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1.
Nanoscale ; 16(33): 15801-15814, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39120682

ABSTRACT

In disease treatment, maintaining therapeutic drug concentrations often requires multiple doses. Lipid/polymer hybrid nanoparticles (LPHNPs) offer a promising solution by facilitating sustained drug delivery within therapeutic ranges. Here, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were incorporated into gelatin aerogels to ensure uniform distribution and increase the concentration. Our study focused on understanding the release kinetics of hydrophilic (gallic acid) and lipophilic (quercetin) compounds from this system. Nanoparticles exhibited hydrodynamic diameters of 100 ± 15 nm (empty), 153 ± 33 nm (gallic acid-loaded), and 149 ± 21 nm (quercetin-loaded), with encapsulation efficiencies of 90 ± 5% and 70 ± 10% respectively. Gallic acid release followed the Korsmeyer-Peppas kinetics model (n = 1.01), while quercetin showed first-order kinetics. Notably, encapsulated compounds demonstrated delayed release compared to free compounds in gelatin aerogels, illustrating LPHNPs' ability to modulate release profiles independent of the compound type. This study underscores the potential of LPHNPs in optimizing drug delivery strategies for enhanced therapeutic outcomes.


Subject(s)
Gallic Acid , Hydrophobic and Hydrophilic Interactions , Nanoparticles , Polylactic Acid-Polyglycolic Acid Copolymer , Quercetin , Quercetin/chemistry , Nanoparticles/chemistry , Gallic Acid/chemistry , Kinetics , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Lecithins/chemistry , Gelatin/chemistry , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Drug Liberation , Lipids/chemistry , Drug Carriers/chemistry , Particle Size
2.
J Biomed Mater Res A ; 112(12): 2273-2288, 2024 12.
Article in English | MEDLINE | ID: mdl-39015005

ABSTRACT

The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration.


Subject(s)
Dental Pulp , Dentin , Gelatin , Tissue Engineering , Dentin/chemistry , Tissue Engineering/methods , Animals , Cattle , Gelatin/chemistry , Humans , Dental Pulp/cytology , Methacrylates/chemistry , Cross-Linking Reagents/chemistry , Hydrogels/chemistry , Tissue Scaffolds/chemistry , Bone and Bones , Cells, Cultured , Porosity
3.
ACS Biomater Sci Eng ; 10(8): 4791-4801, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39012256

ABSTRACT

Scaffolds for the filling and regeneration of osteochondral defects are a current challenge in the biomaterials field, and solutions with greater functionality are still being sought. The novel approach of this work was to obtain scaffolds with biologically active additives possessing microstructural, permeability, and mechanical properties, mimicking the complexity of natural cartilage. Four types of scaffolds with a gelatin/alginate matrix modified with hydroxyapatite were obtained, and the relationship between the modifiers and substrate properties was evaluated. They differed in the type of second modifier used, which was hydrated MgCl2 in two proportions, ZnO, and nanohydroxyapatite. The samples were obtained by freeze-drying by using two-stage freezing. Based on microstructural observations combined with X-ray microanalysis, the microstructure of the samples and the elemental content were assessed. Permeability and mechanical tests were also performed. The scaffolds exhibited a network of interconnected pores and complex microarchitecture, with lower porosity at the surface (15 ± 7 to 29 ± 6%) and higher porosity at the center (67 ± 8 to 75 ± 8%). The additives had varying effects on the pore sizes and permeabilities of the samples. ZnO yielded the most permeable scaffolds (5.92 × 10-11 m2), whereas nanohydroxyapatite yielded the scaffold with the lowest permeability (1.18 × 10-11 m2), values within the range reported for trabecular bone. The magnesium content had no statistically significant effect on the permeability. The best mechanical parameters were obtained for ZnO samples and those containing hydrated MgCl2. The scaffold's properties meet the criteria for filling osteochondral defects. The developed scaffolds follow a biomimetic approach in terms of hierarchical microarchitecture and mechanical parameters as well as chemical composition. The obtained composite materials have the potential as biomimetic scaffolds for the regeneration of osteochondral defects.


Subject(s)
Hydrogels , Magnesium Chloride , Tissue Scaffolds , Zinc Oxide , Zinc Oxide/chemistry , Tissue Scaffolds/chemistry , Magnesium Chloride/chemistry , Hydrogels/chemistry , Porosity , Alginates/chemistry , Durapatite/chemistry , Permeability , Gelatin/chemistry , Materials Testing
4.
Biomed Mater Eng ; 35(4): 387-399, 2024.
Article in English | MEDLINE | ID: mdl-38968040

ABSTRACT

BACKGROUND: Polymeric electrospun mats have been used as scaffolds in tissue engineering for the development of novel materials due to its characteristics. The usage of synthetic materials has gone in decline due to environmental problems associated with their synthesis and waste disposal. Biomaterials such as biopolymers have been used recently due to good compatibility on biological applications and sustainability. OBJECTIVE: The purpose of this work is to obtain novel materials based on synthetic and natural polymers for applications on tissue engineering. METHODS: Aloe vera mucilage was obtained, chemically characterized, and used as an active compound contained in electrospun mats. Polymeric scaffolds were obtained in single, coaxial and tri-layer structures, characterized and evaluated in cell culture. RESULTS: Mucilage loaded electrospun fibers showed good compatibility due to formation of hydrogen bonds between polymers and biomolecules from its structure, evidenced by FTIR spectra and thermal properties. Cell viability test showed that most of the obtained mats result on viability higher than 75%, resulting in nontoxic materials, ready to be used on scaffolding applications. CONCLUSION: Mucilage containing fibers resulted on materials with potential use on scaffolding applications due to their mechanical performance and cell viability results.


Subject(s)
Aloe , Cell Survival , Gelatin , Plant Mucilage , Polyesters , Tissue Engineering , Tissue Scaffolds , Polyesters/chemistry , Tissue Engineering/methods , Gelatin/chemistry , Tissue Scaffolds/chemistry , Cell Survival/drug effects , Aloe/chemistry , Plant Mucilage/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Materials Testing , Humans , Membranes, Artificial , Animals
5.
PeerJ ; 12: e17502, 2024.
Article in English | MEDLINE | ID: mdl-38952971

ABSTRACT

Background: Desserts with vegetable ingredients are a constantly expanding global market due to the search for alternatives to cow's milk. Fermentation of these matrices by lactic acid bacteria can add greater functionality to the product, improving its nutritional, sensory, and food safety characteristics, as well as creating bioactive components with beneficial effects on health. Concern for health and well-being has aroused interest in byproducts of the industry that have functional properties for the body, such as mature coconut water, a normally discarded residue that is rich in nutrients. This study aimed to develop a probiotic gelatin based on pulp and water from mature coconuts and evaluate the physicochemical characteristics, viability of the Lacticaseibacillus rhamnosus LR32 strain in the medium, as well as the texture properties of the product. Methods: After collection and cleaning, the physicochemical characterization, mineral analysis, analysis of the total phenolic content and antioxidant activity of mature coconut water were carried out, as well as the centesimal composition of its pulp. Afterwards, the gelling was developed with the addition of modified corn starch, gelatin, sucrose, and probiotic culture, being subjected to acidity analysis, texture profile and cell count, on the first day and every 7 days during 21 days of storage, under refrigeration at 5 °C. An analysis of the centesimal composition was also carried out. Results: The main minerals in coconut water were potassium (1,932.57 mg L-1), sodium (19.57 mg L-1), magnesium (85.13 mg L-1) calcium (279.93 mg L-1) and phosphorus (11.17 mg L- 1), while the pulp had potassium (35.96 g kg-1), sodium (0.97 g kg-1), magnesium (2.18 g kg-1), 37 calcium (1.64 g kg-1), and phosphorus (3.32 g kg-1). The phenolic content of the water and pulp was 5.72 and 9.77 mg gallic acid equivalent (GAE) 100 g-1, respectively, and the antioxidant capacity was 1.67 and 0.98 39 g of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) mg-1, respectively. The coconut pulp had 2.81 g 100 g-1of protein, 1.11 g 100 g-1 of 40 ash, 53% moisture, and 5.81 g 100 g-1 of carbohydrates. The gelatin produced during the storage period presented firmness parameters ranging from 145.82 to 206.81 grams-force (gf), adhesiveness from 692.85 to 1,028.63 gf sec, cohesiveness from 0.604 to 0.473, elasticity from 0.901 to 0.881, gumminess from 86.27 to 97.87 gf, and chewiness from 77.72 to 91.98 gf. Regarding the viability of the probiotic microorganism, the dessert had 7.49 log CFU g-1 that remained viable during the 21-day storage, reaching 8.51 CFU g-1. Acidity ranged from 0.15 to 0.64 g of lactic acid 100 g-1. The centesimal composition of the product showed 4.88 g 100 g-1 of protein, 0.54 g 100 g-1 of ash, 85.21% moisture, and 5.37g 100 g-1 of carbohydrates. The development of the gelatin made it possible to obtain a differentiated product, contributing to diversification in the food sector, providing a viable alternative for maintaining consumer health and reducing costs compared to desserts already available on the market.


Subject(s)
Cocos , Gelatin , Lacticaseibacillus rhamnosus , Probiotics , Cocos/chemistry , Cocos/microbiology , Gelatin/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Fermentation
6.
Int J Biol Macromol ; 273(Pt 1): 133064, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38866288

ABSTRACT

Bone tissue regeneration strategies have incorporated the use of natural polymers, such as hydroxyapatite (nHA), chitosan (CH), gelatin (GEL), or alginate (ALG). Additionally, platelet concentrates, such as platelet-rich fibrin (PRF) have been suggested to improve scaffold biocompatibility. This study aimed to develop scaffolds composed of nHA, GEL, and CH, with or without ALG and lyophilized PRF, to evaluate the scaffold's properties, growth factor release, and dental pulp stem cells (DPSC), and osteoblast (OB) derived from DPSC viability. Four scaffold variations were synthesized and lyophilized. Then, degradation, swelling profiles, and morphological analysis were performed. Furthermore, PDGF-BB and FGF-B growth factors release were quantified by ELISA, and cytotoxicity and cell viability were evaluated. The swelling and degradation profiles were similar in all scaffolds, with pore sizes ranging between 100 and 250 µm. FGF-B and PDGF-BB release was evidenced after 24 h of scaffold immersion in cell culture medium. DPSC and OB-DPSC viability was notably increased in PRF-supplemented scaffolds. The nHA-CH-GEL-PRF scaffold demonstrated optimal physical-biological characteristics for stimulating DPSC and OB-DPSC cell viability. These results suggest lyophilized PRF improves scaffold biocompatibility for bone tissue regeneration purposes.


Subject(s)
Alginates , Cell Survival , Chitosan , Dental Pulp , Durapatite , Gelatin , Osteoblasts , Platelet-Rich Fibrin , Stem Cells , Tissue Scaffolds , Humans , Dental Pulp/cytology , Chitosan/chemistry , Chitosan/pharmacology , Gelatin/chemistry , Platelet-Rich Fibrin/chemistry , Platelet-Rich Fibrin/metabolism , Tissue Scaffolds/chemistry , Stem Cells/drug effects , Stem Cells/cytology , Stem Cells/metabolism , Cell Survival/drug effects , Durapatite/chemistry , Durapatite/pharmacology , Alginates/chemistry , Alginates/pharmacology , Osteoblasts/drug effects , Osteoblasts/cytology , Cell Adhesion/drug effects , Tissue Engineering/methods , Cells, Cultured
7.
Biofabrication ; 16(4)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38866003

ABSTRACT

Tumor-on-chips (ToCs) are useful platforms for studying the physiology of tumors and evaluating the efficacy and toxicity of anti-cancer drugs. However, the design and fabrication of a ToC system is not a trivial venture. We introduce a user-friendly, flexible, 3D-printed microfluidic device that can be used to culture cancer cells or cancer-derived spheroids embedded in hydrogels under well-controlled environments. The system consists of two lateral flow compartments (left and right sides), each with two inlets and two outlets to deliver cell culture media as continuous liquid streams. The central compartment was designed to host a hydrogel in which cells and microtissues can be confined and cultured. We performed tracer experiments with colored inks and 40 kDa fluorescein isothiocyanate dextran to characterize the transport/mixing performances of the system. We also cultured homotypic (MCF7) and heterotypic (MCF7-BJ) spheroids embedded in gelatin methacryloyl hydrogels to illustrate the use of this microfluidic device in sustaining long-term micro-tissue culture experiments. We further demonstrated the use of this platform in anticancer drug testing by continuous perfusion of doxorubicin, a commonly used anti-cancer drug for breast cancer. In these experiments, we evaluated drug transport, viability, glucose consumption, cell death (apoptosis), and cytotoxicity. In summary, we introduce a robust and friendly ToC system capable of recapitulating relevant aspects of the tumor microenvironment for the study of cancer physiology, anti-cancer drug transport, efficacy, and safety. We anticipate that this flexible 3D-printed microfluidic device may facilitate cancer research and the development and screening of strategies for personalized medicine.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Printing, Three-Dimensional , Spheroids, Cellular , Humans , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology , Spheroids, Cellular/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Female , MCF-7 Cells , Hydrogels/chemistry , Lab-On-A-Chip Devices , Cell Line, Tumor , Drug Screening Assays, Antitumor , Dextrans/chemistry , Gelatin/chemistry , Doxorubicin/pharmacology , Doxorubicin/chemistry , Cell Survival/drug effects , Methacrylates
8.
Eur J Pharm Biopharm ; 201: 114370, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38880402

ABSTRACT

The difficulty in swallowing is a frequent problem when oral solid dosage forms (conventional tablets or capsules) are administered to paediatric population or patients with dysphagia. An interesting alternative to overcome these problems are non-conventional formulations like chewable gels, commonly known as 'gummies'. Therefore, this work addresses the design, development and characterization of gummies using gelatine and pectin, for the vehiculization of the antiarrhythmic amiodarone (AMIO). Applying a Design of Experiments (DoE) approach, four gelatine (GG1-GG4) and eight pectin formulations (PG1-PG8) were developed. Considering the obtained results for responses during DoE evaluation (i.e., volume, syneresis, hardness, and gumminess), GG3 and PG8 were selected for complete characterization. Water activity, pH, drug content, texture parameters (adhesiveness, springiness, cohesiveness, and fracturability), disintegration time, in vitro dissolution, and microbiological features were evaluated. The obtained results were within the expected values for this type of formulation. The dissolution profiles showed a 94 % - 99 % of the AMIO content released for GG3 and PG8, respectively, so they could be considered suitable as immediate release dosage forms. In conclusion, the chewable gels were successfully developed and characterised, suggesting a potential means to accomplish a final prototype for the improvement of congenital cardiopathies treatment.


Subject(s)
Amiodarone , Anti-Arrhythmia Agents , Gels , Heart Defects, Congenital , Pectins , Amiodarone/administration & dosage , Amiodarone/chemistry , Humans , Pectins/chemistry , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/chemistry , Heart Defects, Congenital/drug therapy , Gelatin/chemistry , Animals , Child , Administration, Oral , Drug Liberation , Drug Compounding/methods , Solubility , Chemistry, Pharmaceutical/methods
9.
Methods ; 228: 1-11, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38759909

ABSTRACT

The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical-chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min-1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.


Subject(s)
Ophthalmic Solutions , Poloxamer , Poloxamer/chemistry , Ophthalmic Solutions/chemistry , Administration, Ophthalmic , Fluconazole/administration & dosage , Printing, Three-Dimensional , Cornea/drug effects , Cornea/metabolism , Animals , Chitosan/chemistry , Animal Testing Alternatives/methods , Tears/chemistry , Humans , Gelatin/chemistry
10.
Biomacromolecules ; 25(6): 3312-3324, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38728671

ABSTRACT

3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing and filler concentration on cell differentiation were further quantitatively evaluated. The nanocomposited hydrogels render high MSC proliferation and viability, exhibiting intrinsic chondroinductive capacity without any exogenous factor when used to print scaffolds or bioprint constructs. The bioactivity depended on the GO concentration, with the best performance at 0.1 mg mL-1. These results were explained by the rational combination of the three biopolymers, with GO nanoparticles having carboxylate and sulfate groups in their structures, therefore, biomimicking the highly negatively charged ECM of cartilage. The bioactivity of this biomaterial and its good processability for 3D printing scaffolds and 3D bioprinting techniques open up a new approach to developing novel biomimetic materials for cartilage repair.


Subject(s)
Alginates , Bioprinting , Cell Differentiation , Chondrogenesis , Chondroitin Sulfates , Gelatin , Hydrogels , Mesenchymal Stem Cells , Nanocomposites , Printing, Three-Dimensional , Tissue Scaffolds , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Alginates/chemistry , Alginates/pharmacology , Gelatin/chemistry , Bioprinting/methods , Cell Differentiation/drug effects , Chondrogenesis/drug effects , Nanocomposites/chemistry , Tissue Scaffolds/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Tissue Engineering/methods , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Graphite/chemistry , Graphite/pharmacology , Cell Proliferation/drug effects , Cells, Cultured
11.
Sci Rep ; 14(1): 10931, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740842

ABSTRACT

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.


Subject(s)
Cell Differentiation , In Vitro Meat , Tissue Scaffolds , Transcriptome , Animals , Alginates/chemistry , Biocompatible Materials/chemistry , Biopolymers , Gelatin/chemistry , Gene Expression Profiling , Muscle Cells/metabolism , Muscle Development/genetics , Salmon , Sepharose/chemistry , Tissue Scaffolds/chemistry
12.
J Control Release ; 365: 617-639, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043727

ABSTRACT

Among non-communicable diseases, cardiovascular diseases are the most prevalent, accounting for approximately 17 million deaths per year. Despite conventional treatment, cardiac tissue engineering emerges as a potential alternative for the advancement and treatment of these patients, using biomaterials to replace or repair cardiac tissues. Among these materials, gelatin in its methacrylated form (GelMA) is a biodegradable and biocompatible polymer with adjustable biophysical properties. Furthermore, gelatin has the ability to replace and perform collagen-like functions for cell development in vitro. The interest in using GelMA hydrogels combined with nanomaterials is increasingly growing to promote the responsiveness to external stimuli and improve certain properties of these hydrogels by exploring the incorporation of nanomaterials into these hydrogels to serve as electrical signaling conductive elements. This review highlights the applications of electrically conductive nanomaterials associated with GelMA hydrogels for the development of structures for cardiac tissue engineering, by focusing on studies that report the combination of GelMA with nanomaterials, such as gold and carbon derivatives (carbon nanotubes and graphene), in addition to the possibility of applying these materials in 3D tissue engineering, developing new possibilities for cardiac studies.


Subject(s)
Gelatin , Nanotubes, Carbon , Humans , Gelatin/chemistry , Tissue Scaffolds/chemistry , Nanotubes, Carbon/chemistry , Hydrogels/chemistry , Biocompatible Materials/chemistry , Tissue Engineering
13.
ACS Appl Mater Interfaces ; 15(42): 48930-48944, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37827196

ABSTRACT

An increasing number of studies have shown that the local release of nitric oxide (NO) from hydrogels stimulates tissue regeneration by modulating cell proliferation, angiogenesis, and inflammation. The potential biomedical uses of NO-releasing hydrogels can be expanded by enabling their application in a fluid state, followed by controlled gelation triggered by an external factor. In this study, we engineered a hydrogel composed of methacrylated hyaluronic acid (HAGMA) and thiolated gelatin (GELSH) with the capacity for in situ photo-cross-linking, coupled with localized NO release. To ensure a gradual and sustained NO release, we charged the hydrogels with poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with S-nitrosoglutathione (GSNO), safeguarding SNO group integrity during photo-cross-linking. The formation of thiol-ene bonds via the reaction between GELSH's thiol groups and HAGMA's vinyl groups substantially accelerated gelation (by a factor of 6) and increased the elastic modulus of hydrated hydrogels (by 1.9-2.4 times). HAGMA/GELSH hydrogels consistently released NO over a 14 day duration, with the release of NO depending on the hydrogels' equilibrium swelling degree, determined by the GELSH-to-HAGMA ratio. Biocompatibility assessments confirmed the suitability of these hydrogels for biological applications as they display low cytotoxicity and stimulated fibroblast adhesion and proliferation. In conclusion, in situ photo-cross-linkable HAGMA/GELSH hydrogels, loaded with PLGA-GSNO nanoparticles, present a promising avenue for achieving localized and sustained NO delivery in tissue regeneration applications.


Subject(s)
Gelatin , Hyaluronic Acid , Hyaluronic Acid/chemistry , Gelatin/chemistry , Nitric Oxide , Hydrogels/pharmacology , Hydrogels/chemistry , Sulfhydryl Compounds/chemistry
14.
Drug Deliv Transl Res ; 13(12): 3223-3238, 2023 12.
Article in English | MEDLINE | ID: mdl-37474880

ABSTRACT

Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young's moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA significantly accelerated wound closure, improved collagenization, increased histological grading, and hastened myofibroblast differentiation in comparison to the control, GelMA, and GEA. GelMA containing AEPG (GPG) improved wound healing, and although gallic acid is the major responsible for such biological activity, a potential synergic effect played by other polyphenols present in the extract is evident.


Subject(s)
Gelatin , Hydrogels , Hydrogels/chemistry , Gelatin/chemistry , Ellagic Acid/pharmacology , Wound Healing , Gallic Acid , Methacrylates/chemistry
15.
Biomed Mater ; 18(4)2023 05 24.
Article in English | MEDLINE | ID: mdl-37167997

ABSTRACT

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsin vivoformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,in vivosubcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Gelatin/chemistry , Porosity , Biocompatible Materials/chemistry , Hydrogels/chemistry , Printing, Three-Dimensional
16.
J Texture Stud ; 54(5): 646-658, 2023 10.
Article in English | MEDLINE | ID: mdl-37218085

ABSTRACT

Gels combined with honey might generate new possibilities of textures in food development. This work explores the structural and functional properties of gelatin (5 g/100 g), pectin (1 g/100 g), and carrageenan (1 g/100 g) gels with different content of honey (0-50 g/100 g). Honey decreased the transparency of gels and made them more yellow-greenish; all of them were firm and uniform, especially at the highest honey content. The water holding capacity increased (63.30-97.90 g/100 g) and moisture content, water activity (0.987-0.884) and syneresis (36.03-1.30 g/100 g) decreased with the addition of honey. This ingredient modified mainly the textural parameters of gelatin (Hardness: 0.82-1.35 N) and carrageenan gels (Hardness: 2.46-2.81 N), whereas only the adhesiveness and the liquid like-behavior were increased in the pectin gels. Honey increased the solid behavior of gelatin gels (G': 54.64-173.37 Pa) but did not modify the rheological parameters of the carrageenan ones. Honey also had a smoothing effect on the microstructure of gels as observed in the scanning electron microscopy micrographs. This effect was also confirmed by the results of the gray level co-occurrence matrix and fractal model's analysis (fractal dimension: 1.797-1.527; lacunarity: 1.687-0.322). The principal component and cluster analysis classified samples by the hydrocolloid used, except the gelatin gel with the highest content of honey, which was differentiated as a separate group. Honey modified the texture, rheology, and microstructure of gels indicating that it is possible to generate new products to be used in other food matrices as texturizers.


Subject(s)
Carrageenan , Food Handling , Gelatin , Honey , Pectins , Carrageenan/chemistry , Gelatin/chemistry , Gels/chemistry , Pectins/chemistry , Water/analysis , Food Handling/methods
17.
J Biomed Mater Res B Appl Biomater ; 111(9): 1705-1722, 2023 09.
Article in English | MEDLINE | ID: mdl-37178328

ABSTRACT

Cartilage damage caused by trauma or osteoarthritis is a common joint disease that can increase the social and economic burden in society. Due to its avascular characteristics, the poor migration ability of chondrocytes, and a low number of progenitor cells, the self-healing ability of cartilage defects has been significantly limited. Hydrogels have been developed into one of the most suitable biomaterials for the regeneration of cartilage because of its characteristics such as high-water absorption, biodegradation, porosity, and biocompatibility similar to natural extracellular matrix. Therefore, the present review article presents a conceptual framework that summarizes the anatomical, molecular structure and biochemical properties of hyaline cartilage located in long bones: articular cartilage and growth plate. Moreover, the importance of preparation and application of hyaluronic acid - gelatin hydrogels for cartilage tissue engineering are included. Hydrogels possess benefits of stimulating the production of Agc1, Col2α1-IIa, and SOX9, molecules important for the synthesis and composition of the extracellular matrix of cartilage. Accordingly, they are believed to be promising biomaterials of therapeutic alternatives to treat cartilage damage.


Subject(s)
Cartilage, Articular , Hyaline Cartilage , Humans , Hyaline Cartilage/metabolism , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Gelatin/pharmacology , Gelatin/chemistry , Molecular Structure , Chondrocytes , Cartilage, Articular/metabolism , Tissue Engineering , Biocompatible Materials/pharmacology , Biocompatible Materials/metabolism , Tissue Scaffolds
18.
Int J Mol Sci ; 24(8)2023 Apr 19.
Article in English | MEDLINE | ID: mdl-37108653

ABSTRACT

For biomedical applications, gelatin is usually modified with methacryloyl groups to obtain gelatin methacryloyl (GelMA), which can be crosslinked by a radical reaction induced by low wavelength light to form mechanically stable hydrogels. The potential of GelMA hydrogels for tissue engineering has been well established, however, one of the main disadvantages of mammalian-origin gelatins is that their sol-gel transitions are close to room temperature, resulting in significant variations in viscosity that can be a problem for biofabrication applications. For these applications, cold-water fish-derived gelatins, such as salmon gelatin, are a good alternative due to their lower viscosity, viscoelastic and mechanical properties, as well as lower sol-gel transition temperatures, when compared with mammalian gelatins. However, information regarding GelMA (with special focus on salmon GelMA as a model for cold-water species) molecular conformation and the effect of pH prior to crosslinking, which is key for fabrication purposes since it will determine final hydrogel's structure, remains scarce. The aim of this work is to characterize salmon gelatin (SGel) and salmon methacryloyl gelatin (SGelMA) molecular configuration at two different acidic pHs (3.6 and 4.8) and to compare them to commercial porcine gelatin (PGel) and methacryloyl porcine gelatin (PGelMA), usually used for biomedical applications. Specifically, we evaluated gelatin and GelMA samples' molecular weight, isoelectric point (IEP), their molecular configuration by circular dichroism (CD), and determined their rheological and thermophysical properties. Results showed that functionalization affected gelatin molecular weight and IEP. Additionally, functionalization and pH affected gelatin molecular structure and rheological and thermal properties. Interestingly, the SGel and SGelMA molecular structure was more sensitive to pH changes, showing differences in gelation temperatures and triple helix formation than PGelMA. This work suggests that SGelMA presents high tunability as a biomaterial for biofabrication, highlighting the importance of a proper GelMA molecular configuration characterization prior to hydrogel fabrication.


Subject(s)
Gelatin , Tissue Engineering , Animals , Gelatin/chemistry , Transition Temperature , Viscosity , Suspensions , Tissue Engineering/methods , Methacrylates/chemistry , Salmon , Hydrogels/chemistry , Molecular Conformation , Water , Mammals
19.
Biomed Phys Eng Express ; 9(3)2023 03 10.
Article in English | MEDLINE | ID: mdl-36821850

ABSTRACT

Periodontitis is a highly prevalent infectious disease that causes the progressive destruction of the periodontal supporting tissues. If left untreated, it can lead to tooth loss impairing oral function, aesthetics, and the patient's overall quality of life. Guided and Bone Tissue Regeneration (GTR/BTR) are surgical therapies based on the placement of a membrane that prevents epithelial growth into the defect, allowing the periodontal/bone cells (including stem cells) to regenerate or restore the affected tissues. The success of these therapies is commonly affected by the local bacterial colonization of the membrane area and its fast biodegradation, causing postoperative infections and a premature rupture of the membrane limiting the regeneration process. This study presents the antibacterial and osteogenic differentiation properties of polycaprolactone-gelatin (PCL-G) electrospun membranes modified with ZnO nanoparticles (ZnO-NPs). The membranes´ chemical composition, surface roughness, biodegradation, water wettability, and mechanical properties under simulated physiological conditions, were analyzed by the close relationship with their biological properties. The PCL-G membranes modified with 1, 3, and 6% w/w of ZnO-NPs showed a significant reduction in the planktonic and biofilm formation of four clinically relevant bacteria;A. actinomycetemcomitansserotype b, P. gingivalis,E. coli, andS. epidermidis. Additionally, the membranes presented appropriate mechanical properties and biodegradation rates to be potentially used in clinical treatments. Notably, the membranes modified with the lowest concentration of ZnO-NPs (1% w/w) stimulated the production of osteoblast markers and calcium deposits in human bone marrow-derived mesenchymal stem cells (BM-MSC) and were biocompatible to human osteoblasts cells (hFOB). These results suggest that the PCL-G membranes with 1% w/w of ZnO-NPs are high-potential candidates for GTR/BTR treatments, as they were the most effective in terms of better antibacterial effectiveness at a lower NPs-concentration while creating a favorable cellular microenvironment for bone growth.


Subject(s)
Osteogenesis , Zinc Oxide , Humans , Gelatin/chemistry , Zinc Oxide/pharmacology , Tissue Scaffolds/chemistry , Escherichia coli , Quality of Life , Bone Regeneration , Anti-Bacterial Agents/pharmacology , Cell Differentiation
20.
Prep Biochem Biotechnol ; 53(8): 942-953, 2023.
Article in English | MEDLINE | ID: mdl-36592021

ABSTRACT

Polysaccharides and proteins are compatible macromolecules that can be used to obtain biopolymeric hydrogels through physical interactions. In this study, an environmentally friendly strategy is being proposed to produce gelatin-xanthan gum- cellulose hydrogels, without the addition of chemical synthetic crosslinkers. Xanthan gum was employed as an alternative crosslinking agent, and cellulose was used as a potential reinforcing agent in the polymeric matrix. Firstly, the biopolymers were mixed by the extrusion process, and glycerol was used as a plasticizer. Then, the polymeric mixture was molded by thermopressing to obtain hydrogels as laminated films. All hydrogels formulations resulted in films with smooth surfaces, without pores or cracks, resulting in amorphous polymeric matrices. The obtained hydrogels had a pH-dependent degree of swelling, the highest swelling values were obtained at pH 4 (5.3-7.9 g/g) after 24 h of immersion. Cellulose acted as a reinforcing agent for hydrogels, increasing thermal stability, tensile strength, and Young's modulus of films when employed at the higher level (7%). The strategy employed in this study to obtain nontoxic hydrogels without synthetic crosslinkers was effective, resulting in materials with promising properties to be used as pharmaceutical forms to deliver active compounds in cosmetic or pharmaceutical products.


Subject(s)
Cellulose , Gelatin , Gelatin/chemistry , Hydrogels/chemistry , Polysaccharides, Bacterial/chemistry , Polymers/chemistry
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