Nitric Oxide-Releasing Silicone Oil with Tunable Payload for Antibacterial Applications.

Bacterial infections are a hurdle to the application of medical devices, and in the United States alone, more than one million infection cases are reported annually from indwelling medical devices. Infections not only affect the function of medical devices but also risk the lives and health of patients. Nitric oxide (NO) has been used as an antibacterial therapy that kills bacteria without causing resistance and provides many therapeutic effects such as anti-inflammation, antithrombosis, and angiogenesis. Silicone oils have been widely utilized in manufacturing consumer goods, healthcare products, and medical products. Specifically, liquid silicone oils are used as a medical lubricant that creates lubricated interfaces between medical devices and the exterior physiological environment to improve the performance of medical devices. Herein, we report the first primary S-nitrosothiol-based NO-releasing silicone oil (RSNO-Si) that exhibits proactive antibacterial effects. S-nitrosothiol silicone oils (RSNO-Si) were synthesized and the NO payloads ranged from 34.0 to 603.9 µM. The increased NO payload induced higher-viscosity RSNO-Si oils, as RSNO0.1-Si, RSNO0.5-Si, and RSNO1-Si had viscosities of 12.8 ± 0.1 cP, 32.0 ± 0.2 cP, and 35.1 ± 0.3 cP, respectively. RSNO-Si-SR interfaces were fabricated by infusing silicone rubber (SR) in RSNO-Si oil, and the resulting RSNO-Si-SR disks demonstrated NO release without NO donor leaching. RSNO0.1-Si-SR, RSNO0.5-Si-SR, and RSNO1-Si-SR exhibited maximum NO flux at 0.8, 6.5, and 21.5 × 10 -10 mol cm-2 min-1 in 24 h, respectively. RSNO-Si-SR disks also demonstrated 97.45, 95.40, and 96.08% of inhibition against S. aureus in a 4 h bacterial adhesion assay. Considering the easy synthesis, simple fabrication of non-leaching NO-releasing interfaces, tunable payloads, NO flux levels, and antimicrobial effects, RSNO-Si oils exhibited their potential use as platform chemicals for creating antimicrobial medical device surfaces and other antibacterial materials.

Endothelialized silicone aneurysm models for in vitro evaluation of flow diverters.

OBJECTIVE: The goal of this work was to endothelialize silicone aneurysm tubes for use as in vitro models for evaluating endothelial cell interactions with neurovascular devices. The first objective was to establish consistent and confluent endothelial cell linings and to evaluate the silicone vessels over time. The second objective was to use these silicone vessels for flow diverter implantation and assessment. METHODS: Silicone aneurysm tubes were coated with fibronectin and placed into individual bioreactor systems. Human umbilical vein endothelial cells were deposited within tubes to create silicone vessels, then cultivated on a peristaltic pump and harvested at 2, 5, 7, or 10 days to evaluate the endothelial cell lining. A subset of silicone aneurysm vessels was used for flow diverter implantation, and evaluated for cell coverage over device struts at 3 or 7 days after deployment. RESULTS: Silicone vessels maintained confluent, PECAM-1 (platelet endothelial cell adhesion molecule 1) positive endothelial cell linings over time. These vessels facilitated and withstood flow diverter implantation, with robust cell linings disclosed after device deployment. Additionally, the endothelial cells responded to implanted devices through coverage of the flow diverter struts with increased cell coverage over the aneurysm seen at 7 days after deployment as compared with 3 days. CONCLUSIONS: Silicone aneurysm models can be endothelialized and successfully maintained in vitro over time. Furthermore, these silicone vessels can be used for flow diverter implantation and assessment.

Antifertility effectiveness of a novel polymer matrix composite and its influence on the endometrium in rhesus macaques (Macaca mulatta).

OBJECTIVE(S): To explored the antifertility effectiveness and influence on the endometrium of a micro-copper/low-density polyethylene/methyl vinyl silicone rubber (Cu/LDPE/MVQ) composite in rhesus macaques. STUDY DESIGN: Healthy reproductive aged female rhesus macaques underwent abdominal hysterotomy for surgical placement of either the experimental Cu/LDPE/MVQ composite (Cu/LDPE/MVQ, n=5), bare copper wire (Cu, n=5), or hysterotomy only sham-operation group [(SOI, n=4), (SOII, n=6)]. Females in the Cu/LPDE/MVQ, Cu, and SOI groups were housed with fertile males for approximately three menstrual cycles. We assessed pregnancy by hysterectomy. Females in the Cu/LDPE/MVQ, Cu, and SOII groups underwent hysterectomy at about 4 months post-insertion for histologic assessment of morphologic changes of the endometrium, evaluation of materials using scanning electron microscopy (SEM), and evaluation of the inflammatory markers, including substance P receptor (SPR), associated with endometrial bleeding using enzyme linked immunosorbent assay, quantitative RT-PCR, and Western blot analyses. RESULTS: All of the SOI group females became pregnant (4/4, 100%). In contrast, no pregnancies occurred in either the Cu/LDPE/MVQ (0/5, 0%) or Cu (0/5, 0%) groups. We observed histologic features consistent with chronic endometrial inflammation in all females of the Cu group, but none of the SOII or Cu/LDPE/MVQ animals. Levels of inflammatory markers were significantly increased in the Cu group, compared with SOII or Cu/LDPE/MVQ groups (p<.05). SEM showed evidence of corrosion in the Cu wire not seen in the Cu/LDPE/MVQ group. CONCLUSION(S): Cu/LDPE/MVQ material provided a contraceptive effect similar to Cu in macaques, with a lower impact on inflammation and inflammatory markers of the endometrium. IMPLICATIONS: This study demonstrates the possibility of a Cu/LDPE/MVQ composite as an alternative to conventional copper device materials.

Two-Dimensional X-Ray Angiography to Examine Fine Vascular Structure Using a Silicone Rubber Injection Compound.

Angiography is an essential tool for the study of vascular structures in various research fields. The aim of this study is to introduce a simple angiographic method for examining the fine vascular structure of unfixed, fresh tissue using a silicone rubber injection compound and soft tissue X-ray system. This study is especially focused on flap territories used in reconstructive surgery. This study employs angiography with a silicone rubber injection compound in various experimental conditions using Sprague-Dawley rats. First, 15 mL of MV compound and 15 mL of diluent is mixed. Then, 1.5 mL of the curing agent is prepared, and a 24G catheter is cannulated in the common carotid artery of the rat. A three-way stopcock is then connected to a catheter, and the radiopaque agent, after being mixed with the prepared curing agent, is injected immediately without spillage. Finally, as the agent solidifies, the specimen is harvested, and an angiographic image is obtained using a soft tissue X-ray system. This method indicates that high-quality angiography showing fine vascular structures can be easily and simply obtained within in a short period of time.

Antifertility effectiveness of a novel copper-containing intrauterine device material and its influence on the endometrial environment in rats.

This study was designed to investigate the antifertility effectiveness of a novel copper-containing intrauterine device material containing a composite of micro-copper (Cu), low-density polyethylene (LDPE), and methyl vinyl silicone rubber (MVQ) and its effects on the endometrial environment in rats. The contraceptive effectiveness was examined 12 days after pregnancy. The pathological changes; factors associated with bleeding, pain, and inflammation in the endometrium; and the surface condition of the implants were investigated after insertion for 90 days. Furthermore, the release rate of copper ions in simulated uterine solution (SUS) was investigated for 270 days. The contraceptive effectiveness was 100% in both the bulk Cu and micro-Cu/LDPE/MVQ groups, and that in the LDPE/MVQ group was 30%. On day 90 after insertion, histopathological observation and the ultrastructural changes in the endometrium showed that the damage caused by bulk Cu was much more severe than that caused by the Cu/LDPE/MVQ microcomposite and that the surface of the latter was much smoother than that of the former. Furthermore, compared with the sham-operated control group, the concentrations of tissue plasminogen activator and prostaglandin E2 were significantly increased 90 days after insertion in all of the experimental groups except for the LDPE/MVQ group (P < 0.05), and the parameters in the Cu/LDPE/MVQ group were significantly lower than those in the Cu group (P < 0.05). In addition, the expression levels of matrix metalloproteinase 9, metalloproteinase 1 tissue inhibitor, plasminogen inhibitor 1, CD34, vascular endothelial growth factor, substance P, and substance P receptor in the endometrium in all of the experimental groups were significantly lower than those in the Cu group 90 days after insertion (P < 0.05). The results of this study indicate that micro-Cu/LDPE/MVQ exhibits satisfactory contraceptive efficacy and causes fewer side effects than Cu.

Novel Proteomic Assay of Breast Implants Reveals Proteins With Significant Binding Differences: Implications for Surface Coating and Biocompatibility.

BACKGROUND: Silicone elastomer, a ubiquitous biomaterial and main constituent of breast implants, has been used for breast augmentation and reconstruction for over 50 years. Breast implants have direct local and purported systemic effects on normal tissue homeostasis dictated by the chemical and physical presence of the implant. OBJECTIVES: Protein adsorption has been demonstrated to be a key driver of local reactions to silicone. We sought to develop an assay and identify the proteins that coat implants during breast implantation. METHODS: Wound fluid was salvaged from women who had undergone breast reduction and incubated in contact with the surface of 13 commercially available implant surfaces. An in situ digestion technique was optimized to elute bound proteins. Samples were analyzed on an Orbitrap elite analyser, proteins identified in Mascot Demon and analyzed in Progenesis. RESULTS: A total of 822 proteins were identified, bound to the surfaces of the implants. Extracellular proteins were the most abundant ontology, followed by intracellular proteins. Fibrinogen, a proinflammatory protein and Albumin, an anti-inflammatory protein had significant (P < 0.0001) binding differences between the surfaces studied. Complement C3, C5, and factor H were also shown to have significantly different binding affinities for the implants included in the study (P < 0.05). CONCLUSIONS: We have developed a novel assay of breast implant protein binding and demonstrated significant binding affinities for relevant proteins derived from breast tissue wound fluid.

Injectable silicone rubber for ocular implantation after evisceration.

OBJECTIVE: To investigate the usefulness of addition type liquid silicone rubber (ATLSR) as injectable implant after evisceration to maintain the eyeball volume in an animal experiment. METHODS: Twelve adult New Zealand white rabbits were included. One eye of each rabbit was randomly selected for evisceration with the fellow eye as control. ATLSR was injected to fill the eyeball socket after evisceration. In vivo observation and photographs were performed up to 24 weeks post-op. Two rabbits were sacrificed respectively at post-operative week 1, 2, 4, 8, 12 and 24. After enucleation, the vertical, horizontal and sagittal diameters of the experimental eyeballs were measured and compared with the control eyes. Histopathological studies were performed to evaluate signs of inflammation. RESULTS: Cornea remained clear throughout the observation period despite mild epithelial edema and neovascularization. Compared to the control eyes, the experimental eyes were significantly smaller in vertical diameter (17.00±1.17 vs. 17.54±1.11 mm, P<0.001), but larger in sagittal diameter (16.85±1.48 vs. 16.40±1.38 mm, P = 0.008), and had no significant difference in horizontal diameter (17.49±1.53 vs. 17.64±1.21 mm, P = 0.34). Postoperative inflammation was observed at one week after surgery, which peaked at 2-3 weeks, then regressed gradually. At week 12 and week 24, most of the inflammatory cells disappeared with some residual plasma cells and eosinophils. CONCLUSION: Injectable addition type silicon rubber may be a good choice for ocular implantation after evisceration, maintaining eyeball volume and cosmetically satisfactory when compared to the fellow eye. Spontaneous regression of inflammation implied good biocompatibility for at least 24 weeks.

Development of resorbable nanocomposite tracheal and bronchial scaffolds for paediatric applications.

BACKGROUND: Congenital tracheal defects and prolonged intubation following premature birth have resulted in an unmet clinical need for tracheal replacement. Advances in stem cell technology, tissue engineering and material sciences have inspired the development of a resorbable, nanocomposite tracheal and bronchial scaffold. METHODS: A bifurcated scaffold was designed and constructed using a novel, resorbable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone) urea urethane (POSS-PCL). Material characterization studies included tensile strength, suture retention and surface characteristics. Bone marrow-derived mesenchymal stem cells (bmMSCs) and human tracheobronchial epithelial cells (HBECs) were cultured on POSS-PCL for up to 14 days, and metabolic activity and cell morphology were assessed. Quantum dots conjugated to RGD (l-arginine, glycine and l-aspartic acid) tripeptides and anticollagen type I antibody were then employed to observe cell migration throughout the scaffold. RESULTS: POSS-PCL exhibited good mechanical properties, and the relationship between the solid elastomer and foam elastomer of POSS-PCL was comparable to that between the cartilaginous U-shaped rings and interconnective cartilage of the native human trachea. Good suture retention was also achieved. Cell attachment and a significant, steady increase in proliferation were observed for both cell types (bmMSCs, P = 0·001; HBECs, P = 0·003). Quantum dot imaging illustrated adequate cell penetration throughout the scaffold, which was confirmed by scanning electron microscopy. CONCLUSION: This mechanically viable scaffold successfully supports bmMSC and HBEC attachment and proliferation, demonstrating its potential as a tissue-engineered solution to tracheal replacement.

Stromal vascular fraction combined with silicone rubber chamber improves sciatic nerve regeneration in diabetes.

PURPOSE: To study the effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on sciatic nerve regeneration. METHODS: A 10-mm sciatic nerve defect was bridged using a silicone conduit filled with SVF. In control group, silicone conduit was filled with phosphate-buffered saline alone. In sham-operated group, the sciatic nerve was only exposed and manipulated. The regenerated nerve fibers were studied 8 and 12 weeks after surgery. RESULTS: Behavioral and functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (p<0.05). Gastrocnemius muscle mass in SVF transplanted animal was found to be significantly more than that in control group. Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in SVF transplanted animals than in control group. In immunohistochemistry, the location of reactions to S- 100 in SVF transplanted animals was clearly more positive than that in control group. CONCLUSION: SVF transplantation combined with silicone conduit could be considered as a readily accessible source of stromal cells that improves functional recovery of sciatic nerve. It may have clinical implications for the surgical management of acute diabetic patients after facial nerve transection.

VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation.

Vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) have been widely used in the fields of tissue engineering and regenerative medicine to stimulate angiogenesis and bone formation. The goal of this study was to determine whether VEGF and BMP-2 are involved in the homing of bone marrow stem cells (BMSCs) for bone regeneration and to provide insights into their mechanism of action. The chemoattraction of BMSCs to VEGF and BMP-2 was analysed in vitro using a checkerboard assay. VEGF and BMP-2 stimulated the chemotaxis of BMSCs but not chemokinesis. In vivo, both VEGF and BMP-2 also have been confirmed to induce the homing of tail vein injected BMSCs to the site of silk scaffold subcutaneous implantation in nude mice. When the scaffolds were implanted in the rabbit skull defects, more SSEA+ mesenchymal stem cells were mobilised and homed to silk scaffolds containing VEGF and/or BMP-2. More importantly, autogenic BMSCs were reinjected via the ear vein after labelling with lenti-GFP, and the cells were detected to home to the defects and differentiate into endothelial cells and osteogenic cells induced by VEGF and BMP-2. Finally, perfusion with Microfil showed that initial angiogenesis was enhanced in tissue-engineered complexes containing VEGF. Observations based on µCT assay and histological study revealed that bone formation was accelerated on BMP-2-containing scaffolds. These findings support our hypothesis that the localised release of VEGF and BMP-2 promote bone regeneration, in part by facilitating the mobilisation of endogenous stem cells and directing the differentiation of these cells into endothelial and osteogenic lineages.

Atmospheric pressure plasma induced grafting of poly(ethylene glycol) onto silicone elastomers for controlling biological response.

This study investigates the role that surface functionalisation of silicone elastomer (SE) by atmospheric pressure plasma induced graft immobilisation of poly(ethylene glycol) methyl ether methacrylate (PEGMA) plays in the attendant biological response. SE is used in modern ophthalmic medical devices and samples of the material were initially plasma treated using a dielectric barrier discharge reactor (DBD) to introduce reactive oxygen functionalities, prior to in situ grafting of two molecular weights of PEGMA (MW 1000 Da: PEGMA(1000), MW 2000 Da: PEGMA(2000)). The variously processed surfaces were characterised by water contact angle analysis, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry and atomic force microscopy. Lens epithelial cells were then cultured on the PEGMA grafted SE surfaces. It was found that cells on the pristine surface were not well spread and had shrunken morphology. On the DBD pre-treated surfaces, the cells were well spread. On the PEGMA(1000) surface, the cells displayed evidence of shrinkage and were on the verge of detaching. Remarkably, on the PEGMA(2000) surface, no cell adhesion was detection. Bacterial adhesion to the surfaces was studied using Staphylococcus aureus NTC8325. There was no difference in the number of bacteria adhering to any of the surfaces studied.

Endocannabinoids limit excessive mast cell maturation and activation in human skin.

BACKGROUND: Mast cells (MCs) crucially contribute to many inflammatory diseases. However, the physiological controls preventing excessive activities of MCs in human skin are incompletely understood. OBJECTIVE: Since endocannabinoids are important neuroendocrine MC modifiers, we investigated how stimulation/inhibition of cannabinoid 1 (CB1) receptors affect the biology of human skin MCs in situ. METHODS: This was investigated in the MC-rich connective tissue sheath of organ-cultured human scalp hair follicles by quantitative (immuno)histomorphometry, ultrastructural, and quantitative PCR techniques with the use of CB1 agonists or antagonists, CB1 knockdown, or CB1 knockout mice. RESULTS: Kit+ MCs within the connective tissue sheath of human hair follicles express functional CB1 receptors, whose pharmacological blockade or gene silencing significantly stimulated both the degranulation and the maturation of MCs from resident progenitor cells in situ (ie, enhanced the number of tryptase+, FcεRIα, or chymase+ connective tissue sheath-MCs). This was, at least in part, stem cell factor-dependent. CB1 agonists counteracted the MC-activating effects of classical MC secretagogues. Similar phenomena were observed in CB1 knockout mice, attesting to the in vivo relevance of this novel MC-inhibitory mechanism. CONCLUSION: By using human hair follicle organ culture as an unconventional, but clinically relevant model system for studying the biology of MCs in situ, we show that normal skin MCs are tightly controlled by the endocannabinoid system. This limits excessive activation and maturation of MCs from resident progenitors via "tonic" CB1 stimulation by locally synthesized endocannabinoids. The excessive numbers and activation of MCs in allergic and other chronic inflammatory skin diseases may partially arise from resident intracutaneous MC progenitors, for example, because of insufficient CB1 stimulation. Therefore, CB1 stimulation is a promising strategy for the future management of allergy and MC-dependent skin diseases.

Periprosthetic bleeding 18 years post-silicone reconstruction of the orbital floor.

BACKGROUND: Periprosthetic orbital haemorrhage is an uncommon complication of the alloplastic implants used in post-traumatic orbital floor repair. The small case series or individual reports provide no definite causative explanation for this delayed bleeding around silicone implants. It is likely that it is related to the disruption of fine capillaries within the pseudocapsule surrounding the implant, since the material does cause low-grade irritation with evidence of chronic inflammation. CASE REPORT: We report the case of a patient who developed a spontaneous periprosthetic bleeding 18 years' post-silicone sheet reconstruction of the orbital floor. RESULTS: Urgent removal of the implant insured prompt resolution of all symptoms and no further problem during the 2-year follow-up. CONCLUSION: This report emphasizes that periprosthetic orbital haemorrhage can occur years after the initial repair. Awareness of this rare complication allows for prompt diagnosis, decreasing the possibility of permanent damage of the orbital content. The removal of implant is necessary to relieve the symptoms and prevent potential infective complications.

In vivo 7.1 T magnetic resonance imaging to assess the lens geometry in rabbit eyes 3 years after lens-refilling surgery.

PURPOSE: To evaluate the utility of high-resolution magnetic resonance imaging (MRI) in assessing the normal and refilled lens geometry in rabbits after lens-refilling surgery. SETTING: University of Rostock, Rostock, Germany. DESIGN: Experimental study. METHODS: High-resolution ocular MRIs were acquired (7.1 T ClinScan) using a 2-channel coil with 4 coil elements and T2-weighted turbo spin-echo sequences (slice thickness 700 µm, field of view 40 mm × 40 mm) in rabbits after lens refilling surgery combined with intraoperative treatment to prevent lens epithelial cell proliferation. Single slices were used to assess the refilled lenses 3 years postoperatively. RESULTS: The entire geometry (cross-sectional area, radius of curvature, axial and equatorial diameters) of the crystalline and refilled lenses was visualized by in vivo 7.1T MRI 3 years postoperatively (in-plane resolution: 125 µm × 125 µm). In refilled eyes, the capsule and the homogenous silicone polymer remained in close contact with no visible interface. The dimensions of the refilled lens were significantly smaller than those of the crystalline lens of the contralateral eye. CONCLUSIONS: High-resolution MRI allows in vivo visualization and analysis of the spatial arrangement of the lens in rabbit eyes after lens refilling surgery and overcomes a number of major limitations in the quantitative evaluation of the lens shape. Further efforts are required to optimize the amount of polymer injected during lens refilling to achieve a predictable refractive outcome after lens refilling surgery. FINANCIAL DISCLOSURE: Drs. Stachs, Langner, Sternberg, Martin, Schmitz, Hosten and Guthoff have no financial or proprietary interest in any material or method mentioned. Additional financial disclosure is found in the footnotes.

Aortic customize: a new alternative endovascular approach to aortic aneurysm repair using injectable biocompatible elastomer. An in vitro study.

PURPOSE: Aortic Customize is a new concept for endovascular aortic aneurysm repair in which a non polymerized elastomer is injected to fill the aneurysm sac around a balloon catheter. The aim of this in vitro study was to investigate the extent of aneurysm wall stress reduction by the presence of a noncompliant elastomer cuff. METHODS: A thin-walled latex aneurysm (inner radius sac 18 mm, inner radius neck 8 mm), equipped with 12 tantalum markers, was attached to an in vitro circulation model. Fluoroscopic roentgenographic stereo photogrammetric analysis (FRSA) was used to measure marker movement during six cardiac cycles. The radius of three circles drawn through the markers was measured before and after sac filling. Wall movement was measured at different systemic pressures. Wall stress was calculated from the measured radius (sigma = pr/2t). RESULTS: The calculated wall stress was 7.5-15.6 N/cm(2) before sac filling and was diminished to 0.43-1.1 N/cm(2) after sac filling. Before sac filling, there was a clear increase (P < .001) in radius of the proximal (range, 7.9%-33.5%), middle (range, 3.3%-25.2%), and distal (range, 10.5%-184.3%) rings with increasing systemic pressure. After sac filling with the elastomer, there remained a small, significant (P < .001) increase in the radius of the circles (ranges: 6.8%-8.8%; 0.7%-1.1%; 5.3%-6.7%). The sac filling reduced the extent of radius increase. The treated aneurysm withstood systemic pressures up to 220/140 mm Hg without noticeable wall movement. After the sac filling, there was no pulsation visible in the aneurysm wall. CONCLUSIONS: Filling the aneurysm sac of a simplified in vitro latex model with a biocompatible elastomer leads to successful exclusion of the aneurysm sac from the circulation. Wall movement and calculated wall stress are diminished noticeably by the injection of biocompatible elastomer.

Mechanical and biological evaluations of beta-tricalcium phosphate/silicone rubber composite as a novel soft-tissue implant.

BACKGROUND: Although silicone rubber (SR) implants are most commonly used and effective for soft-tissue augmentation, they still have been implicated in many adverse reactions. To overcome this problem, a novel composite beta-tricalcium phosphate/silicone rubber (beta-TCP/SR) was prepared by adding beta-TCP into a SR matrix. This study was to evaluate its application potential by investigating the mechanical properties and biocompatibility of beta-TCP/SR. METHODS: Mechanical properties, including Shore A hardness and tensile strength, were evaluated with 3-mm-thick samples and a universal testing machine. Cytocompatibility tests were conducted in vitro using 0.2-mm-thick beta-TCP/SR samples by seeding fibroblasts onto different samples. Soft-tissue response to beta-TCP/SR and pull-out measurements were investigated 4 weeks and 24 weeks after implantation. RESULTS: The main mechanical properties were all significantly changed after mixing beta-TCP into the SR matrix, except for tearing strength. The cytocompatibility test showed enhanced adhesion and proliferation of fibroblasts onto beta-TCP/SR. Fibrous tissue ingrowth after resorption of beta-TCP was observed by in vivo histologic analysis. The peri-implant capsules in the beta-TCP/SR group were thinner than in the SR group 24 weeks after implantation. In a 24-week test, the maximum force required to pull out the beta-TCP/SR sheet was about six times greater than that needed for SR. CONCLUSION: Although some mechanical properties were significantly changed, the results of the cytocompatibility test and in vivo animal study still suggest that beta-TCP/SR may be more suitable as a soft-tissue implant than SR and has the potential to be used in plastic surgery.

Histopathologic study of rat connective tissue responses to maxillofacial silicone elastomers.

The aim of this histopathologic study was to assess and compare the subcutaneous connective tissue reaction to three different maxillofacial silicone elastomers (Cosmesil, Multisil, Episil). The test materials were directly inserted subcutaneously into the dorsal subcutaneous tissue of Wistar albino rats. Histopathological examinations were done at 7, 30, and 90 days after the implantation procedure. The presence of inflammation, presence of inflammatory giant cells, and the thickness of fibrous connective tissue adjacent to each inserted sample were recorded. Data was evaluated by analysis of variance, Wilcoxon signed ranks test and Kruskal Wallis test. Cosmesil, Multisil and Episil silicone elastomers at 7 days elicited a severe inflammatory reaction. However, these reactions decreased by the 30 and 90 days. All silicone elastomers elicited a moderate inflammatory reaction at 30 and 90 days. There were no significant differences in tissue reaction between the materials at 7, 30, and 90 days (P > 0.05). All the maxillofacial silicone elastomers evaluated can not be assigned a favorable biocompatibility level based on this study's histologic findings.

A review of the biologic effects, clinical efficacy, and safety of silicone elastomer sheeting for hypertrophic and keloid scar treatment and management.

Silicone elastomer sheeting is a medical device used to prevent the development of and improve the appearance and feel of hypertrophic and keloid scars. The precise mechanism of action of silicone elastomer sheeting has not been defined, but clinical trials report that this device is safe and effective for the treatment and prevention of hypertrophic and keloid scars if worn over the scar for 12 to 24 hours per day for at least 2 to 3 months. Some of the silicone elastomer sheeting products currently on the market are durable and adhere well to the skin. These products are an attractive treatment option because of their ease of use and low risk of adverse effects compared to other treatments, such as surgical excision, intralesional corticosteroid injections, pressure therapy, radiation, laser treatment, and cryotherapy. Additional controlled clinical trials with large patient populations may provide further evidence for the efficacy of silicone elastomer sheeting in the treatment and prevention of hypertrophic and keloid scars. The purpose of this article is to review the literature on silicone elastomer sheeting products and to discuss their clinical application in the treatment and prevention of hypertrophic and keloid scars.

PSNCBAM-1, a novel allosteric antagonist at cannabinoid CB1 receptors with hypophagic effects in rats.

BACKGROUND AND PURPOSE: Rimonabant (Acomplia, SR141716A), a cannabinoid CB1 receptor inverse agonist, has recently been approved for the treatment of obesity. There are, however, concerns regarding its side effect profile. Developing a CB1 antagonist with a different pharmacological mechanism may lead to a safer alternative. To this end we have screened a proprietary small molecule library and have discovered a novel class of allosteric antagonist at CB1 receptors. Herein, we have characterized an optimized prototypical molecule, PSNCBAM-1, and its hypophagic effects in vivo. EXPERIMENTAL APPROACH: A CB1 yeast reporter assay was used as a primary screen. PSNCBAM-1 was additionally characterized in [35S]-GTPgammaS, cAMP and radioligand binding assays. An acute rat feeding model was used to evaluate its effects on food intake and body weight in vivo. KEY RESULTS: In CB1 receptor yeast reporter assays, PSNCBAM-1 blocked the effects induced by agonists such as CP55,940, WIN55212-2, anandamide (AEA) or 2-arachidonoyl glycerol (2-AG). The antagonist characteristics of PSNCBAM-1 were confirmed in [35S]-GTPgammaS binding and cAMP assays and was shown to be non-competitive by Schild analyses. PSNCBAM-1 did not affect CB2 receptors. In radioligand binding assays, PSNCBAM-1 increased the binding of [3H]CP55,940 despite its antagonist effects. In an acute rat feeding model, PSNCBAM-1 decreased food intake and body weight. CONCLUSIONS AND IMPLICATIONS: PSNCBAM-1 exerted its effects through selective allosteric modulation of the CB1 receptor. The acute effects on food intake and body weight induced in rats provide a first report of in vivo activity for an allosteric CB1 receptor antagonist.

Inhibition of macrophage development and foreign body giant cell formation by hydrophilic interpenetrating polymer network.

The ability of monocytes to adhere, differentiate into macrophages, and fuse to form foreign body giant cells (FBGCs) on an implanted material surface is a critical step toward biomaterial degradation. Novel homogeneous surfaces were utilized to mediate adhesion. These surfaces consisted of N-(2 aminoethyl)-3-aminopropyltrimethoxysilane (EDS) and an interpenetrating polymer network (IPN) of polyacrylamide and poly(ethylene glycol). These surfaces were designed to control cell adhesion and morphology and mediate cell differentiation, activation, metabolic ability, and apoptosis, resulting in a reduced or controlled inflammatory response. The EDS surface promotes cell adhesion and the IPN minimizes protein adsorption and subsequent cell adhesion. Both surfaces had similar cellular adhesion rates at each respective time point. However, the adherent macrophage morphology was similar at 2 h and day 3, and at days 7 and 10 adherent macrophages on the EDS surface formed FBGCs (46% at day 7 and 40% at day 10). Adherent cells on the IPN surface did not form FBGCs but instead formed monocyte aggregates (73% of adherent cells formed aggregates at day 7 and 63% at day 10). It is indicated that the two surface chemistries differentially controlled monocyte differentiation into macrophages and subsequent macrophage fusion to form FBGCs.