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1.
Food Res Int ; 188: 114496, 2024 Jul.
Article En | MEDLINE | ID: mdl-38823843

Agro-industrial co-products, such as fish gelatin, stand out for their capacity in forming biopolymeric films, being biocompatible and non-toxic; however, its hydrophilicity poses a challenge. Essential oils, rich in bioactives, attract research interest aiming to enhance the protective barrier of films and enable their application in packaging. This study produced films based on cross-linked Nile tilapia skin gelatin, incorporating garlic essential oil. Gelatin obtained through partial collagen hydrolysis from the fish skin and cross-linked with gallic acid had hydroxyproline content of 10.02 g 100 g-1 and gel strength of 287 g, which were consistent with other studies. Oil extraction used supercritical CO2 as a solvent and ethanol as a cosolvent, following a factorial experimental design, evaluating the extraction temperature (40 °C and 70 °C) and cosolvent ratio (1:1 and 1:3), with three central points. Extraction was successful, with higher yields on a dry basis at 70 °C (88.35 %), using a 1:1 cosolvent ratio. Films incorporated with oil exhibited lower water vapor permeability (WVP) than those with only cross-linked gelatin (1.59 (g m-1 s-1 Pa-1) 1011). The film with the most suitable tensile strength (19.07 MPa), elongation (120.91 %), and WVP (1.09 (g m-1 s-1 Pa-1) 1011) properties contained garlic oil extracted at the central point (55 °C and 1:2). Thermal analysis indicated increased melting temperatures in films with added oil, suggesting low thermal degradation. These results suggest that garlic oil addition can improve the properties of fish gelatin-based films, making them promising for biodegradable packaging.


Food Packaging , Garlic , Gelatin , Oils, Volatile , Permeability , Gelatin/chemistry , Oils, Volatile/chemistry , Animals , Garlic/chemistry , Food Packaging/methods , Tensile Strength , Steam , Sulfides/chemistry , Hydrophobic and Hydrophilic Interactions , Skin/chemistry
2.
Carbohydr Polym ; 339: 122288, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823936

This paper reports on biofunctionalisation of a poly(lactic acid) (PLA) film by surface activation through cold plasma treatment followed by coating with a chitosan-gelatin xerogel. The UV cross-linking of the xerogel precursor was simultaneously performed with the fixation onto the PLA support. This has a strong effect on surface properties, in terms of wettability, surface free energy, morphology and micromechanical features. The hydrophilic - hydrophobic character of the surface, determined by contact angle measurements, was tuned along the process, passing from moderate hydrophobic PLA to enhanced hydrophilic plasma activated surface, which favors coating adhesion, then to moderate hydrophobic chitosan-gelatin coating. The coating has a Lewis amphoteric surface, with a porous xerogel-like morphology, as revealed by scanning electron microscopy images. By riboflavin mediated UV cross-linking the chitosan-gelatin coating becomes high adhesive and with a more pronounced plasticity, as shown by AFM force-distance spectroscopy. Thus prepared surface-coated PLA supports were successfully tested for growth of dermal fibroblasts, which are known for their induction potential of chondrogenic cells, which is very important in cartilage tissue engineering.


Chitosan , Fibroblasts , Gelatin , Polyesters , Chitosan/chemistry , Gelatin/chemistry , Polyesters/chemistry , Fibroblasts/drug effects , Fibroblasts/cytology , Humans , Surface Properties , Gels/chemistry , Ultraviolet Rays , Plasma Gases/chemistry , Hydrophobic and Hydrophilic Interactions , Coated Materials, Biocompatible/chemistry , Cross-Linking Reagents/chemistry , Wettability
3.
Carbohydr Polym ; 339: 122174, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823938

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.


Bone Regeneration , Freeze Drying , Gelatin , Hyaluronic Acid , Hydrogels , Iridoids , Platelet-Rich Fibrin , Animals , Iridoids/chemistry , Iridoids/pharmacology , Gelatin/chemistry , Rabbits , Hydrogels/chemistry , Hydrogels/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Bone Regeneration/drug effects , Platelet-Rich Fibrin/chemistry , Tissue Engineering/methods , Cross-Linking Reagents/chemistry , Tissue Scaffolds/chemistry , Tibia/drug effects , Tibia/surgery
4.
Food Microbiol ; 122: 104559, 2024 Sep.
Article En | MEDLINE | ID: mdl-38839223

Listeria monocytogenes is a concerning foodborne pathogen incriminated in soft cheese and meat-related outbreaks, highlighting the significance of applying alternative techniques to control its growth in food. In the current study, eco-friendly zinc oxide nanoparticles (ZnO-NPs) were synthesized using Rosmarinus officinalis, Punica granatum, and Origanum marjoram extracts individually. The antimicrobial efficacy of the prepared ZnO-NPs against L. monocytogenes was assessed using the agar well diffusion technique. Data indicated that ZnO-NPs prepared using Origanum marjoram were the most effective; therefore, they were used for the preparation of gelatin-based bionanocomposite coatings. Furthermore, the antimicrobial efficacy of the prepared gelatin-based bionanocomposite coatings containing eco-friendly ZnO-NPs was evaluated against L. monocytogenes in Talaga cheese (an Egyptian soft cheese) and camel meat during refrigerated storage at 4 ± 1 oC. Talaga cheese and camel meat were inoculated with L. monocytogenes, then coated with gelatin (G), gelatin with ZnO-NPs 1% (G/ZnO-NPs 1%), and gelatin with ZnO-NPs 2% (G/ZnO-NPs 2%). Microbiological examination showed that the G/ZnO-NPs 2% coating reduced L. monocytogenes count in the coated Talaga cheese and camel meat by 2.76 ± 0.19 and 2.36 ± 0.51 log CFU/g, respectively, by the end of the storage period. Moreover, G/ZnO-NPs coatings controlled pH changes, reduced water losses, and improved the sensory characteristics of Talaga cheese and camel meat, thereby extending their shelf life. The obtained results from this study indicate that the application of gelatin/ZnO-NPs 2% bionanocomposite coating could be used in the food industry to control L. monocytogenes growth, improve quality, and extend the shelf life of Talaga cheese and camel meat.


Camelus , Cheese , Food Storage , Gelatin , Listeria monocytogenes , Nanocomposites , Zinc Oxide , Listeria monocytogenes/drug effects , Listeria monocytogenes/growth & development , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Cheese/microbiology , Gelatin/chemistry , Gelatin/pharmacology , Animals , Nanocomposites/chemistry , Food Preservation/methods , Meat/microbiology , Food Microbiology , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Pomegranate/chemistry , Food Contamination/prevention & control , Food Contamination/analysis , Rosmarinus/chemistry , Refrigeration , Plant Extracts/pharmacology , Plant Extracts/chemistry
5.
Sci Rep ; 14(1): 12945, 2024 06 05.
Article En | MEDLINE | ID: mdl-38839791

Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days. Rheological stiffness measurements revealed two soft gels with similar storage moduli. The cells did not have a significant impact on the overall stiffness, whereas ADA-GEL (2.5/2.5%) was significantly stiffer than Alg/HA/Gel (0.5/0.1/3%). Regarding the shrinkage of printed constructs, cells had a significant influence, especially in ADA-GEL, which has covalent bonds between the oxidized alginate and gelatin. Multi-photon microscopy exhibited proliferation, cell spreading and migration in ADA-GEL with cell-cell and cell-matrix interaction, dissimilarly to Alg/HA/Gel, in which cells formed spherical, encapsulated colonies. Scanning electron microscopy and histology showed degradation and multi-layered growth on ADA-GEL and fewer examples of escaped cells on Alg/HA/Gel. Both gels serve as proliferation bioink for melanoma with more necrosis in deeper Alg/HA/Gel colonies and differences in spreading and matrix interaction. These findings show the importance of proper characterization of the bioinks for different applications.


Alginates , Bioprinting , Cell Proliferation , Gelatin , Melanoma , Printing, Three-Dimensional , Alginates/chemistry , Melanoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Gelatin/chemistry , Bioprinting/methods , Humans , Ink , Hyaluronic Acid/chemistry , Rheology , Tissue Scaffolds/chemistry , Tissue Engineering/methods
6.
Sci Rep ; 14(1): 12670, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830883

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.


Amnion , Bioprinting , Fibroblasts , Gelatin , Human Umbilical Vein Endothelial Cells , Keratinocytes , Tissue Engineering , Tissue Scaffolds , Keratinocytes/drug effects , Keratinocytes/cytology , Keratinocytes/metabolism , Gelatin/chemistry , Humans , Tissue Engineering/methods , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/cytology , Tissue Scaffolds/chemistry , Amnion/cytology , Amnion/metabolism , Amnion/chemistry , Bioprinting/methods , Printing, Three-Dimensional , Skin/metabolism , Skin/cytology , Methacrylates/chemistry , Cell Survival/drug effects , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Endothelial Cells/cytology
7.
BMC Biotechnol ; 24(1): 38, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38831403

BACKGROUND: Antibiotic-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 ß-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a ß-TCP ceramic and higher biodegradability than pure alginate. METHODS: Dual 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. RESULTS: Daptomycin 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.


Anti-Bacterial Agents , Bone Morphogenetic Protein 2 , Calcium Phosphates , Ceramics , Daptomycin , Gelatin , Bone Morphogenetic Protein 2/chemistry , Bone Morphogenetic Protein 2/metabolism , Daptomycin/chemistry , Daptomycin/pharmacology , Gelatin/chemistry , Ceramics/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Calcium Phosphates/chemistry , Animals , Microbial Sensitivity Tests , Mice , Drug Carriers/chemistry , Drug Liberation
8.
J Appl Biomater Funct Mater ; 22: 22808000241245298, 2024.
Article En | MEDLINE | ID: mdl-38733215

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract-loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds.


Bandages , Diabetes Mellitus, Experimental , Gelatin , Wound Healing , Animals , Gelatin/chemistry , Wound Healing/drug effects , Rats , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Experimental/pathology , Male , Humans , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Tissue Scaffolds/chemistry
9.
Eur J Med Res ; 29(1): 270, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704575

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.


Hair , Insulin-Like Growth Factor I , Mesenchymal Stem Cells , Umbilical Cord , Animals , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Humans , Culture Media, Conditioned/pharmacology , Mice , Umbilical Cord/cytology , Hair/growth & development , Hair/drug effects , Insulin-Like Growth Factor I/metabolism , Vascular Endothelial Growth Factor A/metabolism , Hepatocyte Growth Factor/metabolism , Gelatin/chemistry , Tissue Scaffolds/chemistry , Mice, Inbred C57BL , Cells, Cultured , Fibroblast Growth Factor 7/metabolism
10.
J Nanobiotechnology ; 22(1): 289, 2024 May 27.
Article En | MEDLINE | ID: mdl-38802863

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.


Alginates , Contrast Media , Gadolinium , Hydrogels , Magnetic Resonance Imaging , Microspheres , Magnetic Resonance Imaging/methods , Gadolinium/chemistry , Animals , Alginates/chemistry , Hydrogels/chemistry , Contrast Media/chemistry , Wound Healing/drug effects , Cross-Linking Reagents/chemistry , Gelatin/chemistry , Mice , Tissue Scaffolds/chemistry
11.
Braz Dent J ; 35: e245461, 2024.
Article En | MEDLINE | ID: mdl-38775590

This study aimed to evaluate the osteogenic potential of hydroxyapatite (HA), Alginate (Alg), and Gelatine (Gel) composite in a critical-size defect model in rats. Twenty-four male rats were divided into three groups: a negative control with no treatment (Control group), a positive control treated with deproteinized bovine bone mineral (DBBM group), and the experimental group treated with the new HA-Alg-Gel composite (HA-Alg-Gel group). A critical size defect (8.5mm) was made in the rat's calvaria, and the bone formation was evaluated by in vivo microcomputed tomography analysis (µCT) after 1, 15, 45, and 90 days. After 90 days, the animals were euthanized and histological and histomorphometric analyses were performed. A higher proportion of mineralized tissue/biomaterial was observed in the DBBM group when compared to the HA-Alg-Gel and Control groups in the µCT analysis during all analysis periods. However, no differences were observed in the mineralized tissue/biomaterial proportion observed on day 1 (immediate postoperative) in comparison to later periods of analysis in all groups. In the histomorphometric analysis, the HA-Alg-Gel and Control groups showed higher bone formation than the DBBM group. Moreover, in histological analysis, five samples of the HA-Alg-Gal group exhibited formed bone spicules adjacent to the graft granules against only two of eight samples in the DBBM group. Both graft materials ensured the maintenance of defect bone thickness, while a tissue thickness reduction was observed in the control group. In conclusion, this study demonstrated the osteoconductive potential of HA-Alg-Gel bone graft by supporting new bone formation around its particles.


Alginates , Bone Regeneration , Durapatite , Gelatin , Skull , X-Ray Microtomography , Animals , Bone Regeneration/drug effects , Durapatite/pharmacology , Skull/surgery , Skull/diagnostic imaging , Rats , Male , Biocompatible Materials , Glucuronic Acid , Rats, Wistar , Hexuronic Acids , Osteogenesis/drug effects , Bone Substitutes
12.
Int J Mol Sci ; 25(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38791348

Hybrid nanomaterials have attracted considerable interest in biomedicine because of their fascinating characteristics and wide range of applications in targeted drug delivery, antibacterial activity, and cancer treatment. This study developed a gelatin-coated Titanium oxide/palladium (TiO2/Pd) hybrid nanomaterial to enhance the antibacterial and anticancer capabilities. Morphological and structural analyses were conducted to characterize the synthesized hybrid nanomaterial. The surface texture of the hybrid nanomaterials was examined by high-resolution transmission electron microscopy (HR-TEM) and field-emission scanning electron microscopy (FE-SEM). The FE-SEM image revealed the bulk of the spherically shaped particles and the aggregated tiny granules. Energy dispersive X-ray spectroscopy (EDS) revealed Ti, Pd, C, and O. X-ray diffraction (XRD) revealed the gelatin-coated TiO2/Pd to be in the anatase form. Fourier transform infrared spectroscopy examined the interactions among the gelatin-coated TiO2/Pd nanoparticles. The gelatin-coated TiO2/Pd nanomaterials exhibited high antibacterial activity against Escherichia coli (22 mm) and Bacillus subtilis (17 mm) compared to individual nanoparticles, confirming the synergistic effect. More importantly, the gelatin-coated TiO2/Pd hybrid nanomaterial exhibited remarkable cytotoxic effects on A549 lung cancer cells which shows a linear increase with the concentration of the nanomaterial. The hybrid nanomaterials displayed higher toxicity to cancer cells than the nanoparticles alone. Furthermore, the cytotoxic activity against human cancer cells was verified by the generation of reactive oxygen species and nuclear damage. Therefore, gelatin-coated TiO2/Pd nanomaterials have potential uses in treating cancer and bacterial infections.


Anti-Bacterial Agents , Antineoplastic Agents , Escherichia coli , Gelatin , Nanostructures , Palladium , Titanium , Titanium/chemistry , Titanium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Gelatin/chemistry , Palladium/chemistry , Palladium/pharmacology , Escherichia coli/drug effects , Nanostructures/chemistry , A549 Cells , Bacillus subtilis/drug effects , Microbial Sensitivity Tests , X-Ray Diffraction , Metal Nanoparticles/chemistry
13.
Int J Mol Sci ; 25(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38791364

The use of natural active substances and the development of new formulations are promising directions in the cosmetic and pharmacy industries. The primary purpose of this research was the production of microparticles based on whey protein isolate (WPI) and calcium alginate (ALG) containing Calendula officinalis flower extract and their incorporation into films composed of gelatin, WPI, and glycerol. Both swollen and dry microparticles were studied by optical microscopy and their sizes were measured. Water absorption by the microparticles, their loading capacity, and the release profile of flower extract were also characterized. The films were analyzed by mechanical tests (Young's modulus, tensile strength, elongation at break), swelling capacity, contact angle, and moisture content measurements. The presented data showed that the active ingredient was successfully enclosed in spherical microparticles and completely released after 75 min of incubation at 37 °C. The incorporation of the microparticles into polymer films caused a decrease in stiffness and tensile strength, simultaneously increasing the ductility of the samples. Moreover, the films containing microparticles displayed higher swelling ability and moisture content compared to those without them. Hence, the materials prepared in this study with Calendula officinalis flower extract encapsulated into polymeric microspheres can be a starting point for the development of new products intended for skin application; advantages include protection of the extract against external factors and a controlled release profile.


Calendula , Delayed-Action Preparations , Flowers , Plant Extracts , Tensile Strength , Whey Proteins , Calendula/chemistry , Flowers/chemistry , Plant Extracts/chemistry , Whey Proteins/chemistry , Delayed-Action Preparations/chemistry , Alginates/chemistry , Gelatin/chemistry , Microspheres
14.
Int J Pharm ; 658: 124205, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38734278

The current wound healing process faces numerous challenges such as bacterial infection, inflammation and oxidative stress. However, wound dressings used to promote wound healing, are not well suited to meet the clinical needs. Hyaluronic acid (HA) not only has excellent water absorption and good biocompatibility but facilitates cell function and tissue regeneration. Dopamine, on the other hand, increases the overall viscosity of the hydrogel and possesses antioxidant property. Furthermore, chitosan exhibits outstanding performance in antimicrobial, anti-inflammatory and antioxidant activities. Basic fibroblast growth factor (bFGF) is conducive to cell proliferation and migration, vascular regeneration and wound healing. Hence, we designed an all-in-one hydrogel patch containing dopamine and chitosan framed by hyaluronic acid (HDC) with sprayed gelatin methacryloyl (GelMA) microspheres loaded with bFGF (HDC-bFGF). The hydrogel patch exhibits excellent adhesive, anti-inflammatory, antioxidant and antibacterial properties. In vitro experiments, the HDC-bFGF hydrogel patch not only showed significant inhibitory effect on RAW cell inflammation and Staphylococcus aureus (S. aureus) growth but also effectively scavenged free radicals, in addition to promoting the migration of 3 T3 cells. In the mice acute infected wound model, the HDC-bFGF hydrogel patch adhered to the wound surface greatly accelerated the healing process via its anti-inflammatory and antioxidant activities, bacterial inhibition and pro-vascularization effects. Therefore, the multifunctional HDC-bFGF hydrogel patch holds great promise for clinical application.


Anti-Bacterial Agents , Anti-Inflammatory Agents , Antioxidants , Chitosan , Fibroblast Growth Factor 2 , Gelatin , Hydrogels , Methacrylates , Microspheres , Staphylococcus aureus , Wound Healing , Animals , Wound Healing/drug effects , Mice , Fibroblast Growth Factor 2/administration & dosage , Fibroblast Growth Factor 2/chemistry , Fibroblast Growth Factor 2/pharmacology , Gelatin/chemistry , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/administration & dosage , Chitosan/chemistry , Chitosan/administration & dosage , Antioxidants/administration & dosage , Antioxidants/pharmacology , Antioxidants/chemistry , Methacrylates/chemistry , Methacrylates/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Male , Dopamine/administration & dosage , Dopamine/chemistry , Dopamine/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/pharmacology , RAW 264.7 Cells , Cell Movement/drug effects , Wound Infection/drug therapy
15.
ACS Appl Mater Interfaces ; 16(19): 25317-25332, 2024 May 15.
Article En | MEDLINE | ID: mdl-38706308

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.


Femur , Glass , Mandible , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Glass/chemistry , Mandible/diagnostic imaging , Mandible/surgery , Mandible/drug effects , Femur/drug effects , Femur/diagnostic imaging , Femur/pathology , Gelatin/chemistry , Bone Regeneration/drug effects , Alginates/chemistry , Porosity , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering
16.
Sci Rep ; 14(1): 10931, 2024 05 13.
Article En | MEDLINE | ID: mdl-38740842

Biomaterial scaffolds play a pivotal role in the advancement of cultured meat technology, facilitating essential processes like cell attachment, growth, specialization, and alignment. Currently, there exists limited knowledge concerning the creation of consumable scaffolds tailored for cultured meat applications. This investigation aimed to produce edible scaffolds featuring both smooth and patterned surfaces, utilizing biomaterials such as salmon gelatin, alginate, agarose and glycerol, pertinent to cultured meat and adhering to food safety protocols. The primary objective of this research was to uncover variations in transcriptomes profiles between flat and microstructured edible scaffolds fabricated from marine-derived biopolymers, leveraging high-throughput sequencing techniques. Expression analysis revealed noteworthy disparities in transcriptome profiles when comparing the flat and microstructured scaffold configurations against a control condition. Employing gene functional enrichment analysis for the microstructured versus flat scaffold conditions yielded substantial enrichment ratios, highlighting pertinent gene modules linked to the development of skeletal muscle. Notable functional aspects included filament sliding, muscle contraction, and the organization of sarcomeres. By shedding light on these intricate processes, this study offers insights into the fundamental mechanisms underpinning the generation of muscle-specific cultured meat.


Cell Differentiation , Meat , Tissue Scaffolds , Transcriptome , Tissue Scaffolds/chemistry , Animals , Biopolymers , Muscle Development/genetics , Alginates/chemistry , Gene Expression Profiling , Sepharose/chemistry , Biocompatible Materials/chemistry , Gelatin/chemistry , Muscle Cells/metabolism , Salmon , In Vitro Meat
17.
Nano Lett ; 24(19): 5690-5698, 2024 May 15.
Article En | MEDLINE | ID: mdl-38700237

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.


Hydrogels , Hydrogels/chemistry , Animals , Mice , Humans , Cell Line, Tumor , Female , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Immunotherapy , Gelatin/chemistry , Methacrylates/chemistry , Methacrylates/pharmacology , Breast Neoplasms/immunology
18.
Int J Mol Sci ; 25(9)2024 May 03.
Article En | MEDLINE | ID: mdl-38732231

Regenerative medicine is an interdisciplinary field aiming at restoring pathologically damaged tissues and whole organs by cell transplantation in combination with proper supporting scaffolds. Gelatine-based ones are very attractive due to their biocompatibility, rapid biodegradability, and lack of immunogenicity. Gelatine-based composite hydrogels, containing strengthening agents to improve their modest mechanical properties, have been demonstrated to act as extracellular matrices (ECMs), thus playing a critical role in "organ manufacturing". Inspired by the lysyl oxidase (LO)-mediated process of crosslinking, which occurs in nature to reinforce collagen, we have recently developed a versatile protocol to crosslink gelatine B (Gel B) in the presence or absence of LO, using properly synthesized polystyrene- and polyacrylic-based copolymers containing the amine or aldehyde groups needed for crosslinking reactions. Here, following the developed protocol with slight modifications, we have successfully crosslinked Gel B in different conditions, obtaining eight out of nine compounds in high yield (57-99%). The determined crosslinking degree percentage (CP%) evidenced a high CP% for compounds obtained in presence of LO and using the styrenic amine-containing (CP5/DMAA) and acrylic aldehyde-containing (CPMA/DMAA) copolymers as crosslinking agents. ATR-FTIR analyses confirmed the chemical structure of all compounds, while optical microscopy demonstrated cavernous, crater-like, and labyrinth-like morphologies and cavities with a size in the range 15-261 µm. An apparent density in the range 0.10-0.45 g/cm3 confirmed the aerogel-like structure of most samples. Although the best biodegradation profile was observed for the sample obtained using 10% CP5/DMAA (M3), high swelling and absorption properties, high porosity, and good biodegradation profiles were also observed for samples obtained using the 5-10% CP5/DMAA (M4, 5, 6) and 20% CPMA/DMAA (M9) copolymers. Collectively, in this work of synthesis and physicochemical characterization, new aerogel-like composites have been developed and, based on their characteristics, which fit well within the requirements for TE, five candidates (M3, M4, M5, M6, and M9) suitable for future biological experiments on cell adhesion, infiltration and proliferation, to confirm their effective functioning, have been identified.


Biocompatible Materials , Gelatin , Hydrogels , Regenerative Medicine , Tissue Scaffolds , Gelatin/chemistry , Tissue Scaffolds/chemistry , Regenerative Medicine/methods , Biocompatible Materials/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Humans , Tissue Engineering/methods , Cross-Linking Reagents/chemistry
19.
Int J Mol Sci ; 25(9)2024 May 04.
Article En | MEDLINE | ID: mdl-38732241

Biodegradable (BP) poly(D,L-lactic acid) (PDLLA) membranes are widely used in tissue engineering. Here, we investigate the effects of varying concentrations of PDLLA/gelatin membranes electrospun in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP; C3H2F6O) solvent on their mechanical and physical properties as well as their biocompatibility. Regardless of the environmental conditions, increasing the gelatin content resulted in elevated stress and reduced strain at membrane failure. There was a remarkable difference in strain-to-failure between dry and wet PDLLA/gelatin membranes, with wet strains consistently higher than those of the dry membranes because of the hydrophilic nature of gelatin. A similar wet strain (εw = 2.7-3.0) was observed in PDLLA/gelatin membranes with a gelatin content between 10 and 40%. Both dry and wet stresses increased with increasing gelatin content. The dry stress on PDLLA/gelatin membranes (σd = 6.7-9.7 MPa) consistently exceeded the wet stress (σw = 4.5-8.6 MPa). The water uptake capacity (WUC) improved, increasing from 57% to 624% with the addition of 40% gelatin to PDLLA. PDLLA/gelatin hybrid membranes containing 10 to 20 wt% gelatin exhibited favorable wet mechanical properties (σw = 5.4-6.3 MPa; εw = 2.9-3.0); WUC (337-571%), degradability (11.4-20.2%), and excellent biocompatibility.


Gelatin , Membranes, Artificial , Polyesters , Gelatin/chemistry , Polyesters/chemistry , Biocompatible Materials/chemistry , Materials Testing , Tissue Engineering/methods , Water/chemistry , Stress, Mechanical , Humans
20.
ACS Appl Mater Interfaces ; 16(20): 25923-25937, 2024 May 22.
Article En | MEDLINE | ID: mdl-38725122

The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catechol-modified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.


Chitosan , Exosomes , Gelatin , Hyaluronic Acid , Hydrogels , Mesenchymal Stem Cells , Skin , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Exosomes/chemistry , Exosomes/metabolism , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Skin/drug effects , Skin/pathology , Skin/radiation effects , Chitosan/chemistry , Chitosan/pharmacology , Mice , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Gelatin/chemistry , Gelatin/pharmacology , Light , Humans , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Proliferation/drug effects
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