Firouzeh Sabri

Investigation of polyurea-crosslinked silica aerogels as a neuronal scaffold: a pilot study.

Background Polymer crosslinked aerogels are an attractive class of materials for future implant applications particularly as a biomaterial for the support of nerve growth. The low density and nano-porous structure of this material combined with large surface area, high mechanical strength, and tunable surface properties, make aerogels materials with a high potential in aiding repair of injuries of the peripheral nervous system. However, the interaction of neurons with aerogels remains to be investigated. Methodology In this work the attachment and growth of neurons on clear polyurea crosslinked silica aerogels (PCSA) coated with: poly-L-lysine, basement membrane extract (BME), and laminin1 was investigated by means of optical and scanning electron microscopy. After comparing the attachment and growth capability of neurons on these different coatings, laminin1 and BME were chosen for nerve cell attachment and growth on PCSA surfaces. The behavior of neurons on treated petri dish surfaces was used as the control and behavior of neurons on treated PCSA discs was compared against it. Conclusions/Significance This study demonstrates that: 1) untreated PCSA surfaces do not support attachment and growth of nerve cells, 2) a thin application of laminin1 layer onto the PCSA discs adhered well to the PCSA surface while also supporting growth and differentiation of neurons as evidenced by the number of processes extended and b3-tubulin expression, 3) three dimensional porous structure of PCSA remains intact after fixing protocols necessary for preservation of biological samples and 4) laminin1 coating proved to be the most effective method for attaching neurons to the desired regions on PCSA discs. This work provides the basis for potential use of PCSA as a biomaterial scaffold for neural regeneration.

Histological Evaluation of the Biocompatibility of Polyurea Crosslinked Silica Aerogel Implants in a Rat Model: A Pilot Study

Background Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here. Methodology This study assessed the short and long term biocompatibility of polyurea crosslinked silica aerogel implants in a Sprague-Dawley rat model. Implants were inserted at two different locations a) subcutaneously (SC), at the dorsum and b) intramuscularly (IM), between the gluteus maximus and biceps femoris of the left hind extremity. Nearby muscle and other internal organs were evaluated histologically for inflammation, tissue damage, fibrosis and movement (travel) of implant. Conclusion/Significance In general polyurea crosslinked silica aerogel (PCSA) was well tolerated as a subcutaneous and an intramuscular implant in the Sprague-Dawley rat with a maximum incubation time of twenty months. In some cases a thin fibrous capsule surrounded the aerogel implant and was interpreted as a normal response to foreign material. No noticeable toxicity was found in the tissues surrounding the implants nor in distant organs. Comparison was made with control rats without any implants inserted, and animals with suture material present. No obvious or noticeable changes were sustained by the implants at either location. Careful necropsy and tissue histology showed age-related changes only. An effective sterilization technique for PCSA implants as well as staining and sectioning protocol has been established. These studies further support the notion that silica-based aerogels could be useful as biomaterials.

In Vivo Ultrasonic Detection of Polyurea Crosslinked Silica Aerogel Implants

Background Polyurea crosslinked silica aerogels are highly porous, lightweight, and mechanically strong materials with great potential for in vivo applications. Recent in vivo and in vitro studies have demonstrated the biocompatibility of this type of aerogel. The highly porous nature of aerogels allows for exceptional thermal, electric, and acoustic insulating capabilities that can be taken advantage of for non-invasive external imaging techniques. Sound-based detection of implants is a low cost, non-invasive, portable, and rapid technique that is routinely used and readily available in major clinics and hospitals. Methodology In this study the first in vivo ultrasound response of polyurea crosslinked silica aerogel implants was investigated by means of a GE Medical Systems LogiQe diagnostic ultrasound machine with a linear array probe. Aerogel samples were inserted subcutaneously and sub-muscularly in a) fresh animal model and b) cadaveric human model for analysis. For comparison, samples of polydimethylsiloxane (PDMS) were also imaged under similar conditions as the aerogel samples. Conclusion/significance Polyurea crosslinked silica aerogel (X-Si aerogel) implants were easily identified when inserted in either of the regions in both fresh animal model and cadaveric model. The implant dimensions inferred from the images matched the actual size of the implants and no apparent damage was sustained by the X-Si aerogel implants as a result of the ultrasonic imaging process. The aerogel implants demonstrated hyperechoic behavior and significant posterior shadowing. Results obtained were compared with images acquired from the PDMS implants inserted at the same location.

Effect of surface plasma treatments on the adhesion of Mars JSC 1 simulant dust to RTV 655, RTV 615, and Sylgard 184.

Background Dust accumulation on surfaces of critical instruments has been a major concern during lunar and Mars missions. Operation of instruments such as solar panels, chromatic calibration targets, as well as Extra Vehicular Activity (EVA) suits has been severely compromised in the past as a result of dust accumulation and adhesion. Wind storms with wind speeds of up to 70 mph have not been effective in removing significant amounts of the deposited dust. This is indeed an indication of the strength of the adhesion force(s) involved between the dust particles and the surface(s) that they have adhered to. Complications associated with dust accumulation are more severe for non-conducting surfaces and have been the focus of this work. Methodology Argon plasma treatment was investigated as a mechanism for lowering dust accumulation on non-conducting polymeric surfaces. Polymers chosen for this study include a popular variety of silicones routinely used for space and terrestrial applications namely RTV 655, RTV 615, and Sylgard 184. Surface properties including wettability, surface potential, and surface charge density were compared before and after plasma treatment and under different storage conditions. Effect of ultraviolet radiation on RTV 655 was also investigated and compared with the effect of Ar plasma treatment. Conclusion/Significance Gravimetric measurements proved Ar plasma treatment to be an effective method for eliminating dust adhesion to all three polymers after short periods of exposure. No physical damage was detected on any of the polymer surfaces after Ar plasma treatment. The surface potential of all three polymers remained zero up to three months post plasma exposure. Ultraviolet radiation however was not effective in reducing surface and caused damage and significant discoloration to RTV 655. Therefore, Ar plasma treatment can be an effective and non-destructive method for treating insulating polymeric surfaces in order to eliminate dust adhesion and accumulation.

Investigation of crosslinked silica aerogels for implant applications

Silica-based Aerogels have a number of unique properties that make them suitable for a range of applications. These include superior thermal, acoustic, and electrical insulation capabilities, all associated with the highly-porous nature of this class of materials. Crosslinked (X) silica aerogels have improved mechanical and surface properties making them suitable for biomedical device applications, particularly in the peripheral regions of the body. Aerogels ability to dampen sounds waves is particularly important since it would allow an external non-invasive imaging technique for aerogel based implants. The biocompatibility of this class of material must be addressed prior to the development of in vivo imaging data. In this work, the authors report on the growth and interaction of Opossum Kidney cells and dorsal root ganglia on crosslinked silica aerogels, paving the way for implant applications.

Novel Technique for Repair of Severed Peripheral Nerves in Rats Using Polyurea Crosslinked Silica Aerogel Scaffold

ABSTRACT Purpose/Aim: To design, synthesize, and test in vivo an aerogel-based top-open peripheral nerve scaffold to simultaneously support and guide multiple completely severed peripheral nerves in a rat model. Also, to explore options for immobilizing severed nerves on the aerogel material without the use of sutures resulting in reduced surgical time. Materials and Method: A novel material and approach was developed for the reattachment of severed peripheral nerves. Nerve confinement and alignment in this case relies on the surface properties of a lightweight, highly porous, polyurea crosslinked silica aerogel scaffold. The distal and proximal ends of completely transected nerve terminals were positioned inside prefabricated “top-open” corrugated channels that cradled approximately two thirds of the circumference of the nerve trunk and connectivity of the severed nerves was evaluated using sciatic function index (SFI) technique for five months post-surgery on 10 female Sprague–Dawley rats then compared with the gold standard for peripheral nerve repair. The interaction of nerves with the surface of the scaffold was investigated also. Results and Conclusion: Multichannel aerogel-based nerve support scaffold showed similar SFI recovery trend as the case suture repair technique. Usage of an adhesion-promoting coating reduced the friction between the nerve and the scaffold leading to slippage and lack of attachment between nerve and surface. The aerogel scaffold used in this study did not collapse under pressure during the incubation period and allowed for a rapid and non-invasive peripheral nerve repair approach without the demands of microsurgery on both time and surgical expertise. This technique may allow for simultaneous repair and reconnection of multiple severed nerves particularly relevant to nerve branching sites.

Effect of Aerogel Particle Concentration on Mechanical Behavior of Impregnated RTV 655 Compound Material for Aerospace Applications

Aerogels are a unique class of materials with superior thermal and mechanical properties particularly suitable for insulating and cryogenic storage applications. It is possible to overcome geometrical restrictions imposed by the rigidity of monolithic polyurea cross-linked silica aerogels by encapsulating micrometer-sized particles in a chemically resistant thermally insulating elastomeric “sleeve.” The ultimate limiting factor for the compound material’s performance is the effect of aerogel particles on the mechanical behavior of the compound material which needs to be fully characterized. The effect of size and concentration of aerogel microparticles on the tensile behavior of aerogel impregnated RTV655 samples was explored both at room temperature and at 77 K. Aerogel microparticles were created using a step-pulse pulverizing technique resulting in particle diameters between 425 μm and 90 μm and subsequently embedded in an RTV 655 elastomeric matrix. Aerogel particle concentrations of 25, 50, and 75 wt% were subjected to tensile tests and behavior of the compound material was investigated. Room temperature and cryogenic temperature studies revealed a compound material with rupture load values dependent on (1) microparticle size and (2) microparticle concentration. Results presented show how the stress elongation behavior depends on each parameter.

Polymer-Encapsulated Phosphor Particles for In Vivo Phosphor Luminescence Applications

Phosphor thermometry is a highly sensitive, rapid, and portable thermal sensing technique that offers advantages over traditional contact-based thermometry techniques. Phosphor particles would however require an encapsulation medium that is biocompatible and yet optically transparent to permit optical access to the embedded phosphor particles. Here, phosphor-doped silicone implants with varying concentrations were prepared and tested in a rat model. Results indicate that such phosphor-doped polymeric implants are stable, produce a detectable signal, and demonstrate the feasibility of phosphor thermometry as a noninvasive remote thermal sensing technique for in vivo applications. Also, encapsulation in silicone did not lead to significant attenuation of the incoming signal. GRAPHICAL ABSTRACT

In Vivo X-Ray Imaging of Phosphor-Doped PDMS and Phosphor-Doped Aerogel Biomaterials

Noninvasive rapid in vivo imaging and detection of biomedical implants is a critical part of the design and implementation of smart implants. Thermographic phosphors offer a precise and remotely accessible sensing method that has been utilized here. We present the first in vivo X-ray images of La2O2S:Eu-doped crosslinked silica aerogels and polydimethylsiloxane (PDMS) with increasing dopant concentrations. Results show that native PDMS and crosslinked silica aerogel do not show noticeable attenuation of X-rays while image analysis yields values of the absorption coefficient of 0.014 for the doped aerogel and a range of 0.015–0.017 for the doped PDMS. GRAPHICAL ABSTRACT

Investigation of surface topography and stiffness on adhesion and neurites extension of PC12 cells on crosslinked silica aerogel substrates

Fundamental understanding and characterization of neural response to substrate topography is essential in the development of next generation biomaterials for nerve repair. Aerogels are a new class of materials with great potential as a biomaterial. In this work, we examine the extension of neurites by PC12 cells plated on matrigel-coated and collagen-coated mesoporous aerogel surfaces. We have successfully established the methodology for adhesion and growth of PC12 cells on polyurea crosslinked silica aerogels. Additionally, we have quantified neurite behaviors and compared their response on aerogel substrates with their behavior on tissue culture (TC) plastic, and polydimethylsiloxane (PDMS). We found that, on average, PC12 cells extend longer neurites on crosslinked silica aerogels than on tissue culture plastic, and, that the average number of neurites per cluster is lower on aerogels than on tissue culture plastic. Aerogels are an attractive candidate for future development of smart neural implants and the work presented here creates a platform for future work with this class of materials as a substrate for bioelectronic interfacing.