Last papers – Page 2 – Grupo de Biomateriales

Ketoprofen-based polymer-drug nanoparticles provide anti-inf lammatory properties to HA/collagen hydrogels

Biomateriales27 March, 2023

Current limitations of wound dressings for treating chronic wounds require the development of novel approaches. One of these is the immune-centered approach, which aims to restore the pro-regenerative and anti-inflammatory properties of macrophages. Under inflammatory conditions, ketoprofen nanoparticles (KT NP) can reduce pro-inflammatory markers of macrophages and increase anti-inflammatory cytokines. To assess their suitability as part of wound dressings, these NP were combined with hyaluronan (HA)/collagen-based hydro- (HG) and cryogels (CG). Different HA, NP concentrations and loading techniques for NP incorporation were used. The NP release, gel morphology and mechanical properties were studied. Generally, colonialization of the gels with macrophages resulted in high cell viability and proliferation. Furthermore, direct contact of the NP to the cells reduced the level of nitric oxide (NO). The formation of multinucleated cells on the gels was low and further decreased by the NP. For the HG that produced the highest reduction in NO, extended ELISA studies showed reduced levels of the pro-inflammatory markers PGE2, IL-12 p40, TNF-α, and IL-6. Thus, HA/collagen-based gels con-taining KT NP may represent a novel therapeutic approach for treating chronic wounds. Whether effects observed in vitro translate into a favorable profile on skin regeneration in vivo will require rigorous testing.

Antiaging properties of antioxidant photoprotective polymeric nanoparticles loaded with coenzyme-Q10

Biomateriales13 March, 2023

Skin is the most extensive organ within our body. It is continually subjected to stress factors, among which ultraviolet irradiation, a key factor responsible in skin aging since it leads to reactive oxygen species production. In order to fight against these oxidative species, the human body has an innate robust antioxidant mechanism composed of several different substances, one of which is coenzyme Q10. Its capacity to increase cellular energy production and excellent antioxidant properties have been proved, as well as its antiaging properties being able to attenuate cellular damage induced by ultraviolet irradiation in human dermal fibroblasts. However, its high hydrophobicity and photolability hampers its therapeutic potential. In this context, the objective of this work consists of the preparation of chitosan-rosmarinic acid conjugate-based nanoparticles to encapsulate coenzyme Q10 with high encapsulation efficiencies in order to improve its bioavailability and broaden its therapeutic use in skin applications. Hyaluronic acid coating was performed giving stable nanoparticles at physiological pH with 382 ± 3 nm of hydrodynamic diameter (0.04 ± 0.02 polydispersity) and − 18 ± 3 mV of surface charge. Release kinetics studies showed a maximum of 82 % mass release of coenzyme Q10 after 40 min, and radical scavenger activity assay confirmed the antioxidant character of chitosan-rosmarinic acid nanoparticles. Hyaluronic acid-coated chitosan-rosmarinic acid nanoparticles loaded with coenzyme Q10 were biocompatible in human dermal fibroblasts and exhibited interesting photoprotective properties in ultraviolet irradiated cells. In addition, nanoparticles hindered the production of reactive oxygen species, interleukin-6 and metalloproteinase-1, as well as caspase-9 activation maintaining high viability values upon irradiation of dermal fibroblasts. Overall results envision a great potential of these nanovehicles for application in skin disorders or antiaging treatments.

DEAE/Catechol-Chitosan Conjugates as Bioactive Polymers: Synthesis, Characterization, and Potential Applications

Biomateriales9 March, 2023

This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups onto the Cs backbone (Cs–DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution [DS (%)] was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs–DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC₅₀). An EC₅₀ of 1.20 μg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan–catechol (Cs–Ca) and Cs–DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 μg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs–DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 μg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter (D_h) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.

Chemically crosslinked hyaluronic acid-chitosan hydrogel for application on cartilage regeneration

Biomateriales12 January, 2023

Articular cartilage is an avascular tissue that lines the ends of bones in diarthrodial joints, serves as support, acts as a shock absorber, and facilitates joint’s motion. It is formed by chondrocytes immersed in a dense extracellular matrix (principally composed of aggrecan linked to hyaluronic acid long chains). Damage to this tissue is usually associated with traumatic injuries or age-associated processes that often lead to discomfort, pain and disability in our aging society. Currently, there are few surgical alternatives to treat cartilage damage: the most commonly used is the microfracture procedure, but others include limited grafting or alternative chondrocyte implantation techniques, however, none of them completely restore a fully functional cartilage. Here we present the development of hydrogels based on hyaluronic acid and chitosan loaded with chondroitin sulfate by a new strategy of synthesis using biodegradable di-isocyanates to obtain an interpenetrated network of chitosan and hyaluronic acid for cartilage repair. These scaffolds act as delivery systems for the chondroitin sulfate and present mucoadhesive properties, which stabilizes the clot of microfracture procedures and promotes superficial chondrocyte differentiation favoring a true articular cellular colonization of the cartilage. This double feature potentially improves the microfracture technique and it will allow the development of next-generation therapies against articular cartilage damage

A study on Sr/Zn phytate complexes: structural properties and antimicrobial synergistic effects against Streptococcus mutans

Biomateriales11 January, 2023

Phytic acid (PA) is an abundant natural plant component that exhibits a versatility of applications benefited from its chemical structure, standing out its use as food, packing and dental additive due to its antimicrobial properties. The capacity of PA to chelate ions is also well-established and the formation and thermodynamic properties of different metallic complexes has been described. However, research studies of these compounds in terms of chemistry and biological features are still demanded in order to extend the application scope of PA complexes. The main goal of this paper is to deepen in the knowledge of the bioactive metal complexes chemistry and their bactericide activity, to extend their application in biomaterial science, specifically in oral implantology. Thus, this work presents the synthesis and structural assessment of two metallic phytate complexes bearing the bioactive cations Zn²⁺ and Sr²⁺ (ZnPhy and SrPhy respectively), along with studies on the synergic biological properties between PA and cations. Metallic phytates were synthesized in the solid-state by hydrothermal reaction leading to pure solid compounds in high yields. Their molecular formulas were C₆H₁₂0₂₄P₆Sr₄·5H₂O and C₆H₁₂0₂₄P₆Zn₆·6H₂O, as determined by ICP and HRES-TGA. The metal coordination bond of the solid complexes was further analysed by EDS, Raman, ATR-FTIR and solid ¹³C and ³¹P-NMR spectroscopies. Likewise, we evaluated the in vitro ability of the phytate compounds for inhibiting biofilm production of Streptococcus mutans cultures. Results indicate that all compounds significantly reduced biofilm formation (PA < SrPhy < ZnPhy), and ZnPhy even showed remarkable differences with respect to PA and SrPhy. Analysis of antimicrobial properties shows the first clues of the possible synergic effects created between PA and the corresponding cation in different cell metabolic processes. In overall, findings of this work can contribute to expand the applications of these bioactive metallic complexes in the biotechnological and biomedical fields, and they can be considered for the fabrication of anti-plaque coating systems in the dentistry field.

Development of Methotrexate Complexes Endowed with New Biological Properties Envisioned for Musculoskeletal Regeneration in Rheumatoid Arthritis Environments

Biomateriales18 September, 2022

Methotrexate (MTX) administration is the gold standard treatment for rheumatoid arthritis (RA), but its effects are limited to preventing the progression of the disease. Therefore, effective egenerative therapies for damaged tissues are still to be developed. In this regard, MTX complexes of general molecular formula M(MTX)xH2O, where M = Sr, Zn, or Mg, were synthesized and physicochemically characterized by TGA, XRD, NMR, ATR–FTIR, and EDAX spectroscopies. Characterization results demonstrated the coordination between the different cations and MTX via two monodentate bonds with the carboxylate groups of MTX. Cation complexation provided MTX with new bioactive properties such as increasing the deposition of glycosaminoglycans (GAGs) and alternative anti-inflammatory capacities, without compromising the immunosuppressant properties of MTX on macrophages. Lastly, these new complexes were loaded into spray-dried chitosan microparticles as a proof of concept that they can be encapsulated and further delivered in situ in RA-affected joints, envisioning them as a suitable alternative to oral MTX therapy.

The Role of Polymeric Biomaterials in the Treatment of Articular Osteoarthritis

Biomateriales16 September, 2022

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing symptomatology, and favoring adequate cartilage regeneration properties.

Injectable Tripeptide/Polymer Nanoparticles Supramolecular Hydrogel: A Candidate for the Treatment of Inflammatory Pathologies

Biomateriales15 September, 2022

Supramolecular peptide-based hydrogels attract great attention in several fields, i.e., biomedicine, catalysis, energy, and materials chemistry, due to the noncovalent nature of the self-assembly and functional tunable properties defined by the amino acid sequence. In this work, we developed an injectable hybrid supramolecular hydrogel whose formation was triggered by electrostatic interactions between a phosphorylated tripeptide, Fmoc-FFpY (F: phenylalanine, pY: phosphorylated tyrosine), and cationic polymer nanoparticles made of vinylimidazole and ketoprofen (poly(HKT-co-VI) NPs). Hydrogel formation was assessed through inverted tube tests, and its fibrillary structure, around polymer NPs, was observed by transmission electron microscopy. Interestingly, peptide self-assembly yields the formation of nontwisted and twisted fibers, which could be attributed to β-sheets and α-helix structures, respectively, as characterized by circular dichroism and infrared spectroscopies. An increase of the elastic modulus of the Fmoc-FFpY/polymer NPs hybrid hydrogels was observed with peptide concentration as well as its injectability property, due to its shear thinning behavior and self-healing ability. After checking their stability under physiological conditions, the cytotoxicity properties of these hybrid hydrogels were evaluated in contact with human dermal fibroblasts (FBH) and murine macrophages (RAW 264.7). Finally, the Fmoc-FFpY/polymer NPs hybrid hydrogels exhibited a great nitric oxide reduction (∼67%) up to basal values of pro-inflammatory RAW 264.7 cells, thus confirming their excellent anti-inflammatory properties for the treatment of localized inflammatory pathologies.

Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering

Biomateriales14 September, 2022

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue

Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting

Biomateriales2 November, 2021

Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanoprecipitation and presented hydrodynamic diameters of 100 and 75 nm respectively. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrices. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1) support controlled release of bioactive catechol NPs to the wound site; 2) can incorporate additional therapeutic functions by co-encapsulating drugs; 3) can be printed into 3D scaffolds with tailored geometries based on patient requirements.