Structure Of Hydrogels Research Articles

Engineering Conductive Hydrogels with Tissue‐like Properties: A 3D Bioprinting and Enzymatic Polymerization Approach

Hydrogels are promising materials for medical devices interfacing with neural tissues due to their similar mechanical properties. Traditional hydrogel‐based bio‐interfaces lack sufficient electrical conductivity, relying on low ionic conductivity, which limits signal transduction distance. Conducting polymer hydrogels offer enhanced ionic and electronic conductivities and biocompatibility but often face challenges in processability and require aggressive polymerization methods. Herein, we demonstrate in situ enzymatic polymerization of π‐conjugated monomers in a hyaluronan (HA)‐based hydrogel bioink to create cell‐compatible, electrically conductive hydrogel structures. These structures were fabricated using 3D bioprinting of HA‐based bioinks loaded with conjugated monomers, followed by enzymatic polymerization via horseradish peroxidase. This process increased the hydrogels’ stiffness from about 0.6 to 1.5 kPa and modified their electroactivity. The components and polymerization process were well‐tolerated by human primary dermal fibroblasts and PC12 cells. This work presents a novel method to fabricate cytocompatible and conductive hydrogels suitable for bioprinting. These hybrid materials combine tissue‐like mechanical properties with mixed ionic and electronic conductivity, providing new ways to use electricity to influence cell behavior in a native‐like microenvironment.

Biocompatible Quince Seed Mucilage Hydrogel: A Versatile Platform for Efficient Drug Delivery of Ceftriaxone with Enhanced Adsorption Properties

AbstractThe objective of this study was to explore the applicability of biocompatible quince seed mucilage hydrogel as a promising material for drug delivery systems. In this investigation, the hydrogel was synthesized through the graft copolymerization of acrylic acid and allyl polyvinyl alcohol onto quince seed mucilage in an aqueous solution under an argon atmosphere. Characterization of the synthesized hydrogel was performed using Fourier‐transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FE‐SEM), and thermogravimetric analysis (TGA). Subsequently, the developed hydrogel served as a carrier for ceftriaxone antibiotic release in both distilled water and a buffer solution with a pH of 7.4. The results demonstrated an impressive encapsulation efficiency of 96.1% for ceftriaxone within the hydrogel matrix. Additionally, the adsorption properties of ceftriaxone onto the proposed hydrogel structures (I, II, and III) were theoretically investigated in the aqueous phase using Monte Carlo adsorption locator calculations in Materials Studio2017. Our findings revealed strong adsorption on structure (III) compared to structures (I and II), with respective theoretical energies of −2.836 kcal/mol, −2.840 kcal/mol, and −2.127 kcal/mol. Therefore, the proposed hydrogel structure (III) emerges as a promising candidate for drug delivery applications, emphasizing its potential as an efficient carrier system.

The Effect of High Hydrostatic Pressure (HHP) Induction Parameters on the Formation and Properties of Inulin-Soy Protein Hydrogels.

The aim of this study was to determine the effect of high hydrostatic pressure (HHP) induction parameters on the formation and properties of inulin-soy protein hydrogels. Solutions containing 20 g/100 g of inulin and 3 or 6 g/100 g of soy protein isolate (3 SPI; 6 SPI) were subjected to HHPs of 150, 300, or 500 MPa for 5, 10, or 20 min. The HHP parameters had no significant impact on the effectiveness of hydrogel formation. In most cases, the time of solution pressurization had no significant effect on the characteristics of hydrogels. However, increasing the induction pressure from 150 to 300 MPa resulted in hydrogels with different characteristics being obtained, e.g., more flattened microstructure; higher stability (only 3 SPI); higher yield stress, firmness, and adhesiveness; and lower spreadability. These changes were more noticeable in the hydrogels with lower protein content. An increase in the induction pressure (to 500 MPa) did not result in a significant strengthening of the hydrogel structure. However, in the case of 6 SPI hydrogels, induction with a pressure of 500 MPa had an unfavorable effect on their stability. The results indicate that HHP (300 MPa) can be used as an effective method for strengthening the structure of inulin-protein hydrogels.

Magnetic Porous Hydrogel-Enhanced Wearable Patch Sensor for Sweat Zinc Ion Monitoring.

Wearable sensors for sweat trace metal monitoring have the challenges of effective sweat collection and the real-time recording of detection signals. The existing detection technologies are implemented by generating enough sweat through exercise, which makes detecting trace metals in sweat cumbersome. Generally, it takes around 20 min to obtain enough sweat, resulting in dallied and prolonged detection signals that cannot reflect the endogenous fluctuations of the body. To solve these problems, we prepared a multifunctional hydrogel as an electrolyte and combined it with a flexible patch electrode to realize real-time monitoring of sweat Zn2+. Such hydrogel has magnetic and porous properties, and the porous structure of hydrogel enables a fast absorption of sweat, and the magnetic property of the addition of fabricated Fe3O4 NPs not only improves the conductivity but also ensures the adjustable internal structures of the hydrogel. Such a sensing platform for sweat Zn2+ monitoring shows a satisfied linear relationship in the concentration range of 0.16-16 µg/mL via differential pulsed anodic striping voltammetry (DPASV) and successfully detects the sweat Zn2+ of four volunteers during exercise and resting, displaying a promising path for commercial application.

Development of Phase-Separating Microfiber Network Hydrogels to Promote In Vitro Vascularization.

Engineered vascularized tissues in vitro exhibit the potential for transplantation therapy and disease modeling. Despite efforts to design hydrogels as cell culture platforms for in vitro vascularization, development of vascularized tissues recapitulating the natural structures and functions remains difficult due to a poor understanding of the relationships between the matrix microstructures and tube formation of endothelial cells. Herein, we developed microfiber network hydrogels with microporous structures by controlling the liquid-liquid phase separation (LLPS) of proteins and matrix structures in hydrogels. Extracellular matrix protein gelatin was modified with hydrogen-bonding moieties and mixed with hyaluronic acid sodium salt to form microfiber network structures. Gelatin gelation and hyaluronic acid sodium salt dissolution led to the formation of a microporous microfiber network hydrogel formation. Matrix structures of hydrogels were modified by controlling LLPS that affects endothelial cell tube formation. Vascularization was improved using laminin peptides and coculturing with mesenchymal stem cells. Overall, our approach exhibits the potential to induce in vitro vascularization for regenerative medicine and disease modeling applications.

Fish Gelatin-Based Flexible and Self-Healing Hydrogel Modified by Fe2(SO4)3.

The application of fish gelatin (FG) is limited due to its poor mechanical properties and thermal stability, both of which could be significantly improved by gellan gum (GG) found in previous research. However, the FG/GG composite hydrogel was brittle and easily damaged by external forces. It was found that the composite hydrogel with Fe2(SO4)3 showed good flexibility and self-healing properties in the pre-experiment. Thus, the synergistic effect of FG, GG and Fe2(SO4)3 on the mechanical properties of the composite hydrogel was investigated in this study. According to one-way experiments, response surface tests and Texture Profile Analysis, it was found that under the optimum condition of FG concentration 186.443 g/L, GG concentration 8.666 g/L and Fe2(SO4)3 concentration 56.503 g/L, the springiness of the composite cylindrical hydrogel with the height of 25 mm formed in 25 mL beakers (bottom diameter 30 mm) was 7.602 mm. Determination of the rheological properties, compression performance, adhesive performance and self-healing properties showed that the composite hydrogel had good thermal stability, flexibility and self-healing properties with good adhesion, skin compliance and compressive strength, and it was easy to remove. The composite hydrogel showed strong antimicrobial activity against A. salmonicida and V. parahaemolyticus. All hydrogels showed a uniform and porous structure. The 3D structure of the composite hydrogel was much looser and more porous than the pure FG hydrogel. The flexible and self-healing composite hydrogel with some antimicrobial activity is suitable for the development of medical dressings, which broadens the applications of the composite hydrogel.

Enzymatic Insitu Crosslinking Can Improve Hydrogel Stability While Maintaining Matrix Stiffness

AbstractNext to the choice of a material, the crosslinking characteristics play an important role in the development of hydrogels for applications in the biomedical field. By decreasing crosslinking time or concentration one can reduce the density of the network and hence the stiffness of the hydrogel. However, at the same time in many cases the stability of the matrix is significantly reduced, leading to a rapidly degrading hydrogel structure. In this study, we evaluate and compare two different crosslinking methods while maintaining the material chemistry. The hydrogel system evaluated consisted of oxidized hyaluronic acid and gelatin, and it was crosslinked with microbial transglutaminase. We found that by in situ crosslinking (CL) instead of post CL we can significantly increase the stability of the hydrogel while maintaining the matrix stiffness. Encapsulated embryonic mouse fibroblasts showed an increased viability in in situ crosslinked samples. These findings indicate that it is possible to change hydrogel parameters independently, even if they are otherwise interrelated.

An adhesive hydrogel functionalized silica sphere for polar analytes separation and analysis

In response to the challenges associated with the chromatographic separation of polar compounds, this study aims to devise a solution by introducing a novel stationary phase. Hydrogels, characterized by a three-dimensional network structure, have aroused wide attention owing to its functional designability, multiple interaction sites and good adhesion, etc. In this work, an adhesive hydrogel functionalized silica stationary phase (Sil@PVA/TA) was synthesized using physical coating technique. Due to the co-existence of hydroxyl and benzene ring in the hydrogel structure, the obtained composites materials exhibited excellent separation performance for various of compounds and excellent column efficiency up to 71385.6 plates/m for thymidine. Furthermore, the hydrogel functionalized silica demonstrated superior selectivity to bare silica, diol-column and NH2-column for the separation of various of polar molecules, including, nucleosides/bases, alkaloids, organic acids, antibiotics and amino acids. Notably, for alkaloids, which frequently encounter peak tailing issues, Sil@PVA/TA demonstrated superior peak shape compared with C18 column. In short, this study successfully synthesized a hydrogel functionalized silica stationary phase, offering a novel method for the separation and analysis of polar compounds.

In situ forming hydrogels based on modified gellan gum/chitosan for ocular drug delivery of timolol maleate

In situ forming hydrogels are suitable candidates for increasing drug residence time in ocular drug delivery. In this study, gellan gum (GG) was oxidized to form aldehyde groups and in situ gelling hydrogels were synthesized based on a Schiff-base reaction between oxidized GG (OGG) and chitosan (CS) in the presence of β-glycerophosphate. The effect of OGG and CS concentration on the physical and chemical properties of the resulting hydrogels was investigated. The FT-IR spectroscopy confirmed the chemical modification of OGG as well as the functional groups of the prepared hydrogels. The scanning electron microscope (SEM) revealed the highly porous structure of hydrogels. The obtained hydrogels indicated a high swelling degree and degradability. Also, the rheological studies demonstrated self-healing behavior, shear thinning, thixotropy, and mucoadhesion properties for the developed hydrogels. The results of in vitro and ex vivo studies showed that the timolol-loaded hydrogel with a higher amount of OGG has a higher release rate. Moreover, the MTT cytotoxicity test on bone marrow mesenchymal stem cells (BMSCs) confirmed that developed hydrogels are not toxic. The obtained results revealed that the developed hydrogels can be a desirable choice for the ocular drug delivery of timolol in the treatment of glaucoma.

Gels/Hydrogels in Different Devices/Instruments-A Review.

Owing to their physical and chemical properties and stimuli-responsive nature, gels and hydrogels play vital roles in diverse application fields. The three-dimensional polymeric network structure of hydrogels is considered an alternative to many materials, such as conductors, ordinary films, constituent components of machines and robots, etc. The most recent applications of gels are in different devices like sensors, actuators, flexible screens, touch panels, flexible storage, solar cells, batteries, and electronic skin. This review article addresses the devices where gels are used, the progress of research, the working mechanisms of hydrogels in those devices, and future prospects. Preparation methods are also important for obtaining a suitable hydrogel. This review discusses different methods of hydrogel preparation from the respective raw materials. Moreover, the mechanism by which gels act as a part of electronic devices is described.

Injectable interface-bonded fiber-reinforced thiolated chitosan hydrogels for enhanced cellular activities and cartilage regeneration

Injectable hydrogels with heterogeneous fibrous structures possessing good mechanical and biological characteristics are attracting increasing research interest in cartilage repair. The integration of nanofibers into hydrogel would largely enhance mechanical property, but impedes the gelation process and formation of hydrogel structures. Construction of biocompatible and mechanical supporting hydrogel with low fiber content remains a challenge. In this study, we developed a chemical cross-linked fibrous hydrogel, namely Thiol chitosan-Poly (lactic-co-glycolic acid)-Polydopamine (CSSH-PP), for facilitating cell proliferation and promoting cartilage tissues regeneration. Compared to conventional CSSH hydrogels, the compressive strength of CSSH-PP scaffolds exhibited a significant increase percentage of 100 %. Incorporation of CSSH-PP upgraded the cell migration with a four-fold increase. Besides, the infiltration of host cells and the formation of new blood vessels were observed in rat models when implanted with CSSH-PP, enhancing the native tissue microenvironmental reconstruction and leading a sustained repair in articular cartilage.

The fracture and toughening mechanism of double-network hydrogel using the network mechanics method

Double-network hydrogels have received considerable attention due to their superior mechanical properties. However, a comprehensive understanding of their fracture and toughening mechanisms is still lacking, primarily due to the complex network structures of double-network hydrogels and the highly non-linear characteristics of the fracture. In this study, we address this gap by developing a mesoscopic model for double-network hydrogels using the network mechanics method, in which the fracture of polymer chains is realized by introducing the stretch criterion to each polymer chain. Through numerical analysis, we find that the stretch criterion ratio of polymer chains in two networks λ2c/λ1c is the key factor that influences the necking and hardening phenomena of double-network hydrogels. By changing this stretch criterion ratio, the fracture mode of double-network hydrogels can transit between ductile and brittle. When the fracture stretching criteria of the polymer chains in the first and second networks are 1.8 and 6, the necking and hardening phenomena can be observed. It is also found that a more uniform network structure of the first network enhances the toughness of double-network hydrogels. This study sheds light on the fundamental fracture and toughening mechanisms of double-network hydrogels, providing new insights for their further applications.

Visible-Light-Induced Silk Fibroin Hydrogels with Carbon Quantum Dots as Initiators for 3D Bioprinting Applications.

Digital light processing (DLP) 3D bioprinting technology has attracted increasing attention in tissue engineering in recent years. However, it still faces significant technical and operational challenges such as cell carcinogenesis caused by prolonged exposure to ultraviolet light and the presence of heavy metal ions in complex photoinitiator systems. In this study, a novel strategy is designed to introduce carbon quantum dots into visible-light-induced silk fibroin bioink as initiators (CDs/SilMA) applied for DLP 3D bioprinting technology. The incorporation of carbon quantum dots facilitates the formation of precise hydrogel structures at 415 nm visible wavelength, enabling the creation of brain, bronchus, spine, and ear models. Replacing heavy metal photoinitiators with carbon quantum dots imparts fluorescence properties to the bioink and enhances its mechanical properties. Meanwhile, the fibroin protein-based hydrogel exhibits favorable properties, such as drug loading, slow release, degradability, and biocompatibility. This is the first study to propose the application of carbon quantum dots in silk fibroin-based bioink. Moreover, the resulting product demonstrates excellent compatibility with the DLP printing process, making it promising for practical applications in various tissue engineering scenarios with specific requirements.

Amphiphilic silica monomers induced superhydrophilic and flexible silica aerogels for radiative cooling and atmospheric water harvesting

Silica aerogels have attracted extensive attention owing to their exceptional porous structures and crucial applications for sustainable environments. However, the inherent fragility and complex manufacturing process of silica aerogels present a challenge for their prolonged applications. In this study, an amphiphilic silica monomer, triethoxysilane end-capped poly(ethylene oxide) (PEO-TES), is designed and synthesized, which can co-gelled with methyltrimethoxysilane in water and gives birth to flexible and superhydrophilic silica aerogels via ambient pressure drying (APD). PEO-TES plays a dual role as both co-monomers and surfactants, effectively stabilizing the sol–gel transition, adjusting the porous structure of hydrogels, and imparting superhydrophilicity. The silica aerogel has low density (0.147 g cm−3), zero water contact angle, high elasticity (80 % compression), high solar reflectance (0.888), and high IR emissivity (0.967). These features make them robust all-day passive radiative cooling materials with 10.5 °C sub-ambient cooling capacity and atmospheric water harvesting capacities for both vapor (a water harvesting rate of 0.041 kg m−2h−1) and fog (harvesting capacity of 2.9 g g−1). The strategy provides a simple APD method for synthesizing flexible and superhydrophilic silica aerogels with controllable porous structures, passive cooling, and water harvesting performance, which may help address global climate change and water scarcity challenges.

Effects of Sequential Induction Combining Thermal Treatment with Ultrasound or High Hydrostatic Pressure on the Physicochemical and Mechanical Properties of Pea Protein-Psyllium Hydrogels as Elderberry Extract Carriers.

Entrapping bioactive ingredients like elderberry extract in hydrogels improves their stability and functionality in food matrices. This study assessed the effect of sequential thermal treatment with ultrasound (US) or high hydrostatic pressure (HHP) and treatment duration on pea protein-psyllium hydrogels as elderberry extract carriers. Measurements included color parameters, extract entrapment efficiency, physical stability, textural properties, microrheology, FT-IR, thermal degradation (TGA), SEM images, total polyphenols content, antioxidant activity, and reducing power. The control hydrogel was obtained using only thermal induction. Both treatments impacted physical stability by affecting biopolymer aggregate structures. Thermal and US combined induction resulted in hydrogels with noticeable color changes and reduced entrapment efficiency. Conversely, thermal and HHP-combined induction, especially with extended secondary treatment (10 min), enhanced hydrogel strength, uniformity, and extract entrapment efficiency (EE = 33% for P10). FT-IR and TGA indicated no chemical structural alterations post-treatment. Sequential thermal and HHP induction preserved polyphenol content, antioxidant activity (ABTS = 5.8 mg TE/g d.m.; DPPH = 11.1 mg TE/g d.m.), and reducing power (RP = 1.08 mg TE/g d.m.) due to the dense hydrogel structure effectively enclosing the elderberry extract. Sequential thermal and HHP induction was more effective in developing pea protein-psyllium hydrogels for elderberry extract entrapment.

Evaluation of the synergistic effect of nanocomposite hydrogel based on imidazolium nitrate ionic liquids for enhanced oil recovery

A comprehensive research study was conducted to examine the synergistic properties of ionic liquids, and hydrogels. Two nanocomposite hydrogel samples were created: one with ionic liquid and the other without. The samples were made using hydrogel with acrylamide (AM) backbone, Al2O3 nanoparticles, and ionic liquid [C8mim][NO3]. The effectiveness of a nanocomposite hydrogel containing an ionic liquid was tested to improve the wettability alteration and sweeping efficiency of reservoirs. Various tests were performed including IFT, electroconductivity, micromodel, SEM, and equilibrium swelling tests. The tests showed that the presence of the ionic liquid increased the swelling up to 102 %. IL increased conductivity by 124.24 % and 44.86 % at ambient temperature and 90 °C respectively. In the strain sweep test, the maximum elastic modulus for NCH-IL was recorded as 40,350 Pa, while for the sample without ionic liquid, it was 27,100 Pa. The frequency sweep test confirmed the three-dimensional structure of the gel. IL increased the maximum elastic modulus from 13,200 Pa to 27,400 Pa. The critical frequency value also increased by 87.5 %. Moreover, the suspension, which contains 1 wt% of Nanocomposite Hydrogel based on Imidazolium Nitrate Ionic Liquids, has shear-thinning properties, making it easy to inject into reservoirs. The reduction of the contact angle from 109° to 14.2° demonstrated the ability of IL to alter the wettability of NCHs. This result stemmed from the release of part of the ionic liquid within the hydrogel structure, as confirmed by the UV test. During the emulsion stability test, it was observed that the NCH-IL sample created a stable emulsion and a more complete two-phase separation than the sample without the ionic liquid. The sample that contained IL recorded 85 % and 78.4 % oil recovery in homogeneous and heterogeneous micromodels, respectively. Whereas, the sample without IL recorded 71.27 % and 60.73 % in the same micromodels.

3D-printed multifunctional biomass hydrogel device for controlled photothermal distribution and molecular release

Photothermal therapy based on photothermal conversion has received increasing attention due to its non-invasiveness and low side effects. In this study, a 3D-printed biomass photothermal therapy device was prepared for accurate control of photothermal conversion and molecular release. The prepared black phosphorus nanosheets (BPNSs) showed excellent photothermal performance and antibacterial activity. A temperature-regulated sol-gel reversible system was prepared with konjac glucomannan (KGM), tara gum (TG), BPNSs, and manganese dioxide (MnO2) nanoparticles. The sol-gel transition was attributed to the change of interactions of hydrogen bond, and molecular entanglement. Photothermal conversion films with accurate multi-layer and array structures were prepared by 3D printing using the biomass sol-gel conversion system. The photothermal conversion efficiency was regulated by the concentration of BPNSs and MnO2. Under infrared radiation (808 nm, 1 W/cm2) for 5 min, the temperatures of hydrogel films with a MnO2 concentration of 0, 0.5, and 1 % were raised from 25 to 29.3, 61.8, and 90.8 °C, respectively. The accurate temperature distribution induced the controlled release of small active molecules such as epigallocatechin gallate (EGCG) loaded in hydrogels, which was resulted from the changes in the hydrogel structure and the decrease in adsorption energy between polysaccharide and EGCG at high temperatures. This study provides a biomass 3D-printed multifunctional photothermal therapy device and more understanding of the molecular release during photothermal conversion.

Electric-field assisted cascade reactions to create alginate/carboxymethyl chitosan composite hydrogels with gradient architecture and reconfigurable mechanical properties

Rational designs of polysaccharide-based hydrogels with organ-like three-dimensional architecture provide a great possibility for addressing the shortages of allograft tissues and organs. However, spatial-temporal control over structure in bulk hydrogel and acquire satisfied mechanical properties remain an intrinsic challenge to achieve. Here, we show how electric-field assisted molecular self-assembly can be coupled to a directional reaction-diffusion (RD) process to produce macroscopic hydrogel in a controllable manner. The electrical energy input was not only to generate complex molecule gradients and initiate the molecular self-assembly, but also to guide/facilitate the RD processes for the gel rapid growth via a cascade construction interaction. The hydrogel mechanical properties can be tuned and enhanced by using an interpenetrating biopolymer network and multiple ionic crosslinkers, leading to a wide-range of mechanical modulus to match with biological organs or tissues. We demonstrate diverse 3D macroscopic hydrogels can be easily prepared via field-assisted directional reaction-diffusion and specific joint interactions. The humility-triggered dissipation of functional gradients and antibacterial performance confirm that the hydrogels can serve as an optically variable soft device for wound management. Therefore, this work provides a general approach toward the rational fabrication of soft hydrogels with controlled architectures and functionality for advanced biomedical systems.

Tailoring the Structure and Physico-Chemical Features of Cellulose-Based Hydrogels Using Multi-Epoxy Crosslinking Agents.

Hydrogel features can be designed and optimized using different crosslinking agents to meet specific requirements. In this regard, the present work investigates the physico-chemical features of cellulose-based hydrogels, designed by using different epoxy crosslinkers from the same glycidyl family, namely epichlorohydrin (ECH), 1,4-butanediol diglycidyl ether (BDDE), and trimethylolpropane triglycidyl ether (TMPTGE). The effect of the crosslinker's structure (from simple to branched) and functionality (mono-, bi- and tri-epoxy groups) on the hydrogels' features was studied. The performances of the hydrogels were investigated through the gel fraction, as well as by ATR-FTIR, DVS, SEM, DSC, and TG analyses. Also, the swelling and rheological behaviors of the hydrogels were examined. The advantages and limitations of each approach were discussed and a strong correlation between the crosslinker structure and the hydrogel properties was established. The formation of new ether bonds was evidenced by ATR-FTIR spectroscopy. It was emphasized that the pore size is directly influenced by the crosslinker type, namely, it decreases with the increasing number of epoxy groups from the crosslinker molecule, i.e., from 46 ± 11.1 µm (hydrogel CE, with ECH) to 12.3 ± 2.5 µm (hydrogel CB, with BDDE) and 6.7 ± 1.5 µm (hydrogel CT, with TMPTGE). The rheological behavior is consistent with the swelling data and hydrogel morphology, such as CE with the highest Qmax and the largest pore size being relatively more elastic than CB and CT. Instead, the denser matrices obtained by using crosslinkers with more complex structures have better thermal stability. The experimental results highlight the possibility of using a specific crosslinking agent, with a defined structure and functionality, in order to establish the main characteristics of hydrogels and, implicitly, to design them for a certain field of application.

Collagen-Based Hydrogel with Incorporated Nano-Hydroxyapatite for the Delivery of a Poorly Water-Soluble Drug

The goal of our research described here was to prepare a class of biocompatible composite hydrogel beads as a delivery system for the poorly soluble drug, cefixime. Hydrogel beads were synthesized using collagen (Col) and hydroxyapatite (HA) nanoparticles both extracted from fish wastes, and chitosan (Chi), for oral drug delivery. The in-vitro cytotoxicity of the Col showed good enough cell viability (95.51%) to be used as a potential candidate for biomedical applications, including tissue engineering and drug delivery. X-ray diffraction (XRD) patterns and Fourier transform infrared (FTIR) spectroscopy were used to determine the crystallinity and functional groups of the synthesized hydrogel beads. The fibrous structure of the beads was confirmed using scanning electron microscopy (SEM) images. The 1:1 ratio of Col:Chi without HA, resulted in a maximum swelling degree of 2010% and a drug release percentage of 93%. As the concentration of Col was increased, the swelling and cefixime release decreased. Adding HA NPs to the hydrogel structure led to an average 10% reduction in cefixime release compared to samples without HA. The release rate kinetics followed the first order and Korsmeyer-Peppas models, proving the diffusion was the controlling factor. The results showed that the mentioned hydrogel beads had a great potential delivery platform to achieve the controlled release of cefixime.