Advances and challenges in developing smart, multifunctional microneedles for biomedical applications.

Microneedles (MNs) have been developed as minimally invasive tools for diagnostic and therapeutic applications. However, in recent years, there has been an increasing interest in developing smart multifunctional MN devices to provide automated and closed-loop systems for body fluid extraction, biosensing, and drug delivery in a stimuli-responsive manner. Although this technology is still in its infancy and far from being translated into the clinic, preclinical trials have shown some promise for the broad applications of multifunctional MN devices. The main challenge facing the fabrication of smart MN patches is the integration of multiple modules, such as drug carriers, highly sensitive biosensors, and data analyzers in one miniaturized MN device. Researchers have shown the feasibility of creating smart MNs by integrating stimuli-responsive biomaterials and advanced microscale technologies, such as microsensors and microfluidic systems, to precisely control the transportation of biofluids and drugs throughout the system. These multifunctional MN devices can be envisioned in two distinct strategies. The first type includes individual drug delivery and biosensing MN units with a microfluidic system and a digital analyzer responsible for fluid transportation and communication between these two modules. The second type relies on smart biomaterials that can function as drug deliverers and biosensors by releasing drugs in a stimuli-responsive manner. These smart biomaterials can undergo structural changes when exposed to external stimuli, such as pH and ionic changes, mimicking the biological systems. Studies have demonstrated a high potential of hydrogel-based MN devices for a wide variety of biomedical applications, such as drug and cell delivery, as well as interstitial fluid extraction. Biodegradable hydrogels have also been advantageous for fabricating multifunctional MNs due to their high loading capacity and biocompatibility with the drug of choice. Here, we first review a set of MN devices that can be employed either for biosensing or delivery of multiple target molecules and compare them to the conventional and more simple systems, which are mainly designed for single-molecule sensing or delivery. Subsequently, we expand our insight into advanced MN systems with multiple competencies, such as body fluid extraction, biosensing, and drug delivery at the point of care. The improvement of biomaterials knowledge and biofabrication techniques will allow us to efficiently tune the next generation of smart MNs and provide a realistic platform for more effective personalized therapeutics.

Advances in microfabrication technologies in tissue engineering and regenerative medicine.

BACKGROUND: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close-to-native three-dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. METHODS: In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self-assembly of microstructures, microfluidics, fiber spinning, and bioprinting. RESULTS: These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. CONCLUSIONS: This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications.

Micro and Nanoscale Technologies for Diagnosis of Viral Infections.

Viral infection is one of the leading causes of mortality worldwide. The growth of globalization significantly increases the risk of virus spreading, making it a global threat to future public health. In particular, the ongoing coronavirus disease 2019 (COVID-19) pandemic outbreak emphasizes the importance of devices and methods for rapid, sensitive, and cost-effective diagnosis of viral infections in the early stages by which their quick and global spread can be controlled. Micro and nanoscale technologies have attracted tremendous attention in recent years for a variety of medical and biological applications, especially in developing diagnostic platforms for rapid and accurate detection of viral diseases. This review addresses advances of microneedles, microchip-based integrated platforms, and nano- and microparticles for sampling, sample processing, enrichment, amplification, and detection of viral particles and antigens related to the diagnosis of viral diseases. Additionally, methods for the fabrication of microchip-based devices and commercially used devices are described. Finally, challenges and prospects on the development of micro and nanotechnologies for the early diagnosis of viral diseases are highlighted.

A novel approach to producing uniform 3-D tumor spheroid constructs using ultrasound treatment.

Producing three-dimensional (3-D) multicellular tumor spheroids (TSs) is valuable for characterizing anticancer drugs since they provide a more representative model of the 3-D in vivo tumor than conventional two-dimensional (2-D) monolayer culture. The interaction of tumor cells with the extracellular matrix (ECM) in a 3-D culture environment is more similar to a tumor in vivo than in a 2-D environment; cell-cell and cell-ECM interaction can influence cell behaviour, such as in response to drug treatment. In vitro tumor spheroid models have been developed using microfluidic systems to generate 3-D hydrogel beads containing components of alginate and ECM protein, such as collagen, with high uniformity and throughput. Cell-laden hydrogel droplets are formed using a flow focusing process wherein the hydrogel precursors should be a homogeneous mixture. During gelation of the droplets into beads, the alginate acts as a fast gelling component helping to maintain the spherical shape of beads and preventing coalescence as the temperature-sensitive collagen I component gels more slowly. To produce uniform hydrogel droplets using the microfluidic flow focusing system, the mixtures must be homogeneous. However, collagen's sensitivity to temperature can lead to formation of chunks of collagen gel inside of the mixture, causing the mixture to become non-uniform and risking chip clogging. In order to overcome this limitation, previous approaches have used a cooling system during bead encapsulation while tumor cells were also present in the mixture, but this procedure can contribute to a delay in cell proliferation. Here a novel yet simple method is developed to prepare homogeneous pre-bead-encapsulation-mixtures containing collagen type I through ultrasonication. This method allows the cultivation of homogenous TS cultures with high uniformity and compact structure, and not only maintains cell viability but also the proliferation of cells in alginate/collagen hydrogel bead cultures. Depending on the sonication parameters, time and temperature, collagen can form small sized fibrils to thick fibers. Here, the mixtures containing collagen are assessed for morphology of collagen fibers/fibrils, cell viability, and proliferation. Human source Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are successfully incorporated into alginate/collagen mixtures, followed by sonication, and then bead production. After bead gelation, the encapsulated MCF-7 cells remained viable and proliferated to form uniform TSs when the beads contained alginate and collagen. Results indicate that ultrasound treatment (UST) provides a powerful technique to change the structure of collagen from fiber to fibril, and to disperse collagen fibers in the mixture homogeneously for an application to generate uniform hydrogel beads and spheroids while not inhibiting cell proliferation.

Emerging 2D Nanomaterials-Integrated Hydrogels: Advancements in Designing Theragenerative Materials for Bone Regeneration and Disease Therapy.

This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D-material integrated hydrogels, with a focus on their performance in bone-related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near-infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D-material-based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug-loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D-materials -infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug-resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio-imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real-time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D-materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment.

Blood loss by hemorrhaging wounds accounts for over one-third of ∼5 million trauma fatalities worldwide every year. If not controlled in a timely manner, exsanguination can take lives within a few minutes. Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need. Here, biocompatible, and biodegradable microneedle arrays (MNAs) based on gelatin methacryloyl (GelMA) biomaterial hybridized with silicate nanoplatelets (SNs) are developed for hemorrhage control. The SNs render the MNAs hemostatic, while the needle-shaped structure increases the contact area with blood, synergistically accelerating the clotting time from 11.5 min to 1.3 min in vitro. The engineered MNAs reduce bleeding by ∼92% compared with the untreated injury group in a rat liver bleeding model. SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro- and nanoengineered features. Furthermore, the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications. These hemostatic MNAs may enable rapid hemorrhage control, particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.

Aerogel-Based Biomaterials for Biomedical Applications: From Fabrication Methods to Disease-Targeting Applications.

Aerogel-based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol-gel, aging, drying, and self-assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic-based technologies and 3D printing can be combined with aerogel-based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel-based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.

Synthesis, structures and properties of hydrophobic Alkyltrimethoxysilane-Polyvinyltrimethoxysilane hybrid aerogels with different alkyl chain lengths.

HYPOTHESIS: Alkyltrimethoxysilane (ATMS) is among most widely used silane coupling agents. These commercially available, reasonably priced chemicals are often utilized to improve the compatibility of inorganic surfaces with organic coatings. With three hydrolysable moieties, ATMS is an outstanding candidate for solving the hydrophilicity, moisture sensitivity and high cost of silica aerogels. However, ATMS has a non-hydrolysable alkyl chain that undergoes cyclization reactions. The alkyl chain prevents ATMS from being incorporated in aerogel structures. Polyvinyltrimethoxysilane (PVTMS) is a silica precursor that offers two types of crosslinking to the final aerogel product. This strong doubly-crosslinked network can potentially suppress the cyclization reactions of ATMS and include it in aerogel structure. EXPERIMENTS: PVTMS was used with ATMS having different alkyl lengths (3-16 carbons) and loadings (25 or 50 wt%) as the silica precursors. Acid and base catalysts were used to perform hydrolysis and condensation reactions on the mixture and ATMS:PVTMS aerogels were obtained via supercritical drying. FINDINGS: The incorporation of ATMS in the aerogels was approved by different characterization methods. Results showed that ATMS:PVTMS aerogels possess hydrophobicity (θ âˆ¼ 130°), moisture resistance, varying surface area (44-916 m2·g-1), meso/microporous structure and thermal insulation properties (λ âˆ¼ 0.03 W·m-1K-1). These samples also showed excellent performance in oil and organic solvent adsorption.

Recent advances in tailoring and improving the properties of polyimide aerogels and their application.

With the rapid advancements in technology and growing aerospace applications, there is a need for effective low-weight and thermally insulating materials. Aerogels are known for their ultra-lightweight and they are highly porous materials with nanopores in a range of 2 to 50 nm with very low thermal conductivity values. However, due to hygroscopic nature and brittleness, aerogels are not used commercially and in daily life. To enhance the mechanical and hydrophobic properties, reinforcement materials such as styrene, cyanoacrylates, epoxy along with hydroxyl, amines, vinyl groups are added to the surface. The addition of organic materials resulted in lower service temperatures which reduce its potential applications. Polyimides (PI) are commonly used in engine applications due to their suitable stability at high temperatures along with excellent mechanical properties. Previous research on polyimide aerogels reported high flexibility or even foldability. However, those works' strategy was mainly limited to altering the backbone chemistry of polyimide aerogels by changing either the monomer's compositions or the chemical crosslinker. This work aims to summarize, categorize, and highlight the recent techniques for improving and tailoring properties of polyimide aerogels followed by the recent advancements in their applications.

Laponite-Based Nanomaterials for Drug Delivery.

Laponite is a clay-based material composed of synthetic disk-shaped crystalline nanoparticles with highly ionic, large surface area. These characteristics enable the intercalation and dissolution of biomolecules in Laponite-based drug delivery systems. Furthermore, Laponite's innate physicochemical properties and architecture enable the development of tunable pH-responsive drug delivery systems. Laponite's coagulation capacity and cation exchangeability determine its exchange capabilities, drug encapsulation efficiency, and release profile. These parameters are exploited to design highly controlled and efficacious drug delivery platforms for sustained drug release. In this review, they provide an overview of how to design efficient delivery of therapeutics by leveraging the properties and specific interactions of various Laponite-polymer composites and drug moieties.

Lab-on-a-Contact Lens: Recent Advances and Future Opportunities in Diagnostics and Therapeutics.

The eye is one of the most complex organs in the human body, containing rich and critical physiological information (e.g., intraocular pressure, corneal temperature, and pH) as well as a library of metabolite biomarkers (e.g., glucose, proteins, and specific ions). Smart contact lenses (SCLs) can serve as a wearable intelligent ocular prosthetic device capable of noninvasive and continuous monitoring of various essential physical/biochemical parameters and drug loading/delivery for the treatment of ocular diseases. Advances in SCL technologies and the growing public interest in personalized health are accelerating SCL research more than ever before. Here, the current status and potential of SCL development through a comprehensive review from fabrication to applications to commercialization are discussed. First, the material, fabrication, and platform designs of the SCLs for the diagnostic and therapeutic applications are discussed. Then, the latest advances in diagnostic and therapeutic SCLs for clinical translation are reviewed. Later, the established techniques for wearable power transfer and wireless data transmission applied to current SCL devices are summarized. An outlook, future opportunities, and challenges for developing next-generation SCL devices are also provided. With the rise in interest of SCL development, this comprehensive and essential review can serve as a new paradigm for the SCL devices.

Recent developments in mussel-inspired materials for biomedical applications.

Over the decades, researchers have strived to synthesize and modify nature-inspired biomaterials, with the primary aim to address the challenges of designing functional biomaterials for regenerative medicine and tissue engineering. Among these challenges, biocompatibility and cellular interactions have been extensively investigated. Some of the most desirable characteristics for biomaterials in these applications are the loading of bioactive molecules, strong adhesion to moist areas, improvement of cellular adhesion, and self-healing properties. Mussel-inspired biomaterials have received growing interest mainly due to the changes in mechanical and biological functions of the scaffold due to catechol modification. Here, we summarize the chemical and biological principles and the latest advancements in production, as well as the use of mussel-inspired biomaterials. Our main focus is the polydopamine coating, the conjugation of catechol with other polymers, and the biomedical applications that polydopamine moieties are used for, such as matrices for drug delivery, tissue regeneration, and hemostatic control. We also present a critical conclusion and an inspired view on the prospects for the development and application of mussel-inspired materials.

Advances in precursor system for silica-based aerogel production toward improved mechanical properties, customized morphology, and multifunctionality: A review.

Conventional silica-based aerogels are among the most promising materials considering their special properties, such as extremely low thermal conductivity (~15 mW/mK) and low-density (∼0.003-0.5 g.cm-3) as well as high surface area (500-1200 m2. g-1). However, they have relatively low mechanical properties and entail extensive and energy-consuming processing steps. Silica-based aerogels are mostly fragile and possess minimal mechanical properties as well as a long processing procedure which hinders their application range. The key point in improving the mechanical properties of such a material is to increase the connectivity in the aerogel backbone. Several methods of mechanical improvement of silica-based aerogels have been explored by researchers such as (i) use of flexible silica precursors in silica gel backbone, (ii) surface-crosslinking of silica particles with a polymer, (iii) prolonged aging step in different solutions, (iv) distribution of flexible nanofillers into the silica solution prior to gelation, and, most recently, (v) polymerizing the silica precursor prior to gelation. The polymerized silica precursor, as in the most recent approach, can be gelled either by binodal decomposition (nucleation and growth), resulting in a particulate structure, or by spinodal decomposition, resulting in a non-particulate structure. By optimizing the material composition and processing conditions of materials, the aerogel can be tailored with different functional capabilities. This review paper presents a literature survey of precursor modification toward increased connectivity in the backbone, and the synthesis of inorganic and hybrid systems containing siloxane in the backbone of the silica-based aerogels and its composite version with carbon nanofillers. This review also explains the novel properties and applications of these material systems in a wide area. The relationship among the materials-processing-structure-properties in these kinds of aerogels is the most important factor in the development of aerogel products with given morphologies (particulate, fiber-like, or non-particulate) and their resultant properties. This approach to advancing precursor systems leads to the next-generation, multifunctional silica-based aerogel materials.

In Situ Interface Design in Graphene-Embedded Polymeric Silica Aerogel with Organic/Inorganic Hybridization.

For many practical applications, the most important factor is to have an improved interface between the matrix and dispersed phase in a compressible composite aerogel having a high degree of porosity and a large surface area. Although some measure of compressibility is obtained in polymer-based aerogels with a continuous backbone through the hybridization of the stiff backbone [polyvinyltrimethoxysilane (P-VTMS), -C-C-] and flexible backbone [poly(3-glycidyloxypropyl)trimethoxysilane (P-GPTMS), -C-O-C-], it seems that the extent of improvement is insignificant in terms of interface improvement, surface area increase, and ordered mesoporous network. In this study, the effects of the incorporation of graphene nanoplatelets (GnPs) on aerogels made of a backbone consisting of -C-O-C- (flexible backbone) were examined in terms of structural improvement and were compared with aerogels made of a backbone consisting of -C-C- (stiff backbone). Moreover, the inorganic siloxane cross-link density between the underlying polymer chains was controlled by inducing hydrogen bonding between polymer chains and GnPs. This approach reduces the structural shrinkage during gelation and drying. The integration of only 1 wt % GnP integrated into the backbone by using spinodal decomposition phase separation processing allowed control of the pore size and the surface area. Integration of GnPs through in situ exfoliation during sol-gel transition is shown to be the best approach using the lowest possible amount of GnPs to improve aerogels' mesoporous network made from polymerized GPTMS. A flexible backbone such as P-GPTMS chains is supposed to result in a compliant aerogel, but the chains tend to shrink extensively during gelation and drying, reducing the porosity. P-GPTMS-derived aerogel suffers from a wrong combination of flexible backbone conjugated with an extensive number of permanent chemical cross-links and abundant remaining unreacted hydroxyl groups that undergo permanent chemical shrinkage. To counteract this, the GnP-reinforced prepolymer precursor (P-GPTMS) with fewer siloxane cross-links was synthesized and studied. By use of this strategy, the same elastic properties as those seen with the hybrid P-VTMS- and hybrid P-GPTMS-derived aerogels were imparted, while also improving the mechanical strength by up to 138% and the surface area by up to 205% by controlling the extent of GnP exfoliation during the sol-gel transition. This exceptional effect of GnP on the surface area improvement was shown to be of up to 2.05-fold for P-GPTMS and 2.63-fold for P-VTMS material.

Polyimide aerogels with novel bimodal micro and nano porous structure assembly for airborne nano filtering applications.

Aerogels have presented a very high potential to be utilized as airborne nanoparticles' filtration media due to their nanoscale pore size and extremely high porosity. The filtering performance of aerogels, such as air permeability and filtration efficiency, is highly related to the configuration of aerogels' nanostructure assembly. However, as aerogel morphology is formed with respect to the intermolecular forces during the gelation stage, tailoring the aerogel nanostructure assembly is still a challenge. In this work, a novel strategy for tailoring polyimide aerogel nanostructure assembly is proposed by controlled disturbing of the intermolecular forces. From the results, the nanostructure assembly of the 4,4'-oxydianiline (ODA)-biphenyl-tetracarboxylic acid dianhydride (BPDA) polyimide aerogel is tailored to a uniform bimodal micro and nano porous structure. This was achieved by introducing the proper fraction of thermoplastic polyurethane (TPU) chains to the polyimide chains in the solution state and through a controlled process. The fabricated polyimide/TPU aerogels with bimodal morphology presented enhanced filtration performance, with 30% improved air permeability and reduced cell size of 3.51 nm over the conventional ODA-BPDA polyimide aerogels. Moreover, the fabricated bimodal aerogels present the reduced shrinkage, density, and effective thermal conductivity of 6.3% and 0.063 g cm-3, 28.7 mW m-1 K-1, respectively. Furthermore, the bimodal polyimide/TPU aerogels show the higher porosity of 96.5 vol% along with increased mechanical flexibility over the conventional polyimide aerogel with comparable backbone chemistry.

The effect of graphene-nanoplatelets on gelation and structural integrity of a polyvinyltrimethoxysilane-based aerogel.

Aerogels suffer greatly from poor mechanical properties resulting from their particulate structure. They also experience noticeable pore shrinkage during drying due to their low structural integrity. These shortfalls limit their broad application. To enhance the mechanical properties and improve the structural integrity of silica-based aerogels, graphene nanoplatelets (GnPs), as a nanofiller, were embedded into the solution of polymerized vinyltrimethoxysilane (VTMS) to prepare P-VTMS-based silica/GnP (PE-b-Si/GnP) hybrid aerogel monoliths based on sol-gel synthesis and supercritical drying. The inclusion of GnPs in our polymer-based silica aerogel processes reinforced the nanostructure and suppressed PE-b-Si nanopore shrinkage during supercritical drying, thus acting as an effective anti-shrinkage nanofiller. Accordingly, the GnPs significantly contributed to the PE-b-Si solution's uniform gelation and to the change of the hydrophilic nature to a hydrophobic one even with 1 wt% addition. In this study, the influence of the GnP content on the sol-gel process, structure, and physical properties of PE-based silica aerogels is studied.

Robust, ultra-insulative and transparent polyethylene-based hybrid silica aerogel with a novel non-particulate structure.

Aerogels derived from pre-polymerized vinyl trimethoxy silane (VTMS) precursor with nano-size particles are known to exhibit outstanding mechanical and insulation properties. However, the density reduction has been limited by the poor connectivity. This paper presents an innovative technology to generate a new class of VTMS-based hybrid silica aerogels that possess outstanding non-particulate, reticulated structure and superior properties. This technology relies on spinodal decomposition instead of conventionally exploited binodal decomposition, which leads to a particulate structure. This new aerogel technology has significantly increased the void fraction of the pre-polymerized VTMS-based aerogel, which could not be achieved previously using binodal decomposition. The increased void fraction in the form of nano-pores with an average pore size of 21.75 nm nullifies the gas thermal conductivity effectively. Another consequence of the non-particulate structure is decreased processing time by removing the aging step. These improvements are due to the non-particulate structure's increased connectivity produced by spinodal decomposition. This novel structure was then compared to a particulate counterpart aerogel of the same material derived from the conventional binodal decomposition of the pre-polymerized VTMS precursor. To further decrease the processing cost, a lower molecular-weight polymeric precursor was synthesized under milder polymerization conditions. The effects of the polymeric precursor's molecular weight on the mechanical and thermal properties of the aerogel created via spinodal decomposition were also investigated.