Ultrastretchable,Super Tough,and Rapidly Recoverable Nanocomposite Double‐Network Hydrogels by Dual Physically Hydrogen Bond and Vinyl‐Functionalized Silica Nanoparticles Macro‐Crosslinking

It remains a challenge to develop tough hydrogels with recoverable or healable properties after damage. Herein, a new nanocomposite double‐network hydrogel (NC‐DN) consisting of first agar network and a homogeneous vinyl‐functionalized silica nanoparticles (VSNPs) macro‐crosslinked polyacrylamide (PAM) second network is reported. VSNPs are prepared via sol‐gel process using vinyltriethoxysilane as a silicon source. Then, Agar/PAM‐SiO₂ NC‐DN hydrogels are fabricated by dual physically hydrogen bonds and VSNPs macro‐crosslinking. Under deformation, the reversible hydrogen bonds in agar network and PAM nanocomposite network successively break to dissipate energy and then recombine to recover the network, while VSNPs in the second network could effectively transfer stress to the network chains grafted on their surfaces and maintain the gel network. As a result, the optimal NC‐DN hydrogels exhibit ultrastretchable (fracture strain 7822%), super tough (fracture toughness 18.22 MJ m^‐3, tensile strength 431 kPa), rapidly recoverable (≈92% toughness recovery after 5 min resting at room temperature), and self‐healable (can be stretched to 1331% after healing) properties. The newly designed Agar/PAM‐SiO₂ NC‐DN hydrogels with tunable network structure and mechanical properties by multi‐bond crosslinking provide a new avenue to better understand the fundamental structure‐property relationship of DN hydrogels and broaden the current hydrogel research and applications.     

Composite double network hydrogels with thermoresponsive colloidal nanoemulsions

We report the formulation and mechanical characterization of double network (DN) composite hydrogels. The first network consists of covalently crosslinked poly(ethylene glycol diacrylate) (PEGDA), which forms a strong, brittle network that provides elasticity to the gel. The second network, sodium alginate, is ionically crosslinked with Ca²⁺ to allow increased dissipation of mechanical energy. The novelty of this system over existing DN hydrogels is the additional incorporation of a third mesoscale network, composed of thermoresponsive poly(dimethyl siloxane) (PDMS) nanoemulsions, which undergo colloidal gelation through the bridging of the PEGDA hydrophobic end groups into the PDMS droplets. The colloidally gelled microstructures are photopolymerized into a solid hydrogel by crosslinking the precursors with ultraviolet (UV) light. Tensile mechanical experiments performed on the crosslinked DN nanoemulsion hydrogels show that their rupture stress (0.17–0.34 MPa), fracture energy (144–421 J/m²), and Young's modulus (1–2.1 MPa) are comparable to similar systems in the literature. These mechanical measurements suggest that the gels may be suitable for manufacturing processes in which large shear rates and deformations are encountered.     

Tough and recoverable triple‐network hydrogels based on multiple pairs of toughing mechanisms with excellent ionic conductivity as stable strain sensors

The emerging applications of hydrogels in flexible devices require it possess multifunctional properties including stable mechanical and functions under various deformations or external environments. Herein, a multifunctional polyvinyl alcohol/M‐alginate/PAM hydrogel with very excellent mechanical properties and sensing functions was fabricated by introducing multiple pairs of toughing mechanisms into triple network (TN). The multiple supramolecular physical networks work as sacrificial networks to toughen the materials when hydrogel deforms. The broken bonds can reform upon unloading endowing the recovery of hydrogels' properties and functions with the assistance of the elastic covalent network. The optimal TN hydrogels are extremely tough (a fracture strength of 512 kPa, a fracture toughness of 3 MJ/m³) and recoverable from fatigue damage (~77% toughness recovery after 5 min resting at room temperature). The presence of abundant ionic species endows the tough and recoverable TN hydrogels high ionic conductivity and high sensitivity as strain sensors. Moreover, such TN hydrogels with multi‐bond crosslinking in three networks can potentially guarantee stable mechanical and sensor functions under various deformations or external environments compared to the DN candidates. This work provides a simple strategy for fabricating multifunctional hydrogels with high stability to fulfill its flexible devices applications. POLYM. ENG. SCI., 59:1657–1666 2019. © 2019 Society of Plastics Engineers     

A Dual‐Crosslinked Strategy to Construct Physical Hydrogels with High Strength,Toughness, Good Mechanical Recoverability,and Shape‐Memory Ability

A novel type of physical hydrogel based on dual‐crosslinked strategy is successfully synthesized by micellar copolymerization of stearyl methacrylate, acrylamide, and acrylic acid, and subsequent introduction of Fe³⁺. Strong hydrophobic associations among poly(stearyl methacrylate) blocks form the first crosslinking point and ionic coordination bonds between carboxyl groups and Fe³⁺ serve as the second crosslinking point. The mechanical properties of the hydrogel can be tuned in a wide range by controlling the densities of two crosslinks. The optimal hydrogel shows excellent mechanical properties (tensile strength of ≈6.8 MPa, elastic modulus of ≈8.0 MPa, elongation of ≈1000%, toughness of 53 MJ m^?3) and good self‐recovery property. Furthermore, owing to stimuli responsiveness of physical interaction, this hydrogel also shows a triple shape memory effect. The combination of two different physical interactions in a single network provides a general strategy for designing of high‐strength hydrogels with functionalities.     

Agar/PAAc-Fe<Superscript>3+</Superscript> hydrogels with pH-sensitivity and high toughness using dual physical cross-linking

As promising structural materials, various tough hydrogels have been developed recently by incorporating various kinds of bonds. An important challenge is to use dual physical cross-linking to develop both toughness and self-recovery in a single material. Here we report smart, strain-responsive hydrogels composed of a fully physically linked agarose/poly(acrylic acid)-ferric ion (agar/PAAc-Fe³⁺) double network (DN) with high toughness and pH-sensitivity. These hydrogels were fabricated in a one-pot reaction to generate dual physical cross-linking through, first, a hydrogen-bonded cross-linked agarose network, and, second, a physically linked PAAc-Fe³⁺ network via Fe³⁺ coordination interactions. The DN hydrogels possessed high toughness, with breaking strain of 1130%, fast self-recovery properties in ambient conditions (100% recovery in 30 min) and self-healing properties (the healed hydrogels can be manually stretched up to 700% of their original length after self-healing for 60 h from the cut-off state). In addition, the hydrogels exhibited pH-sensitivity due to the dissociation of ionic coordinate bonds between –COO^? ions of the PAAc chains and Fe³⁺ ions. Double-layer hydrogel strips with two different concentrations of PAAc formed a “C”-shaped material when initially immersed in pH 7 solution and then soaked in a pH 3 solution. These characteristics make the hydrogels attractive candidates for tissue engineering, soft actuators and flexible electronics.     

A novel designed high strength and thermoresponsive double network hydrogels cross-linked by starch-based microspheres

A new kind of nanocomposite double network (DN) hydrogels consisting of starch-based microspheres cross-linked oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) as soft network and diethylene glycol dimethacrylate (DEGMA) cross-linked poly(2-(2-methoxyethoxy) ethyl methacrylate (PMEO₂MA) as brittle network (named POEGMA/PMEO₂MA DN hydrogels) were synthesized by a two-step free radical polymerization. The chemical structure of DN hydrogels was characterized by ¹H NMR, the temperature sensitive properties were measured by the lower critical solution temperature (LCST) tested by UV-Vis spectrophotometer as a function of temperature, the mechanical properties were measured by tensile test. The LCST showed only one transition at 20.2 °C measured by the transmittance variation as a function of the ambient temperature from 5 to 70 °C. The fracture toughness and the hysteresis behaviors were also tested and showed that they were affected by the content of starch-based microspheres cross-linker in the soft POEGMA network, the content of small-molecular cross-linkers and monomer concentration in the brittle PMEO₂MA network. They are related to perfect network and physical adherence and entanglements between microspheres and the networks brought by AAS microspheres, the increment of “sacrifice bond” brought by DEGMA and polymer chains entanglement brought by MEO₂MA. These studies will provide theoretical support for the future research of DN hydrogel and macromolecular microspheres cross-linked hydrogel.     

Highly stretchable,tough, and self‐recoverable and self‐healable dual physically crosslinked hydrogels with synergistic “soft and hard” networks

Strength, toughness and self‐recoverability are among the most important properties of hydrogels for tissue‐engineering applications. Yet, it remains a challenge to achieve these desired properties from the synthesis of a single‐polymer hydrogel. Here, we report our one‐pot, a monomer‐polymerization approach to addressing the challenge by creating dual physically crosslinked hybrid networks, in particular, synergistic “soft and hard” polyacrylic acid‐Fe³⁺ hydrogels (SHPAAc‐Fe³⁺). Favorable mechanical properties achieved from such SHPAAc‐Fe³⁺ hydrogels included high tensile strength (about 1.08 MPa), large elongation at break (about 38 times), excellent work of extension (about 19 MJ m^?3), and full self‐recoverability (100% recovery of initial properties within 15 min at 50°C and within 60 min in ambient conditions, respectively). In addition, the hydrogels exhibited good self‐healing capabilities at ambient conditions (about 40% tensile strength recovery without any external stimuli). This work demonstrates that dual physical crosslinking combining hydrophobic interaction and ionic association can be achieved in single‐polymer hydrogels with significantly improved mechanical performance but without sacrificing favorable properties. POLYM. ENG. SCI., 59:145–154, 2019. © 2018 Society of Plastics Engineers     

Dual-responsive shape memory hydrogels with self-healing and dual-responsive swelling behaviors

Shape memory hydrogels (SMHs) can fix the hydrogels in a provisional shape and restore the initial shape under external stimulation. Herein, a dual-responsive shape memory hydrogel with dual-responsive swelling and self-healing properties is presented in this work. The SMHs were fabricated by one-step emulsion copolymerization of acrylic acid (AAc), acrylamide (AAm) and stearyl methacrylate (SMA). Sodium alginate (SA) was introduced as an interpenetrating polymer in the network. With ionic cross-linking between -COO⁻ and Fe³⁺ or saline-reinforced hydrophobic association, the hydrogels can be fixed in a provisional shape, which can be restored by immersing the hydrogels in vitamin C solution or pure water, respectively. When the as-prepared hydrogels were immersed in FeCl₃ solutions, additional ionic cross-linking between Fe³⁺ and -COO⁻ could be formed, thus constructing the dual physically cross-linked (DPC) network, which endows the hydrogels with excellent fracture stress (2.6 MPa) and toughness (5.47 MJ/m³). Besides, the reversible physical cross-linkings endowed the hydrogel with outstanding self-healing capability. Furthermore, the pH and saline responsive swelling properties of the SMHs are additional fantastic properties. Therefore, we believe that this simple strategy provides a great opportunity for the preparation of SMHs with multiple intellectual performances.     

Dual Cross‐Linked Hydrogels with High Strength,Toughness, and Rapid Self‐Recovery Using Dynamic Metal–Ligand Interactions

A dual cross‐linking design principle enables access to hydrogels with high strength, toughness, fast self‐recovery, and robust fatigue resistant properties. Imidazole (IMZ) containing random poly(acrylamide‐co‐vinylimidazole) based hydrogels are synthesized in the presence of Ni²⁺ ions with low density of chemical cross‐linking. The IMZ‐Ni²⁺ metal–ligand cross‐links act as sacrificial motifs to effectively dissipate energy during mechanical loading of the hydrogel. The hydrogel mechanical properties can be tuned by varying the mol% of vinylimidazole (VIMZ) in the copolymer and by changing the VIMZ/Ni²⁺ ratio. The resultant metallogels under optimal conditions (15 mol% VIMZ and VIMZ/Ni²⁺ = 2:1) show the best mechanical properties such as high tensile strength (750 kPa) and elastic modulus (190 kPa), combined with high fracture energy (1580 J m^?2) and stretchability (800–900% strain). The hydrogels are pH responsive and the extent of energy dissipation can be drastically reduced by exposure to acidic pH. These hydrogels also exhibit excellent anti‐fatigue properties (complete recovery of dissipated energy within 10 min after ten successive loading–unloading cycles at 400% strain), high compressive strength without fracture (17 MPa at 96% strain), and self‐healing capability due to the reversible dissociation and re‐association of the metal ion mediated cross‐links.     

Dual‐Crosslinking of Hyaluronic Acid–Calcium Phosphate Nanocomposite Hydrogels for Enhanced Mechanical Properties and Biological Performance

Herein, a facile approach for synthesizing mechanically enhanced nanocomposite hydrogels via a dual‐crosslinking process is described. Additional ionic crosslinking using various cations is introduced after an in situ precipitation process for hydroxyapatite immobilization in hyaluronic acid hydrogels (HAc–CaP). Ca²⁺, Ba²⁺, and Sr²⁺ ions exhibit the highest efficiencies in reinforcing the mechanical properties of HAc–CaP hydrogels. In addition, the dual‐crosslinked HAc–CaP hydrogels promote the biological responses of preosteoblast cells, which exhibit highly stretched shapes and greatly enhanced proliferation. Furthermore, the nanocomposite hydrogels achieve enhanced bioactivity by supporting osteogenic differentiation. Thus, enhancement on both the mechanical and biological properties of hyaluronic‐acid‐based nanocomposite hydrogels is achieved through this dual‐crosslinking process, extending the potential application of these materials to hard tissue engineering.     

Site‐Specific Oxidation‐Induced Stiffening and Shape Morphing of Soft Tough Hydrogels

Living biological tissues are made of structures with properly defined mechanical properties (toughness and stiffness) toward specific biological functions. Herein, a chemical manipulation strategy is developed to locally vary the oxidation state of Fe ions from divalent to trivalent in the tough hydrogels. The resultant trivalent ionically cross‐linked networks become less flexible and lead to a significant enhancement of the stiffness of the tough hydrogels. The mechanical strengthening of Fe²⁺/Ca²⁺‐alginate/polyacrylamide tough hydrogels is demonstrated by the oxidation with ammonium persulfate (APS). Moreover, by applying surface patterning, the mechanical properties of the tough hydrogels are spatially stiffened and thus can serve as anisotropic elements to guide the shape morphing of tough hydrogels into complex 3D structures. This method opens up a simple strategy not only to dynamically vary the mechanics of tough hydrogels, both in bulk and locally from prefabricated soft tough hydrogels, but also toward their shape morphing behaviors on demand.     

Preparation and characterization of PAM/SA tough hydrogels reinforced by IPN technique based on covalent/ionic crosslinking

In order to fabricate tough hydrogels with superior formability, polyacrylamide/sodium alginate (PAM/SA) interpenetrating polymer network (IPN) hydrogels were produced with ionically crosslinked SA interpenetrated in covalently crosslinked PAM. TGA results show that the heat resistance of PAM/SA IPN hydrogel is improved as compared to that of the individual component. Swelling studies indicate that increasing either chemical crosslinker content or ionic crosslinking via adding more N,N′‐methylenebisacrylamide (MBA) or SA results in lower ESR. It is concluded by tensile test that loosely crosslinked PAM coupled with tightly crosslinked SA improve mechanical strength for hydrogels based on covalent/ionic crosslinking. PAM/SA hydrogels via “one‐pot” method can form different complex shapes with mechanical properties comparable to conventional double network (DN) gels. The fracture strength of PAM_0.05/SA₂₀ reaches level of MPa, approaching 2.0 MPa. The work strives to provide method to tune mechanical and physical properties for hydrogels, which is hopefully to guide the design of hydrogel material with desirable properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41342.     

Tough and Tear‐Resistant Double‐Network Hydrogels Based on a Facile Strategy: Micellar Polymerization Followed by Solution Polymerization

How to prepare a hydrogel with high strength and excellent tearing fracture energy is a problem faced by researchers. Here, tough and tear‐resistant double‐network hydrogels (Cx‐SMy gels) are successfully prepared via a facile strategy: micellar polymerization followed by solution polymerization. The strength and fracture energy of these hydrogels are up to 13 MPa and 26500 J m^?2, respectively, which are attributed to the synergy of quatra‐crosslinking interactions inside the double‐network. The quatra‐crosslinking interactions include hydrophobic interaction, crystallization, electrostatic attraction, and hydrogen bonding. Moreover, it is confirmed that the facile strategy is a general way to prepare tough hydrogels by using electrolytic monomers and hydrophobic acrylates.     

Synthesis and properties of self-healing hydrogel plugging agent

The P(AM-co-AMPS)/SA DN hydrogel was synthesized through aqueous polymerization in this study. It formed a crosslinking network with hydrophobic associations between acrylamide (AM) and lauryl methacrylate (LMA), as well as an ionic bond network involving sodium alginate and Ca²⁺. To enhance its high-temperature resistance, 2-acrylamide-2-methylpropane sulfonic acid (AMPS) was incorporated into the hydrogel formulation. The structure of the hydrogel was characterized using Fourier transform infrared spectrometer (FTIR), thermogravimetric analyzer (TGA), and scanning electron microscopy (SEM) techniques. Results demonstrated that the hydrogel exhibited excellent temperature resistance and possessed a porous structure. Mechanical testing revealed a high tensile strength of 110 kPa, elongation at break of 995.31%, along with good fatigue resistance and self-recovery performance during multiple cyclic stretching. Healing experiments indicated that the healing strength of the hydrogel was influenced by temperature variations. Furthermore, pressure plugging tests were conducted on steel models with crack widths of 0.5 and 1 mm, respectively; it was found that the 0.8%P(AM-co-AMPS)/SA DN hydrogel could withstand pressures up to 4.5 MPa at a temperature of 70°C. This novel hydrogel material exhibits remarkable mechanical properties along with certain self-healing capabilities, making it suitable for leak control applications.     

A Dual Physical Cross-Linking Strategy to Construct Tough Hydrogels with High Strength,Excellent Fatigue Resistance,and Stretching-Induced Strengthening Effect

Hydrogels with excellent stiffness, toughness, anti-fatigue, and self-recovery properties are regarded as promising water-containing materials. In this work, a dual physically cross-linked (DPC) sodium alginate (SA)/poly[acrylamide (AAm)-acrylic acid (AAc)-octadecyl methacrylate (OMA)]-Fe³⁺ hydrogel is reported, which is constructed by hydrophobic association (HA) and ionic coordination (IC). The optimal DPC hydrogel demonstrates excellent mechanical performance: tensile modulus of 0.65 MPa, tensile strength of 3.31 MPa, elongation at break of 1547%, and toughness of 27.8 MJ m^–3. SA/P(AAm-AAc-OMA)-Fe³⁺ DPC hydrogels also exhibit prominent anti-fatigue and self-recovery performance (99.1–109.7% modulus recovery and 90.4–108.9% dissipated energy recovery after resting for 5 min without additional stimuli at ambient temperature) through the reconstruction of reversible physical cross-linking. Some of the SA/P(AAm-AAc-OMA)-Fe³⁺ DPC hydrogels even exhibit a stretching-induced strengthening effect, which is similar to the performance of muscle—“the more training, the more strength.” Hence, the combination of HA and IC will provide an effective approach to design DPC hydrogels with desirable mechanical performances and a longer service life for wider applications of soft materials.     

High strength and toughness of double physically cross-linked hydrogels composed of polyvinyl alcohol and calcium alginate

The weak mechanical properties of hydrogels, especially physically cross-linked hydrogels are usually a major factor to hinder their application. To solve this problem, in this work, we prepared a high strength and toughness of double physically cross-linked (PDN) hydrogels composed of crystalline domain cross-linked polyvinyl alcohol (PVA) and Ca²⁺-cross-linked alginate (Alg). With a further annealing treatment, the noncovalent cross-linked network via the formed crystalline promote the as-prepared PDN PVA/Alg hydrogel to exhibit well mechanical properties with the tensile strength of ~1.94 MPa, elongation at break of ~607% and Young's modulus of ~0.45 MPa (above 70 wt% of water content). By analyzing the mechanism of improving the hydrogel mechanical properties, it is found that annealing can effectively improve the crystallinity of PVA in the hydrogel, and then greatly improve the mechanical properties of the hydrogel. This provides a general method for improving the mechanical properties of PVA PDN hydrogels. In addition, the PDN PVA/Alg hydrogel was also proved to have good ionic conductivity of 1.70 S m⁻¹. These desirable properties make the prepared physically cross-linked hydrogels promising materials for medical and biosensing fields.     

Facile preparation and characterization of sodium alginate/graphite conductive composite hydrogel

Conductive composite hydrogels based on sodium alginate (SA) and graphite were fabricated by a facile method via dispersing homogeneously conductive graphite into SA hydrogel matrix. The hydrogel was formed by in situ release of Ca²⁺ from Ca–EDTA, thus eliminating the multistep reactions and tedious purification compared to the previous work. Raman spectra, scanning electron microscopy (SEM), X‐ray diffraction (XRD), and thermogravimetric analysis (TGA) were used to characterize the structure, crystalline nature, and thermostability of SA/graphite composite hydrogels. The SA/graphite composite hydrogels exhibited the improved network and layer‐type structure. The thermal stability of the hydrogel decreased slightly after the graphite was incorporated into the SA hydrogel matrix regardless of the content of graphite. The enhanced mechanical strength of SA/graphite composite hydrogel was achieved via increasing the f value (i.e., [Ca²⁺]/[COO^‐ in alginate]) and lowering graphite content. The conductivity of the composite hydrogels could be varied in a broad range, reaching up to 10⁻³ S/cm, mainly depending on the content of graphite and the f value. POLYM. COMPOS., 37:3050–3056, 2016. © 2015 Society of Plastics Engineers     

Mechanical and Rheological Behavior of Hybrid Cross‐Linked Polyacrylamide/Cationic Micelle Hydrogels

In this work, a hybrid cross‐linked polyacrylamide (PAM)/cationic micelle hydrogel is fabricated by introducing the cationic micelles into the chemically cross‐linked PAM network. The cationic micelles act as the physical cross‐linking points through the strong electrostatic interaction with anionic initiator potassium persulfate. Thereafter, in situ free radical polymerization is initiated thermally from the cationic micelle surface to form the hybrid cross‐linked network. The synergistic effect between chemical and physical cross‐link endows the hydrogel with excellent mechanical and recoverable properties. The resulting hydrogel exhibits tensile stress of 481 kPa and fracture toughness of 1.65 MJ m⁻³. It is found that the chemical cross‐linking can inhibit the hysteresis of the hybrid hydrogel, exhibiting good elasticity in the tensile loading–unloading test. Moreover, dynamic rheological measurements show that the hybrid hydrogels possess fewer defects of network and exhibit excellent self‐recovery behavior. Thus, this investigation provides a different view for the design of new high elastic and tough hydrogels containing hybrid physical and chemical cross‐linking networks.     

Controlled mechanical and swelling properties of poly(vinyl alcohol)/sodium alginate blend hydrogels prepared by freeze–thaw followed by Ca2+ crosslinking

Poly(vinyl alcohol) (PVA)/sodium alginate (SA) blend hydrogels have immense potential for use as functional biomaterials. Understanding of influences of processing parameters and compositions on mechanical and swelling properties of PVA/SA blend hydrogels is very important. In this work, PVA/SA blend hydrogels with different SA contents were prepared by applying freeze–thaw method first to induce physical crosslinking of PVA chains and then followed by Ca²⁺ crosslinking SA chains to form interpenetrating networks of PVA and SA. The effects of number of freeze–thaw cycles, SA content and Ca²⁺ concentration on mechanical properties, swelling kinetics, and pH‐sensitivity of the blend hydrogels were investigated. The results showed that the blend hydrogels have porous sponge structure. Gel fraction, which is related to crosslink density of the blend hydrogels, increased with the increase of freeze–thaw cycles and strongly depended on SA content. The SA content exerts a significant effect on mechanical properties, swelling kinetics, and pH‐sensitivity of the blend hydrogels. The number of freeze–thaw cycles has marked impact on mechanical properties, but no obvious effect on the pH‐sensitivity of the PVA/SA blend hydrogels. Concentration of CaCl₂ aqueous solution also influences mechanical properties and pH‐sensitivity of the blend hydrogel. By altering composition and processing parameters such as freeze–thaw cycles and concentration of CaCl₂ aqueous solution, the mechanical properties and pH‐sensitivity of PVA/SA blend hydrogels can be tightly controlled. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Construction and evaluation of the hydroxypropyl methyl cellulose-sodium alginate composite hydrogel system for sustained drug release

We prepared a hydroxypropyl methyl cellulose-sodium alginate (HPMC-SA) composite hydrogel with a membrane covering the semi-interpenetrating network based on a semi-synthetic polymer hydroxypropyl methyl cellulose (HPMC) and a natural polymer sodium alginate (SA) by Ca²⁺ crosslinking and polyelectrolyte complexation with chitosan (CS) covering the hydrogel surface. The physiochemical properties of HPMC-SA hydrogels were evaluated by scanning electron microscopy, infrared spectrum, X-ray diffraction, and thermogravimetric analysis. The swelling ratio of the HPMC-SA composite hydrogel in simulated gastrointestinal fluid was measured. The drug release behavior of the HPMC-SA composite hydrogel for macro-molecular and small-molecule drugs was evaluated by using bovine serum albumin, metformin hydrochloride, and indomethacin as model drugs. The results showed that the HPMC-SA hydrogel had good water absorption and degradability, an increased swelling ratio of 55, and a prolonged time for maximum swelling degree of 50 h. Moreover, the hydrogel exhibited higher drug-loading capacity and improvements in the sustained release of bio-macromolecules, demonstrating its potential as a drug carrier for biomedical applications.