Crosslinked Polyethyleneimine Hydrogel: Synthesis, Properties, And Advanced Applications In Biomedical And Environmental Engineering

Molecular Composition And Structural Characteristics Of Crosslinked Polyethyleneimine Hydrogel

Crosslinked polyethyleneimine hydrogel is constructed from polyethyleneimine (PEI), a cationic polymer featuring primary, secondary, and tertiary amine groups in its backbone, which undergoes three-dimensional network formation through chemical or physical crosslinking mechanisms123. The polymer backbone comprises repeating ethylenimine units (–CH₂–CH₂–NH–), with branched PEI typically exhibiting a branching ratio of approximately 25% primary, 50% secondary, and 25% tertiary amines, while linear PEI contains predominantly secondary amines511. The crosslinking process transforms the soluble PEI into a water-swellable, insoluble gel matrix capable of retaining 10–1000 times its dry weight in water, depending on crosslink density13.

The structural architecture of crosslinked PEI hydrogels is governed by several critical parameters:

• Crosslink Density: Controlled by crosslinking agent concentration (typically 0.01–50 mol% relative to amine groups), directly influencing mesh size (5–100 nm), swelling ratio, and mechanical strength136. Higher crosslink density (>10 mol%) yields compressive moduli of 10–500 kPa, suitable for load-bearing applications718.
• Molecular Weight Distribution: PEI precursors range from 600 Da to 750 kDa, with higher molecular weights (>25 kDa) providing enhanced entanglement and mechanical integrity post-crosslinking21115.
• Functional Group Accessibility: Residual unreacted amine groups (typically 30–70% remain after crosslinking) serve as active sites for secondary functionalization, metal ion chelation, or electrostatic interactions with anionic species1412.

The hydrogel network exhibits pH-responsive swelling behavior due to protonation of amine groups below pH 9, with maximum swelling observed at pH 4–6 where electrostatic repulsion between protonated amines dominates35. Thermal stability analysis via TGA reveals decomposition onset at 200–250°C for uncrosslinked PEI, increasing to 280–380°C post-crosslinking due to restricted chain mobility79.

Crosslinking Chemistries And Synthesis Routes For Polyethyleneimine Hydrogel

The formation of crosslinked PEI hydrogels employs diverse chemical strategies, each imparting distinct structural and functional properties to the final material235.

Epoxide-Based Crosslinking

Epichlorohydrin and diepoxide compounds (e.g., ethylene glycol diglycidyl ether) react with PEI amine groups via nucleophilic ring-opening, forming stable ether and secondary amine linkages357. A representative synthesis involves dissolving branched PEI (Mw = 25 kDa, 10 wt%) in deionized water, adding epichlorohydrin at a molar ratio of 1:0.05 (amine:epoxide), and heating at 60–80°C for 4–12 hours under continuous stirring7. The reaction proceeds through:

R-NH₂ + epoxide → R-NH-CH₂-CH(OH)-CH₂-O-polymer

This method yields hydrogels with compressive moduli of 50–200 kPa and swelling ratios of 15–40 g/g in distilled water7. Polyhedral oligomeric silsesquioxane (POSS) containing epoxy groups has been employed as a multifunctional crosslinker, enhancing thermal stability (Td > 350°C) and mechanical properties (tensile strength ~2.5 MPa) compared to conventional epoxides7.

Aldehyde-Mediated Crosslinking

Glutaraldehyde and other dialdehydes form Schiff base (imine) linkages with primary amines of PEI, creating dynamic covalent networks412. The crosslinking reaction is typically conducted at pH 7–9, where amine nucleophilicity is optimal:

R-NH₂ + OHC-R'-CHO → R-N=CH-R'-CH=N-R + 2H₂O

For instance, a self-healing PEI-polyvinyl alcohol hydrogel was synthesized by mixing PEI (Mw = 10 kDa, 5 wt%), polyvinyl alcohol (PVA, 8 wt%), and 4-formylphenylboronic acid (2 wt%) in aqueous solution at 25°C for 2 hours, yielding a gel with rapid self-healing capability (<30 seconds) due to reversible imine and boronate ester bonds4. Magnetic nanoparticle-loaded PEI-cellulose hydrogels crosslinked with glutaraldehyde (1–3 mL per gram cellulose) demonstrated adsorption capacities of 150–300 mg/g for anionic dyes, with crosslinking conducted at 50°C for 6 hours12.

Biomass-Derived Crosslinkers

Aldaroyl-based crosslinkers derived from oxidized sugars (e.g., glucaric acid derivatives) provide sustainable alternatives to petroleum-based agents356. These bifunctional compounds contain carboxyl or activated ester groups that react with PEI amines to form amide linkages:

R-NH₂ + HOOC-aldaroyl-COOH → R-NH-CO-aldaroyl-CO-NH-R + 2H₂O

Hydrogels prepared with 5–15 mol% aldaroyl crosslinkers exhibit viscosities of 5,000–50,000 cP at 25°C (1% aqueous solution) and are biodegradable under physiological conditions, making them suitable for agricultural and biomedical applications36.

Photopolymerization And Radical-Initiated Crosslinking

PEI functionalized with acrylate or methacrylate groups undergoes UV-initiated radical polymerization in the presence of photoinitiators (e.g., Irgacure 2959, 0.1–0.5 wt%)1115. Acrylate-modified PEI (degree of substitution 20–40%) is dissolved in water (10–20 wt%), exposed to UV light (365 nm, 5–10 mW/cm²) for 5–15 minutes, forming hydrogels with tunable mesh sizes (10–50 nm) and elastic moduli (1–100 kPa) depending on irradiation time and initiator concentration11. This method enables spatial patterning and in situ gelation for 3D bioprinting applications1518.

Dual Crosslinking Strategies

Combining physical (hydrogen bonding, electrostatic interactions) and chemical crosslinking enhances mechanical robustness and functional versatility4818. A two-field coupling approach involves initial non-covalent assembly of PEI-coated gelatin particles (20 nm–50 μm diameter) via hydrogen bonding, followed by covalent crosslinking with glutaraldehyde or genipin, yielding injectable hydrogels with compressive moduli of 0.1–1000 kPa and self-healing efficiency >85% within 10 minutes18.

Physicochemical Properties And Performance Metrics Of Crosslinked Polyethyleneimine Hydrogel

Swelling Behavior And Water Retention

Crosslinked PEI hydrogels exhibit pH-dependent swelling, with equilibrium swelling ratios (ESR) ranging from 10 g/g at pH 2 to 50 g/g at pH 7 for moderately crosslinked systems (5 mol% crosslinker)13. The swelling kinetics follow Fickian diffusion at early stages (<60% equilibrium), transitioning to non-Fickian behavior due to polymer chain relaxation3. Swelling capacity decreases with increasing ionic strength (e.g., ESR reduces by 40–60% in 0.15 M NaCl compared to deionized water) due to electrostatic screening of charged amine groups112.

Mechanical Properties

The mechanical performance of PEI hydrogels is highly tunable through crosslink density and polymer concentration:

• Compressive Modulus: Ranges from 1 kPa (soft, lightly crosslinked gels) to 500 kPa (densely crosslinked networks), measured via unconfined compression testing at 10% strain718.
• Tensile Strength: Typically 0.05–2.5 MPa for hydrogels containing 10–20 wt% polymer, with elongation at break of 50–300%716.
• Viscoelastic Behavior: Dynamic mechanical analysis reveals storage moduli (G') of 100–10,000 Pa and loss moduli (G'') of 10–1,000 Pa at 1 Hz, indicating predominantly elastic character (G' > G'')418.

POSS-crosslinked PEI hydrogels demonstrate superior mechanical stability, retaining >90% of initial compressive strength after 1000 loading cycles (10% strain, 1 Hz), compared to 60–70% retention for epichlorohydrin-crosslinked analogs7.

Thermal And Chemical Stability

Crosslinked PEI hydrogels exhibit enhanced thermal stability compared to linear PEI, with degradation temperatures (Td, 5% weight loss) of 250–380°C depending on crosslinker type79. Chemical stability in acidic (pH 2–4) and neutral (pH 6–8) aqueous media is excellent, with <5% mass loss over 30 days at 37°C212. However, prolonged exposure to strong bases (pH >12) or oxidizing agents (e.g., H₂O₂ >1 M) can induce hydrolytic or oxidative degradation of amine groups and crosslinks35.

Biocompatibility And Cytotoxicity

The biocompatibility of PEI hydrogels is critically dependent on crosslink density and residual unreacted PEI content210. Highly crosslinked gels (>10 mol% crosslinker) with minimal leachable PEI (<1 wt%) exhibit cell viabilities >80% in MTT assays with fibroblasts and endothelial cells over 72 hours24. Conversely, loosely crosslinked or incompletely washed gels can release cytotoxic PEI oligomers, reducing viability to <50%2. Surface modification with polyethylene glycol (PEG) or zwitterionic groups significantly improves hemocompatibility, reducing hemolysis rates from 15–30% to <5%210.

Advanced Applications Of Crosslinked Polyethyleneimine Hydrogel In Biomedical Engineering

Tissue Engineering Scaffolds And Wound Healing

Crosslinked PEI hydrogels serve as three-dimensional scaffolds for cell culture and tissue regeneration due to their tunable porosity (pore sizes 10–200 μm), mechanical compliance matching soft tissues (E = 1–50 kPa), and capacity for bioactive molecule incorporation2418. PEI-PVA hydrogels with self-healing properties (healing efficiency 85–95% in 30 seconds) have been developed for dynamic wound dressings, where reversible imine and boronate ester bonds enable adaptation to tissue movement while maintaining structural integrity4. In vitro studies demonstrate that these hydrogels support fibroblast proliferation (cell density increasing 3–5 fold over 7 days) and collagen deposition (>50 μg/cm² after 14 days), critical for wound closure4.

Injectable PEI-gelatin granular hydrogels (particle size 20 nm–50 μm, volume fraction 2–100 v/v%) exhibit shear-thinning behavior (viscosity decreasing from 10⁴ to 10² Pa·s at shear rates 0.1–100 s⁻¹), enabling minimally invasive delivery via syringe (18–22 gauge needles)18. Post-injection, these materials undergo in situ covalent crosslinking within 5–15 minutes, forming mechanically robust scaffolds (compressive modulus 10–200 kPa) that conform to irregular tissue defects18. Subcutaneous implantation in rat models shows minimal inflammatory response (inflammatory cell infiltration <10% of implant area after 14 days) and gradual biodegradation over 4–8 weeks, with tissue integration scores of 4.2/5.0 at 28 days18.

Drug Delivery Systems And Controlled Release

The cationic nature and pH-responsive swelling of PEI hydrogels enable electrostatic loading and controlled release of anionic drugs, proteins, and nucleic acids1215. Doxorubicin-loaded PEI hydrogels (drug loading 5–15 wt%) exhibit biphasic release profiles: an initial burst release of 20–30% within 6 hours at pH 7.4, followed by sustained release over 72–120 hours, with cumulative release reaching 70–85%2. At acidic pH (5.5–6.0, mimicking tumor microenvironments), release rates increase by 40–60% due to enhanced gel swelling and protonation-induced electrostatic repulsion12.

For gene delivery, PEI hydrogels crosslinked with photopolymerizable groups or bifunctional linkers form polyplexes with plasmid DNA or siRNA (N/P ratio 5–20), protecting nucleic acids from enzymatic degradation while facilitating cellular uptake15. Transfection efficiencies of 30–50% in HEK293 and HeLa cells have been reported, with gene expression sustained for 5–10 days post-transfection15. The hydrogel matrix provides spatial control over gene delivery, enabling localized transfection in 3D cell cultures and tissue engineering constructs15.

Surgical Sealants And Adhesives

PEI-based hydrogels functionalized with reactive electrophilic groups (e.g., N-hydroxysuccinimide esters, isocyanates) rapidly crosslink with tissue proteins upon contact, forming strong adhesive bonds (lap shear strength 10–40 kPa on porcine skin)210. A two-component system comprising PEI-NHS ester and PEG-amine achieves gelation within 10–30 seconds, with burst pressure resistance of 80–150 mmHg, suitable for sealing dural, pleural, and ophthalmic wounds210. In vivo studies in rabbit dural defect models demonstrate 100% leak prevention over 28 days, with adhesive degradation synchronized with tissue healing (complete resorption by 8–12 weeks)2.

Amino-acid-based polyamine crosslinkers (e.g., lysine derivatives) have been developed to enhance biocompatibility and reduce inflammatory responses compared to synthetic PEG-based systems10. These formulations exhibit adhesive strengths of 15–30 kPa and support fibroblast migration across the adhesive-tissue interface, promoting seamless integration10.

Environmental And Industrial Applications Of Crosslinked Polyethyleneimine Hydrogel

CO₂ Capture And Gas Separation

Crosslinked PEI hydrogels demonstrate exceptional CO₂ adsorption capacities (1.5–3.5 mmol CO₂/g gel at 400 ppm CO₂, 25°C, 60% RH) due to the high density of amine groups that react with CO