrofia muscular após 12 meses em 6,14% à esquerda e 6,43% à direita, as pacientes do grupo controle não apresentaram atrofia. A força muscular apresentou redução do valor de torque máximo durante a flexão do quadril a 30 /s em ambos os grupos e aumento do torque máximo durante a adução a 60 /s apenas no grupo de estudo. Concluímos que a introdução de implante de silicone no interior do músculo glúteo máximo causa atrofia muscular após 12 meses. As variações na força deste músculo nesse período não podem ser atribuídas primariamente à operação ou à presença dos implantes em seu interior. Os implantes permaneceram em posição obliqua. O aumento de glúteos com implantes gera mudanças antropométricas nas mulheres submetidas a esta operação.

Perfectly Hydrophobic Silicone Nanofiber Coatings: Preparation from Methyltrialkoxysilanes and Use as Water-Collecting Substrate

Perfectly hydrophobic (PHO) coatings consisting of silicone nanofibers have been obtained via a solution process using methyltrialkoxysilanes as precursors. On the basis of thermal gravimetry and differential thermal analysis (TG-DTA) and Fourier transform infrared spectroscopy (FTIR) results, the formula of the nanofibers was tentatively given and a possible growth mechanism of the nanofibers was proposed. Because of the low affinity between the coatings and the small water droplet, when using these coatings as substrate for collecting water vapor, the harvesting efficiency could be enhanced as compared with those from bare glass substrate for more than 50% under 25 degrees C and 60-90% relative humidity. By removing the surface methyl group by heat treatment or ultraviolet (UV) irradiation, the as-prepared perfectly hydrophobic surface can be converted into a superhydrophilic surface.

Effect of polymeric properties on the operation of gel-type audio transducers.

A novel design of a moving-coil transducer coupled with a low-hardness elastomer called “the gel surround” is presented in this thesis. This device is termed a “gel-type audio transducer”. The gel-type audio transducer has been developed to overcome the problems that conventional loudspeakers have suffered - that is, the problem with size of the audio device against the quality of sound at low frequency range. Therefore the research work presented herein aims to develop the “gel-type audio transducer” as a next-generation audio transducer for miniaturized woofers. The gel-type audio transducer consists of the magnetic and coil-drive plate assembly, and these parts are coupled by the gel surround. The transducer is driven by the electromagnetic conversion mechanism (a moving-coil transducer) and its output driving force can be greatly enhanced by applying the novel mechanism of the gel surround especially at low frequency range, resulting in the enhanced acoustic efficiency. The transducer can be attached to a stiff and light panel with both the optimized impedance matching and minimised wave collisions. The performance of the gel-type audio transducer is greatly influenced by the mass of the magnetic assembly and compliance of the “gel surround”. But as the size of the magnet and its weight have to be kept minimal for a miniaturisation of the device, the focus of the research is on the effect of the of the gel surround. As a result, the effect of the gel surround, made of the RTV (room-temperature vulcanising) silicone elastomer, TPE (thermoplastic elastomer), and the silicone foam, on generation of the output driving force, the energy transfer from the transducer to a panel to which the transducer is attached, and sound radiation from the vibrating panel, was investigated. This effect was studied by COMSOL multiphysics (FE analysis) and thereby, the simulated results were verified by experiments such as the laser scanning measurement, DMA (dynamic mechanical analyzer), and the acoustic test. Successful development of prototypes of the gel-type audio transducers, with an enhanced acoustic efficiency at reduced size and weight, was achieved. Implementation of the transducers into consumer applications was also demonstrated with their commercial values.