RESUMO
UNLABELLED: Several companies offer anatomically shaped breast implants but differences among manufacturers are often misunderstood. The shell texture is a crucial parameter for anatomically shaped implants to prevent rotation and to decrease the risk of capsular contracture, even though concerns have recently been raised concerning the complications associated with textured breast implants. The aim of this study was to characterize differences in terms of texture, cell adhesion, shape, and stiffness between some commonly used anatomically shaped implants from three different manufacturers. METHODS: Five commercially available anatomically shaped breast implants from 3 different manufacturers (Allergan, Mentor, and Sebbin) were used. Scanning electron microscopy, X-ray microtomography, and scanning mechanical microscopy were used to characterize the shell texture. Human fibroblast adhesion onto the shells was evaluated. 3D models of the implants were obtained using CT-scan acquisitions to analyze their shape. Implant stiffness was evaluated using a tractiometer. RESULTS: Major differences were observed in the topography of the textures of the shells, but this was not conveyed by a statistically significant fibroblast adhesion difference. However, fibroblasts adhered better on anatomically shaped textured implants than on smooth implants (p < 0.01). Our work pointed out differences in the Biocell® texture in comparison with older studies. The 3D analysis showed significant shape differences between the anatomically shaped implants of the 3 companies, despite similar dimensions. Implant stiffness was comparable among the 3 brands. CONCLUSIONS: Each texture had its specific topography, and this work is the first description of Sebbin anatomic breast implant texturation. Moreover, major discrepancies were found in the analysis of the Biocell® texture when comparing our results with previous reports. These differences may have clinical implications and are discussed. This study also highlighted major shape differences among breast implants from different manufacturers, which is quite counterintuitive. The clinical impact of these differences however needs further investigation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Implantes de Mama , Desenho de Prótese , Géis de Silicone , Fenômenos Biomecânicos , Teste de MateriaisRESUMO
The risk of infections and the appearance of symptoms (e.g., odors) represent the main troubles resulting from malignant wounds. The aim of this study was to characterize the balance of bacterial floras and the relationships between biofilms and bacteria and the emergence of symptoms. Experimental research was carried out for 42 days on malignant wounds associated with breast cancer. Investigations of bacterial floras (aerobes, aero-anaerobes, and anaerobes), detection of the presence of biofilms by microscopic epifluorescence, and clinical assessment were performed. We characterized biofilms in 32 malignant wounds associated with breast cancer and bacterial floras in 25 such wounds. A mixed group of floras, composed of 54 different bacterial types, was identified, with an average number per patient of 3.6 aerobic species and 1.7 anaerobic species; the presence of strict anaerobic bacterial strains was evidenced in 70% of the wounds; biofilm was observed in 35% of the cases. Odor was a reliable indicator of colonization by anaerobes, even when this symptom was not directly linked to any of the identified anaerobic bacteria. Bacteria are more likely to be present during myelosuppression and significantly increase the emergence of odors and pain when present at amounts of >10(5) · g(-1). The presence of biofilms was not associated with clinical signs or with precise types of bacteria. No infections occurred during the 42-day evaluation period. This study provides a dynamic description of the bacterial floras of tumoral wounds. The study results highlight the absolute need for new therapeutic options that are effective for use on circulating bacteria as well as on bacteria organized in biofilm.
Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , Biofilmes/crescimento & desenvolvimento , Biota , Neoplasias da Mama/complicações , Infecção dos Ferimentos/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Coinfecção/microbiologia , Coinfecção/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecção dos Ferimentos/patologiaRESUMO
The behavior of a hydrolytic enzyme (pullulanase) toward its substrate (pullulan) in the presence of a nonsubstrate (alginate), both below and above the critical entanglement concentration (C*), was studied. The hydrolysis kinetics were studied with the enzyme and alginate concentrations varied using two main methods: a colorimetric assay of the reducing extremities (RE), which allowed the number-average molar masses (Mn) of the oligosaccharides to be determined, and size exclusion chromatography with on-line, multiangle light scattering, viscometer, and differential refractive index detectors, which allowed the average molar masses, Mn and Mw, of the oligosaccharides during hydrolysis to be determined. Free pullulanase acts via an "endo" process. The presence of alginate slows the hydrolysis kinetics, particularly when the alginate concentration is greater than the C*. These results were confirmed by the evolution of the kinetic parameters (KM, Vmax) obtained via isothermal titration calorimetry (ITC). The amount of oligosaccharides produced is not dependent on the alginate concentration, and the endo enzyme behavior is not modified by the entanglement in the medium. These observations were also confirmed by ITC analysis in the presence of degraded alginate (without entanglement). Our results correlated with the substrate diffusion in entangled media. The pullulanase reaction in the presence of alginate is shown to be diffusion-dependent.
Assuntos
Alginatos/química , Glucanos/química , Glicosídeo Hidrolases/química , Calorimetria , Cromatografia em Gel , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrólise , Cinética , Oligossacarídeos/metabolismoRESUMO
A fibrin hydrogel at physiological concentration (5 mg/mL) was associated with polyvinyl alcohol (PVA) inside an interpenetrating polymer networks (IPN) architecture. Previously, PVA has been modified with methacrylate functions in order to cross-link it by free-radical polymerization. The fibrin network was synthesized by the enzymatic hydrolysis of fibrinogen by thrombin. The resulting self-supported materials simultaneously exhibit the properties of the fibrin hydrogel and those of the synthetic polymer network. Their storage modulus is 50-fold higher than that of the fibrin hydrogel and they are completely rehydratable. These materials are noncytotoxic toward human fibroblast and the fibrin present on the surface of PVAm-based IPNs favors cell development.
Assuntos
Materiais Biocompatíveis/química , Fibrina/química , Álcool de Polivinil/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibrina/metabolismo , Fibrinogênio/química , Fibrinogênio/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Prepúcio do Pênis/metabolismo , Humanos , Hidrólise , Masculino , Tamanho da Partícula , Álcool de Polivinil/metabolismo , Álcool de Polivinil/farmacologia , Relação Estrutura-Atividade , Propriedades de Superfície , Trombina/metabolismo , Água/química , Água/metabolismoRESUMO
Culture-adapted human mesenchymal stromal cells (hMSCs) are appealing candidates for regenerative medicine applications. However, these cells implanted in lesions as single cells or tissue constructs encounter an ischemic microenvironment responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. We hereby propose a paradigm shift for enhancing hMSC survival by designing, developing, and testing an enzyme-controlled, nutritive hydrogel with an inbuilt glucose delivery system for the first time. This hydrogel, composed of fibrin, starch (a polymer of glucose), and amyloglucosidase (AMG, an enzyme that hydrolyze glucose from starch), provides physiological glucose levels to fuel hMSCs via glycolysis. hMSCs loaded in these hydrogels and exposed to near anoxia (0.1% pO2) in vitro exhibited improved cell viability and angioinductive functions for up to 14 days. Most importantly, these nutritive hydrogels promoted hMSC viability and paracrine functions when implanted ectopically. Our findings suggest that local glucose delivery via the proposed nutritive hydrogel can be an efficient approach to improve hMSC-based therapeutic efficacy.
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Hidrogéis , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Sobrevivência Celular , Glucose/metabolismo , Amido/metabolismoRESUMO
Fibrin gels are of interest as biomaterials for regenerative medicine but present poor mechanical properties, undergo fast degradation and strongly contract in presence of cells. To face these drawbacks, a fibrin network can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN) architecture. In this study, we report the properties of an IPN comprising a fibrin (Fb) network and a silk fibroin (SF) network. This IPN is synthesized through the action of 2 enzymes, each one being specific of one protein gelation, i.e. thrombin (Tb) for Fb gelation, and horseradish peroxidase (HRP) for SF gelation. The effective formation of both Fb and SF networks in an IPN architecture was first verified at qualitative and quantitative levels. The resulting IPN was easily manipulable, displayed high viscoelastic properties and showed homogeneous macro- and micro-structure. Then the degradability of the IPN by two proteases, thermolysin (TL) and trypsin (TRY), obeying different mechanisms was presented. Finally, two-dimensional culture of human fibroblasts on the IPN surface induced little material contraction, while fibroblasts showed healthy morphology, displayed high viability and produced mature extracellular matrix (ECM) proteins. Taken together, the results suggest that this new IPN have a strong potential for tissue engineering and regenerative medicine.
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Fibrina/farmacologia , Fibroínas/farmacologia , Peroxidase do Rábano Silvestre/metabolismo , Polímeros/farmacologia , Trombina/metabolismo , Proliferação de Células , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/biossíntese , Fibronectinas/biossíntese , Humanos , Recém-Nascido , MasculinoRESUMO
Ephemeral gels, called Enzgels, successively undergo sol-gel and then gel-sol transition under the action of two antagonistic enzymes, transglutaminase and protease. Molecular and macroscopic properties of Enzgels are directly dependent on the enzymatic activities and their ratios. This work studies the characteristics of Enzgels according to the specificity of three different proteases: thermolysin, trypsin, and collagenase. The experiments are conducted using three types of gelatin networks, one created only by triple helices, one only by covalent bonds, and the last network by both triple helices and covalent bonds. Rheology and polarimetry measurements show that the evolution of Enzgels is directly dependent on the specificity of the protease used. Moreover, gelatin network conformation has different influences according to this proteolytic specificity. Collagenase is not very sensitive to gelatin conformation, whereas trypsin is very limited by the presence of covalent bonds. This study considerably expands the knowledge of Enzgel properties.
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Géis , Peptídeo Hidrolases/metabolismo , Transglutaminases/metabolismo , Ligação de Hidrogênio , Reologia , Especificidade por SubstratoRESUMO
Chronic wound colonization by bacterial biofilms is common and can cause various complications. An anti-biofilm strategy was developed around the co-entrapment of a commercially available antiseptic, PHMB (polyhexamethylene biguanide 4mgmL-1), with EDTA (Ethylen diamine tetra acetic acid, 20mM) in a gelatin gel. The two active compounds act synergistically against bacterial biofilms, but their efficiency is strongly reduced (16-fold) when entrapped inside the 5% gelatin gel, and they weaken the mechanical properties (50-fold) of the gel. Increasing the gelatin concentration to 7% allows for good mechanical properties but large diffusional constraints. An active ephemeral gel, a chemical gel with controlled hydrolysis, was conceived and developed. When the ephemeral gel was solubilized after 48h, PHMB delivery increased, leading to good anti-biofilm activity. The various gels were examined over 24 and 48h of contact with P. aeruginosa and S. aureus biofilms, two types of bacterial biofilms frequently encountered in chronic wounds. The ephemeral gel eradicated the dense biofilms (>6.107CFU·cm-2) produced by either single or mixed strains; a similar efficiency was measured for biofilms from strains of both laboratory and clinical origin. The formulation was then adapted to develop a dressing prototype that is active against biofilms and fulfils the requirements of an efficient wound care system.
Assuntos
Antibacterianos/farmacologia , Biguanidas/química , Biofilmes/efeitos dos fármacos , Ácido Edético/química , Géis/química , Antibacterianos/síntese química , Antibacterianos/química , Bandagens , Biguanidas/farmacologia , Ácido Edético/farmacologia , Gelatina/química , Pseudomonas aeruginosa/fisiologia , Reologia , Staphylococcus aureus/fisiologiaRESUMO
Carbamylation is a post-translational modification due to nonenzymatic binding of cyanate, a by-product of urea, on free amino groups of proteins. Post-translational modifications are known to induce alterations in structural and functional properties of proteins, thus disturbing protein-protein or cell-protein interactions. We report the impact of carbamylation on type I collagen sensitivity to enzymatic proteolysis. Type I collagen was extracted from rat tail tendons and carbamylated by incubation with 0.1 M potassium cyanate at 37 degrees C for 2, 6 or 24 h. Degradation assays revealed that carbamylated collagen exhibited a greater resistance to collagenases (i.e. bacterial collagenase, matrix metalloproteinase(MMP)-1, MMP-8 and MMP-13), together with an increased sensitivity to MMP-2. Evaluation of collagen triple helix conformation by polarimetry indicated that local destabilizations of triple helix structure related to carbamylation could be responsible for the observed differences in sensitivity. These results confirm the crucial role of triple helix integrity in the degradation of type I collagen by MMPs, and support the deleterious impact of post-translational modifications in vivo by altering the balanced remodeling of collagen within connective tissue.
Assuntos
Carbamatos/metabolismo , Colágeno Tipo I/metabolismo , Colagenases/metabolismo , Animais , Colágeno Tipo I/química , Processamento de Proteína Pós-Traducional , Estrutura Quaternária de Proteína , Ratos , Ratos Sprague-DawleyRESUMO
A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-linked carboxymethylcellulose (CMC) is developed to achieve localized and sustained release of lipophilic drugs. The analysis of LNP stability as well as the hydrogel swelling and mechanical properties confirm the successful incorporation of particles up to a concentration of 50% w/wCMC . The initial LNP release rate can be prolonged by increasing the particle diameter from 50 to 120 nm, while the amount of long-term release can be adjusted by tailoring the particle surface charge or the cross-linking density of the polymer. After 30 d, 58% of 50 nm diameter negatively charged LNPs escape from the matrix while only 17% of positively charged nanoparticles are released from materials with intermediate cross-linking density. A mathematical diffusion model based on Fick's second law is efficient to predict the diffusion of the particles from the hydrogels.
Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis/química , Nanopartículas/química , Carboximetilcelulose Sódica/química , Difusão , Liberação Controlada de Fármacos , Lipídeos/químicaRESUMO
Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts. We further evaluated their biocompatibility ex vivo with a chick embryo organotypic culture model. Subcutaneous implantations of the matrices were subsequently conducted on nude mice to investigate their biocompatibility in vivo. Our preliminary data highlighted that our biomaterials were non-cytotoxic (viability above 90%). The organotypic culture showed that the IPN matrices induced higher cell adhesion (across all the explanted organ tissues) and migration (skin, intestine) than the control groups, suggesting the advantages of using a biomimetic, yet mechanically-reinforced IPN-based matrix. We observed no major inflammatory response up to 12 weeks post implantation. All together, these data suggest that these fibrin-based IPNs are promising biomaterials for tissue engineering.
RESUMO
It was observed that fibronectin precipitates when deposited on hydroxyapatite (HA) ceramics. Fibronectin's known affinity for calcium and the composition of the ceramic itself suggested that calcium release could be the main cause of this aggregation effect. It was then decided to investigate the effect of a surface chelation treatment on fibronectin adsorption, and MG63 cell adhesion, onto porous ceramics of hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and HA/TCP biphasic material (BCP). Those ceramics were immersed in an EDTA solution and the effect of this treatment on the material composition was assayed. X-ray diffraction data showed the presence of alpha- and beta-TCP phases in HA and BCP materials, which were both completely removed by the chelation treatment in the case of HA. On BCP, alpha-TCP was removed and beta-TCP partially dissolved. The TCP material, which was pure beta-TCP, underwent a mass loss, but no change in composition was observed. Adhesion of MG63 cells was overall higher on the fibronectin-coated EDTA-treated HA material, but was especially enhanced on EDTA-treated HA. Changes in surface morphologies, as compared with the use of scanning electron microscopy, did not seem to be related to the effects observed. The EDTA treatment proved to be a very efficient way of removing by-products of HA sintered materials, and thus enhancing the biocompatibility of the material.
Assuntos
Adesão Celular , Quelantes/química , Durapatita/química , Fibronectinas/química , Adsorção , Humanos , Microscopia Eletrônica de Varredura , Propriedades de SuperfícieRESUMO
A multistep strategy was used to generate a combined antibiofilm treatment that could efficiently decrease the biomass of dense biofilms (≥6 × 10(7) CFU/cm(2)). Several compounds that exhibited activity against various targets were tested individually and in combination to search for possible synergistic effects. First, the antibiofilm activity of various commercially available antiseptics was tested on Pseudomonas aeruginosa and Staphylococcus aureus. Second, antiseptics were mixed with ethylene diamine tetra-acetic acid (EDTA), which is an ion chelator that can disturb biofilm organisation, and additive effects on biofilm biomass degradation were found for both strains. Then, enzymes with the ability to destabilise the biofilm matrix by hydrolysing either its proteins or its polysaccharides were used; as expected, they did not decrease bacterial viability but were revealed as efficient biomass reducers. The combination of antiseptics, EDTA and proteases, all at low concentrations, revealed a synergistic effect leading to total eradication of dense biofilms both of P. aeruginosa and S. aureus.
Assuntos
Anti-Infecciosos Locais/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Ácido Edético/farmacologia , Enzimas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologiaRESUMO
The release of molecules entrapped within biogels is dictated by diffusion laws. Innovative biogel architectures are conceived and tested to control small molecule delivery from gelatin gels. The ionic interactions modulate the release of small molecules. Alginate is then added to gelatin gels and further hydrolyzed; the influence of viscosity is discussed. Next, various mixed gels are compared, such as a gelatin-alginate IPN and the original architecture of an alginate gel entrapped in a gelatin gel with or without a polysaccharidase. The relative influence of ionic interactions and diffusional constraints on the delivery of small charged molecules is explored, and a solution for controlling diffusion is proposed for any situation.
Assuntos
Alginatos/metabolismo , Corantes/metabolismo , Sistemas de Liberação de Medicamentos , Gelatina/metabolismo , Géis/metabolismo , Polissacarídeo-Liases/metabolismo , Animais , Azul de Bromotimol/metabolismo , Difusão , Módulo de Elasticidade , Amarelo de Eosina-(YS)/metabolismo , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/metabolismo , Íons , Azul de Metileno/metabolismo , Microesferas , Polissacarídeos/química , Sus scrofa , Fatores de TempoRESUMO
Two enzymes, thrombin and transglutaminase, both participate in the formation of fibrin networks and contribute to the mechanical strength of biogels. A theoretical model built from the available kinetic data showed that a competition may take place between the two enzymes for their common substrate, fibrinogen. To evidence this phenomenon experimentally, the concentrations of the reactants were varied and the rheological properties of the resulting fibrin gels explored. The elasticity of the gels was not a singular function of the transglutaminase concentration, the optimum being also related to fibrinogen and thrombin concentrations. Thrombin concentration influenced the kinetics of gelation, but not the evolution of the mechanical properties of the gel. An indirect relationship between gel elasticity and thrombin concentration was observed upon covalent binding. The liquid phase inside the gel contained a high amount of soluble proteins when a high transglutaminase concentration was used. The impact of this competition between the two enzymes, demonstrated here for the first time, is evaluated for biomaterial elaboration.
Assuntos
Fibrina , Fibrinogênio/química , Géis , Trombina/química , Elasticidade , Cinética , Modelos TeóricosRESUMO
In some biological processes, two enzymes with antagonistic activities--the one creating a bond, the other destroying it--are involved in a reaction cycle. Several catalysts have the ability to modify the rheological properties of biological media participating in the production of a solid gel phase which later dissolves. Transglutaminase, catalyzing intermolecular protein cross-linking, is considered here as a reverse protease as far as the physical state of a proteic gel is concerned. A kinetic model including diffusion constraints and based on a protease/transglutaminase cycle interconverting insoluble gel and soluble proteolysis fragments showed that alternate sol/gel and gel/sol transitions could occur within such a system, generating transient gel phases. Then, ephemeral gels were obtained in vitro using an experimental system consisting of gelatin, transglutaminase, and thermolysin. Modulating the enzyme activity ratio allows us to "program" the global behavior: polymerization/solubilization cycle of a mixture containing at least one protein and two enzymes without any change in temperature or medium composition.
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Enzimas/química , Enzimas/metabolismo , Animais , Bacillus/enzimologia , Fenômenos Biofísicos , Biofísica , Gelatina/química , Géis , Técnicas In Vitro , Cinética , Modelos Biológicos , Streptomycetaceae/enzimologia , Suínos , Termodinâmica , Termolisina/química , Termolisina/metabolismo , Transglutaminases/química , Transglutaminases/metabolismoRESUMO
The enzyme-catalyzed gel-sol transition of calcium-alginate obtained by internal gelling strategy with the help of an entrapped alginate lyase is described. We show that alginate molecules and enzyme-produced oligoalginates shorten the gel time of physical gelatin gels (5% and 1.5%), probably due to local protein concentration increase. Interpenetrated networks composed of calcium-alginate and of gelatin were obtained only if elongation of gelatin helices inside a pre-existing calcium-alginate network could occur and only for low gelatin concentration (1.5%). The physical gelatin network is almost reversible inside the alginate one. Both networks can be obtained in the presence of alginate lyase, but gel-sol transition of calcium-alginate cannot be obtained in the presence of gelatin.
Assuntos
Alginatos/química , Gelatina/química , Gelatina/metabolismo , Transição de Fase , Alginatos/metabolismo , Cálcio/química , Catálise , Elasticidade , Flavobacterium/enzimologia , Géis/química , Géis/metabolismo , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Macrocystis/metabolismo , Estrutura Molecular , Polissacarídeo-Liases/metabolismo , Reologia , ViscosidadeRESUMO
Extracellular matrix mass balance is implied in many physiological and pathological events, such as metastasis dissemination. Widely studied, its destructive part is mainly catalysed by extracellular proteinases. Conversely, the properties of the constructive part are less obvious, cellular neo-synthesis being usually considered as its only element. In this paper, we introduce the action of transglutaminase in a mathematical model for extracellular matrix remodeling. This extracellular enzyme, catalysing intermolecular protein cross-linking, is considered here as a reverse proteinase as far as the extracellular matrix physical state is concerned. The model is based on a proteinase/transglutaminase cycle interconverting insoluble matrix and soluble proteolysis fragments, with regulation of cellular proteinase expression by the fragments. Under "closed" (batch) conditions, i.e. neglecting matrix influx and fragment efflux from the system, the model is bistable, with reversible hysteresis. Extracellular matrix proteins concentration abruptly switches from low to high levels when transglutaminase activity exceeds a threshold value. Proteinase concentration usually follows the reverse complementary kinetics, but can become apparently uncoupled from extracellular matrix concentration for some parameter values. When matrix production by the cells and fragment degradation are taken into account, the dynamics change to sustained oscillations because of the emergence of a stable limit cycle. Transitions out of and into oscillation areas are controlled by the model parameters. Biological interpretation indicates that these oscillations could represent the normal homeostatic situation, whereas the other exhibited dynamics can be related to pathologies such as tumor invasion or fibrosis. These results allow to discuss the insights that the model could contribute to the comprehension of these complex biological events.