Chemical Cross-linking Research Articles

Optical characterization of molecular interaction strength in protein condensates.

Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques - Brillouin microscopy and quantitative phase imaging (QPI) - to address this scarcity. We establish Brillouin shift and linewidth as measures for average molecular interaction and dissipation strength, respectively, and we used QPI to obtain the protein concentration within the condensates. We monitored the response of condensates formed by FUS and by the low-complexity domain of hnRNPA1 (A1-LCD) to altering temperature and ion concentration. Conditions favoring phase separation increased Brillouin shift, linewidth, and protein concentration. In comparison to solidification by chemical crosslinking, the ion-dependent aging of FUS condensates had a small effect on the molecular interaction strength inside. Finally, we investigated how sequence variations of A1-LCD, that change the driving force for phase separation, alter the physical properties of the respective condensates. Our results provide a new experimental perspective on the material properties of protein condensates. Robust and quantitative experimental approaches such as the presented ones will be crucial for understanding how the physical properties of biological condensates determine their function and dysfunction.

The small membrane protein CcoS is involved in cofactor insertion into the cbb3-type cytochrome c oxidase.

Respiratory complexes, such as cytochrome oxidases, are cofactor-containing multi-subunit protein complexes that are critically important for energy metabolism in all domains of life. Their intricate assembly strictly depends on accessory proteins, which coordinate subunit associations and cofactor deliveries. The small membrane protein CcoS was previously identified as an essential assembly factor to produce an active cbb3-type cytochrome oxidase (cbb3-Cox) in Rhodobacter capsulatus, but its function remained unknown. Here we show that the ΔccoS strain assembles a heme b deficient cbb3-Cox, in which the CcoN-CcoO subunit association is impaired. Chemical crosslinking demonstrates that CcoS interacts with the CcoN and CcoP subunits of cbb3-Cox, and that it stabilizes the interaction of the Cu-chaperone SenC with cbb3-Cox. CcoS lacks heme- or Cu-binding motifs, and we did not find evidence for direct heme or Cu binding; rather our data indicate that CcoS, together with SenC, coordinates heme and Cu insertion into cbb3-Cox.

Optimizing the % swelling and removal of carcinogenic dye from waste-water using polyacrylamide-based hydrogels

Nowadays due to rapid industrialization to assist humans, hazardous and non-biodegradable dyes are eliminated from leather and textile industries in water streams. To eradicate these toxic dyes, the adsorption process opted for wastewater reclamation. Therefore, polyacrylamide-based hydrogels were fabricated using methylene Bis acrylamide and FeCl3 as chemical and physical cross-linkers. Sodium alginate-co-Polyacrylamide-co-acrylic acid a ter-copolymer hydrogel cross-linked via N, N’ ˊ methylene bisacrylamide shows maximum %swelling at pH 9 i.e. 751.42% and an equilibrium time of 200 min. The sorption capacity obtained for ASM0.1 was maximum i.e. 43.809 ± 0.569 mg/g as compared to the sorption capacity of AAM0.05 and AAF0.05 i.e. 41.18 ± 0.541 mg/g and 35.588 ± 0.924 mg/g. The kinetic model followed by sorption of methylene blue onto polyacrylamide-based hydrogels was pseudo-second-order whereas diffusion occurred in two phases through macropores and mesopores. The optimized pH recorded for sorption is pH 9 having an adsorption value of 94.16 ± 1.326 mg/g. Batch experiments revealed that adsorption increases from 37.52 ± 0.743 mg/g to 104.56 ± 1.194 mg/g for ASM 0.1 with an increase in concentration from 20 mg/L to 60 mg/L. The isotherm model followed by MB sorption is the Freundlich isotherm model which infers the physical nature of sorption. Moreover, with an increase in temperature, the adsorption slightly increased from 89.31 mg/g to 92.14 mg/g due to an increase in kinetic energy with temperature rise. % Removal stability was investigated for 5 consecutive cycles and inferred that ASM0.1 has decreased its % removal by only 6.5% after five cycles.

Regulation of Glass Transition Temperature in Thermo‐Responsive Epoxy Shape Memory Polymers: The Roles of Chemical Crosslinking Density and Chain Flexibility

ABSTRACTShape memory polymers (SMPs) are novel kinds of smart materials whose shape can be changed in external conditions such as heat stimulus. Due to their excellent structural versatility and high elastic strain, they have important applications in the field of biomaterials. Here, a series of amorphous shape memory polymer materials are prepared and their shape memory properties and glass transition temperature (Tg) are also investigated. A special kind of epoxy polymer, whose shape can be changed at around physiological temperature, is synthesized by regulating the crosslinking density and introducing flexible aliphatic epoxy chains. The shape memory function of this epoxy polymer is studied by deformation test. In addition, to explore their application in the field of biomedical materials, the biocompatibility of the materials are evaluated, including the effects on the erythrocyte hemolysis rate and cell activity. The experimental results show that this kind of epoxy polymer has good shape memory function and biocompatibility.

Tertiary nitrogen carbonization and imine cross‐linking facilitated solid‐phase flame retardant for anti‐dripping PA6 fiber

AbstractA developing society requires polycaprolactam (PA6) fibers with flame retardant. Currently, the additive flame retardants commonly used in PA6 fibers cannot solve the molten droplet problem. In this work, (1E,1′ E)‐N,N′‐(6‐phenyl‐1,3,5‐triazine‐2,4‐diyl)bis(1‐(4‐methoxyphenyl) methanimine) (NBM) with triazine ring structure was synthesized. The triazine ring structure was used to expand into carbon and benzoguanimine structure to produce irreversible chemical crosslinking in NBM, thereby achieving anti‐dripping and flame retardant of PA6 fiber. LOI of PA6/NBM8 reaches 30.0 vol.%, UL‐94 reaches V‐0 when the NBM addition amount is 8 wt.%, meanwhile, the residual carbon content is 235.7% higher than that of PA6. The mechanical strength can still reach to 3.22 cN/dTex. From structural design to synthesis, the effects of NBM addition on the flame retardants, rheology, thermal stability and residual carbon morphology of PA6/NBMx were analyzed in detail in this work. It is hoped that in the future work, the structural characteristics and performance requirements can be matched to provide reference for conception and synthesis of flame retardants oriented to other polymers.

The Role of Freeze-Drying as a Multifunctional Process in Improving the Properties of Hydrogels for Medical Use

Background/Objectives: Freeze-drying is a dehydration method that extends the shelf life and stability of drugs, vaccines, and biologics. Recently, its role has expanded beyond preservation to improve novel pharmaceuticals and their carriers, such as hydrogels, which are widely studied for both drug delivery and wound healing. The main aim of this study was to explore the multifunctional role of freeze-drying in improving the physicochemical properties of sodium alginate/poly(vinyl alcohol)-based hydrogels for medical applications. Methods: The base matrix and hydrogels containing a nanocarrier-drug system, were prepared by chemical cross-linking and then freeze-dried for 24 h at −53 °C under 0.2 mBa. Key analyses included determination of gel fraction, swelling ratio, FT-IR, SEM, TG/DTG, in vitro drug release and kinetics, and cytotoxicity assessment. Results: Freeze-drying caused an increase in the gel fraction of the hydrogel with the dual drug delivery system from 55 ± 1.6% to 72 ± 0.5%. Swelling ability was pH-dependent and remained in the same range (175–282%). Thermogravimetric analysis showed that freeze-dried hydrogels exhibited higher thermal stability than their non-freeze-dried equivalents. The temperature at 10% weight loss increased from 194.0 °C to 198.9 °C for the freeze-dried drug-loaded matrix, and from 188.4 °C to 203.1 °C for the freeze-dried drug-free matrix. The average pore size of the freeze-dried hydrogels was in the range of 1.07 µm ± 0.54 to 1.74 µm ± 0.92. In vitro drug release revealed that active substances were released in a controlled and prolonged way, according to the Korsmeyer–Peppas model. The cumulative amount of salicylic acid released at pH = 9.0 after 96 h was 63%, while that of fluocinolone acetonide reached 73%. Both hydrogels were non-toxic to human fibroblast cells, maintaining over 90% cell viability after 48 h of incubation. Conclusions: The results show a high potential for commercialisation of the obtained hydrogels as medical dressings.

Effects of Moisture Content and Heat Treatment on the Viscoelasticity and Gelation of Polyacrylonitrile/Dimethylsulfoxide Solutions

Polyacrylonitrile (PAN) gels create significant obstacles in industrial fiber spinning by forming insoluble networks that compromise solution stability and uniformity. This study investigates the rheological properties of PAN/dimethyl sulfoxide (DMSO) solutions, examining how aging time, moisture content, and polymer concentration affect gelation behavior. Dynamic rheological analysis revealed that both physical and chemical crosslinks play crucial roles in gel formation, with gelation accelerating markedly when moisture content exceeds 3% and aging progresses. Under heat treatment at 80 °C, samples with increased moisture content demonstrated rapid transitions to solid-like states, indicating a critical moisture threshold for enhanced gelation kinetics. Additionally, reductions in polymer concentration disrupted physical crosslink density, thereby mitigating gel formation. These results underscore the importance of precisely controlling moisture and concentration parameters in PAN solutions to stabilize solution properties and minimize gel formation, thus enhancing process efficiency and quality in PAN-based carbon fiber production.

Enlightenment the dynamic behavior of norbornene–modified ’click’ 4–arm polyethylene glycol hydrogel: Delving into framework properties and transport properties through molecular dynamics simulations

The thiol-norbornene cross-linked 4-arm Polyethylene Glycol (PEG) ’click’ hydrogel is a synthetic, sustainable, and bio-inspired polymer extensively used in biomedical applications. Experimental techniques are widely used to study this system, whereas all-atom molecular dynamics simulations, which offer insight into the dynamic behaviours of the system, are never used to study this system. Three models of thiol-norbornene cross-linked PEG ’click’ hydrogel and a base PEG hydrogel are crafted. It is immersed in water to study its structural and transport properties. Structural properties are analysed through root-mean-square deviation (RMSD), radial distribution function (RDF), hydrogen bonds (H-bond), and stress–strain behavior. The RMSD reveals that the norbornene component enhances hydrogel stability compared to the base model. The RDF illustrates interactions between oxygen in PEG chains and water. H-bond results underscore PEG’s strong H-bond acceptance. The norbornene-functionalized crosslinked PEG hydrogel displays maximum H-bonding. It demonstrates a superior swelling ratio attributed to freezing and non-freezing water effects, indicating high stability and potential suitability for applications. Mean square displacements (MSD) unveil the diffusion coefficients of the hydrogel. The base hydrogel model shows the diffusive behavior, and the diffusion coefficient is 1.97 × 10-10 m2/s. The base model has the highest MSD value compared to other systems. The thiol-norbornene crosslinked click hydrogel has the highest Young’s modulus, which signifies the stiffness of the material. Findings illuminate thiol-norbornene ’click’ PEG hydrogel behaviour, emphasising chemical cross-linking’s crucial role in advanced biomedical applications.

Comprehensive Review of Hydrogel Synthesis, Characterization, and Emerging Applications

Hydrogels play a crucial role due to their high-water content and 3D structure, which make them ideal for various applications in biomedicine, sensing, and beyond. They can be prepared from a variety of biomaterials, polymers, and their combinations, allowing for versatility in properties and applications. Hydrogels include natural types derived from collagen, gelatin, alginate, and hyaluronic acid, as well as synthetic types based on polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide (PAAm). Each type possesses distinct properties, such as mechanical strength, biodegradability, and biocompatibility, which can be tailored for applications such as wound healing, contact lenses, 3D bioprinting, and tissue engineering. The high-water content of hydrogels mimics natural tissue environments, promoting cell growth and allowing nutrient and waste exchange, which supports the development of functional tissues. They serve as scaffolds in tissue engineering applications, including wound healing, cartilage and bone regeneration, vascular tissue engineering, and organ-on-a-chip systems. Additionally, hydrogels can encapsulate and deliver therapeutic agents, such as growth factors or drugs, to specific target sites in the body. Hydrogels can be prepared through three primary methods: physical crosslinking, which relies on non-covalent interactions such as physical entanglements or hydrogen bonding; chemical crosslinking, which forms covalent bonds between polymer chains to create a stable structure; and irradiation-based crosslinking, where UV irradiation induces rapid hydrogel formation. The choice of crosslinking method depends on the desired properties and applications of the hydrogel. By providing a biomimetic environment, hydrogels facilitate cell growth and differentiation, support tissue formation, and aid in the regeneration of damaged or diseased tissues while delivering therapeutic agents. This review focuses on the critical advancements in processing routes for hydrogel development, summarizing the characterization and application of hydrogels. It also details key applications, including wound healing and cartilage and bone regeneration, as well as the challenges and future perspectives in the field.

Novel rubber-steel adhesive based on resole phenol formaldehyde/unsaturated polyester/soybean oil polyol blends with high thermal stability performance

One of the main challenges in rubber-metal adhesive is improving the adhesion strength performance with high thermal stability. A novel rubber-steel adhesives based on resole phenol formaldehyde/unsaturated polyester/soybean oil polyol blends were fabricated to tackle this challenge. SEM investigated the morphology of the fabricated blends, while the curing reaction and the components’ interactions were evaluated using FT-IR and XRD. The heat resistance and curing properties were studied by TGA and DSC. The adhesion properties for rubber-metal adhesive specimens were tested at room temperature. The impact of soybean oil polyol modifier addition was investigated on adhesion performance. The curing conditions (touch dry, full curing, and shelf life) and hardness were investigated. It is obvious that polyol improves the heat resistance of the prepared films and enhances their adhesion behavior. The fabricated adhesive exhibits good adhesion and thermal stability due to the integration of chemical cross-linking in the matrix. It can adhere extensively to substrate surfaces via intermolecular forces with small physical movements. Controlling the curing time and delaying the shelf life could be possible for samples that take a long time to cure completely. The designed fabricated adhesive appeared to desired properties of satisfactory rubber-metal adhesion and good thermal stability.

The synergistic effect of nano-Al2O3 size and concentration on the interfacial adhesion properties of SMA/PDMS composites and their enhancement mechanism

Soft actuators composed of shape memory alloy (SMA) wires embedded in polydimethylsiloxane (PDMS) matrix hold potential for shape-morphing structures and soft robots. However, SMA exhibits poor bonding with PDMS due to its smooth and nonpolar surfaces. Nanoparticles show promise in interfacial strengthening of polymer composites. In this work, KH590 was used to modify nano-Al2O3 particles and deposited on the SMA surface, creating a three-dimensional nanostructure bridging SMA and PDMS to enhance interface strength. The synergistic effects of particle size and content of nano-Al2O3 particles on the interface strength were investigated in detail. It founds that interfacial strength decreased exponentially with particle size at content of 1 wt%, while when the content exceeds 1 wt%, the interface strength firstly increases with the particle size and then decreases in a logarithmic trend. Specifically, the interface strength is enhanced by 110 % with 3 wt% 50 nm particles. The interface enhancement mechanism was also discussed. The proposed nanoparticle modification approach was to strengthen SMA/PDMS interphase by increasing and extending fracture path, consuming more fracture energy. Chemical cross-linking also contributed to interface enhancement. This work enhances understanding of interfacial bonding mechanisms and provides valuable guide for interfacial strengthening of SMA/PDMS.

A novel bio-aerogel based on agroforestry waste chestnut shell for enhanced oil-water separation performance

Bio-based aerogels have attracted much attention due to their biodegradability and excellent oil-water separation properties. However, the preparation of inexpensive green aerogels with high separation efficiency is still a great challenge. In this paper, low-density, high-adsorption capacity and superhydrophobic chestnut shell-based bio-aerogels were prepared by chemical cross-linking and chemical vapor deposition using agricultural and forestry waste chestnut shells as the precursor of aerogels to achieve high efficiency of oil-water separation and to achieve the goal of “treating waste with waste”. The covalent cross-linking of chestnut shell cellulose and cross-linking agent to form silicone-containing functional groups improved the pore structure, hydrophobicity and mechanical properties of chestnut shell cellulose, and under the action of capillary force, the oil was retained in the pores of the bio-aerogels, which achieved the selective adsorption of oil and organic solvents in the oil-water mixture, with a separation efficiency of more than 98%. After 10 cycles, the bio-aerogel still has good reusability. This eco-friendly and low-cost aerogel provides a practical method for resource conversion and recycling, as well as a green and innovative way for the treatment of oily wastewater.

Novel high-strength, recyclable, microbial-resistant, and freeze-thaw dual topological network hydrogel cooling media

The demand for multifunctional hydrogels, offering high mechanical strength, efficient cooling, and antimicrobial properties, is growing in food preservation. Here, a dual-network (DN) hydrogel PM@Cur, which includes curcumin, is fabricated through chemical crosslinking and hydrogen bonding interactions. The resulting hydrogels can withstand more than five freeze-thaw cycles at −80 °C, and resist brittleness after liquid nitrogen treatment. PM@Cur also exhibits surface hydrophobicity (contact angle >90°) for both water and organic solvents. These properties meet the mechanical, anti-fouling, and recyclable demands for hydrogel coolants. The antimicrobial assays in vitro confirmed that the inclusion of curcumin provided the PM@Cur with photodynamic antimicrobial capacity. Finally, the prepared PM@Cur hydrogel ice cubes have been confirmed to exhibit better anti-melting properties than traditional ice cubes, thus enabling the preservation of strawberries and shrimp. This study presents an innovative solution for producing advanced functional integrated hydrogels, offering a promising and safer option for food coolants.\\.

Enhanced high-temperature energy storage performance in all-organic dielectric films through synergistic crosslinking of chemical and physical interaction

Advanced electronic devices and energy systems urgently require high-temperature polymer dielectrics that can offer both high discharge energy density and energy storage efficiency. However, the capacitive properties of most polymers sharply deteriorate at elevated temperatures, due to the significant rise in leakage current density and energy loss. Herein, a new design approach is adopted to fabricate high-temperature polyetherimide (PEI) dielectrics with chemical and physical cooperative crosslinking networks, the dual-crosslinked PEI dielectrics are prepared through amine crosslinking agent and the electrostatic interaction of oppositely charged phenyl groups between triptycene (TE) and PEI chain segments. Benefiting from the increased crosslinking sites, the dual-crosslinked PEI films achieve the simultaneously enhancement in Tg, modulus and bandgap compared to un-crosslinked and single-crosslinked polymers. Meanwhile, the PEI with dual-crosslinked network displays higher chain packing density, effectively reducing the mean motion pathways of charge carriers and the conduction loss inside polymer dielectric. Consequently, the dual-crosslinked PEI containing 0.25 wt% TE delivers an outstanding discharge energy density of 2.69 J/cm3 and retains excellent cyclability after 100,000 charge–discharge cycles at 200 ℃. Additionally, finite element analysis and molecular dynamics simulation further confirm that less Joule heat and tighter chain structure are formed in the dual-crosslinked polymer dielectric. This research offers a novel methodology to prepare high-performance polymer dielectrics for high-temperature applications.

High salt-resistant and robust MXene@oleylamine/PET composite nonwoven for efficient and long-term solar desalination

2D transition metal carbides/nitrides/carbonitrides (MXenes) have received extensive attention in solar seawater desalination due to their hydrophilicity, 100 % photothermal conversion efficiency, and efficient light-trapping by enhancing localized surface plasmon resonance (LSPR). Nevertheless, the easily oxidizable characteristics of MXenes, along with salt accumulation and structural weakness impede their practical application in solar-driven interfacial evaporators. Herein, a hydrophobic MXene@oleylamine/polyethylene terephthalate (MXene@OAm/PET) nonwoven with long-term operational stability is fabricated via firmly chemical cross-linking between oleylamine (OAm) modified MXene (MXene@OAm) and NH2-PEG-COOH treated PET nonwoven (PEG-PET). The MXene@OAm endows excellent oxidation resistance and hydrophobicity. The prepared MXene@OAm/PET nonwoven which exhibits broad-spectrum solar absorption and high efficiency, can achieve an average evaporation rate in 3.5 wt% NaCl solution at 1.26 kg·m−2·h−1 and no seeable salt deposition during 15 irradiation cycles for 8 h a day indicates its superior salt resistance and long-term stability. Most importantly, after being soaked in 3.5 wt% NaCl solution for 40 days, the evaporation rate of MXene@OAm/PET nonwoven still remains stable at around 1.22 kg·m−2·h−1, indicating the significant potential of this prepared nonwoven for long-term seawater desalination and its suitability for industrial applications. Even in industrial wastewater, the evaporation rate can reach 1.27 kg·m−2·h−1. This work demonstrates a successful strategy for achieving high efficiency, stability, and superior salt resistance, which can be potentially utilized in seawater desalination and wastewater treatment.

Preparation of PAAS/GL/GO anti-freezing conductive hydrogels based on chemical cross-linking networks and their application in wearable sensors

Preparation of PAAS/GL/GO anti-freezing conductive hydrogels based on chemical cross-linking networks and their application in wearable sensors

Water as a Structural Marker in Gelatin Hydrogels with Different Cross-Linking Nature.

We have studied the molecular properties of water in physically and chemically cross-linked gelatin hydrogels by FTIR-spectroscopy, NMR relaxation, and diffusivity and broadband dielectric spectroscopy, which are sensitive to dynamical properties of water, being a structural marker of polymer network. All experiments demonstrated definite reinforcement of the hydrogel net structure and an increase in the amount of hydrate water. FTIR experiments have shown that the chemical cross-linking of gelatin molecules initiates an increase in the collagen-like triple helices "strength", as a result of infused restriction on protein molecular mobility. The "strengthening" of protein chains hinders the mobility of protein fragments, introducing complex modifications into the structural properties of water which are remained practically unchanged up to up to 30-40 °C.

Emerging Frontiers in In Situ Forming Hydrogels for Enhanced Hemostasis and Accelerated Wound Healing.

With a surge in the number of accidents and chronic wounds worldwide, there is a growing need for advanced hemostatic and wound care solutions. In this regard, in situ forming hydrogels have emerged as a revolutionary biomaterial due to their inherent properties, which include biocompatibility, biodegradability, porosity, and extracellular matrix (ECM)-like mechanical strength, that render them ideal for biomedical applications. This review demonstrates the advancements of in situ forming hydrogels, tracing their evolution from injectable to more sophisticated forms, such as sprayable and 3-D printed hydrogels. These hydrogels are designed to modulate the pathophysiology of wounds, enhancing hemostasis and facilitating wound repair. The review presents different methodologies for in situ forming hydrogel synthesis, spanning a spectrum of physical and chemical cross-linking techniques. Furthermore, it showcases the adaptability of hydrogels to the dynamic requirements of wound healing processes. Through a detailed discussion, this article sheds light on the multifunctional capabilities of these hydrogels such as their antibacterial, anti-inflammatory, and antioxidant properties. This review aims to inform and inspire continued advancement in the field, ultimately contributing to the development of sophisticated wound care solutions that meet the complexity of clinical needs.

Targeted Analysis of Mitochondrial Protein Conformations and Interactions by Endogenous ROS-Triggered Cross-Linker Release.

The study of in situ conformations and interactions of mitochondrial proteins plays a crucial role in understanding their biological functions. Current chemical cross-linking mass spectrometry (CX-MS) has difficulty in achieving in-depth analysis of mitochondrial proteins for cells without genetic modification. Herein, this work develops the reactive oxygen species (ROS)-responsive cross-linker delivery nanoparticles (R-CDNP) targeting mitochondria. R-CDNP contains mitochondria-targeting module triphenylphosphine, ROS-responsive module thioketal, loading module poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), and cross-linker module disuccinimidyl suberate (DSS). After targeting mitochondria, ROS-triggered cross-linker release improves the cross-linking coverage of mitochondria in situ. In total, this work identifies 2103 cross-linked sites of 572 mitochondrial proteins in HepG2 cells. 1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions.

Recent advances in H2 purification and CO2 capture: Evolving from flat sheet to hollow fiber membranes

Hydrogen (H2) production and demand have steadily increased, leading to a rise in carbon dioxide (CO2) emissions since fossil fuels are the current raw material for H2 production. Thin film composite (TFC) hollow fiber membranes have become significant in H2 purification and CO2 capture, playing a critical role in developing next-generation fuels and supporting the United Nations Sustainable Development Goal 7 (SDG 7) – Affordable and Clean Energy, with the goal of providing universal access to clean, advanced, and renewable energy for all. However, the polymeric selective layer of TFC membranes faces a trade-off between permeability and selectivity, as well as challenges including CO2 plasticization and physical aging. Additionally, H2/CO2 separation remains particularly challenging because H2, being diffusivity-selective, permeates more quickly through the membrane due to its smaller molecular size and higher kinetic energy, while CO2, being solubility-selective, has a high affinity for dissolving in most polymeric membranes. Herein, this review provides an in-depth exploration of innovative modification strategies designed to overcome these challenges in glassy polymeric membranes and enhance H2 separation performance in the recent 10 years. Various nanofillers, such as metal-organic frameworks (MOFs) such as University of Oslo (UiO), Materials Institute Lavoisier (MILs), and Zeolitic Imidazolate Frameworks (ZIFs), have shown remarkable potential in boosting gas separation capabilities due to their superior compatibility with polymer matrices and tunable properties. The review also explores different types of hollow fiber membranes, including single layer, dual-layer, and TFC, alongside fabrication techniques like interfacial polymerization and dip-coating. Critically, the analysis highlights cutting-edge strategies to improve membrane performance, such as (i) thermal cross-linking, (ii) chemical cross-linking, (iii) ultraviolet (UV) cross-linking, (iv) polymer blends, and (v) modified fillers, along with their objectives and expected outcome. Furthermore, the review spotlights breakthroughs in H2/CO2, H2/CH4, and H2/N2 separation technologies, emphasizing the critical need for continued innovation to drive sustainable H2 production and meet the growing clean energy demand.