Interpenetrating Network Hydrogels Research Articles

Functionalized Collagen/Poly(ethylene glycol) Diacrylate Interpenetrating Network Hydrogel Enhances Beta Pancreatic Cell Sustenance.

Three-dimensional matrices are a new strategy used to tackle type I diabetes, a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), a component that has been used to support cell growth. However, pure collagen possesses some difficulties, including a low stiffness and strength and a high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly (ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta pancreatic cells. We analyzed the physicochemical characteristics of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced the viability, proliferation, respiratory capacity, and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

Self-powered information conversion based on thermogalvanic hydrogel with interpenetrating networks for nursing aphasic patients

In recent years, an increase in the use of wearable electronics has been observed in daily life due to the rapid development of personal medical health systems and the Internet of Things. Environment-friendly quasi-solid-state thermogalvanic hydrogels are enabled to convert low-grade heat into electricity and expected to be used for signal conversion in smart medical applications. However, existing wearable models in nursing are not entirely applicable for aphasic patients. Herein, we introduced a thermogalvanic interpenetrating network hydrogel (TG-IPNH) with [Fe(CN)6]3-/[Fe(CN)6]4- as a redox pair and KCl as a ion provider for thermodiffusion, which not only has good flexibility but also prominent thermoelectric property with the thermal current up to 124 μA at the temperature difference of 10 K. Relying on the gel’s sensitive correlative thermoelectric response to temperature triggered by a finger and in combination with Morse Code, a self-powered gel wristband for information conversion has been developed to provide real-time help and assistance to aphasic patients. This gel-based wristband device can be potentially applied as a supplementary interaction route for them who have language impairment, especially in intelligent healthcare and emergency rescue.

Self-healing interpenetrating network hydrogel based on GelMA/alginate/nano-clay

Today, tissue engineering strategies need the improvement of advanced hydrogels with biological and mechanical properties similar to natural cartilage for joint regeneration. In this study, an interpenetrating network (IPN) hydrogel composed of gelatin methacrylate (GelMA)/alginate (Algin)/nano-clay (NC) with self-healing ability was developed with particular consideration to balancing of the mechanical properties and biocompatibility of bioink material. Subsequently, the properties of the synthesized nanocomposite IPN, including the chemical structure, rheological behavior, physical properties (i.e. porosity and swelling), mechanical properties, biocompatibility, and self-healing performance were evaluated to investigate the potential application of the developed hydrogel for cartilage tissue engineering (CTE). The synthesized hydrogels showed highly porous structures with dissimilar pore sizes. The results revealed that the NC incorporation improved the properties of GelMA/Algin IPN, such as porosity, and mechanical strength (reached 170 ± 3.5 kPa), while the NC incorporation decreased the degradation (63.8 %) along with retaining biocompatibility. Therefore, the developed hydrogel showed a promising potential for the treatment of tissue defects in cartilage.

Impact of pH on pea protein–hydroxypropyl starch hydrogel based on interpenetrating network and its application in 3D-printing

Improving the mechanical and 3D printing performance of pea protein (PeaP) hydrogels contributes to the development of innovative plant-based gel products. Herein, we proposed a strategy for constructing PeaP–hydroxypropyl starch (HPS) interpenetrating network hydrogels, in which the structure, strength, and 3D printing properties of the hydrogels were regulated by changing pH. Results showed that pH significantly affected the gelation process of PeaP/HPS hydrogels. The hydrogels formed a lamellar structure at pH 3, a granule aggregation network structure at pH 5, porous structures at pH 7 and 9, and a honeycomb structure at pH 11. The strength of hydrogels formed at different pH values had the following order: pH 3 ＞pH 11 ＞ pH 7 ＞pH 9 ＞pH 5. The storage modulus (G') of the hydrogel at pH 3 was up to 4149 Pa, but only 695 Pa at pH 5. Moreover, hydrogel at pH 3 had the best self-recovery of 55%. 3D printed objects from gel inks at pH 3 exhibited high structural integrity and fidelity at 60 °C. Gelling force analysis indicated hydrogen bonds were the dominant interaction within all hydrogels. Overall, this study suggested that PeaP/HPS hydrogel formed at pH 3 possessed the most excellent mechanical properties and 3D printing capabilities, which may provide insights into the development of novel PeaP-based gel food ingredients and promote the application of PeaP in the food industry.

Conducting polymer-based nanostructured materials for brain-machine interfaces.

As scientists discovered that raw neurological signals could translate into bioelectric information, brain-machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

A tough and mechanically stable adhesive hydrogel for non-invasive wound repair.

Wound healing has been a great challenge throughout human history. Improper treatment for wounds is so easy to lead to infection and a series of serious symptoms, even death. Because of the ability of absorbing fluid and keeping a moist environment, the hydrogel with 3D networks is ideal candidate for wound dressing. More important, it has good biocompatibility. However, most of the hydrogel dressings reported have weak mechanical properties and adhesion properties, which greatly limit their clinical application. Herein, a tough adhesive hydrogel with good mechanical stability for non-invasive wound repair is reported. The hydrogel is composed of polyethylene glycol dimethacrylate (PEGDA), chitosan (CS) and chitin nano-whisker (CW). PEGDA and CS form interpenetrating network hydrogel through free radical polymerization reaction under the UV light. The introduction of CW further enhances the toughness of the hydrogel. The pH-sensitive CS can form adhesion to various materials through topological adhesion. As a wound closure repair material, PEGDA/CS/CW hydrogel not only has the characteristic of effectively closing the wound, defending against invading bacteria, and keeping the wound clean, but also has good tensile and mechanical stability, which is expected to realize the closure and repair of joints and other moving parts of the wound. This adhesive hydrogel is proven a promising material for wound closure repair.

Strong, self-healing, shape memory PAA-PANI/PVA/PDA/AOP conductive hydrogels with interpenetrating network and hydrogen bond interaction

Conductive hydrogels have attracted much attention in soft electronic devices. However, it is still a challenging to be integrated with outstanding mechanical performance, self-healing, shape memory and conductive capability. Herein, we developed a multifunctional conductive hydrogel via interpenetrating network (IPN) and multiple hydrogen bond interaction. Poly (acrylic acid)-polyaniline (PAA-PANI) and polyvinyl alcohol (PVA) form bones of IPN through chemical and physical double cross-linking. Chemically crosslinking of IPN was obtained by in situ polymerization of acrylic acid and aniline. Physical crosslinking is realized by more multiple hydrogen bonds (N–H···O, O–H···O, O–H···N, N–H···N) interaction among PVA, polydopamine and PF127 diamino oxygen derivatives. PANI forms a conductive path in the IPN to ensure its conductivity. IPN hydrogels with multiple hydrogen bonds has excellent mechanical strength, which is much higher than conventional conductive hydrogels. Moreover, the structure endowed the hydrogel low swelling property, good self-healing and thermal-responsive shape memory effect. The multifunctional IPN conductive hydrogel have potential applications in smart devices including self-healing electronic devices, soft robot, and sensors.

The influence of pregelatinized starch on the rheology of a gellan gum-collagen IPN hydrogel for 3D bioprinting

Hydrogel scaffolds infused with stem cells are valuable alternatives to skin grafts in replacement of lost host tissues. In a prior study, we developed an adipose-derived stem cells (ADSC)-laden gellan gum-collagen interpenetrating network (IPN) hydrogel with enhanced wound healing properties upon application on murine full thickness burn wounds. With the perspective of enabling the clinical translation and healthcare adaptation of the hydrogel wound-dressing, we report a novel ADCS-laden collagen-gellan gum full IPN hydrogel formula compatible with 3D bioprinting technology. The stable new bio-ink showed improved printability for extrusion-based 3D biofabrication and preserved scaffold quality for stem cell proliferation. Pregelatinized starch (PGF, PREGEFLO®PI10) and glycerol were successfully incorporated to the bio-ink as molecular lubricant and hydrophilic plasticizer. When subjected to rheological measurements, the new glycerol-PGF-gellan gum composite hydrogel demonstrated good shear recovery ability, improved resistance to step-strain deformations and adequate stiffness as cell-conducive environment. Subsequently, a dual-head two-step temperature-guided 3D bioprinting methodology was developed to extrude ADSC-laden collagen into the composite hydrogel thick film to achieve in-situ polymer interpenetration. After their fabrication, the printed cell-laden hydrogel constructs were able to maintain high shape fidelity and stability after 21 days of incubation in cell culture media. Results from cell proliferation assay (MTS) and confocal laser scanning microscopy (CLSM) suggested that ADSC retained their normal cellular functions of adhesion, proliferation, and migration within the 3D bioprinted hydrogel scaffold. Taken together, our study brings forward the use of PREGEFLO®PI10 in upgrading the ADSC-laden IPN hydrogel formula towards potential clinical translation of synthetic skin grafts.

Facile fabrication of a broad-spectrum starch/poly(α-l-lysine) hydrogel adsorbent with thermal/pH-sensitive IPN structure through simultaneous dual-click strategy

A thermal/pH-sensitive interpenetrating network (IPN) hydrogel was prepared facilely from starch and poly(α-l-lysine) through amino-anhydride and azide-alkyne double-click reactions in one pot. The synthesized polymers and hydrogels were systematically characterized using different analytical techniques such as Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and rheometer. The preparation conditions of the IPN hydrogel were optimized via one-factor experiments. Experimental results indicated the IPN hydrogel possessed pH and temperature sensitivity. Effect of different parameters (pH, contact time, adsorbent dosage, initial concentration, ionic strength, and temperature) on adsorption behavior were investigated in monocomponent system with cationic methylene blue (MB) and anionic Eosin Y (EY) as model pollutants. The results indicated that the adsorption process of the IPN hydrogel for MB and EY followed pseudo-second-order kinetics. The adsorption data for MB and EY fitted well with the Langmuir isotherm model, indicating monolayer chemisorption. The good adsorption performance was due to various active functional groups (–COOH, –OH, –NH2, etc.) in the IPN hydrogel. The strategy described here opens up a new way for preparing IPN hydrogel. The as-prepared hydrogel exhibits potential application and bright prospects as an adsorbent in wastewater treatment.

Controlled delivery of aspirin from nanocellulose-sodium alginate interpenetrating network hydrogels

An interpenetrating network (IPN) hydrogel was developed by the miscibility between nanocellulose and sodium alginate through an acetic acid coagulation bath and Ca2+ chelation. Double crosslinking played a key role during the construction of the IPN hydrogel network. The nanofibers significantly prolonged the aspirin release time to ∼ 60 h, which benefits from the rich and regular network structure of the hydrogel. Carboxyl groups contribute to the variation in release capacity in different pH environments. The strategy proposed in this study would guide the preparation of purely physically crosslinked IPN hydrogels with good mechanical properties and cytocompatibility and their application in the drug delivery field. This study aimed to explore the double crosslinking process for prolonged aspirin release capacity between nanocellulose and sodium alginate. The obtained results suggested that a pH-sensitive nanocellulose-sodium alginate IPN hydrogel would be an ideal aspirin carrier for long-term release.

A cellulose-based interpenetrating network hydrogel electrolyte for flexible solid-state supercapacitors

A cellulose-based interpenetrating network hydrogel electrolyte for flexible solid-state supercapacitors

BMSCs-Seeded Interpenetrating Network GelMA/SF Composite Hydrogel for Articular Cartilage Repair.

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration.

Extracellular matrix mimicking dynamic interpenetrating network hydrogel for skin tissue engineering

Tissue engineering scaffolds with tunable viscoelasticity and adaptability for cell behavior and fate regulation are highly desired. Here a dynamic interpenetrating polymer network (IPN) hydrogel was fabricated via photopolymerization and oxidation of methacryloyl gelatin (GelMA) and hyaluronic acid (HASH). The permanent GelMA network formed by CC bonds provides stable support for cells while the dynamic HASH network formed by disulfide bonds provides an adaptable microenvironment for cell growth. The proposed IPN hydrogel exhibits extensive and tunable porosity, swelling, degradation, and mechanical properties. Remarkably, the dynamic IPN hydrogel mimics the viscoelasticity and adaptability of the extracellular matrix (ECM), which can regulate cellular behaviors such as morphogenesis, alignment, proliferation, migration while offering resistance to cell mediated shrinkage and enzymatic digestion, maintaining the structural integrity of the scaffold. Our results suggest that dynamic IPN 3/7 (HASH/GelMA) hydrogels had more similar physical properties to human skin and were more favorable for human skin fibroblasts (HSF) and human immortalized keratinocytes (HaCaT) growth. Moreover, bilayer tissue-engineered skin prepared using the dynamic IPN hydrogel exhibited satisfactory mechanical stability, dermal-epidermal stratification, matrix secretion, structural differentiation, and barrier functions. In addition, the bilayer tissue-engineered skin can significantly promote healing of full-thickness skin defects through accelerated wound re-epithelialization, collagen deposition, and angiogenesis, without causing non-specific or specific immune rejection. This work based on the novel dynamic IPN hydrogel with biomimetic viscoelasticity and adaptability demonstrates the promising application in tissue engineering.

Poly(methacrylic acid)/gelatin interpenetrating network hydrogels reinforced by nano-structured hydroxyapatite particles—improved drug delivery systems

Novel poly(methacrylic acid)/gelatin (PMAG) interpenetrating networks reinforced by different amounts of nanostructured particles of hydroxyapatite (HA) (HA/polymer weight ratios from 0% to 40%) were synthesized. The introduction of HA significantly enhanced mechanical properties, but slightly reduced swelling ability, pH sensibility and porosity. The increase of HA/polymer ratio to 40% increased the compressive strength from 29.83 (pure PMAG hydrogel) to 68.16 kPa. Drug release behavior investigated in simulated physiological conditions, using ciprofloxacin (hydrophilic) and oxaprozin (hydrophobic), demonstrated different drug release kinetics. In vitro antimicrobial testing demonstrated bactericidal and fungicidal activity of the drug-loaded hydrogels against E. coli, S. aureus and C. albicans.

Bioprinted anisotropic scaffolds with fast stress relaxation bioink for engineering 3D skeletal muscle and repairing volumetric muscle loss.

Viscoelastic hydrogels can enhance 3D cell migration and proliferation due to the faster stress relaxation promoting the arrangement of the cellular microenvironment. However, most synthetic photocurable hydrogels used as bioink materials for 3D bioprinting are typically elastic. Developing a photocurable hydrogel bioink with fast stress relaxation would be beneficial for 3D bioprinting engineered 3D skeletal muscles in vitro and repairing volumetric muscle loss (VML) in vivo; however, this remains an ongoing challenge. This study aims to develop an interpenetrating network (IPN) hydrogel with tunable stress relaxation using a combination of gelatin methacryloyl (GelMA) and fibrinogen. These IPN hydrogels with faster stress relaxation showed higher 3D cellular proliferation and better differentiation. A 3D anisotropic biomimetic scaffold was further developed via a printing gel-in-gel strategy, where the extrusion printing of cell-laden viscoelastic FG hydrogel within Carbopol supported gel. The 3D engineered skeletal muscle tissue was further developed via 3D aligned myotube formation and contraction. Furthermore, the cell-free 3D printed scaffold was implanted into a rat VML model, and both the short and long-term repair results demonstrated its ability to enhance functional skeletal muscle tissue regeneration. These data suggest that such viscoelastic hydrogel provided a suitable 3D microenvironment for enhancing 3D myogenic differentiation, and the 3D bioprinted anisotropic structure provided a 3D macroenvironment for myotube organization, which indicated the potential in skeletal muscle engineering and VML regeneration. STATEMENT OF SIGNIFICANCE: The development of a viscoelastic 3D aligned biomimetic skeletal muscle scaffold has been focused on skeletal muscle regeneration. However, a credible technique combining viscoelastic hydrogel and printing gel-in-gel strategy for fabricating skeletal muscle tissue was rarely reported. Therefore, in this study, we present an interpenetrating network (IPN) hydrogel with fast stress relaxation for 3D bioprinting engineered skeletal muscle via a printing gel-in-gel strategy. Such IPN hydrogels with tunable fast stress relaxation resulted in high 3D cellular proliferation and adequate differentiation in vitro. Besides, the 3D hydrogel-based scaffolds also enhance functional skeletal muscle regeneration in situ. We believe that this study provides several notable advances in tissue engineering that can be potentially used for skeletal muscle injury treatment in clinical.

Modeling the Additive Effects of Nanoparticles and Polymers on Hydrogel Mechanical Properties Using Multifactor Analysis.

Interpenetrating networks (IPN)s have been conceived as a biomimetic tool to tune hydrogel mechanical properties to the desired target formulations. In this study, the rheological behavior of acrylamide (AAm) [2.5-10%] hydrogels crosslinked with N,N'-methylenebis(acrylamide) (Bis) [0.0625-0.25%] was characterized in terms of the saturation modulus affected by the interaction of silica nanoparticle (SiNP) nanofillers [0-5%] and dextran [0-2%] at a frequency of 1 Hz and strain rate of 1% after a gelation period of 90 min. For single-network hydrogels, a prominent transition was observed at 0.125% Bis for 2.5% AAm and 0.25% Bis for 5% AAm across the SiNP concentrations and was validated by retrospective 3-level factorial design models, as characterized by deviation from linearity in the saturation region (R2 = 0.86). IPN hydrogels resulting from the addition of dextran to the single network in the pre-saturation region, as outlined by the strong goodness of fit (R2= 0.99), exhibited a correlated increase in the elastic (G') and viscous moduli (G"). While increasing the dextran concentrations [0-2%] and MW [100 kDa and 500 kDa] regulated the increase in G', saturation in G" or the loss tangent (tan(δ)) was not recorded within the observed operating windows. Results of multifactor analysis conducted on Han plots in terms of the elastic gains indicate that amongst the factors modulating the viscoelasticity of the IPN hydrogels, dextran concentration is the most important (RDex = 35.3 dB), followed by nanoparticle concentration (RSiNP = 7.7 dB) and dextran molecular weight (RMW = 2.9 dB). The results demonstrate how the Han plot may be systematically used to quantify the main effects of intensive thermodynamic properties on rheological phase transition in interpenetrating networks where traditional multifactor analyses cannot resolve statistical significance.

Fabrication of chitosan-based interpenetrating network hydrogel via sequential amino-maleimide click reaction and photopolymerization in water

Fabrication of chitosan-based interpenetrating network hydrogel via sequential amino-maleimide click reaction and photopolymerization in water

Rational design cold-set interpenetrating network hydrogel based on wheat bran arabinoxylans and pea protein isolates for regulating the release of riboflavin in simulated digestion

Cold-set interpenetrating polymer network gels as riboflavin (RF) delivery vehicles based on wheat bran arabinoxylans (AX) and pea protein isolate (PPI) were developed via enzymatic-crosslinking. The impact of AX concentrations on the physicochemical property, in vitro digestion property and microstructure of IPN gels was explored. Increased concentrations of AX enhanced the viscoelasticity of IPN gels and resulted in a more compact microstructure. However, at a concentration of 5.0 % (w/v), the faster and stronger crosslinking of AX molecules caused separate network gel between PPI and AX. The IPN gel improved the encapsulation efficiency and release property of embedded RF as compared to PPI gel. SEM results showed that IPN gel maintained a complete network structure after gastric digestion. Particularly, the IPN gel with 1.0 % AX exhibited a homogeneous and complete network structure even after intestinal digestion, which explained the reason for the highest encapsulation efficiency and lowest release ratios of RF.

Silk fibroin based interpenetrating network hydrogel for corneal stromal regeneration

There is a need to develop tissue engineering based approaches to address the shortage of donor corneas worldwide for transplantation. To do this a novel approach to fabricate three-dimensional hydrogels using free-radical polymerization was investigated to generate constructs for corneal stromal tissue regeneration. Different ratios of silk fibroin (SF) to polyacrylamide (PA) were used to fabricate semi-interpenetrating hydrogels. Scanning electron micrograph displayed the interconnectivity of pores within the fabricated hydrogels. Pore sizes ranged from 25 to 66 μm. Scaffolds with increasing concentration of SF had enhanced β-sheet structure (verified by Fourier transform infrared spectroscopy). The biological response of human corneal stromal cells to these hydrogels was examined using cellular adhesion, proliferation, cytoskeleton organization, gene expression and immunocytochemical analysis. The fabricated hydrogels possess rapid gelation (∼3 min) at 37 °C, 84 % porosity facilitating keratocyte migration during healing, improved cellular adhesion and no cytotoxicity, indicating their efficiency for in-situ corneal tissue regeneration. Presence of SF in semi-interpenetrating network hydrogel enhanced cellular proliferation, elevated GAG deposition, and increased expression of keratocyte genes, normally associated with healthy corneal stromal tissue. This study acts as an initial step towards fabricating SF based semi-interpenetrating network hydrogels for developing clinically applicable ocular implants.

In Vitro and In Vivo Biocompatible and Controlled Resveratrol Release Performances of HEMA/Alginate and HEMA/Gelatin IPN Hydrogel Scaffolds.

Scaffold hydrogel biomaterials designed to have advantageous biofunctional properties, which can be applied for controlled bioactive agent release, represent an important concept in biomedical tissue engineering. Our goal was to create scaffolding materials that mimic living tissue for biomedical utilization. In this study, two novel series of interpenetrating hydrogel networks (IPNs) based on 2-hydroxyethyl methacrylate/gelatin and 2-hydroxyethyl methacrylate/alginate were crosslinked using N-ethyl-N′-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Characterization included examining the effects of crosslinker type and concentration on structure, morphological and mechanical properties, in vitro swelling, hydrophilicity as well as on the in vitro cell viability (fibroblast cells) and in vivo (Caenorhabditis elegans) interactions of novel biomaterials. The engineered IPN hydrogel scaffolds show an interconnected pore morphology and porosity range of 62.36 to 85.20%, favorable in vitro swelling capacity, full hydrophilicity, and Young’s modulus values in the range of 1.40 to 7.50 MPa. In vitro assay on healthy human fibroblast (MRC5 cells) by MTT test and in vivo (Caenorhabditis elegans) survival assays show the advantageous biocompatible properties of novel IPN hydrogel scaffolds. Furthermore, in vitro controlled release study of the therapeutic agent resveratrol showed that these novel scaffolding systems are suitable controlled release platforms. The results revealed that the use of EDC and the combination of EDC/NHS crosslinkers can be applied to prepare and tune the properties of the IPN 2-hydroxyethyl methacrylate/alginate and 2-hydroxyethyl methacrylate/gelatin hydrogel scaffolds series, which have shown great potential for biomedical engineering applications.