Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

High elasticity,strength, and biocompatible amphiphilic hydrogel via click chemistry and ferric ion coordination

An amphiphilic interpenetrating polymer network hydrogel was designed and synthesized using click chemistry and ferric ion coordination. The first polymer network was formed through the reaction of azide‐modified PEG (N₃‐PEG_n‐N₃) and alkynyl‐pendant linear PPG derivatives ((PPG_m(C≡CH))_n) through click chemistry and mixed with poly(ethylene glycol‐dopamine) macromolecules. The second polymer network was formed through ferric ion coordination with poly(ethylene glycol‐dopamine). Interpenetrating polymer networks give the hydrogel unique amphiphilic properties and higher mechanical strength and thermal stability. Swelling ratio and degradation rate could be adjusted by controlling the ratio of poly(ethylene glycol‐dopamine) in the hydrogel network. Given that in vivo subcutaneous implantation revealed no infection and no obvious abnormalities, the hydrogel exhibits high biocompatibility. The feature indicates that these hydrogels have a promising application in the field of biomaterials and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.     

Autoinducer Sensing Microarrays by Reporter Bacteria Encapsulated in Hybrid Supramolecular‐Polysaccharide Hydrogels

A generally applicable strategy to obtain mechanically robust hydrogels for the incorporation and containment of functional reporter bacteria for the microarray and microparticle‐based detection and signaling of N‐acyl homoserine lactone autoinducers (3OC₁₂HSL) at relevant concentrations is reported. For reinforcing hydrogels of 1,4‐bi(phenylalanine‐diglycol)‐benzene (PDB), a hybrid hydrogel is formed by the combination of PDB self‐assembly with Ca²⁺ mediated alginate crosslinking. The different assembly mechanisms are shown not to interfere with each other and despite the more than four‐fold increased moduli of the hydrogels, diffusion of autoinducers into the gels remains efficient and Escherichia coli pLuxR‐green fluorescent protein (GFP) reporter bacteria are proliferating. Templating affords reporter bacteria‐loaded hydrogels with controllable shape and size. Upon exposure to 3OC₁₂HSL, the embedded bacteria exhibit an up to 12 ± 3 times increase in fluorescence intensity due to autoinducer‐triggered GFP expression. This approach can serve as a potentially generally applicable strategy to sensitively detect bacteria via their secreted autoinducers.     

Antimicrobial loading into and release from poly(ethylene glycol)/poly(acrylic acid) semi‐interpenetrating hydrogels

Electrostatic interactions within a semi‐interpenetrating network (semi‐IPN) gel can control the postsynthesis loading, long‐term retention, and subsequent release of small‐molecule cationic antibiotics. Here, electrostatic charge is introduced into an otherwise neutral gel [poly(ethylene glycol) (PEG)] by physically entrapping high‐molecular‐weight poly(acrylic acid) (PAA). The network structure is characterized by small‐angle neutron scattering. PEG/PAA semi‐IPN gels absorb over 40 times more antibiotic than PAA‐free PEG gels. Subsequent soaking in physiological buffer (pH 7.4; 0.15 M NaCl) releases the loaded antibiotics for periods as long as 30 days. The loaded gels elute antibiotics with diffusivities of 4.46 × 10^?8 cm²/s (amikacin) and 2.08 × 10^?8 cm²/s (colistin), which are two orders of magnitude less than those in pure PEG gels where diffusion is controlled purely by gel tortuosity. The release and hindered diffusion can be understood based on the partial shielding of the charged groups within the loaded gel, and they have a significant effect on the antimicrobial properties of these gels. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 64–72     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

Temperature and pH-Sensitive Polymers with Hydrophobic Spacers for the Controlled Delivery of Drugs

Summary: Acid methacrylates containing hydrophobic aliphatic and aromatic spacers were used to prepare pH-sensitive ampholytic hydrogels and bidimensional temperature- (T) and pH-sensitive hydrogels. Their swelling behaviour was studied by changing the pH and temperature of buffer solutions. Salicylamide, salicylic acid and green fluorescent protein (GFP) as model drugs were loaded into the gels and their release kinetics studied under simulated gastric and intestinal conditions. T- and pH-sensitive hydrogels containing aliphatic spacers show sustained release of analgesics depending on pH (e.g. 7.4); while longer aliphatic spacers resulted in drug release depending on pH and temperature (T < transition T). GFP was released from temperature- and pH-sensitive ampholytic hydrogels after different lag times depending on hydrogel composition.     

Preparation of interpenetrating polymer network composed of poly(ethylene glycol) and poly(acrylamide) hydrogels as a support of enzyme immobilization

Poly(ethylene glycol)(PEG)‐based interpenetrating polymeric network (IPN) hydrogels were prepared for the application of enzyme immobilization. Poly(acrylamide)(PAAm) was chosen as the other network of IPN hydrogel and different concentration of PAAm networks were incorporated inside the PEG hydrogel to improve the mechanical strength and provide functional groups that covalently bind the enzyme. Formation of IPN hydrogels was confirmed by observing the weight per cent gain of hydrogel after incorporation of PAAm network and by attenuated total reflectance/Fourier transform infrared (ATR/FTIR) analysis. Synthesis of IPN hydrogels with higher PAAm content produced more crosslinked hydrogels with lower water content (WC), smaller M_c and mesh size, which resulted in enhanced mechanical properties compared to the PEG hydrogel. The IPN hydrogels exhibited tensile strength between 0.2 and 1.2 MPa while retaining high levels of hydration (70–81% water). For enzyme immobilization, glucose oxidase (GOX) was immobilized to PEG and IPN hydrogel beads. Enzyme activity studies revealed that although all the hydrogels initially had similar enzymatic activity, enzyme‐immobilizing PEG hydrogels lost most of the enzymatic activity within 2 days due to enzyme leaching while IPN hydrogels maintained a maximum 80% of the initial enzymatic activity over a week due to the covalent linkage between the enzyme and amine groups of PAAm. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and On‐Demand Gelation of Multifunctional Poly(ethylene glycol)‐Based Polymers

The synthesis of a novel photoreactive poly(ethylene glycol) (PEG)‐based polymer with caged carbonyl groups is reported. We further demonstrate its use for the on‐demand fabrication of hydrogels. For rapid gelation, a hydrazide‐functionalized PEG is used as the second component for the hydrogel preparation. The photoreactive PEG‐based polymer is designed for controlled cleavage of the protecting groups upon exposure to UV light releases free aldehyde moieties, which readily react with hydrazide groups in situ. This hydrogel system may find applications in controlled release drug delivery applications, when combined with in situ gelation. Furthermore, the possibility of forming gels specifically upon UV irradiation gives an opportunity for 3D fabrication of degradable scaffolds.

     

Glucose‐Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery

Effective delivery of therapeutic proteins is important for many biomedical applications. Yet, the stabilization of proteins during delivery and long‐term storage remains a significant challenge. Herein, a trehalose‐based hydrogel is reported that stabilizes insulin to elevated temperatures prior to glucose‐triggered release. The hydrogel is synthesized using a polymer with trehalose side chains and a phenylboronic acid end‐functionalized 8‐arm poly(ethylene glycol) (PEG). The hydroxyls of the trehalose side chains form boronate ester linkages with the PEG boronic acid cross‐linker to yield hydrogels without any further modification of the original trehalose polymer. Dissolution of the hydrogel is triggered upon addition of glucose as a stronger binder to boronic acid (K_b = 2.57 vs 0.48 m ⁻¹ for trehalose), allowing the insulin that is entrapped during gelation to be released in a glucose‐responsive manner. Moreover, the trehalose hydrogel stabilizes the insulin as determined by immunobinding after heating up to 90 °C. After 30 min heating, 74% of insulin is detected by enzyme‐linked immunosorbent assay in the presence of the trehalose hydrogel, whereas only 2% is detected without any additives.     

Poly(N-isopropylacrylamide-co-N-t-butylacrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropylacrylamide-co-N-t-butylacrylamide) triblock copolymers: synthesis and thermogelation properties of aqueous solutions

Novel triblock copolymers with PEG middle blocks of 1–10 kDa and poly(N-isopropylacrylamide-co-t-butylacrylamide) statistical copolymer side arms with DP_n?≈?88 and different compositions, were synthesized by SET-LRP. The thermogelation properties of their aqueous solutions depended on both hydrophobic monomer content of the side blocks and molecular weight (MW) of the poly(ethylene glycol) (PEG) middle block, as proven by dynamic rheometry, DSC, and tube inversion method measurements. At constant PEG chain length, increasing TBAM proportions led to a gelation process occurring at progressively lower temperatures, as well as to a lower stability of the forming hydrogels in the case of shorter-PEG-chain block copolymers. By employing longer PEG blocks (M_PEG ≥6,000 Da), stable hydrogels with the gelation temperature below 37 °C could be obtained. For a constant composition of the copolyacrylamide blocks, the dependence of the phase transition temperature (T_ph) on M_PEG displayed a different shape at different polymer solution concentrations, because of the stronger variation of T_ph with polymer concentration as M_PEG increased. Also, the viscoelastic properties of the hydrogels resulting from 20 wt.% polymer aqueous solutions at 37 °C were stronger affected by the MW of the PEG middle block than by the hydrophobic character of the thermosensitive side blocks.     

Synthesis and characterization of novel biodegradable unsaturated poly(ester amide)/poly(ethylene glycol) diacrylate hydrogels

A series of novel biodegradable hydrogels were designed and synthesized from four types of unsaturated poly(ester amide) (UPEA) and poly(ethylene glycol) diacrylate (PEG‐DA) precursors by UV photocrosslinking. These newly synthesized biodegradable UPEA/PEG‐DA hydrogels were characterized by their gel fraction (G_f), equilibrium swelling ratio (Q_eq), compressive modulus, and interior morphology. The effect of the precursor feed ratio (UPEAs to PEG‐DA) on the properties of the hydrogels was also studied. The incorporation of UPEA polymers into the PEG‐DA hydrogels increased their hydrophobicity, crosslinking density (denser network), and mechanical strength (higher compressive modulus) but reduced Q_eq. When different types of UPEA precursors were coupled with PEG‐DA at the same feed ratio (20 wt %), the resulting hydrogels had similar Q_eq values and porous three‐dimensional interior morphologies but different G_f and compressive modulus values. These differences in the hydrogel properties were correlated to the chemical structures of the UPEA precursors; that is, the different locations of the >C?C< double bonds in individual UPEA segments resulted in their different reactivities toward PEG‐DA to form hydrogels. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3932–3944, 2005     

Synthesis and characterization of thermoresponsive poly(ethylene glycol)‐based hydrogels and their magnetic nanocomposites

Temperature‐responsive hydrogels are one of the most widely studied types of stimuli‐responsive hydrogel systems. Their ability to transition between their swollen and collapsed states makes them attractive for controlled drug delivery, microfluidic devices, and biosensor applications. Recent work has shown that poly(ethylene glycol) (PEG) methacrylate polymers are temperature‐responsive and exhibit a wide range of lower critical solution temperatures based on the length of ethylene glycol units in the macromer chain. The addition of iron oxide nanoparticles into the hydrogel matrix can provide the ability to remotely heat the gels upon exposure to an alternating magnetic field (AMF). In this work, diethylene glycol (n = 2) methyl ether methacrylate and PEG (n = 4.5) methyl ether methacrylate copolymers were polymerized into hydrogels with 5 mol % PEG 600 (n = 13.6) dimethacrylate as the crosslinker along with 5 wt % iron oxide nanoparticles. Volumetric swelling studies were completed from 22 to 80 °C and confirmed the temperature‐responsive nature of the hydrogel systems. The ability of the gels to collapse in response to rapid temperature changes when exposed to an AMF was demonstrated showing their potential use in biomedical applications such as controlled drug delivery and hyperthermia therapy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3229–3235, 2010     

Fabrication of poly(ethylene glycol)‐based hydrogels entrapping enzyme‐immobilized silica nanoparticles

In this study, we immobilized enzymes by combining covalent surface immobilization and hydrogel entrapment. A model enzyme, glucose oxidase (GOX), was first covalently immobilized on the surface of silica nanoparticles (SNPs) via 3‐aminopropyltriethoxysilane (APTES), and the resultant SNP‐immobilized enzyme was physically entrapped within photopolymerized hydrogels prepared from two different molecular weights (MWs) (575 and 8000 Da) of poly(ethylene glycol)(PEG). The hydrogel entrapment resulted in a decrease in reaction rate and an increase in apparent K_m of SNP‐immobilized GOX, but these negative effects could be minimized by using hydrogel with a higher MW PEG, which provides higher water content and larger mesh size. The catalytic rate of the PEG 8000 hydrogel was about ten times faster than that of the PEG 575 hydrogel because of enhanced mass transfer. Long‐term stability test demonstrated that SNP‐immobilized GOX entrapped within hydrogel maintained more than 60% of its initial activity after a week, whereas non‐entrapped SNP‐immobilized GOX and entrapped GOX without SNP immobilization maintained less than 20% of their initial activity. Incorporation of SNPs into hydrogel enhanced the mechanical strength of the hydrogel six‐fold relative to bare hydrogels. Finally, a hydrogel microarray entrapping SNP‐immobilized GOX was fabricated using photolithography and successfully used for quantitative glucose detection. Copyright © 2009 John Wiley & Sons, Ltd.     

Electrochemical characterization of hydrogels for biomimetic applications

Hydrogels are increasingly being recognized as having potential in bio‐compatible applications. In previous work, we investigated the feasibility of poly(ethylene glycol)‐dimethacrylate (PEG‐1000‐DMA) and poly(ethylene glycol)‐diacrylate (PEG‐400‐DA) polymerized using either a chemical initiator (C) or a photoinitiator (P) to encapsulate and stabilize biomimetic membranes for novel separation technologies or biosensor applications. In this paper, we have investigated the electrochemical properties of the hydrogels used for membrane encapsulation. Specifically, we studied the crosslinked hydrogels by using electrochemical impedance spectroscopy (EIS), and we demonstrated that chemically crosslinked hydrogels had lower values for the effective electrical resistance and higher values for the electrical capacitance compared with hydrogels with photoinitiated crosslinking. Transport numbers were obtained using electromotive force measurements and demonstrated that at low salt concentrations, both PEG‐400‐DA‐C and PEG‐400‐DA‐P hydrogels presented an electropositive character whereas PEG‐1000‐DMA‐P was approximately neutral and PEG‐1000‐DMA‐C showed electronegative character. Sodium transport numbers approached the bulk NaCl electrolyte value at high salt concentrations for all hydrogels, indicating screening of fixed charges in the hydrogels. The average salt diffusional permeability 〈P_s〉 and water permeability 〈P_w〉 were found to correlate with EIS results. Both PEG‐1000‐DMA‐C and PEG‐400‐DA‐C had higher 〈P_s〉 and 〈P_w〉 values than PEG‐1000‐DMA‐P and PEG‐400‐DA‐P hydrogels. In conclusion, our results show that hydrogel electrochemical properties can be controlled by the choice of polymer and type of crosslinking used and that their water and salt permeability properties are congruent with the use of hydrogels for biomimetic membrane encapsulation. Copyright © 2011 John Wiley & Sons, Ltd.     

Hydrogen‐Bonding Toughened Hydrogels and Emerging CO2‐Responsive Shape Memory Effect

A double hydrogen bonding (DHB) hydrogel is constructed by copolymerization of 2‐vinyl‐4,6‐diamino‐1,3,5‐triazine (hydrophobic hydrogen bonding monomer) and N,N‐dimethylacrylamide (hydrophilic hydrogen bonding monomer) with polyethylene glycol diacrylates. The DHB hydrogels demonstrate tunable robust mechanical properties by varying the ratio of hydrogen bonding monomer or crosslinker. Importantly, because of synergistic energy dissipating mechanism of strong diaminotriazine (DAT) hydrogen bonding and weak amide hydrogen bonding, the DHB hydrogels exhibit high toughness (up to 2.32 kJ m⁻²), meanwhile maintaining 0.7 MPa tensile strength, 130% elongation at break, and 8.3 MPa compressive strength. Moreover, rehydration can help to recover the mechanical properties of the cyclic loaded–unloaded gels. Attractively, the DHB hydrogels are responsive to CO₂ in water, and demonstrate unprecedented CO₂‐triggered shape memory behavior owing to the reversible destruction and reconstruction of DAT hydrogen bonding upon passing and degassing CO₂ without introducing external acid. The CO₂ triggering mechanism may point out a new approach to fabricate shape memory hydrogels.     

In Situ Assembly of Au Nanoclusters within Protein Hydrogel Networks

We report a new approach of in situ assembling gold nanoclusters (AuNCs) into hydrogel networks by exploiting the triple roles of protein as a gelator, a reducing agent as well as a template. The strategy simply involves the mixing of BSA and AuCl₄⁻ under alkaline condition. The obtained AuNCs‐protein nanocomposite hydrogels with injectable and moldable features can be made into semi‐transparent films or N‐doped C/Au composites. Our work demonstrates the feasibility of fabricating AuNCs in situ embedded in hybrid hydrogels, which can serve as multifunctional precursors for constructing diverse nanocomposite materials.     

Composite Hydrogels for Sustained Release of Therapeutic Agents

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hydrogel composites were prepared by embedding drug‐loaded, biodegradable poly (DL‐lactide‐co‐glycolide) (PLGA) microparticles in semicrystalline hydrogels of polyvinyl alcohol (PVA). The gels were physically cross‐linked by the formation of the crystallites. The presence of the crystallites and the composite nature of the structure were confirmed by using differential scanning calorimetry and ATR‐FTIR spectroscopy. The distribution of microparticles in the hydrogel matrix was evaluated by using confocal laser scanning microscopy with coumarin‐6 as a fluorescence marker. The numbers of particles in the hydrogel matrix increased along the scanning depth, indicating uneven distribution. The release behavior of a model therapeutic agent, hydrocortisone, was evaluated, and the hydrogel composite system provided for better control of release than the microparticles and hydrogels alone. The addition of outer layers of PVA to the original single‐layer composite further reduced the initial burst effect from the microparticles and allowed for a linear release profile for greater than 1 month.     

Highly Elastic Slide-Ring Hydrogel with Good Recovery as Stretchable Supercapacitor

As a new material with excellent mechanical properties and good stability, slide-ring gels have attracted attention and research. However, they cannot be widely used due to their relatively complicated synthesis. Herein, we use 6-acrylamidomethylether-modified α-cyclodextrin (αCDAAmMe) and PEG₂₀₀₀₀ diacrylate (PEG₂₀₀₀₀DA) to construct a polypseudorotaxane. Then, the polypseudorotaxane reacts with acrylamide via a photo-initiated polymerization in situ to conveniently obtain a slide-ring hydrogel with good elastic property and high recovery property. The hydrogel can be easily stretched to 22.5 times of its original length but recovered rapidly and almost reversibly. These results enable the application of hydrogel to make an intrinsically stretchable and compressible supercapacitor after doping ions and the adhesion of commercially available carbon nanotube (CNT) paper as electrodes, giving the ionic conductivity of 17.0 mS cm⁻¹ (comparable to that of the commercial PVA/H₃PO₄ electrolyte) and the capacitance of 0.87 μF cm⁻² (at the scan speed of 100 mV s⁻¹), and its capacitance can be further enhanced under stretching.     

An Injectable Self‐Healing Hydrogel Based on Chain‐Extended PEO‐PPO‐PEO Multiblock Copolymer

Injectable hydrogels have been commonly used as drug‐delivery vehicles and tried in tissue engineering. Injectable self‐healing hydrogels have great advantage over traditional injectable hydrogels because they can be injected as a liquid and then rapidly form bulk gels in situ at the target site under physiological conditions. This study develops an injectable thermosensitive self‐healing hydrogel based on chain‐extended F127 (PEO₉₀‐PPO₆₅‐PEO₉₀) multi‐block copolymer (m‐F127). The rapid sol–gel transition ability under body temperature allows it to be used as injectable hydrogel and the self‐healing property allows it to withstand repeated deformation and quickly recover its mechanical properties and structure through the dynamic covalent bonds. It is hoped that the novel strategy and the fascinating properties of the hydrogel as presented here will provide new opportunities with regard to the design and practical application of injectable self‐healing hydrogels.

     

Designing Visible Light‐Cured Thiol‐Acrylate Hydrogels for Studying the HIPPO Pathway Activation in Hepatocellular Carcinoma Cells

Various polymerization mechanisms have been developed to prepare peptide‐immobilized poly(ethylene glycol) (PEG) hydrogels, a class of biomaterials suitable for studying cell biology in vitro. Here, a visible light mediated thiol‐acrylate photopolymerization scheme is reported to synthesize dually degradable PEG‐peptide hydrogels with controllable crosslinking and degradability. The influence of immobilized monothiol pendant peptide is systematically evaluated on the crosslinking of these hydrogels. Further, methods are proposed to modulate hydrogel crosslinking, including adjusting concentration of comonomer or altering the design of multifunctional peptide crosslinker. Due to the formation of thioether ester bonds, these hydrogels are hydrolytically degradable. If the dithiol peptide linkers used are susceptible to protease cleavage, these thiol‐acrylate hydrogels can be designed to undergo partial proteolysis. The differences between linear and multiarm PEG‐acrylate (i.e., PEGDA vs PEG4A) are also evaluated. Finally, the use of the mixed‐mode thiol‐acrylate PEG4A‐peptide hydrogels is explored for in situ encapsulation of hepatocellular carcinoma cells (Huh7). The effects of matrix stiffness and integrin binding motif (e.g., RGDS) on Huh7 cell growth and HIPPO pathway activation are studied using PEG4A‐peptide hydrogels. This visible light poly­merized thiol‐acrylate hydrogel system represents an alternative to existing light‐cured hydrogel platforms and shall be useful in many biomedical applications.