Alginate Dialdehyde Research Articles

Dual-Self-Crosslinking Effect of Alginate-Di-Aldehyde with Natural and Synthetic Co-Polymers as Injectable In Situ-Forming Biodegradable Hydrogel.

Injectable, in situ-forming hydrogels, both biocompatible and biodegradable, have garnered significant attention in tissue engineering due to their potential for creating adaptable scaffolds. The adaptability of these hydrogels, made from natural proteins and polysaccharides, opens up a world of possibilities. In this study, sodium alginate was used to synthesize alginate di-aldehyde (ADA) through periodate oxidation, resulting in a lower molecular weight and reduced viscosity, with different degrees of oxidation (54% and 70%). The dual-crosslinking mechanism produced an injectable in situ hydrogel. Initially, physical crosslinking occurred between ADA and borax via borax complexation, followed by chemical crosslinking with gelatin through a Schiff's base reaction, which takes place between the amino groups of gelatin and the aldehyde groups of ADA, without requiring an external crosslinking agent. The formation of Schiff's base was confirmed by Fourier-transform infrared (FT-IR) spectroscopy. At the same time, the aldehyde groups in ADA were characterized using FT-IR, proton nuclear magnetic resonance (¹H NMR), and gel permeation chromatography (GPC), which determined its molecular weight. Furthermore, borax complexation was validated through boron-11 nuclear magnetic resonance (¹¹B NMR). The hydrogel formulation containing 70% ADA, polyethylene glycol (PEG), and 9% gelatin exhibited a decreased gelation time at physiological temperature, attributed to the increased gelatin content and higher degree of oxidation. Rheological analysis mirrored these findings, showing a correlation with gelation time. The swelling capacity was also enhanced due to the increased oxidation degree of PEG and the system's elevated gelatin content and hydrophilicity. The hydrogel demonstrated an average pore size of 40-60 µm and a compressive strength of 376.80 kPa. The lower molecular weight and varied pH conditions influenced its degradation behavior. Notably, the hydrogel's syringeability was deemed sufficient for practical applications, further enhancing its potential in tissue engineering. Given these properties, the 70% ADA/gelatin/PEG hydrogel is a promising candidate and a potential game-changer for injectable, self-crosslinking applications in tissue engineering. Its potential to revolutionize the field is inspiring and should motivate further exploration.

Ferulic acid and human platelet lysate incorporated alginate dialdehyde‐gelatin 3D (bio)printable hydrogels with biological activity

AbstractThis study investigates the creation of multifunctional scaffolds based on alginate dialdehyde (ADA) and gelatin (GEL) incorporating ferulic acid (FA), a phytotherapeutic agent with diverse pharmacological properties, and human platelet lysate (HPL). The multimaterial hydrogels were characterized in terms of degradation/swelling behavior showing that HPL decelerates the degradation process of ADA‐GEL hydrogels in absence of FA. A FA release study confirmed that the presence of HPL does not affect the FA release ability of ADA‐GEL hydrogel. A trinitrobenzenesulfonic acid (TNBS) assay confirmed no influence of HPL on the Schiff's base formation. The addition of HPL was shown to lead to a decrease in stiffness, mechanical stability, and viscosity of ADA‐GEL‐HPL inks. This effect was also observed for ADA‐GEL‐HPL inks when investigating their three‐dimensional (3D) printing ability. Cytocompatibility tests and a 3D bioprinting study confirmed the beneficial impact of the addition of HPL on MC3T3‐E1 cells. Moreover, an antibacterial effect provided by the addition of FA was confirmed while the incorporation of HPL led to higher VEGF‐A expression by MC3T3‐E1 cells. Overall, the addition of HPL and FA to ADA‐GEL hydrogel results in a promising ink, which has potential for future biofabrication applications.

Magnetic alginate core-shell nanoparticles based on Schiff-base imine bonding for pH-responsive doxorubicin delivery system

This research describes the development of a novel pH-responsive drug delivery system (DDS) based on sodium alginate (SA) and magnetic nanoparticles (MNPs) for cancer treatments. One possible approach to creating a wide variety of functional nanoparticles is to graft functional materials onto magnetite nanoparticles. In this study, we demonstrate the effective alteration of Fe3O4 nanoparticles using the alginate dialdehyde (ADA) group through a Schiff-Base imine reaction toward synthesizing Fe3O4@SiO2@APTMS@ADA (FSA@ADA) nanocarrier (NC). doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. The synthesized nanocarriers were thoroughly characterized by various techniques, including FT-IR, FE-SEM, EDX-MAP, TEM, XRD, VSM, TGA, and 1HNMR. In vitro DOX release studies showed a pH-dependent manner and its release rate is lower (< 15 %) at 7.4 than pH 5 (about 75 %) over 25 days. Cytotoxicity results showed good biocompatibility for blank FSA@ADA (over about 85 % cell viability), whereas DOX-loaded FSA@ADA NCs had higher cytotoxic effects (IC50 value: ∼6 µg/mL) as a result of the controlled release of DOX into HeLa cells. Results showed that the magnetic core-shell FSA@ADA/DOX NC has the potential to be used as a targeted stimuli-responsive drug for cancer treatment.

Dual release of daptomycin and BMP-2 from a composite of β-TCP ceramic and ADA gelatin

BackgroundAntibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous β-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a β-TCP ceramic and higher biodegradability than pure alginate.MethodsDual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture.ResultsDaptomycin and the model compound FITC protein A (n = 30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9% were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

Polyethylenimine Inclusion to Develop Aqueous Alginate-Based Core-Shell Capsules for Biomedical Applications.

Aqueous core-shell structures can serve as an efficient approach that allows cells to generate 3D spheroids with in vivo-like cell-to-cell contacts. Here, a novel strategy for fabricating liquid-core-shell capsules is proposed by inverse gelation of alginate (ALG) and layer-by-layer (LbL) coating. We hypothesized that the unique properties of polyethylenimine (PEI) could be utilized to overcome the low structural stability and the limited cell recognition motifs of ALG. In the next step, alginate dialdehyde (ADA) enabled the Schiff-base reaction with free amine groups of PEI to reduce its possible toxic effects. Scanning electron microscopy and light microscopy images proved the formation of spherical hollow capsules with outer diameters of 3.0 ± 0.1 mm for ALG, 3.2 ± 0.1 mm for ALG/PEI, and 4.0 ± 0.2 mm for ALG/PEI/ADA capsules. The effective modulus increased by 3-fold and 5-fold when comparing ALG/PEI/ADA and ALG/PEI to ALG capsules, respectively. Moreover, PEI-coated capsules showed potential antibacterial properties against both Staphylococcus aureus and Escherichia coli, with an apparent inhibition zone. The cell viability results showed that all capsules were cytocompatible (above 75.5%). Cells could proliferate and form spheroids when encapsulated within the ALG/PEI/ADA capsules. Monitoring the spheroid thickness over 5 days of incubation indicated an increasing trend from 39.50 μm after 1 day to 66.86 μm after 5 days. The proposed encapsulation protocol represents a new in vitro platform for developing 3D cell cultivation and can be adapted to fulfill the requirements of various biomedical applications.

Investigating the Effect of Processing and Material Parameters of Alginate Dialdehyde-Gelatin (ADA-GEL)-Based Hydrogels on Stiffness by XGB Machine Learning Model.

To address the limitations of alginate and gelatin as separate hydrogels, partially oxidized alginate, alginate dialdehyde (ADA), is usually combined with gelatin to prepare ADA-GEL hydrogels. These hydrogels offer tunable properties, controllable degradation, and suitable stiffness for 3D bioprinting and tissue engineering applications. Several processing variables affect the final properties of the hydrogel, including degree of oxidation, gelatin content and type of crosslinking agent. In addition, in 3D-printed structures, pore size and the possible addition of a filler to make a hydrogel composite also affect the final physical and biological properties. This study utilized datasets from 13 research papers, encompassing 33 unique combinations of ADA concentration, gelatin concentration, CaCl2 and microbial transglutaminase (mTG) concentrations (as crosslinkers), pore size, bioactive glass (BG) filler content, and one identified target property of the hydrogels, stiffness, utilizing the Extreme Boost (XGB) machine learning algorithm to create a predictive model for understanding the combined influence of these parameters on hydrogel stiffness. The stiffness of ADA-GEL hydrogels is notably affected by the ADA to GEL ratio, and higher gelatin content for different ADA gel concentrations weakens the scaffold, likely due to the presence of unbound gelatin. Pore size and the inclusion of a BG particulate filler also have a significant impact on stiffness; smaller pore sizes and higher BG content lead to increased stiffness. The optimization of ADA-GEL composition and the inclusion of BG fillers are key determinants to tailor the stiffness of these 3D printed hydrogels, as found by the analysis of the available data.

Genipin-Cross-Linked Silk Fibroin/Alginate Dialdehyde Hydrogel with Tunable Gelation Kinetics, Degradability, and Mechanical Properties: A Potential Candidate for Tissue Regeneration.

Genipin-cross-linked silk fibroin (SF) hydrogel is considered to be biocompatible and mechanically robust. However, its use remains a challenge for in situ forming applications due to its prolonged gelation process. In our attempt to facilitate the in situ fabrication of a genipin-mediated SF hydrogel, alginate dialdehyde (ADA) was utilized as a reinforcement template. Here, SF/ADA-based hydrogels with different compositions were synthesized covalently and ionically. Incorporating ADA into the SF hydrogel increased pore size (44.66-174.66 μm), porosity (61.59-80.40%), and the equilibrium swelling degree (7.60-30.17). Moreover, a wide range of storage modulus and compressive modulus were obtained by adjusting the proportions of SF and ADA networks within the hydrogel. The in vitro cell analysis using preosteoblast cells (MC3T3-E1) demonstrated the cytocompatibility of all hydrogels. Overall, the covalently and ionically cross-linked SF/ADA hydrogel represents a promising solution for in situ forming hydrogels for applications in tissue regeneration.

IMPLICATIONS OF STORAGE CONDITIONS ON THE CHARACTERISTICS OF ALGINATE DIALDEHYDE AND ITS HYDROGELS

AbstractA review of recent literature reveals a spurt in the publications using alginate dialdehyde (ADA)‐based hydrogels. This study evaluates the stability and characteristics of ADA solutions stored at different temperatures (4 &amp; −20 °C; designated as ADA4°C &amp; ADA−20°C) and durations (1, 3, and 6 months), and gives valuable insights into the shelf life, a parameter important in a clinical setting. ADA solutions were characterized for their viscosity, aldehyde content, molecular weight, and chemical structure before and after storage. The solution viscosities of ADA4°C showed a decreasing trend over 6 months while that of ADA‐20°C showed an increase. Compared to freshly prepared ADA, a significant reduction in aldehyde content, from 40.1±1.4 % to 37.1±1.01 %, was observed for ADA4°C stored for 6 months, but the aldehyde content was stable for ADA−20°C stored for the same period. Molecular weight remained stable (~6800 g/mol) irrespective of the storage temperatures. Injectable hydrogels were prepared by reacting the stored ADA solutions with 20 % aqueous solutions of gelatin. Hydrogels prepared with ADA stored at 4 °C for 6 months showed a significant increase in gelation time from 4.3±1.5 to 8.79±0.1 min and a decrease in degree of crosslinking from 54.3±1.4 % to 29.2±2.3 %. A decreasing trend was observed for properties such as water uptake (from 470 to 961 %) and tensile strength (from 348 to 282 kPa). Hydrogels made with ADA−20°C demonstrated better retention of physicochemical properties over time. In vitro studies revealed that the hydrogels showed a non‐cytotoxic response towards L929 cells irrespective of the storage conditions. LIVE/DEAD assay and F‐Actin staining revealed good cell proliferation on the hydrogels. In conclusion, retention of the properties of ADA in its aqueous solution requires careful control of storage temperatures.

The alginate dialdehyde crosslinking on curcumin-loaded zein nanofibers for controllable release

In this study, electrospun zein/alginate dialdehyde (AD) nanofibers were prepared by green crosslinking. The degree of crosslinking could reach 50.72 %, and the diameter of electrospun fibers ranged from 446.2 to 541.8 nm. The generation of AD and the bonding of crosslinking were further confirmed by the changes on characteristic peaks and conformational ratios in the infrared spectroscopy and secondary structure analysis. High concentrations of AD led to improved thermal stabilities, mechanical properties, and hydrophobicity. And the highly crosslinked nanofibers (Z-8) owned the highest elastic modulus (24.92 MPa), tensile strength (0.28 MPa), and elongation at break (8.14 %) among five samples. Moreover, Z-8 possessed a high swelling ratio of 5.45 g/g, and a low weight loss of 6.09 %. The samples could encapsulate curcumin efficiently and show controllable release behaviors based on different AD addition. And the oxidation resistance of nanofibers gradually improved, consistent with the release performances. This study indicated AD crosslinking favored the preparation and application of zein nanofibers, and the oxidized polysaccharide acted as the green crosslinking agent, which provided reference value for the application of polysaccharides in food-related electrospun materials.

Engineering peptide-modified alginate-based bioinks with cell-adhesive properties for biofabrication.

Alginate (ALG) and its oxidised form alginate-dialdehyde (ADA) are highly attractive materials for hydrogels used in 3D bioprinting as well as drop-on-demand (DoD) approaches. However, both polymers need to be modified using cell-adhesive peptide sequences, to obtain bioinks exhibiting promising cell-material interactions. Our study explores the modification of ALG- and ADA-based bioinks with the adhesive peptides YIGSR (derived from laminin), RRETEWA (derived from fibronectin) and IKVAV (derived from laminin) for 3D bioprinting. Two coupling methods, carbodiimide and Schiff base reactions, were employed to modify the polymers with peptides. Analytical techniques, including FTIR and NMR were used to assess the chemical composition, revealing challenges in confirming the presence of peptides. The modified bioinks exhibited decreased stability, viscosity, and stiffness, particularly-ADA-based bioinks in contrast to ALG. Sterile hydrogel capsules or droplets were produced using a manual manufacturing process and DoD printing. NIH/3T3 cell spreading analysis showed enhanced cell spreading in carbodiimide-modified ADA, Schiff base-modified ADA, and PEG-Mal-modified ADA. The carbodiimide coupling of peptides worked for ADA, however the same was not observed for ALG. Finally, a novel mixture of all used peptides was evaluated regarding synergistic effects on cell spreading which was found to be effective, showing higher aspect ratios compared to the single peptide coupled hydrogels in all cases. The study suggests potential applications of these modified bioinks in 3D bioprinting approaches and highlights the importance of peptide selection as well as their combination for improved cell-material interactions.

3D bioprinting of multifunctional alginate dialdehyde (ADA)–gelatin (GEL) (ADA-GEL) hydrogels incorporating ferulic acid

The present work explores the 3D extrusion printing of ferulic acid (FA)-containing alginate dialdehyde (ADA)–gelatin (GEL) scaffolds with a wide spectrum of biophysical and pharmacological properties. The tailored addition of FA (≤0.2 %) increases the crosslinking between FA and GEL in the presence of calcium chloride (CaCl2) and microbial transglutaminase, as confirmed using trinitrobenzenesulfonic acid (TNBS) assay. In agreement with an increase in crosslinking density, a higher viscosity of ADA-GEL with FA incorporation was achieved, leading to better printability. Importantly, FA release, enzymatic degradation and swelling were progressively reduced with an increase in FA loading to ADA-GEL, over 28 days. Similar positive impact on antibacterial properties with S. epidermidis strains as well as antioxidant properties were recorded. Intriguingly, FA incorporated ADA-GEL supported murine pre-osteoblast proliferation with reduced osteosarcoma cell proliferation over 7 days in culture, implicating potential anticancer property. Most importantly, FA-incorporated and cell-encapsulated ADA-GEL can be extrusion printed to shape fidelity-compliant multilayer scaffolds, which also support pre-osteoblast cells over 7 days in culture. Taken together, the present study has confirmed the significant potential of 3D bioprinting of ADA-GEL-FA ink to obtain structurally stable scaffolds with a broad spectrum of biophysical and therapeutically significant properties, for bone tissue engineering applications.

Crosslinked fish scale gelatin/alginate dialdehyde functional films incorporated with carbon dots derived from pomelo peel waste for active food packaging

A multifunctional and environmentally friendly composite film was developed by incorporating pomelo peel-derived carbon dots (PCDs) into a fish scale gelatin (FSG)/alginate dialdehyde (ADA) biopolymer matrix. ADA was used to reinforce the physicomechanical properties of the FSG film via Schiff base crosslinking. PCDs with strong antioxidant and antimicrobial activities were synthesized via a hydrothermal method. The effect of various PCDs content on the surface morphological, physicochemical, and functional characteristics of the composite films was investigated. The results showed that the introduction of PCDs into the FSG/ADA matrix effectively reinforced the mechanical performance, enhanced the water vapor and water resistance, increased UV-light blocking, conferred fluorescence properties, and improved the thermal properties of the composite films. Under 3 wt% PCDs content, the FSG/ADA/PCDs-3 % composite film not only presented significant antioxidant capacity with a radical scavenging rate of 91.71 % for DPPH and approximately 100 % for ABTS, but also exhibited excellent antimicrobial ability against bacteria and fungi. Results of a preservation experiment showed that the prepared FSG/ADA/PCDs-3 % film preserved the physiological qualities of strawberries post-harvest and extended their shelf-life to 7 days at room temperature. Overall, the fabricated FSG/ADA/PCDs composite films are promising for use in eco-friendly active food packaging.

Chitosan/alginate dialdehyde trilayer films with cinnamaldehyde nanoemulsions for grass carp preservation

Chitosan (CS) cross-linked films were prepared using the Maillard reaction (CMR). Layer-by-layer casting created additional layers using alginate dialdehyde (ADA) containing cinnamaldehyde nanoemulsions (CANE) and CS. The ability to preserve grass carp fillets was evaluated along with the effects of CANE concentration on the microstructure, physicochemical properties, controlled-release behavior, antioxidation, and antibacterial activities of the films. In all films, Schiff base-induced bonds, electrostatic interactions, and hydrogen bonds brought the layers closer together, improving the mechanical properties (e.g., a 70% increase in tensile strength and a 34% increase in breaking elongation) and barrier capacity (e.g., inhibiting ultraviolet, water vapor, and oxygen transmission). CANE can improve the antioxidant activity, antibacterial activity, and sustained release characteristics of films. More importantly, over the 8-day storage period, the fish packaged using the active films were better than those in the control, commercial PE, and CS films in terms of thiobarbituric acid reactive substances, pH, texture, total viable counts, and volatile basic nitrogen with indicator species. Fish could have a prolonged shelf life due to the prepared CMR/ADA-CA/CS film. In other words, it may be used as a sustainable food packaging material, with the performance of the film being regulated by different CANE concentrations.

Construction and Evaluation of Alginate Dialdehyde Grafted RGD Derivatives/Polyvinyl Alcohol/Cellulose Nanocrystals IPN Composite Hydrogels.

To enhance the mechanical strength and cell adhesion of alginate hydrogel, making it satisfy the requirements of an ideal tissue engineering scaffold, the grafting of Arg-Gly-Asp (RGD) polypeptide sequence onto the alginate molecular chain was conducted by oxidation of sodium periodate and subsequent reduction amination of 2-methylpyridine borane complex (2-PBC) to synthesize alginate dialdehyde grafted RGD derivatives (ADA-RGD) with good cellular affinity. The interpenetrating network (IPN) composite hydrogels of alginate/polyvinyl alcohol/cellulose nanocrystals (ALG/PVA/CNCs) were fabricated through a physical mixture of ion cross-linking of sodium alginate (SA) with hydroxyapatite/D-glucono-δ-lactone (HAP/GDL), and physical cross-linking of polyvinyl alcohol (PVA) by a freezing/thawing method, using cellulose nanocrystals (CNCs) as the reinforcement agent. The effects of the addition of CNCs and different contents of PVA on the morphology, thermal stability, mechanical properties, swelling, biodegradability, and cell compatibility of the IPN composite hydrogels were investigated, and the effect of RGD grafting on the biological properties of the IPN composite hydrogels was also studied. The resultant IPN ALG/PVA/CNCs composite hydrogels exhibited good pore structure and regular 3D morphology, whose pore size and porosity could be regulated by adjusting PVA content and the addition of CNCs. By increasing the PVA content, the number of physical cross-linking points in PVA increased, resulting in greater stress support for the IPN composite hydrogels of ALG/PVA/CNCs and consequently improving their mechanical characteristics. The creation of the IPN ALG/PVA/CNCs composite hydrogels' physical cross-linking network through intramolecular or intermolecular hydrogen bonding led to improved thermal resistance and reduced swelling and biodegradation rate. Conversely, the ADA-RGD/PVA/CNCs IPN composite hydrogels exhibited a quicker degradation rate, attributed to the elimination of ADA-RGD by alkali. The results of the in vitro cytocompatibility showed that ALG/0.5PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels showed better proliferative activity in comparison with other composite hydrogels, while ALG/PVA/0.3%CNCs and ADA-RGD/PVA/0.3%CNCs composite hydrogels displayed obvious proliferation effects, indicating that PVA, CNCs, and ADA-RGD with good biocompatibility were conducive to cell proliferation and differentiation for the IPN composite hydrogels.

Reinforcing Tissue‐Engineered Cartilage: Nanofibrillated Cellulose Enhances Mechanical Properties of Alginate Dialdehyde–Gelatin Hydrogel

Cartilage tissue engineering offers a promising option for treating osteochondral defects. Alginate dialdehyde–gelatin (ADA–GEL) hydrogel has been explored as promising material for soft tissue scaffolds; however, its low stiffness has posed a constraint to load bearing applications. Herein, this limitation is addressed by introducing nanofibrillated cellulose (NFC) into the ADA–GEL matrix. The effect of NFC on the physicochemical properties of hydrogels is evaluated. Fourier transform infrared spectra demonstrate no chemical interaction between NFC and ADA–GEL, while scanning electron microscopy pictures reveal NFC fibers embedded in the hydrogel matrix, thus confirming the fiber‐reinforced composite hypothesis. NFC‐reinforced ADA–GEL (AG‐N) composite hydrogels exhibit increased stiffness, with a maximum compressive effective modulus of 19.6 ± 3.0 kPa at 25% w/w NFC content. ATDC5 cell viability and proliferation as well as chondrogenic differentiation are assessed using immunohistochemical staining for sulfated glycosaminoglycans and collagen type II. A possible application of AG‐N hydrogels as an osteochondral plug is also proposed, with polyetheretherketone as the subchondral bone anchor part. The mechanical properties of the resulting osteochondral device highlight its potential as a promising biomaterial for treatment of osteochondral defects. These findings provide valuable insights into the development of AG‐N hydrogels for load‐bearing tissue engineering applications.

Fabrication of triple-crosslinked gelatin/alginate hydrogels for controlled release applications

Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.

Composite material consisting of microporous beta-TCP ceramic and alginate-dialdehyde-gelatin for controlled dual release of clindamycin and bone morphogenetic protein 2

The aim of this study was to produce a composite of microporous β-TCP filled with alginate-gelatin crosslinked hydrogel, clindamycin and bone morphogenetic protein (BMP-2) to prolong the drug-release behaviour for up to 28 days. The most promising alginate-di-aldehyde(ADA)-gelatin gel for drug release from microcapsules was used to fill microporous β-TCP ceramics under directional flow in a special loading chamber. Dual release of clindamycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21 and 28 by high performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). After release, the microbial efficacy of the clindamycin was checked and the biocompatibility of the composite was tested in cell culture. Clindamycin and the model substance FITC-protein A were released from microcapsules over 28 days. The clindamycin burst release was 43 ± 1%. For the loaded ceramics, a clindamycin release above the minimal inhibitory concentration (MIC) until day 9 and a burst release of 90.56 ± 2.96% were detected. BMP-2 was released from the loaded ceramics in low concentrations over 28 days. The release of active substances from β-TCP and hydrogel have already been extensively studied. Directional flow loading is a special procedure in which the ceramic could act as a stabilizer in the bone and, as a biodegradable system, enables a single-stage surgical procedure. Whether ADA-gelatin gel is suitable for this procedure as a more biodegradable alternative to pure alginate or whether a dual release is possible in this composite has not yet been investigated.Graphical

Synthesis of Schiff's Base Between Dialdehid Alginate and Chitosan and Testing of Antibacterial Properties

Schiff base synthesis has been carried out through a condensation reaction between dialdehyde alginate and chitosan. The first step is to oxidize Na-alginate using a sodium periodate (NaIO4) oxidizer, which produces alginate dialdehyde. The next step is FT-IR analysis, degree of oxidation, swelling ratio, and antibacterial properties. The FT-IR analysis results of alginate dialdehyde, which has been absorption peak at 1627.92 cm-1, show stretching group C=O and wave number 1026.13 cm-,1 stretching group COC (cyclic ether). The Schiff base has been absorption peak at 1635.64 cm-1, a stretching vibration group C=N. The degree of oxidation is 33%, and the swelling ratio is 50%. The testing of antibacterial which is conducted has been antimicrobials zone of Escherichia coli bacteria to Schiff base 0 mm and chitosan 0.225 mm; meanwhile, for Staphylococcus aureus bacteria antimicrobials zone which is Schiff base 1.916 mm and chitosan 0.333 mm. It can be concluded that Schiff base can inhibit the growth of Staphylococcus aureus bacteria than Escherichia coli bacteria were not inhibited.

A 3D-Printed Wound-Healing Material Composed of Alginate Dialdehyde-Gelatin Incorporating Astaxanthin and Borate Bioactive Glass Microparticles.

In this study, a wound dressing composed of an alginate dialdehyde-gelatin (ADA-GEL) hydrogel incorporated by astaxanthin (ASX) and 70B (70:30 B2O3/CaO in mol %) borate bioactive glass (BBG) microparticles was developed through 3D printing. ASX and BBG particles stiffened the composite hydrogel construct and delayed its in vitro degradation compared to the pristine hydrogel construct, mainly due to their cross-linking role, likely arising from hydrogen bonding between the ASX/BBG particles and ADA-GEL chains. Additionally, the composite hydrogel construct could hold and deliver ASX steadily. The composite hydrogel constructs codelivered biologically active ions (Ca and B) and ASX, which should lead to a faster, more effective wound-healing process. As shown through in vitro tests, the ASX-containing composite hydrogel promoted fibroblast (NIH 3T3) cell adhesion, proliferation, and vascular endothelial growth factor expression, as well as keratinocyte (HaCaT) migration, thanks to the antioxidant activity of ASX, the release of cell-supportive Ca2+ and B3+ ions, and the biocompatibility of ADA-GEL. Taken together, the results show that the ADA-GEL/BBG/ASX composite is an attractive biomaterial to develop multipurposed wound-healing constructs through 3D printing.

Neural Tissue Engineering with Rat Adipose-Derived Mesenchymal Stem Cells: The Role of an Injectable, Resorbable Hydrogel Scaffold Derived from Oxidized Alginate and Gelatin.

The central nervous system has limited regeneration potential. The multipotency of adipose-derived mesenchymal stem cells (ADMSC) makes them an ideal autologous cell source for the regeneration of neural tissues. However, the likelihood of their differentiation into unwanted cell lineages when transplanted into a hostile injury environment is a serious disadvantage. Transplanting predifferentiated cells via an injectable carrier may aid in site-specific delivery for better survival of cells. Here, we focus on identifying an appropriate injectable hydrogel system that favors stem/progenitor cell attachment and differentiation for neural tissue engineering. An injectable composition of the hydrogel, derived from alginate dialdehyde (ADA) and gelatin, was formulated for this purpose. This hydrogel promoted proliferation/differentiation of ADMSCs to neural progenitors, visualized from the generation of prominent neurospheres and stage-specific expression of a neural progenitor marker (nestin, day 4), an intermittent neuronal marker (β-III tub, day 5), and a mature neuronal marker (MAP-2, day 8) with neural branching and networking (>85%). The differentiated cells also expressed the functional marker synaptophysin. There was no negative impact on stem/progenitor cell survival (>95%) or differentiation (∼90%) as compared to two-dimensional (2D) culture. Addition of appropriate quantities of asiatic acid specific for neural niche supported cell growth and differentiation without affecting cell survival (>90%) and improved neural branching and elongation. Optimized interconnected porous hydrogel niche exhibited rapid gelation (3 min) and self-healing properties mimicking native neural tissue. Both ADA-gelatin hydrogel by itself and that incorporated with asiatic acid were found to support stem/neural progenitor cell growth and differentiation and have potential applications as antioxidants and growth promoters upon release at the cell transplantation site. In short, the matrix itself or incorporated with phytomoieties could serve as a potential minimally invasive injectable cell delivery vehicle for cell-based therapies of neural diseases.