The unique physicochemical properties of aerogels have made them an attractive class of materials for biomedical applications such as drug delivery, regenerative medicine, and wound healing. Their low density, high porosity, and ability to regulate the pore structure makes aerogels ideal nano/micro-structures for loading of drugs and active biomolecules. As a result of this, the number of in vitro and in vivo studies on the therapeutic efficacy of these porous materials has increased substantially in recent years and continues to be an area of great interest. However, data about their in vivo performance and safety is limited. Studies have shown that polymer-based, silica-based and some hybrid aerogels are generally regarded as safe but given that studies on the acute, subacute, and chronic toxicity for the majority of aerogel types is missing, more work is still needed. This review presents a comprehensive summary of different biomedical applications of aerogels proposed to date as well as new and innovative applications of aerogels in other areas such as decontamination. We have also reviewed their biological effect on cells and living organisms with a focus on therapeutic efficacy and overall safety (in vivo and in vitro).

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. 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. 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.

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. 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. 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.

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. 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. 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.

Externally applied electrical stimulation (ES) has been shown to enhance the nerve regeneration process and to influence the directionality of neurite outgrowth. In addition, the physical and chemical properties of the substrate used for nerve-cell regeneration is critical in fostering regeneration. Previously, we have shown that polyurea-crosslinked silica aerogels (PCSA) exert a positive influence on the extension of neurites by PC-12 cells, a cell-line model widely used to study neurite extension and electrical excitability. In this work, we have examined how an externally applied electric field (EF) influences the extension of neurites in PC-12 cells grown on two substrates: collagen-coated dishes versus collagen-coated crosslinked silica aerogels. The externally applied direct current (DC) bias was applied in vitro using a custom-designed chamber containing polydimethysiloxane (PDMS) embedded copper electrodes to create an electric field across the substrate for the cultured PC-12 cells. Results suggest orientation preference towards the anode, and, on average, longer neurites in the presence of the applied DC bias than with 0 V DC bias. In addition, neurite length was increased in cells grown on silica-crosslinked aerogel when compared to cells grown on regular petri-dishes. These results further support the notion that PCSA is a promising material for nerve regeneration.

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.