Preparation and Characterization of Plasma-Derived Fibrin Hydrogels Modified by Alginate di-Aldehyde.

Fibrin hydrogels are one of the most popular scaffolds used in tissue engineering due to their excellent biological properties. Special attention should be paid to the use of human plasma-derived fibrin hydrogels as a 3D scaffold in the production of autologous skin grafts, skeletal muscle regeneration and bone tissue repair. However, mechanical weakness and rapid degradation, which causes plasma-derived fibrin matrices to shrink significantly, prompted us to improve their stability. In our study, plasma-derived fibrin was chemically bonded to oxidized alginate (alginate di-aldehyde, ADA) at 10%, 20%, 50% and 80% oxidation, by Schiff base formation, to produce natural hydrogels for tissue engineering applications. First, gelling time studies showed that the degree of ADA oxidation inhibits fibrin polymerization, which we associate with fiber increment and decreased fiber density; moreover, the storage modulus increased when increasing the final volume of CaCl2 (1% w/v) from 80 µL to 200 µL per milliliter of hydrogel. The contraction was similar in matrices with and without human primary fibroblasts (hFBs). In addition, proliferation studies with encapsulated hFBs showed an increment in cell viability in hydrogels with ADA at 10% oxidation at days 1 and 3 with 80 µL of CaCl2; by increasing this compound (CaCl2), the proliferation does not significantly increase until day 7. In the presence of 10% alginate oxidation, the proliferation results are similar to the control, in contrast to the sample with 20% oxidation whose proliferation decreases. Finally, the viability studies showed that the hFB morphology was maintained regardless of the degree of oxidation used; however, the quantity of CaCl2 influences the spread of the hFBs.

The Molecular Structure and Self-Assembly Behavior of Reductive Amination of Oxidized Alginate Derivative for Hydrophobic Drug Delivery.

On account of the rigid structure of alginate chains, the oxidation-reductive amination reaction was performed to synthesize the reductive amination of oxidized alginate derivative (RAOA) that was systematically characterized for the development of pharmaceutical formulations. The molecular structure and self-assembly behavior of the resultant RAOA was evaluated by an FT-IR spectrometer, a 1H NMR spectrometer, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), a fluorescence spectrophotometer, rheology, a transmission electron microscope (TEM) and dynamic light scattering (DLS). In addition, the loading and in vitro release of ibuprofen for the RAOA microcapsules prepared by the high-speed shearing method, and the cytotoxicity of the RAOA microcapsules against the murine macrophage RAW264.7 cell were also studied. The experimental results indicated that the hydrophobic octylamine was successfully grafted onto the alginate backbone through the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thereby enhancing its molecular flexibility to achieve the self-assembly performance of RAOA. Consequently, the synthesized RAOA displayed good amphiphilic properties with a critical aggregation concentration (CAC) of 0.43 g/L in NaCl solution, which was significantly lower than that of SA, and formed regular self-assembled micelles with an average hydrodynamic diameter of 277 nm (PDI = 0.19) and a zeta potential of about -69.8 mV. Meanwhile, the drug-loaded RAOA microcapsules had a relatively high encapsulation efficiency (EE) of 87.6 % and good sustained-release properties in comparison to the drug-loaded SA aggregates, indicating the good affinity of RAOA to hydrophobic ibuprofen. The swelling and degradation of RAOA microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Moreover, it also displayed low cytotoxicity against the RAW264.7 cell, similar to the SA aggregates. In view of the excellent advantages of RAOA, it is expected to become the ideal candidate for hydrophobic drug delivery in the biomedical field.

Cross-Linked Alginate Dialdehyde/Chitosan Hydrogel Encompassing Curcumin-Loaded Bilosomes for Enhanced Wound Healing Activity.

The current study aimed to fabricate curcumin-loaded bilosomal hydrogel for topical wound healing purposes, hence alleviating the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated via the thin film hydration technique using cholesterol, Span® 60, and two different types of bile salts (sodium deoxycholate or sodium cholate). Bilosomes were verified for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and in vitro drug release besides their morphological features. The optimum formulation was composed of cholesterol/Span® 60 (molar ratio 1:10 w/w) and 5 mg of sodium deoxycholate. This optimum formulation was composed of a PS of 246.25 ± 11.85 nm, PDI of 0.339 ± 0.030, ZP of -36.75 ± 0.14 mv, EE% of 93.32% ± 0.40, and the highest percent of drug released over three days (96.23% ± 0.02). The optimum bilosomal formulation was loaded into alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel was tested for its water uptake capacity, in vitro drug release, and in vivo studies on male Albino rats. The results showed that the loaded hydrogel possessed a high-water uptake percent at the four-week time point (729.50% ± 43.13) before it started to disintegrate gradually; in addition, it showed sustained drug release for five days (≈100%). In vivo animal testing and histopathological studies supported the superiority of the curcumin-loaded bilosomal hydrogel in wound healing compared to the curcumin dispersion and plain hydrogel, where there was a complete wound closure attained after the three-week period with a proper healing mechanism. Finally, it was concluded that curcumin-loaded bilosomal hydrogel offered a robust, efficient, and user-friendly dosage form for wound healing.

Injectable nanocomposite hydrogels with enhanced lubrication and antioxidant properties for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by progressive cartilage degeneration, synovitis, and osteoid formation. In order to effectively treat OA, it is important to block the harmful feedback caused by reactive oxygen species (ROS) produced during joint wear. To address this challenge, we have developed injectable nanocomposite hydrogels composed of polygallate-Mn (PGA-Mn) nanoparticles, oxidized sodium alginate, and gelatin. The inclusion of PGA-Mn not only enhances the mechanical strength of the biohydrogel through a Schiff base reaction with gelatin but also ensures efficient ROS scavenging ability. Importantly, the nanocomposite hydrogel exhibits excellent biocompatibility, allowing it to effectively remove ROS from chondrocytes and reduce the expression of inflammatory factors within the joint. Additionally, the hygroscopic properties of the hydrogel contribute to reduced intra-articular friction and promote the production of cartilage-related proteins, supporting cartilage synthesis. In vivo experiments involving the injection of nanocomposite hydrogels into rat knee joints with an OA model have demonstrated successful reduction of osteophyte formation and protection of cartilage from wear, highlighting the therapeutic potential of this approach for treating OA.

In situ forming alginate/gelatin hydrogel scaffold through Schiff base reaction embedded with curcumin-loaded chitosan microspheres for bone tissue regeneration.

In this study, we developed a biocompatible composite hydrogel that incorporates microspheres. This was achieved using a Schiff base reaction, which combines the amino and aldehyde groups present in gelatin (Gel) and oxidized alginate (OAlg). We suggest this hydrogel as a promising scaffold for bone tissue regeneration. To further boost its osteogenic capabilities and mechanical resilience, we synthesized curcumin (Cur)-loaded chitosan microspheres (CMs) and integrated them into the Gel-OAlg matrix. This formed a robust composite gel framework. We conducted comprehensive evaluations of various properties, including gelation time, morphology, compressive strength, rheological behavior, texture, swelling rate, in vitro degradation, and release patterns. A remarkable observation was that the inclusion of 30 mg/mL Cur-CMs significantly enhanced the hydrogel's mechanical and bioactive features. Over three weeks, the Gel-OAlg/Cur-CMs (30) composite showed a cumulative curcumin release of 35.57%. This was notably lower than that observed in standalone CMs and Gel-OAlg hydrogels. Additionally, the Gel-OAlg/Cur-CMs (30) hydrogel presented a reduced swelling rate and weight loss relative to hydrogels devoid of Cur-CMs. On the cellular front, the Gel-OAlg/Cur-CMs (30) hydrogel showcased superior biocompatibility. It also displayed increased calcium deposition, alkaline phosphatase (ALP) activity, and elevated osteogenic gene expression in human bone marrow mesenchymal stem cells (hBMSCs). These results solidify its potential as a scaffold for bone tissue regeneration.

Rapidly degrading and mussel-inspired multifunctional carboxymethyl chitosan/montmorillonite hydrogel for wound hemostasis.

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, -CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management.

Partially Oxidized Alginate as a Biodegradable Carrier for Glucose-Responsive Insulin Delivery and Islet Cell Replacement Therapy.

Self-regulated insulin delivery that mimics native pancreas function has been a long-term goal for diabetes therapies. Two approaches towards this goal are glucose-responsive insulin delivery and islet cell transplantation therapy. Here, biodegradable, partially oxidized alginate carriers for glucose-responsive nanoparticles or islet cells are developed. Material composition and formulation are tuned in each of these contexts to enable glycemic control in diabetic mice. For injectable, glucose-responsive insulin delivery, 0.5 mm 2.5% oxidized alginate microgels facilitate repeat dosing and consistently provide 10 days of glycemic control. For islet cell transplantation, 1.5 mm capsules comprised of a blend of unoxidized and 2.5% oxidized alginate maintain cell viability and glycemic control over a period of more than 2 months while reducing the volume of nondegradable material implanted. These data show the potential of these biodegradable carriers for controlled drug and cell delivery for the treatment of diabetes with limited material accumulation in the event of multiple doses.

Dual-crosslinked in-situ forming alginate/silk fibroin hydrogel with potential for bone tissue engineering.

This study aimed to improve the mechanical and biological properties of alginate-based hydrogels. For this purpose, in-situ forming hydrogels were prepared by dual crosslinking of Alginate (Alg)/Oxidized Alginate (OAlg)/Silk Fibroin (SF) through simultaneous ionic gelation using CaCO3-GDL and Schiff-base reaction. The resulting hydrogels were characterized by FTIR, SEM, compressive modulus, and rheological tests. Compared to the physically-crosslinked alginate hydrogel, the compressive modulus of dual-crosslinked Alg/OAlg/SF hydrogel increased from 28 to 67 kPa, due to the covalent imine bond formation. Then, MTT and DAPI staining assays were performed to demonstrate the biocompatibility of hydrogel. Furthermore, the differentiation potential of bone marrow mesenchymal stem cells encapsulated in hydrogel scaffolds to bone tissue was tested by ALP activity, Alizarin Red staining, and real-time PCR. The overall results showed the potential of Alginate/Oxidized Alginate/Silk Fibroin hydrogel scaffold for bone tissue engineering applications.

Bioprinting of structurally organized meniscal tissue within anisotropic melt electrowritten scaffolds.

The meniscus is characterised by an anisotropic collagen fibre network which is integral to its biomechanical functionality. The engineering of structurally organized meniscal grafts that mimic the anisotropy of the native tissue remains a significant challenge. In this study, inkjet bioprinting was used to deposit a cell-laden bioink into additively manufactured scaffolds of differing architectures to engineer fibrocartilage grafts with user defined collagen architectures. Polymeric scaffolds consisting of guiding fibre networks with varying aspect ratios (1:1; 1:4; 1:16) were produced using either fused deposition modelling (FDM) or melt electrowriting (MEW), resulting in scaffolds with different internal architectures and fibre diameters. Scaffold architecture was found to influence the spatial organization of the collagen network laid down by the jetted cells, with higher aspect ratios (1:4 and 1:16) supporting the formation of structurally anisotropic tissues. The MEW scaffolds supported the development of a fibrocartilaginous tissue with compressive mechanical properties similar to that of native meniscus, while the anisotropic tensile properties of these constructs could be tuned by altering the fibre network aspect ratio. This MEW framework was then used to generate scaffolds with spatially distinct fibre patterns, which in turn supported the development of heterogenous tissues consisting of isotropic and anisotropic collagen networks. Such bioprinted tissues could potentially form the basis of new treatment options for damaged and diseased meniscal tissue. STATEMENT OF SIGNIFICANCE: This study describes a multiple tool biofabrication strategy which enables the engineering of spatially organized fibrocartilage tissues. The architecture of MEW scaffolds can be tailored to not only modulate the directionality of the collagen fibres laid down by cells, but also to tune the anisotropic tensile mechanical properties of the resulting constructs, thereby enabling the engineering of biomimetic meniscal-like tissues. Furthermore, the inherent flexibility of MEW enables the development of zonally defined and potentially patient-specific implants.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Tuning the Degradation Rate of Alginate-Based Bioinks for Bioprinting Functional Cartilage Tissue.

Negative foreign body responses following the in vivo implantation of bioprinted implants motivate the development of novel bioinks which can rapidly degrade with the formation of functional tissue, whilst still maintaining desired shapes post-printing. Here, we investigated the oxidation of alginate as a means to modify the degradation rate of alginate-based bioinks for cartilage tissue engineering applications. Raw and partially oxidized alginate (OA) were combined at different ratios (Alginate:OA at 100:0; 75:25; 50:50; 25:75; 0:100) to provide finer control over the rate of bioink degradation. These alginate blends were then combined with a temporary viscosity modifier (gelatin) to produce a range of degradable bioinks with rheological properties suitable for extrusion bioprinting. The rate of degradation was found to be highly dependent on the OA content of the bioink. Despite this high mass loss, the initially printed geometry was maintained throughout a 4 week in vitro culture period for all bioink blends except the 0:100 group. All bioink blends also supported robust chondrogenic differentiation of mesenchymal stem/stromal cells (MSCs), resulting in the development of a hyaline-like tissue that was rich in type II collagen and negative for calcific deposits. Such tuneable inks offer numerous benefits to the field of 3D bioprinting, from providing space in a controllable manner for new extracellular matrix deposition, to alleviating concerns associated with a foreign body response to printed material inks in vivo.

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.

Electroactive Oxidized Alginate/Gelatin/MXene (Ti3C2Tx) Composite Hydrogel with Improved Biocompatibility and Self-Healing Property.

Conductive hydrogels (CHs) have shown promising potential applied as wearable or epidermal sensors owing to their mechanical adaptability and similarity to natural tissues. However, it remains a great challenge to develop an integrated hydrogel combining outstanding conductive, self-healing and biocompatible performances with simple approaches. In this work, we propose a "one-pot" strategy to synthesize multifunctional CHs by incorporating two-dimensional (2D) transition metal carbides/nitrides (MXenes) multi-layer nano-flakes as nanofillers into oxidized alginate and gelatin hydrogels to form the composite CHs with various MXene contents. The presence of MXene with abundant surface groups and outstanding conductivity could improve the mechanical property and electroactivity of the composite hydrogels compared to pure oxidized alginate dialdehyde-gelatin (ADA-GEL). MXene-ADA-GELs kept good self-healing properties due to the dynamic imine linkage of the ADA-GEL network and have a promoting effect on mouse fibroblast (NH3T3s) attachment and spreading, which could be a result of the integration of MXenes with stimulating conductivity and hydrophily surface. This study suggests that the electroactive MXene-ADA-GELs can serve as an appealing candidate for skin wound healing and flexible bio-electronics.

3d oxidized alginate-porcine liver acellular collagen droplets for tumor microenvironment mimicking.

The traditional 2d culture has been proved inferior to reproduce the subtle interaction between cell-to-cell and cell-to-extracellular matrix (ECM) in tumor microenvironment (TME) and collagen in ECM contributes to various malignancies of tumors. Hence, the 3d model contained with collagen may overcome the shortcomings of 2d culture. In this study, the in vitro TME mimicking matrix was prepared by coupling porcine liver-derived collagen (COL) and the dialdehyde group of partially oxidized alginate (OA), namely OA-COL, and the 3d OA-COL droplets were polymerized by divalent calcium ions. In the 3d OA-COL droplets, cancer cells displayed vigorous proliferation, and the cells grew in clusters and formed a unique spindle like clone. Quantitative analysis proved that various gene transcription and protein expression were up-regulated for the cells in the 3d OA-COL droplets, including F-actin reassembling, focal adhesion, pseudopodia formation, and the proteins involved in epithelial-to-mesenchymal transition (EMT). The 3d OA-COL droplets induced the cells with strengthened polarity, invasiveness, higher IC50, and manifested stronger tumorigenicity in vivo. The fabricated 3d OA-COL droplets reproduced a variety of TME parameters, constructed an in vitro model similar to the TME in vivo, and it may facilitate many investigations in cell biology and tumor biology.

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application.

BACKGROUND: The blood-brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. METHODS: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. RESULTS: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 µg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. CONCLUSIONS: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administration.

Biohybrid oxidized alginate/myocardial extracellular matrix injectable hydrogels with improved electromechanical properties for cardiac tissue engineering.

Injectable hydrogels which mimic the physicochemical and electromechanical properties of cardiac tissue is advantageous for cardiac tissue engineering. Here, a newly-developed in situ forming double-network hydrogel derived from biological macromolecules (oxidized alginate (OA) and myocardial extracellular matrix (ECM)) with improved mechanical properties and electrical conductivity was optimized. 3-(2-aminoethyl amino) propyltrimethoxysilane (APTMS)-functionalized reduced graphene oxide (Amine-rGO) was added to this system with varied concentrations to promote electromechanical properties of the hydrogel. Alginate was partially oxidized with an oxidation degree of 5% and the resulting OA was cross-linked via calcium ions which was reacted with amine groups of ECM and Amine-rGO through Schiff-base reaction. In situ forming hydrogels composed of 4% w/v OA and 0.8% w/v ECM showed appropriate gelation time and tensile Young's modulus. The electroactive hydrogels showed electrical conductivity in the range of semi-conductors and a suitable biodegradation profile for cardiac tissue engineering. Cytocompatibility analysis was performed by MTT assay against human umbilical vein endothelial cells (HUVECs), and the optimal hydrogel with 25 µg/ml concentration of Amine-rGO showed higher cell viability than that for other samples. The results of this study present the potential of OA/myocardial ECM-based hydrogel incorporated with Amine-rGO to provide a desirable platform for cardiac tissue engineering.

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels.

Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate-gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.

Injectable hydrogels based on oxidized alginate-gelatin reinforced by carbon nitride quantum dots for tissue engineering.

Stem cell treatment is promising in the various disorders treatment, but its effect is confined by the adverse conditions in the damaged tissues. The utilization of hydrogels has been suggested as a procedure to defeat this issue by developing the engraftment and survival of injected stem cells. Specifically, injectable hydrogels have drawn much attention due to their shape adaptability, ease of use, and the capability to reach body parts that are hard to access. In this study, the thermosensitive injectable hydrogels based on oxidized alginate, gelatin, and carbon nitride quantum dots (CNQDs) have been fabricated for tissue engineering. The mechanical characteristics of the nanocomposite hydrogels were investigated by rheology analysis. The results show that increasing the amount of CNQDs improve the mechanical strength of the nanocomposite hydrogels. The Cross-section morphology of freeze dried hydrogels comprising 0.25, 1.5, and 3.0% CNQDs indicate porous structure with interrelated pores. Besides, the result of in vitro degradation reveals that the hydrogels comprising CNQDs are more durable than the one without CNQDs. A reduction in the biodegradation and swelling ratio is perceived with the addition of CNQDs. The cell viability and attachment show that the nanocomposite hydrogels are biocompatible (>88%) with great cell adhesion to osteosarcoma cell line MG63 depending on the presence of CNQDs.

Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering.

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.

Characterization of an oxidized alginate-gelatin hydrogel incorporating a COS-salicylic acid conjugate for wound healing.

In the present study, chitooligosaccharide (COS) and salicylic acid (SA) conjugates were synthesized using H2O2-induced grafting polymerization and oxidized alginate (OA) and gelatin hydrogels were fabricated using Schiff's base reaction. To confirm the synthesis and improved activity of the COS-SA conjugates, polyphenol assays, ultraviolet absorbance, NMR, and antioxidant activity tests were all conducted. The results showed that the COS-SA conjugates were completely synthesized and improved antioxidant activity. OA was synthesized using a periodate method and a hydrogel was obtained at a mixed ratio of 3:7 via crosslinking between the aldehyde group of the OA and the amine groups of gelatin with COS-SA conjugates. In a cytotoxicity and wound healing model, the hydrogels with COS-SA conjugates did not exhibit cytotoxicity and exhibited wound healing activity in a mouse model. These results provide evidence that OA and gelatin hydrogels with a COS-SA conjugate can be successfully used for wound healing applications.