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1.
Article in English | MEDLINE | ID: mdl-39001760

ABSTRACT

BACKGROUND: Genetic disease has recently emerged as a cause of cardiac conduction disorders (CCDs), but the diagnostic yield of genetic testing and the contribution of the different genes to CCD is still unsettled. OBJECTIVES: This study sought to determine the diagnostic yield of genetic testing in young adults with CCD of unknown etiology requiring pacemaker implantation. We also studied the prevalence of rare protein-altering variants across individual genes and functional gene groups. METHODS: We performed whole exome sequencing in 150 patients with CCD of unknown etiology who had permanent pacemaker implanted at age ≤60 years at 14 Spanish hospitals. Prevalence of rare protein-altering variants in patients with CCD was compared with a reference population of 115,522 individuals from gnomAD database (control subjects). RESULTS: Among 39 prioritized genes, patients with CCD had more rare protein-altering variants than control subjects (OR: 2.39; 95% CI: 1.75-3.33). Significant enrichment of rare variants in patients with CCD was observed in all functional gene groups except in the desmosomal genes group. Rare variants in the nuclear envelope genes group exhibited the strongest association with CCD (OR: 6.77; 95% CI: 3.71-13.87). Of note, rare variants in sarcomeric genes were also enriched (OR: 1.73; 95% CI: 1.05-3.10). An actionable genetic variant was detected in 21 patients (14%), with LMNA being the most frequently involved gene (4.6%). CONCLUSIONS: Unrecognized rare genetic variants increase the risk of CCD in young adults with CCD of unknown etiology. Genetic testing should be performed in patients age ≤60 years with CCD of unknown etiology. The role of genetic variants in sarcomeric genes as a cause of CCD should be further investigated.

2.
Chemistry ; : e202400855, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-39031737

ABSTRACT

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1-11 region of lactoferrin (LF). The RGD-LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide-functionalized hydrogels was excellent, with values higher than 85% at day 1, and higher than 95% after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram-positive and Gram-negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels.

3.
Biomater Adv ; 154: 213654, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37837906

ABSTRACT

The Boston keratoprosthesis (BKPro) is a medical device used to restore vision in complicated cases of corneal blindness. This device is composed by a front plate of polymethylmethacrylate (PMMA) and a backplate usually made of titanium (Ti). Ti is an excellent biomaterial with numerous applications, although there are not many studies that address its interaction with ocular cells. In this regard, despite the good retention rates of the BKPro, two main complications compromise patients' vision and the viability of the prosthesis: imperfect adhesion of the corneal tissue to the upside of the backplate and infections. Thus, in this work, two topographies (smooth and rough) were generated on Ti samples and tested with or without functionalization with a dual peptide platform. This molecule consists of a branched structure that links two peptide moieties to address the main complications associated with BKPro: the well-known RGD peptide in its cyclic version (cRGD) as cell pro-adherent motif and the first 11 residues of lactoferrin (LF1-11) as antibacterial motif. Samples were physicochemically characterized, and their biological response was evaluated in vitro with human corneal keratocytes (HCKs) and against the gram-negative bacterial strain Pseudomonas aeruginosa. The physicochemical characterization allowed to verify the functionalization in a qualitative and quantitative manner. A higher amount of peptide was anchored to the rough surfaces. The studies performed using HCKs showed increased long-term proliferation on the functionalized samples. Gene expression was affected by topography and peptide functionalization. Roughness promoted α-smooth muscle actin (α-SMA) overexpression, and the coating notably increased the expression of extracellular matrix components (ECM). Such changes may favour the development of unwanted fibrosis, and thus, corneal haze. In contrast, the combination of the coating with a rough topography decreased the expression of α-SMA and ECM components, which would be desirable for the long-term success of the prosthesis. Regarding the antibacterial activity, the functionalized smooth and rough surfaces promoted the death of bacteria, as well as a perturbation in their wall definition and cellular morphology. Bacterial killing values were 58 % for smooth functionalised and 68 % for rough functionalised samples. In summary, this study suggests that the use of the dual peptide platform with cRGD and LF1-11 could be a good strategy to improve the in vitro and in vivo performance of the rough topography used in the commercial BKPro.


Subject(s)
Cornea , Corneal Diseases , Humans , Cornea/surgery , Titanium/pharmacology , Corneal Diseases/surgery , Prostheses and Implants , Peptides , Anti-Bacterial Agents
4.
Front Bioeng Biotechnol ; 11: 1192436, 2023.
Article in English | MEDLINE | ID: mdl-37324414

ABSTRACT

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.

5.
Int J Mol Sci ; 24(11)2023 Jun 04.
Article in English | MEDLINE | ID: mdl-37298690

ABSTRACT

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.


Subject(s)
Metal Nanoparticles , Titanium , Titanium/pharmacology , Silver/pharmacology , Coated Materials, Biocompatible/pharmacology , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus , Surface Properties
6.
J Bus Ethics ; : 1-16, 2023 Mar 04.
Article in English | MEDLINE | ID: mdl-37359792

ABSTRACT

We conducted three studies to examine how the recipients of negative workplace gossip judge the gossip sender's morality and how they respond behaviorally. Study 1 provided experimental evidence that gossip recipients perceive senders as low in morality, with female recipients rating the sender's morality more negatively than male recipients. In a follow-up experiment (Study 2), we further found that perceived low morality translates into behavioral responses in the form of career-related sanctions by the recipient on the gossip sender. A critical incident study (Study 3) enhanced the external validity and extended the moderated mediation model by showing that gossip recipients also penalize senders with social exclusion. We discuss the implications for practice and research on negative workplace gossip, gender differences in attributions of morality, and gossip recipients' behavioral responses. Supplementary Information: The online version contains supplementary material available at 10.1007/s10551-023-05355-7.

7.
Biomater Sci ; 11(13): 4602-4615, 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37198968

ABSTRACT

Biomimetic surface modification with cell-adhesive peptides is a promising approach to improve endothelialization of current bioresorbable stents (BRS). Among them, RGDS and YIGSR sequences have been reported to mediate adhesion and migration of endothelial cells (ECs) while preventing platelet activation. This work presents the functionalization of novel 3D-printed poly-L-lactic acid (PLLA) and poly(L-lactic-co-ε-caprolactone) (PLCL) BRS with linear RGDS and YIGSR sequences, as well as a dual platform (PF) containing both motifs within a single biomolecule. Functionalized surfaces were characterized in terms of static contact angle, biomolecule distribution under confocal fluorescence microscopy and peptide quantification via detachment from the surface, showing a biomolecule density in the range of 0.5 to 3.5 nmol cm-2. Biological evaluation comprised a cell adhesion test on functionalized films with ECs and a blood perfusion assay on functionalized stents to assess ECs response and device hemocompatibility, respectively. Cell adhesion assays evidenced significantly increased cell number and spreading onto functionalized films with respect to control samples. Regarding stents' hemocompatibility, platelet adhesion onto PLCL stents was severely decreased with respect to PLLA. In addition, functionalization with RGDS, YIGSR and the PF rendered BRS stents displaying even further reduced platelet adhesion. In conclusion, the combination of intrinsically less prothrombogenic materials such as PLCL and its functionalization with EC-discriminating adhesive biomolecules paves the way for a new generation of BRS based on accelerated re-endothelialization approaches.


Subject(s)
Absorbable Implants , Endothelial Cells , Peptides/chemistry , Stents , Polymers/chemistry , Cell Adhesion , Printing, Three-Dimensional
8.
Eur Radiol ; 33(9): 6569-6581, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37071164

ABSTRACT

OBJECTIVES: N-Acetylcysteine (NAC) may confer protection against post-contrast acute kidney injury (PC-AKI), although evidence is sparse and conflicting. The objective was to analyse the evidence on the efficacy and safety of NAC vs no administration of NAC in preventing PC-AKI in patients with pre-existing kidney impairment undergoing a non-interventional radiological examination requiring intravenous (IV) contrast media (CM) administration. METHODS: We carried out a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE, and Clinicaltrials.gov up to May 2022. The primary outcome was PC-AKI. Secondary outcomes included the requirement of renal replacement therapy, all-cause mortality, serious adverse events, and length of hospital stay. We conducted the meta-analyses using the Mantel-Haenszel method and following a random-effects model. RESULTS: NAC was not associated with a significant reduction in PC-AKI (RR 0.47, 95%CI 0.20 to 1.11; 8 studies; 545 participants; I2: 56%; low certainty), all-cause mortality (RR 0.67, 95%CI 0.29 to 1.54; 2 studies; 129 participants; very low certainty), or length of hospital stay (mean difference 9.2 days, 95%CI - 20.08 to 38.48; 1 study; 42 participants; very low certainty). The impact on other outcomes could not be determined. CONCLUSIONS: NAC may not reduce the risk of PC-AKI or all-cause mortality in people with kidney impairment who receive an IV CM prior to radiological imaging, although the certainty of the evidence is very low or low. CLINICAL RELEVANCE STATEMENT: Our review concludes that prophylactic administration of N-acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging, which may support decision making in this common clinical scenario. KEY POINTS: • N-Acetylcysteine may not significantly reduce the risk of acute kidney injury in patients with kidney impairment receiving an intravenous contrast media prior to non-interventional radiological imaging. • All-cause mortality and length of hospital stay would not be decreased with the administration of N-Acetylcysteine in this setting.


Subject(s)
Acetylcysteine , Acute Kidney Injury , Humans , Acetylcysteine/therapeutic use , Contrast Media/adverse effects , Acute Kidney Injury/etiology , Renal Replacement Therapy/adverse effects , Renal Replacement Therapy/methods , Kidney
9.
Pediatr Infect Dis J ; 42(3): 226-231, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36730092

ABSTRACT

BACKGROUND: The role of children in SARS-CoV-2 transmission and their immune response after infection have been profoundly discussed. Hereby, we analyze both aspects in a Spanish pediatric population. METHODS: Prospective, multicentre, longitudinal study performed from July 2020 to September 2021 in children up to 14 years old. Venous blood samples were collected every 6 months and serum was analyzed for antibodies against SARS-CoV-2 using a spike (S) and a nucleocapsid (N) protein assays. Household contacts of seropositive children were tested. Household transmission, antibody dynamics, and durability were analyzed. RESULTS: Two hundred children were recruited and 28 had SARS-CoV-2 antibodies at the end of the study, resulting in an overall seroprevalence of 16.6% (95% CI: 9.5%-19.6%). Most of children (18/28) were secondary cases. The secondary attack rate (SAR) was lower in households with pediatric index cases than in those with adult index cases ( P = 0.023). The median antibody titers in the first positive serology, for the seropositive patients, were 137 BAU/mL (IQR 83.3-427.4) for the S-assay and 132.5 COI (IQR 14.5-170.5) for the N-assay without significant differences between symptomatic and asymptomatic children. The median time between the RT-PCR and the last serology was 7.5 months (IQR 5.2-8.8), and the duration of SARS-CoV-2 antibodies after infection was proven to be at least 18 months. There were no cases of seroreversion. CONCLUSIONS: (1) Children are not the main drivers of SARS-CoV-2 household transmission. (2) They maintain SARS-CoV-2 antibodies for up to 18 months after infection and the titers are similar between symptomatic and asymptomatic children.


Subject(s)
COVID-19 , Adult , Humans , Child , Prospective Studies , Longitudinal Studies , SARS-CoV-2 , Seroepidemiologic Studies , Spain , Antibodies, Viral
10.
Front Endocrinol (Lausanne) ; 13: 1000662, 2022.
Article in English | MEDLINE | ID: mdl-36452329

ABSTRACT

COMP (Cartilage Oligomeric Matrix Protein), also named thrombospondin-5, is a member of the thrombospondin family of extracellular matrix proteins. It is of clinical relevance, as in humans mutations in COMP lead to chondrodysplasias. The gene encoding zebrafish Comp is located on chromosome 11 in synteny with its mammalian orthologs. Zebrafish Comp has a domain structure identical to that of tetrapod COMP and shares 74% sequence similarity with murine COMP. Zebrafish comp is expressed from 5 hours post fertilization (hpf) on, while the protein is first detectable in somites of 11 hpf embryos. During development and in adults comp is strongly expressed in myosepta, craniofacial tendon and ligaments, around ribs and vertebra, but not in its name-giving tissue cartilage. As in mammals, zebrafish Comp forms pentamers. It is easily extracted from 5 days post fertilization (dpf) whole zebrafish. The lack of Comp expression in zebrafish cartilage implies that its cartilage function evolved recently in tetrapods. The expression in tendon and myosepta may indicate a more fundamental function, as in evolutionary distant Drosophila muscle-specific adhesion to tendon cells requires thrombospondin. A sequence encoding a calcium binding motif within the first TSP type-3 repeat of zebrafish Comp was targeted by CRISPR-Cas. The heterozygous and homozygous mutant Comp zebrafish displayed a patchy irregular Comp staining in 3 dpf myosepta, indicating a dominant phenotype. Electron microscopy revealed that the endoplasmic reticulum of myosepta fibroblasts is not affected in homozygous fish. The disorganized extracellular matrix may indicate that this mutation rather interferes with extracellular matrix assembly, similar to what is seen in a subgroup of chondrodysplasia patients. The early expression and easy detection of mutant Comp in zebrafish points to the potential of using the zebrafish model for large scale screening of small molecules that can improve secretion or function of disease-associated COMP mutants.


Subject(s)
CRISPR-Cas Systems , Zebrafish , Adult , Humans , Mice , Animals , Cartilage Oligomeric Matrix Protein/genetics , Zebrafish/genetics , Phenotype , Thrombospondins/genetics , Mammals
12.
Biomater Adv ; 142: 213148, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36274359

ABSTRACT

Hydroxyapatite nanoparticles are popular tools in bone regeneration, but they have also been used for gene delivery and as anticancer drugs. Understanding their mechanism of action, particularly for the latter application, is crucial to predict their toxicity. To this end, we aimed to elucidate the importance of nanoparticle membrane interactions in the cytotoxicity of MG-63 cells using two different types of nanoparticles. In addition, conventional techniques for studying nanoparticle internalisation were evaluated and compared with newer and less exploited approaches. Hydroxyapatite and magnesium-doped hydroxyapatite nanoparticles were used as suspensions or compacted as specular discs. Comparison between cells seeded on the discs and those supplemented with the nanoparticles allowed direct interaction of the cell membrane with the material to be ruled out as the main mechanism of toxicity. In addition, standard techniques such as flow cytometry were inconclusive when used to assess nanoparticles toxicity. Interestingly, the use of intracellular calcium fluorescent probes revealed the presence of a high number of calcium-rich vesicles after nanoparticle supplementation in cell culture. These structures could not be detected by transmission electron microscopy due to their liquid content. However, by using cryo-soft X-ray imaging, which was used to visualise the cellular ultrastructure without further treatment other than vitrification and to quantify the linear absorption coefficient of each organelle, it was possible to identify them as multivesicular bodies, potentially acting as calcium stores. In the study, an advanced state of degradation of the hydroxyapatite and magnesium-doped hydroxyapatite nanoparticles within MG-63 cells was observed. Overall, we demonstrate that the combination of fluorescent calcium probes together with cryo-SXT is an excellent approach to investigate intracellular calcium, especially when found in its soluble form.


Subject(s)
Durapatite , Nanoparticles , Durapatite/chemistry , Magnesium , Nanoparticles/toxicity , Bone Regeneration , Microscopy, Electron, Transmission
13.
Adv Healthc Mater ; 11(20): e2201339, 2022 10.
Article in English | MEDLINE | ID: mdl-35941083

ABSTRACT

Cell-material interactions are regulated by mimicking bone extracellular matrix on the surface of biomaterials. In this regard, reproducing the extracellular conditions that promote integrin and growth factor (GF) signaling is a major goal to trigger bone regeneration. Thus, the use of synthetic osteogenic domains derived from bone morphogenetic protein 2 (BMP-2) is gaining increasing attention, as this strategy is devoid of the clinical risks associated with this molecule. In this work, the wrist and knuckle epitopes of BMP-2 are screened to identify peptides with potential osteogenic properties. The most active sequences (the DWIVA motif and its cyclic version) are combined with the cell adhesive RGD peptide (linear and cyclic variants), to produce tailor-made biomimetic peptides presenting the bioactive cues in a chemically and geometrically defined manner. Such multifunctional peptides are next used to functionalize titanium surfaces. Biological characterization with mesenchymal stem cells demonstrates the ability of the biointerfaces to synergistically enhance cell adhesion and osteogenic differentiation. Furthermore, in vivo studies in rat calvarial defects prove the capacity of the biomimetic coatings to improve new bone formation and reduce fibrous tissue thickness. These results highlight the potential of mimicking integrin-GF signaling with synthetic peptides, without the need for exogenous GFs.


Subject(s)
Bone Morphogenetic Protein 2 , Osteogenesis , Rats , Animals , Bone Morphogenetic Protein 2/pharmacology , Bone Morphogenetic Protein 2/chemistry , Titanium , Cell Differentiation , Extracellular Matrix , Bone Regeneration , Peptides/pharmacology , Peptides/chemistry , Biocompatible Materials , Integrins , Epitopes
14.
J Bus Ethics ; 181(3): 789-809, 2022.
Article in English | MEDLINE | ID: mdl-34629574

ABSTRACT

Our paper contributes to emerging management research on the effects of societal inequality. It aims to study the relationship between societal-level inequality and perceived unequal HR practices within organizations based on relationships which we term "relation-based inequality" (RBI). We further examine the moderating effect of country corruption on the RBI-employee commitment link. Thus, whereas previous research has looked at single countries, there is still much to know about societal effects of inequality and corruption on employee perceptions and attitudes at work across countries. By surveying 691employees from five countries and using country-level indicators we take a first step in this direction, and establish that inequality (income, health and education) is linked to higher levels of relation-based HR practices. We also show that the effect of RBI is different for continuance, affective and normative commitment, and contingent on country corruption levels.

15.
J Pept Sci ; 28(1): e3335, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34031952

ABSTRACT

Improving cell-material interactions is a major goal in tissue engineering. In this regard, functionalization of biomaterials with cell instructive molecules from the extracellular matrix stands out as a powerful strategy to enhance their bioactivity and achieve optimal tissue integration. However, current functionalization strategies, like the use of native full-length proteins, are associated with drawbacks, thus urging the need of developing new methodologies. In this regard, the use of synthetic peptides encompassing specific bioactive regions of proteins represents a promising alternative. In particular, the combination of peptide sequences with complementary or synergistic effects makes it possible to address more than one biological target at the biomaterial surface. In this review, an overview of the main strategies using peptides to install multifunctionality on biomaterials is presented, mostly focusing on the combination of the RGD motif with other peptides sequences. The evolution of these approaches, starting from simple methods, like using peptide mixtures, to more advanced systems of peptide presentation, with very well defined chemical properties, are explained. For each system of peptide's presentation, three main aspects of multifunctionality-improving receptor selectivity, mimicking the extracellular matrix and preventing bacterial colonization while improving cell adhesion-are highlighted.


Subject(s)
Biocompatible Materials , Peptides , Cell Adhesion
16.
Int J Infect Dis ; 104: 584-591, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33508477

ABSTRACT

OBJECTIVES: Sex differences in adult cellulitis, a frequent cause of hospitalization, have not been analyzed. These differences were investigated in a large cellulitis series. METHODS: This was a prospective observational study of 606 Spanish hospitalized cellulitis patients. Different comorbidities, clinical, diagnostic, and treatment data were compared between the sexes. Multiple logistic regression modeling was performed to determine the variables independently associated with sex. RESULTS: Overall 606 adult cellulitis patients were enrolled; 314 (51.8%) were male and 292 (48.2%) were female. Females were older (mean age 68.8 vs 58.9 years, p < 0.0001), less likely to have prior wounds (p = 0.02), and more likely to have venous insufficiency (p = 0.0002) and edema/lymphedema (p = 0.0003) than males. The location of the infection differed between the sexes (p = 0.02). Males were more likely to have positive pus cultures (p = 0.0008), the causing agent identified (p = 0.04), and higher rates of Staphylococcus aureus infection (p = 0.04) and received longer antibiotic treatment (p = 0.03). Factors independently associated with female sex in the multivariate analysis were older age (p < 0.0001), prior cellulitis (p = 0.01), presence of edema/lymphedema as the predisposing factor (p = 0.004), negative versus positive pus culture (p = 0.0002), and location of cellulitis other than in the lower extremities (p = 0.035). CONCLUSIONS: Differences between male and female patients with cellulitis were age, recurrence, presence of edema/lymphedema, positivity of pus culture, and topography of the infection.


Subject(s)
Cellulitis/diagnosis , Cellulitis/physiopathology , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Cellulitis/drug therapy , Cellulitis/microbiology , Edema , Female , Hospitalization , Humans , Logistic Models , Male , Middle Aged , Prospective Studies , Recurrence , Risk Factors , Sex Characteristics , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Young Adult
17.
Chem Commun (Camb) ; 57(8): 982-985, 2021 Jan 25.
Article in English | MEDLINE | ID: mdl-33438695

ABSTRACT

A novel and versatile toolkit approach for the functionalization of biomaterials of different nature is described. This methodology is based on the solid-phase conjugation of specific anchoring units onto a resin-bound azido-functionalized peptide by using click chemistry. A synergistic multifunctional peptidic scaffold with cell adhesive properties was used as a model compound to showcase the versatility of this new approach. Titanium, gold and polylactic acid surfaces were biofunctionalized by this method, as validated by physicochemical surface characterization with XPS. In vitro assays using mesenchymal stem cells showed enhanced cell adhesion on the functionalized samples, proving the capacity of this strategy to efficiently bioactivate different types of biomaterials.


Subject(s)
Biocompatible Materials/chemistry , Peptides/chemistry , Click Chemistry , Protein Conformation
18.
Adv Healthc Mater ; 10(7): e2001757, 2021 04.
Article in English | MEDLINE | ID: mdl-33336559

ABSTRACT

Recreating the healing microenvironment is essential to regulate cell-material interactions and ensure the integration of biomaterials. To repair bone, such bioactivity can be achieved by mimicking its extracellular matrix (ECM) and by stimulating integrin and growth factor (GF) signaling. However, current approaches relying on the use of GFs, such as bone morphogenetic protein 2 (BMP-2), entail clinical risks. Here, a biomimetic peptide integrating the RGD cell adhesive sequence and the osteogenic DWIVA motif derived from the wrist epitope of BMP-2 is presented. The approach offers the advantage of having a spatial control over the single binding of integrins and BMP receptors. Such multifunctional platform is designed to incorporate 3,4-dihydroxyphenylalanine to bind metallic oxides with high affinity in a one step process. Functionalization of glass substrates with the engineered peptide is characterized by physicochemical methods, proving a successful surface modification. The biomimetic interfaces significantly improve the adhesion of C2C12 cells, inhibit myotube formation, and activate the BMP-dependent signaling via p38. These effects are not observed on surfaces displaying only one bioactive motif, a mixture of both motifs or soluble DWIVA. These data prove the biological potential of recreating the ECM and engaging in integrin and GF crosstalk via molecular-based mimics.


Subject(s)
Biomimetics , Integrins , Cell Adhesion , Cell Differentiation , Intercellular Signaling Peptides and Proteins , Peptides
19.
Chembiochem ; 22(5): 839-844, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33094896

ABSTRACT

Bacterial infections and incomplete biomaterial integration are major problems that can lead to the failure of medical implants. However, simultaneously addressing these two issues remains a challenge. Here, we present a chemical peptide library based on a multifunctional platform containing the antimicrobial peptide LF1-11 and the cell-adhesive motif RGD. The scaffolds were customized with catechol groups to ensure straightforward functionalization of the implant surface, and linkers of different length to assess the effect of peptide accessibility on the biological response. The peptidic platforms significantly improved the adhesion of mesenchymal stem cells and showed antimicrobial effects against Staphylococcus aureus. Of note is that peptides bearing spacers that were too long displayed the lowest efficiency. Subsequently, we designed a platform replacing linear RGD by cyclic RGD; this further enhanced eukaryotic cell adhesion while retaining excellent antimicrobial properties, thus being a suitable candidate for tissue engineering applications.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cell Adhesion , Mesenchymal Stem Cells/physiology , Pore Forming Cytotoxic Proteins/chemistry , Pore Forming Cytotoxic Proteins/pharmacology , Staphylococcus aureus/drug effects , Cells, Cultured , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects
20.
Dermatol Online J ; 26(5)2020 May 15.
Article in English | MEDLINE | ID: mdl-32621703

ABSTRACT

Lipedematous scalp is an uncommon entity of unknown etiology, rarely described in the pediatric age. It is characterized by boggy thickening of the scalp predominantly located at the vertex and occiput, which acquires a cotton-like consistency. This condition is palpable rather than visible. It is a casual finding because it is usually asymptomatic, although it may involve alopecia, pruritus, or dysesthesia. We report a 10-year-old girl with lipedematous scalp without alopecia. Sonographic and MRI findings confirmed the diagnosis of lipidematous scalp.  El lipedema de cuero cabelludo o cuero cabelludo lipedematoso es una entidad infrecuente y de etiología desconocida, rara vez descrita en la edad pediátrica. Se caracteriza por un engrosamiento difuso y de tacto esponjoso del tejido celular subcutáneo localizado principalmente en vértex y occipucio. Suele ser un hallazgo casual dado que habitualmente cursa de forma asintomática, aunque puede asociar alopecia, prurito o disestesias. Presentamos el caso de una niña de 10 años de edad con lipedema de cuero cabelludo sin alopecia asociada. Los hallazgos ecográficos y de resonancia magnética confirmaron el diagnóstico de lipedema de cuero cabelludo.


Subject(s)
Lipedema/pathology , Scalp Dermatoses/pathology , Child , Female , Humans , Lipedema/diagnostic imaging , Magnetic Resonance Imaging , Scalp/pathology , Scalp Dermatoses/diagnostic imaging , Ultrasonography
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