Executive summary of the consensus document for the training and development of clinical ultrasound in Internal Medicine: Recommendations from the Clinical Ultrasound Working Group of the Spanish Society of Internal Medicine (GTECO-SEMI).

INTRODUCTION: Given the increasing adoption of clinical ultrasound in medicine, it is essential to standardize its application, training, and research. OBJECTIVES AND METHODS: The purpose of this document is to provide consensus recommendations to address questions about the practice and operation of clinical ultrasound units. Nineteen experts and leaders from advanced clinical ultrasound units participated. A modified Delphi consensus method was used. RESULTS: A total of 137 consensus statements, based on evidence and expert opinion, were considered. The statements were distributed across 10 areas, and 99 recommendations achieved consensus. CONCLUSIONS: This consensus defines the most important aspects of clinical ultrasound in the field of Internal Medicine, with the aim of standardizing and promoting this healthcare advancement in its various aspects. The document has been prepared by the Clinical Ultrasound Working Group and endorsed by the Spanish Society of Internal Medicine.

Effect of topological cues on material-driven fibronectin fibrillogenesis and cell differentiation.

Fibronectin (FN) assembles into fibrillar networks by cells through an integrin-dependent mechanism. We have recently shown that simple FN adsorption onto poly(ethyl acrylate) surfaces (PEA), but not control polymer (poly(methyl acrylate), PMA), also triggered FN organization into a physiological fibrillar network. FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules. In the present study, we investigate the influence of topological cues on the material-driven FN assembly and the myogenic differentiation process. Aligned and random electrospun fibers were prepared. While FN fibrils assembled on the PEA fibers as they do on the smooth surface, the characteristic distribution of globular FN molecules observed on flat PMA transformed into non-connected FN fibrils on electrospun PMA, which significantly enhanced cell differentiation. The direct relationship between the fibrillar organization of FN at the material interface and the myogenic process was further assessed by preparing FN gradients on smooth PEA and PMA films. Isolated FN molecules observed at one edge of the substrate gradually interconnected with each other, eventually forming a fully developed network of FN fibrils on PEA. In contrast, FN adopted a globular-like conformation along the entire length of the PMA surface, and the FN gradient consisted only of increased density of adsorbed FN. Correspondingly, the percentage of differentiated cells increased monotonically along the FN gradient on PEA but not on PMA. This work demonstrates an interplay between material chemistry and topology in modulating material-driven FN fibrillogenesis and cell differentiation.

Point-of-Care Ultrasound (POCUS) as an Extension of the Physical Examination in Patients with Bacteremia or Candidemia.

BACKGROUND: In general, transthoracic echocardiography (TTE) is the first diagnostic test used for patients with bacteremia or candidemia and clinical signs of Infective Endocarditis (IE). Point-of-care ultrasound (POCUS) may be used in addition to physical examination for the detection of structural heart disease and valve abnormalities. OBJECTIVE: To determine the diagnostic accuracy of POCUS for the detection of signs suggestive of IE, including vegetation, valvular regurgitation, structural heart disease, hepatomegaly, splenomegaly and septic embolisms, in patients with bacteremia or candidemia. DESIGN: Observational, cross-sectional, multicenter study using convenience sampling. SETTING: Six Spanish academic hospitals. PATIENTS: Adult patients with bacteremia or candidemia between 1 February 2018 and 31 December 2020. MEASUREMENTS: The reference test, to evaluate vegetation, valvular regurgitation and structural heart disease, was transesophageal echocardiography (TEE). For patients who did not undergo TEE, transthoracic echocardiography (TTE) was considered the reference test. POCUS was performed by internists, while conventional echocardiography procedures were performed by cardiologists. RESULTS: In 258 patients, for the detection of valvular vegetation, POCUS had sensitivity, specificity, and positive and negative predictive values of 77%, 94%, 82% and 92%, respectively. For valvular regurgitation (more than mild), sensitivity was ≥76% and specificity ≥85%. Sensitivity values for the detection of hepatomegaly and splenomegaly were 92% and 92%, respectively, while those for specificity were 96% and 98%. CONCLUSION: POCUS could be a valuable tool, as a complement to physical examination, at the hospital bedside for patients with bacteremia or candidemia, helping to identify signs suggestive of IE.

[Candidemias: multicentre analysis in 16 hospitals in Andalusia (Spain)]. / Candidemias: análisis multicéntrico en 16 hospitales andaluces.

INTRODUCTION: Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation. MATERIAL AND METHODS: Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included. RESULTS: Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frecuent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in 38.7% of cases. Overall mortality was 40%. On univarite analysis death was found to be significantly associated with: aged > 60 years, unknown candidemia focus, Pitt score ≥ 2, APACHE II, shock at onset, persistents positive second blood cultures, non-removal of the central venous catheter and Candida species different of C. parasilopsis, among others. In the multivariate analysis death was found to be significantly associated with: aged > 60 years, Pitt score ≥ 2, Candida species different of C.parasilopsis and inadequate treatment. CONCLUSIONS: The candidemia clinical epidemiology in our region is similar to other areas and receiving inadequate treatment is the only modifiable risk factor associated with higher odds of mortality. Therefore, this modifiable factor needs to be improved to reduce the mortality.

Lithium Directs Embryonic Stem Cell Differentiation Into Hemangioblast-Like Cells.

Definitive hematopoietic stem cells (HSCs) derive from specialized regions of the endothelium known as the hemogenic endothelium (HE) during embryonic developmental processes. This knowledge opens up new possibilities for designing new strategies to obtain HSCs in vitro from pluripotent stem cells (PSCs). Previous advances in this field show that the Wnt/ß-catenin signaling pathway plays a crucial role in PSC-derived HSC formation. In this work, lithium, a GSK3 inhibitor, is identified as an element capable of stabilizing ß-catenin and inducing embryonic stem cells (ESCs) differentiation in hemangioblast-like cells, highly consistent with the role of Wnt agonists on ESC differentiation. ESCs treated with 10 mm lithium express CD31+, SCA-1+, Nkx2-5+, CD34+, and FLK1+ cells characteristic of the hemangioblast cells that precede HE development. However, 10 mm Li treated cells remain arrested in a hemangioblast-like phase, which switched into the expression of HE markers after stimulation with maturation medium. The ability of lithium-treated ESCs to further derive into HE is confirmed after defined maturation, resulting in a rapid increase in cells positive for the HE markers RUNX1 and SOX17. The results represent a novel strategy for generating HSC precursors in vitro as a multipotent source of stem cells for blood disease therapies.

Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an injury.

Muscle tissue possess an innate regenerative potential that involves an extremely complicated and synchronized process on which resident muscle stem cells play a major role: activate after an injury, differentiate and fuse originating new myofibers for muscle repair. Considerable efforts have been made to design new approaches based on material systems to potentiate muscle repair by engineering muscle extracellular matrix and/or including soluble factors/cells in the media, trying to recapitulate the key biophysical and biochemical cues present in the muscle niche. This work proposes a different and simple approach to potentiate muscle regeneration exploiting the interplay between specific cell membrane receptors. The simultaneous stimulation of borate transporter, NaBC1 (encoded by SLC4A11gene), and fibronectin-binding integrins induced higher number and size of focal adhesions, major cell spreading and actin stress fibers, strengthening myoblast attachment and providing an enhanced response in terms of myotube fusion and maturation. The stimulated NaBC1 generated an adhesion-driven state through a mechanism that involves simultaneous NaBC1/α5ß1/αvß3 co-localization. We engineered and characterized borax-loaded alginate hydrogels for an effective activation of NaBC1 in vivo. After inducing an acute injury with cardiotoxin in mice, active-NaBC1 accelerated the muscle regeneration process. Our results put forward a new biomaterial approach for muscle repair.

Borax induces osteogenesis by stimulating NaBC1 transporter via activation of BMP pathway.

The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications. Efforts have been made to control MSC behavior by using material systems to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a simple approach based on ion transporter stimulation to determine stem cell fate that avoids the use of growth factors. Addition of borax alone, transported by the NaBC1-transporter, enhanced MSC adhesion and contractility, promoted osteogenesis and inhibited adipogenesis. Stimulated-NaBC1 promoted osteogenesis via the BMP canonical pathway (comprising Smad1/YAP nucleus translocation and osteopontin expression) through a mechanism that involves simultaneous NaBC1/BMPR1A and NaBC1/α5ß1/αvß3 co-localization. We describe an original function for NaBC1 transporter, besides controlling borate homeostasis, capable of stimulating growth factor receptors and fibronectin-binding integrins. Our results open up new biomaterial engineering approaches for biomedical applications by a cost-effective strategy that avoids the use of soluble growth factors.

Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors.

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.

Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation.

Embryonic stem cells (ESCs) possess remarkable abilities, as they can differentiate into all cell types (pluripotency) and be self-renewing, giving rise to two identical cells. These characteristics make ESCs a powerful research tool in fundamental embryogenesis as well as candidates for use in regenerative medicine. Significant efforts have been devoted to developing protocols to control ESC fate, including soluble and complex cocktails of growth factors and small molecules seeking to activate/inhibit key signaling pathways for the maintenance of pluripotency states or activate differentiation. Here we describe a novel method for the effective maintenance of mouse ESCs, avoiding the supplementation of complex inhibitory cocktails or cytokines, e.g., LIF. We show that the addition of zinc to ESC cultures leads to a stable pluripotent state that shares biochemical, transcriptional and karyotypic features with the classical LIF treatment. We demonstrate for the first time that ESCs maintained in long-term cultures with added zinc, are capable of sustaining a stable ESCs pluripotent phenotype, as well as differentiating efficiently upon external stimulation. We show that zinc promotes long-term ESC self-renewal (>30 days) via activation of ZIP7 and AKT signaling pathways. Furthermore, the combination of zinc with LIF results in a synergistic effect that enhances LIF effects, increases AKT and STAT3 activity, promotes the expression of pluripotency regulators and avoids the expression of differentiation markers.

Simultaneous Boron Ion-Channel/Growth Factor Receptor Activation for Enhanced Vascularization.

Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here a 3D molecular model for NaBC1 is proposed and it is shown that simultaneous stimulation of NaBC1 and vascular endothelial growth factor receptors (VEGFR) promotes angiogenesis in vitro and in vivo with ultralow concentrations of VEGF. Human umbilical vein endothelial cells' (HUVEC) organization into tubular structures is shown to be indicative of vascularization potential. Enhanced cell sprouting is found only in the presence of VEGF and boron, the effect abrogated after blocking NaBC1. It is demonstrated that stimulated NaBC1 promotes angiogenesis via PI3k-independent pathways and that α5 ß1 /αv ß3 integrin binding is not essential to enhanced HUVEC organization. A novel vascularization mechanism that involves crosstalk and colocalization between NaBC1 and VEGFR receptors is described. This has important translational consequences; just by administering boron, taking advantage of endogenous VEGF, in vivo vascularization is shown in a chorioallantoic membrane assay.

Clinical findings, therapeutic approach, and outcome of brucellar vertebral osteomyelitis.

BACKGROUND: Osteoarticular complications are the most common focal complications of brucellosis. Although vertebral osteomyelitis is the most frequent location in adults >30 years of age, little information is available about this serious complication of brucellosis, and great confusion surrounds its prognosis and the most appropriate treatment. METHODS: We undertook a descriptive, retrospective, observational study of 96 patients who received a diagnosis of brucella vertebral osteomyelitis from September 1982 through December 2005 at a tertiary care hospital. All of the patients were treated for 3 months, after which they were followed up monthly for the first 3 months and then at 2-month intervals for the subsequent 6 months. RESULTS: The incidence of vertebral osteomyelitis was 10.4%. The mean diagnostic delay was 12.7 weeks. Inflammatory spinal pain (occurring in 94.8% of patients) and fever (91.7%) were the most relevant clinical characteristics. Eight patients (8.3%) had motor weakness or paralysis. Paravertebral masses, epidural masses, and psoas abscesses were detected in 45.8%, 27.1%, and 10.4% of patients, respectively. Sixty-three patients (65.6%) received medication only, and 33 (34.4%) required surgical therapy in addition to medication. Twenty percent of patients experienced therapeutic failure. Attributable mortality was 2.1%, and severe functional sequelae were apparent in 6.2% of the patients. No significant differences were seen between patients who were treated with doxycycline-streptomycin and those treated with doxycycline-rifampicin. CONCLUSIONS: Vertebral osteomyelitis is a serious complication of brucellosis. It generates a high rate of therapeutic failure and functional sequelae. In the absence of more-powerful controlled studies, the duration of treatment of brucellar vertebral osteomyelitis should be 3 months.

Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone.

OBJECTIVES: To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS: A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS: In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS: HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.

Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway.

Myogenic regeneration occurs through a chain of events beginning with the output of satellite cells from quiescent state, formation of competent myoblasts and later fusion and differentiation into myofibres. Traditionally, growth factors are used to stimulate muscle regeneration but this involves serious off-target effects, including alterations in cell homeostasis and cancer. In this work, we have studied the use of zinc to trigger myogenic differentiation. We show that zinc promotes myoblast proliferation, differentiation and maturation of myofibres. We demonstrate that this process occurs through the PI3K/Akt pathway, via zinc stimulation of transporter Zip7. Depletion of zinc transporter Zip7 by RNA interference shows reduction of both PI3K/Akt signalling and a significant reduction of multinucleated myofibres and myotubes development. Moreover, we show that mature myofibres, obtained through stimulation with high concentrations of zinc, accumulate zinc and so we hypothesise their function as zinc reservoirs into the cell.

In Situ Hydroxyapatite Content Affects the Cell Differentiation on Porous Chitosan/Hydroxyapatite Scaffolds.

Highly porous chitosan/hydroxyapatite composite structures with different weight ratios (100/0; 90/10; 80/20; 70/30; 60/40; 50/50; 40/60) have been prepared by precipitation method and freeze-gelation technique using calcite, urea phosphate and chitosan as starting materials. The composition of prepared composite scaffolds was characterized by X-ray diffraction analysis and Fourier transformed infrared spectroscopy, while morphology of scaffolds was imaged by scanning electron microscopy. Mercury intrusion porosimetry measurements of prepared scaffolds have shown different porosity and microstructure regarding to the HA content, along with SEM observations of scaffolds after being immersed in physiological medium. The results of swelling capacity and compressive strength measured in Dulbecco's phosphate buffer saline (DPBS) have shown higher values for composite scaffolds with lower in situ HA content. Viability, proliferation and differentiation of MC3T3-E1 cells seeded on different scaffolds have been evaluated by live dead assay and confocal scan microscopy. Our results suggest that the increase of HA content enhance osteoblast differentiation confirming osteogenic properties of highly porous CS/HA scaffolds for tissue engineering applications in bone repair.

[Positive urine pneumococcal antigen test and vaccination]. / Antigenuria positiva a neumococo y vacunación.

INTRODUCTION AND OBJECTIVE: Although urine pneumococcal antigen is an useful test, it has false positives such as pneumococcal vaccination. MATERIAL AND METHODS: Positive urine pneumococcal antigen in Hospital de Denia (January-February/2015). We studied epidemiological, radiological and microbiological variables as well as previous pneumococcal vaccination (neumo-23 and/or neumo-13). RESULTS: Urine pneumococcal antigen test was positive in 12.4% of 385 cases. Only 33.3% of positive cases had pneumonia in chest X-ray, and 35.4% of patients had previous pneumococcal vaccination. In most cases (87.5%), an antibiotic was prescribed. CONCLUSIONS: Pneumococcal vaccination can produce a false positive result in the urine pneumococcal antigen test in clinical practice, leading to an unnecessary prescription of antibiotics.

Borax-Loaded PLLA for Promotion of Myogenic Differentiation.

Boron is an essential metalloid, which plays a key role in plant and animal metabolisms. It has been reported that boron is involved in bone mineralization, has some uses in synthetic chemistry, and its potential has been only recently exploited in medicinal chemistry. However, in the area of tissue engineering, the use of boron is limited to works involving certain bioactive glasses. In this study, we engineer poly(l-lactic acid) (PLLA) substrates with sustained release of boron. Then, we analyze for the first time the uniqueness effects of boron in cell differentiation using murine C2C12 myoblasts and discuss a potential mechanism of action in cooperation with Ca(2+). Our results demonstrate that borax-loaded materials strongly enhance myotube formation at initial steps of myogenesis. Furthermore, we demonstrate that Ca(2+) plays an essential role in combination with borax as chelating or blocking Ca(2+) entry into the cell leads to a detrimental effect on myoblast differentiation observed on borax-loaded materials. This research identifies borax-loaded materials to trigger differentiation mechanisms and it establishes a new tool to engineer microenvironments with applications in regenerative medicine for muscular diseases.

Cell migration within confined sandwich-like nanoenvironments.

AIM: We introduced sandwich-like culture as a tool to engineer the cellular nanoenvironment by tuning protein presentation and activation of dorsal and ventral receptors. We aim at studying cell migration under more similar conditions to the 3D physiological one. MATERIALS & METHODS: We have investigated different nanoenvironments by changing the protein coating and using materials that adsorb proteins in different conformation, seeking to show their specific role in cell migration. RESULTS: Cell migration within sandwich cultures greatly differs from 2D cultures, shares some similarities with migration within 3D environments and is highly dependent on the protein nanoenvironment. Beyond differences in cell morphology and migration, dorsal stimulation promotes cell remodeling of the extracellular matrix over simple ventral receptor activation in traditional 2D cultures. CONCLUSION: Local(nano) stimulation of dorsal and ventral receptors within sandwich cultures alter cell migration in comparison to standard 2D environments.

Controlled Assembly of Fibronectin Nanofibrils Triggered by Random Copolymer Chemistry.

Fibronectin fibrillogenesis is the physiological process by which cells elaborate a fibrous FN matrix. Poly(ethyl acrylate), PEA, has been described to induce a similar process upon simple adsorption of fibronectin (FN) from a protein solution-in the absence of cells-leading to the so-called material-driven fibronectin fibrillogenesis. Poly(methyl acrylate), PMA, is a polymer with very similar chemistry to PEA, on which FN is adsorbed, keeping the globular conformation of the protein in solution. We have used radical polymerization to synthesize copolymers with controlled EA/MA ratio, seeking to modulate the degree of FN fibrillogenesis. The physicochemical properties of the system were studied using dynamic-mechanical analysis, differential scanning calorimetry, and water contact angle. Both the degree of FN fibrillogenesis and the availability of the integrin binding region of FN directly depend on the percentage of EA in the copolymer, whereas the same total amount of FN was adsorbed regardless the EA/MA ratio. Cell morphology adhesion and differentiation of murine C2C12 were shown to depend on the degree of FN fibrillogenesis previously attained on the material surface. Myogenic differentiation was enhanced on the copolymers with higher EA content, i.e. more interconnected FN fibrils.

Epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium kansasii and Mycobacterium tuberculosis in patients infected with human immunodeficiency virus: a multicenter study.

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation.

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII(7-10) fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII(7-10) fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5ß1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII(7-10) fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII(7-10) fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications.