The three-dimensional (3D) printed bone tissue repair guide scaffold is considered a promising method for treating bone defect repair. In this experiment, chitosan (CS), sodium alginate (SA), and mineralized collagen (MC) were combined and 3D printed to form scaffolds. The experimental results showed that the printability of the scaffold was improved with the increase of chitosan concentration. Infrared spectroscopy analysis confirmed that the scaffold formed a cross-linked network through electrostatic interaction between chitosan and sodium alginate under acidic conditions, and X-ray diffraction results showed the presence of characteristic peaks of hydroxyapatite, indicating the incorporation of mineralized collagen into the scaffold system. In the in vitro collagen release experiments, a weakly alkaline environment was found to accelerate the release rate of collagen, and the release amount increased significantly with a lower concentration of chitosan. Cell experiments showed that scaffolds loaded with mineralized collagen could significantly promote cell proliferation activity and alkaline phosphatase expression. The subcutaneous implantation experiment further verified the biocompatibility of the material, and the implantation of printed scaffolds did not cause significant inflammatory reactions. Histological analysis showed no abnormal pathological changes in the surrounding tissues. Therefore, incorporating mineralized collagen into sodium alginate/chitosan scaffolds is believed to be a new tissue engineering and regeneration strategy for achieving enhanced osteogenic differentiation through the slow release of collagen.
Chitosan/chemistry* ; Alginates/chemistry* ; Tissue Scaffolds/chemistry* ; Printing, Three-Dimensional ; Osteogenesis ; Collagen/chemistry* ; Cell Differentiation ; Animals ; Tissue Engineering/methods* ; Cell Proliferation ; Biocompatible Materials ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry*

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

Concrete is widely used in building construction, civil engineering, roads, bridges, etc., but concrete cracking remains a major issue in the engineering industry. To develop an effective and feasible concrete repair technology, this study combined microbial and microencapsulation technologies to prepare a multi-layer compound microcapsule using the piercing method. The formulation and drying method of microcapsules were optimized by taking their embedding rate and mechanical properties as evaluation criteria. The calcium transcrystallization process of microcapsules and the crystal form of products were characterized and compared with the calcium transcrystallization process in free cells. Finally, the effects of microcapsule incorporation on mechanical properties, impermeability, and self-healing performance of concrete specimens were then tested. The results showed that the air-dried multi-layer compound microcapsules, formulated with 1.0% wet cells of Bacillus cereus, 1.5% calcium chloride, 3.0% sodium alginate, 5.0% nutrients, 6.0% glycerol, 0.6% chitosan, and 2.0% urea, achieved an embedding rate of 95.3%, a rupture force of 60.0 N and a hardness of 150.8 N. These microcapsules can transform from a solid state to a flowing colloidal state when the microorganisms inside undergo a calcium formation reaction. Both the microcapsules and free cells produced stable calcite crystal forms of calcium carbonate through the calcium conversion reaction, with the microcapsules producing more uniform-sized particles, which are more conducive to accumulation in cracks, thereby enhancing the stability of repair. When microcapsules were incorporated into the concrete specimen at a content of 0.45%, the flexural strength of the specimen increased by 17.3%, and the compressive strength increased by 12.3%. In the water impermeability test, specimens with microcapsules demonstrated better impermeability compensation for the cement concrete than those with free cells. The self-healing effect of cracks proved that multi-layer compound microcapsules could completely repair cracks up to 0.7 mm wide, and a repair rate of 95% for 0.8 mm wide cracks. In this study, a multi-layer compound microcapsule was developed to protect microorganisms in concrete and provide nutrients required for their growth, which provided a new idea for microbial induced calcium carbonate precipitation in concrete crack repair.
Construction Materials ; Capsules/chemistry* ; Bacillus cereus/metabolism* ; Alginates/chemistry*

We have isolated an intestinal probiotic strain, Pediococcus acidilactici HRQ-1. To improve its gastrointestinal fluid tolerance, transportation and storage stability, and slow-release properties, we employed the extrusion method to prepare the microcapsules with P. acidilactici HRQ-1 as the core material and sodium alginate and chitosan as the wall material. The optimal conditions for preparing the microcapsules were determined by single factor and orthogonal tests, and the optimal ratio was determined by taking the embedding rate, survival rate, storage stability, gastrointestinal fluid tolerance, and release rate as the evaluation indexes. The results showed that under the optimal embedding conditions, the embedding rate reached (89.60±0.02)%. Under the optimal formula of freeze-drying protective agent, the freeze-drying survival rate reached (76.42±0.13)%, and the average size of the microcapsules produced was (1.16±0.03) mm. The continuous gastrointestinal fluid simulation experiments confirmed that the microcapsules ensured the viable bacterial count and can slowly release bacteria in the intestinal fluid. The curve of the viable bacterial count during storage at 4 ℃ and room temperature indicated that the prepared microcapsules achieved strains' live number protection. The formula and preparation process of P. acidilactici microcapsules may provide a technological reserve for the preparation of more live bacterial drugs in the future.
Pediococcus acidilactici/chemistry* ; Probiotics/chemistry* ; Capsules/chemistry* ; Alginates/chemistry* ; Chitosan/chemistry* ; Drug Compounding/methods* ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry* ; Freeze Drying

Background: Neonates and infants experience gastroesophageal reflux as manifested through vomiting, reflux, and coughing. The complaint from many caregivers begins around the 2nd or 3rd month of life and subside around the 6th month of infancy. The standard of care has not been established and treatment options are limited owing to the pharmacological interventions that are deemed safe and effective. Alginate-based formulations, a widely used product in adults such as Gaviscon™, have been explored as another option to treat gastroesophageal reflux. Objectives: To determine the safety and efficacy of alginate-based formulations in reducing symptoms of gastroesophageal reflux in neonates and infants. Methods: An electronic search was conducted for randomized control trials in MEDLINE via PubMed, Herdin Plus, Cochrane Central Register of Controlled Trials, SCOPUS, and Clinical Trials Registry. The search terms were “gastroesophageal reflux,” “acid reflux,” “neonates,” “newborn,” “infants,” “baby,” “babies,”, and “alginate.” Two review authors independently assessed the available full text articles and a third author intervened to settle the discussion. Results: Two studies were identified and included in this study. Due to the difference in the period of measurement of the trials, a meta-analysis was not pursued. However, a systematic review was still conducted. The two studies suggest a significant improvement of symptoms with alginate-based liquid formulations as intervention. No significant adverse events have been noted making this treatment option generally safe for use in infants. Conclusion There is insufficient evidence to conclude that alginate-based formulations ultimately help decrease gastroesophageal reflux in neonates and infants, but initial trials show promising results. There is also insufficient data to conclude the safety profile of this treatment option given the small sample.
Gastroesophageal Reflux ; Infant, Newborn ; Infant ; Alginates

Collagen contains abundant cell binding motifs, which are conducive to adhesion, migration, and differentiation, maintain cell vitality and promote cell proliferation. However, pure collagen hydrogel has some shortcomings such as poor mechanical properties, poor thermal stability and fast degradation. Numerous studies have shown that the properties of collagen can be improved by combining it with natural polysaccharides such as alginate, chitosan, hyaluronic acid and cellulose. In this paper, the research status and biological application fields of four kinds of composite hydrogels, including collagen-alginate composite hydrogels, collagen-chitosan hydrogels, collagen-hyaluronic acid hydrogels and collagen-cellulose hydrogels, were summarized. The common preparation methods of four kinds of composite hydrogels were introduced, and the future development direction of collagen-based composite hydrogels was prospected.
Hydrogels/chemical synthesis* ; Collagen/chemistry* ; Polysaccharides/chemistry* ; Alginates/chemistry* ; Hyaluronic Acid/chemistry* ; Chitosan/chemistry* ; Biocompatible Materials/chemistry* ; Humans ; Tissue Engineering/methods* ; Cellulose/chemistry* ; Tissue Scaffolds

Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.
Alginates ; Biocompatible Materials ; Drug Delivery Systems ; Microspheres ; Plastic Surgery Procedures

OBJECTIVES: To explore the effect of hydrogel loaded with exosomes from Wharton's Jelly-derived mesenchymal stem cell (WJMSC) on wound healing. METHODS: Exosomes were extracted from WJMSC, and the morphology and size of WJMSC-derived exosomes (WEX) were analyzed by transmission electron microscopy and nanoparticle size analyzer, respectively. The surface markers CD9, CD81, and Calnexin of WEX were detected by Western blotting. Exosome-loaded alginate hydrogel (WEX-gel) was prepared; its morphology was studied by scanning electron microscope, and its rheological behavior was examined by a rheometer. The in vitro drug release performance of WEX-gel was investigated by BCA method. RAW264.7 cells were treated with alginate hydrogel, WEX and WEX-gel, respectively; and the expression of CD86 and CD206 in macrophages was detected by flow cytometry. A full-thickness skin wound model was established in mice; the model mice were randomly divided into blank control group, WEX control group and WEX-gel group, and PBS, WEX and WEX-gel were applied to the wound area of mice, respectively. On day 3, the skin tissue of mice was excised, and the antibacterial effect of WEX hydrogel was evaluated by plate counting. On day 15, the mice were euthanized and the percentage of residual wounds was calculated. The histological changes of the skin wound were observed after hematoxylin and eosin (HE) and Masson stainings. The expression of CD86, CD206, CD31 and vascular endothelial growth factor (VEGF) in the skin wound tissue was detected by immunohistochemistry. RESULTS: Exosomes were successfully extracted from WJMSC. WEX-gel presented a regular three-dimensional network structure, good rheology and controlled drug release performance. WEX-gel promoted the polarization of RAW264.7 cells from the M1 phenotype to M2 phenotype in vitro. The residual wound percentage in blank control group, WEX control group and WEX-gel group were (27.5±3.4)%, (15.3±1.2)% and (7.6±1.1)%, respectively (P<0.05). The antibacterial property of WEX-gel is better than that of WEX (P<0.05). The dermis thickness, the number of new hair follicles, and the rate of collagen deposition in the WEX-gel group were significantly higher than those in the other two groups (all P<0.05). The expression of CD206, CD31 and VEGF in skin wound tissue was higher and the expression of CD86 was lower in WEX-gel group than those in other two groups (all P<0.05). CONCLUSIONS WEX-gel can significantly promote wound healing in mice by regulating the polarization of macrophages.
Mice ; Animals ; Vascular Endothelial Growth Factor A ; Wharton Jelly ; Exosomes ; Hydrogels ; Wound Healing/physiology* ; Mesenchymal Stem Cells ; Anti-Bacterial Agents ; Alginates

Biorefinery of chemicals from straw is an effective approach to alleviate the environmental pollution caused by straw burning. In this paper, we prepared gellan gum immobilized Lactobacillus bulgaricus T15 gel beads (LA-GAGR-T15 gel beads), characterized their properties, and established a continuous cell recycle fermentation process for D-lactate (D-LA) production using the LA-GAGR-T15 gel beads. The fracture stress of LA-GAGR-T15 gel beads was (91.68±0.11) kPa, which was 125.12% higher than that of the calcium alginate immobilized T15 gel beads (calcium alginate-T15 gel beads). This indicated that the strength of LA-GAGR-T15 gel beads was stronger, and the strain was less likely to leak out. The average D-LA production was (72.90±2.79) g/L after fermentation for ten recycles (720 h) using LA-GAGR-T15 gel beads as the starting strain and glucose as the substrate, which was 33.85% higher than that of calcium alginate-T15 gel beads and 37.70% higher than that of free T15. Subsequently, glucose was replaced by enzymatically hydrolyzed corn straw and fermented for ten recycles (240 h) using LA-GAGR-T15 gel beads. The yield of D-LA reached (1.74±0.79) g/(L·h), which was much higher than that of using free bacteria. The wear rate of gel beads was less than 5% after ten recycles, which indicated that LA-GAGR is a good carrier for cell immobilization and can be widely used in industrial fermentation. This study provides basic data for the industrial production of D-LA using cell-recycled fermentation, and provides a new way for the biorefinery of D-LA from corn straw.
Fermentation ; Lactobacillus delbrueckii ; Zea mays ; Lactic Acid ; Alginates/chemistry* ; Glucose

Alginate is a group of polyuronic saccharides that are widely used in pharmaceutical and food industry due to its unique physicochemical properties and beneficial health effects. However, the low water solubility and high viscosity of alginate hampered its application. Alginate oligosaccharide (AOS) is a decomposition product of alginate and has received increasing attention due to its low molecular weight, high water solubility, safety, and non-toxicity. The wide-ranging biological functions of AOS are closely related to its structural diversity. AOS with distinct structures and biological functions can be obtained by different methods of preparation. This review summarized the biological functions of AOS reported to date, including anti-tumor, immunomodulatory, anti-inflammatory, antioxidant, prebiotic, and anti-diabetes. The preparation of AOS, as well as the relationship between the structure and biological functions of AOS were discussed, with the aim to provide a reference for further development and application of AOS.
Alginates ; Anti-Inflammatory Agents ; Antioxidants ; Molecular Weight ; Oligosaccharides