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Author: del Campo, Aránzazu × End date: 2024 × Version: publishedVersion × WGL Institute: INM ×

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Now showing 1 - 10 of 22
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    Elastomeric Optical Waveguides by Extrusion Printing
    (Weinheim : Wiley, 2022) Feng, Jun; Zheng, Yijun; Jiang, Qiyang; Włodarczyk‐Biegun, Małgorzata K.; Pearson, Samuel; del Campo, Aránzazu
    Advances in optogenetics and the increasing use of implantable devices for therapies and health monitoring are driving demand for compliant, biocompatible optical waveguides and scalable methods for their manufacture. Molding, thermal drawing, and dip-coating are the most prevalent approaches in recent literature. Here the authors demonstrate that extrusion printing at room temperature can be used for continuous fabrication of compliant optical waveguides with polydimethylsiloxane (PDMS) core and crosslinked Pluronic F127-diacrylate (Pluronic-DA) cladding. The optical fibers are printed from fluid precursor inks and stabilized by physical interactions and photoinitiated crosslinking in the Pluronic-DA. The printed fibers show optical loss values of 0.13–0.34 dB cm–1 in air and tissue within the wavelength range of 405–520 nm. The fibers have a Young's Modulus (Pluronic cladding) of 150 kPa and can be stretched to more than 5 times their length. The optical loss of the fibers shows little variation with extension. This work demonstrates how printing can simplify the fabrication of compliant and stretchable devices from materials approved for clinical use. These can be of interest for optogenetic or photopharmacology applications in extensible tissues, like muscles or heart.
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    Light-Regulated Angiogenesis via a Phototriggerable VEGF Peptidomimetic
    (Weinheim : Wiley-VCH, 2021) Nair, Roshna V.; Farrukh, Aleeza; del Campo, Aránzazu
    The application of growth factor based therapies in regenerative medicine is limited by the high cost, fast degradation kinetics, and the multiple functions of these molecules in the cell, which requires regulated delivery to minimize side effects. Here a photoactivatable peptidomimetic of the vascular endothelial growth factor (VEGF) that allows the light-controlled presentation of angiogenic signals to endothelial cells embedded in hydrogel matrices is presented. A photoresponsive analog of the 15-mer peptidomimetic Ac-KLTWQELYQLKYKGI-NH2 (abbreviated PQK) is prepared by introducing a 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) photoremovable protecting group at the Trp4 residue. This modification inhibits the angiogenic potential of the peptide temporally. Light exposure of PQK modified hydrogels provide instructive cues to embedded endothelial cells and promote angiogenesis at the illuminated sites of the 3D culture, with the possibility of spatial control. PQK modified photoresponsive biomaterials offer an attractive approach for the dosed delivery and spatial control of pro-angiogenic factors to support regulated vascular growth by just using light as an external trigger.
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    PIEZO1-mediated mechanosensing governs NK cell killing efficiency and infiltration in three-dimensional matrices
    ([Cold Spring Harbor] : Cold Spring Harbor Laboratory (CSHL), 2024) Yanamandra, Archana K.; Zhang, Jingnan; Montalvo, Galia; Zhou, Xiangda; Biedenweg, Doreen; Zhao, Renping; Sharma, Shulagna; Hoth, Markus; Lautenschläger, Franziska; Otto, Oliver; del Campo, Aránzazu; Qu, Bin
    Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK cell killing efficiency in 3D is impaired against softened tumor cells, while it is enhanced against stiffened tumor cells. Notably, the durations required for NK cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK cell functions.
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    Encapsulation of bacteria in bilayer Pluronic thin film hydrogels: A safe format for engineered living materials
    (Amsterdam : Elsevier, 2023) Bhusari, Shardul; Kim, Juhyun; Polizzi, Karen; Sankaran, Shrikrishnan; del Campo, Aránzazu
    In engineered living materials (ELMs) non-living matrices encapsulate microorganisms to acquire capabilities like sensing or biosynthesis. The confinement of the organisms to the matrix and the prevention of overgrowth and escape during the lifetime of the material is necessary for the application of ELMs into real devices. In this study, a bilayer thin film hydrogel of Pluronic F127 and Pluronic F127 acrylate polymers supported on a solid substrate is introduced. The inner hydrogel layer contains genetically engineered bacteria and supports their growth, while the outer layer acts as an envelope and does not allow leakage of the living organisms outside of the film for at least 15 days. Due to the flat and transparent nature of the construct, the thin layer is suited for microscopy and spectroscopy-based analyses. The composition and properties of the inner and outer layer are adjusted independently to fulfil viability and confinement requirements. We demonstrate that bacterial growth and light-induced protein production are possible in the inner layer and their extent is influenced by the crosslinking degree of the used hydrogel. Bacteria inside the hydrogel are viable long term, they can act as lactate-sensors and remain active after storage in phosphate buffer at room temperature for at least 3 weeks. The versatility of bilayer bacteria thin-films is attractive for fundamental studies and for the development of application-oriented ELMs.
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    Mechanically reinforced catechol-containing hydrogels with improved tissue gluing performance
    (Basel : MDPI, 2017) Feng, Jun; Ton, Xuan-Anh; Zhao, Shifang; Paez, Julieta I.; del Campo, Aránzazu
    In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol) (PEG)–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation) and cross-linking conditions (pH, oxidant concentration, etc.) have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold) the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications.
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    Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo
    (Weinheim : Wiley-VCH, 2021) Pearson, Samuel; Feng, Jun; del Campo, Aránzazu
    Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials. © 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH.
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    Monitoring the contact stress distribution of gecko-inspired adhesives using mechano-sensitive surface coatings
    (Washington D.C. : American Chemical Society, 2018) Neubauer, Jens W.; Xue, Longjian; Erath, Johann; Drotlef, Dirk-Michael; del Campo, Aránzazu; Fery, Andreas
    The contact geometry of microstructured adhesive surfaces is of high relevance for adhesion enhancement. Theoretical considerations indicate that the stress distribution in the contact zone is crucial for the detachment mechanism, but direct experimental evidence is missing so far. In this work, we propose a method that allows, for the first time, the detection of local stresses at the contact area of biomimetic adhesive microstructures during contact formation, compression and detachment. We use a mechano-sensitive polymeric layer, which turns mechanical stresses into changes of fluorescence intensity. The biomimetic surface is brought into contact with this layer in a well-defined fashion using a microcontact printer, while the contact area is monitored with fluorescence microscopy in situ. Thus, changes in stress distribution across the contact area during compression and pull-off can be visualized with a lateral resolution of 1 μm. We apply this method to study the enhanced adhesive performance of T-shaped micropillars, compared to flat punch microstructures. We find significant differences in the stress distribution of the both differing contact geometries during pull-off. In particular, we find direct evidence for the suppression of crack nucleation at the edge of T-shaped pillars, which confirms theoretical models for the superior adhesive properties of these structures.
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    Regulating Bacterial Behavior within Hydrogels of Tunable Viscoelasticity
    (Weinheim : Wiley-VCH, 2022) Bhusari, Shardul; Sankaran, Shrikrishnan; del Campo, Aránzazu
    Engineered living materials (ELMs) are a new class of materials in which living organism incorporated into diffusive matrices uptake a fundamental role in material's composition and function. Understanding how the spatial confinement in 3D can regulate the behavior of the embedded cells is crucial to design and predict ELM's function, minimize their environmental impact and facilitate their translation into applied materials. This study investigates the growth and metabolic activity of bacteria within an associative hydrogel network (Pluronic-based) with mechanical properties that can be tuned by introducing a variable degree of acrylate crosslinks. Individual bacteria distributed in the hydrogel matrix at low density form functional colonies whose size is controlled by the extent of permanent crosslinks. With increasing stiffness and elastic response to deformation of the matrix, a decrease in colony volumes and an increase in their sphericity are observed. Protein production follows a different pattern with higher production yields occurring in networks with intermediate permanent crosslinking degrees. These results demonstrate that matrix design can be used to control and regulate the composition and function of ELMs containing microorganisms. Interestingly, design parameters for matrices to regulate bacteria behavior show similarities to those elucidated for 3D culture of mammalian cells.
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    Gelation Kinetics and Mechanical Properties of Thiol-Tetrazole Methylsulfone Hydrogels Designed for Cell Encapsulation
    (Weinheim : Wiley-VCH, 2022) de Miguel‐Jiménez, Adrián; Ebeling, Bastian; Paez, Julieta I.; Fink‐Straube, Claudia; Pearson, Samuel; del Campo, Aránzazu
    Hydrogel precursors that crosslink within minutes are essential for the development of cell encapsulation matrices and their implementation in automated systems. Such timescales allow sufficient mixing of cells and hydrogel precursors under low shear forces and the achievement of homogeneous networks and cell distributions in the 3D cell culture. The previous work showed that the thiol-tetrazole methylsulfone (TzMS) reaction crosslinks star-poly(ethylene glycol) (PEG) hydrogels within minutes at around physiological pH and can be accelerated or slowed down with small pH changes. The resulting hydrogels are cytocompatible and stable in cell culture conditions. Here, the gelation kinetics and mechanical properties of PEG-based hydrogels formed by thiol-TzMS crosslinking as a function of buffer, crosslinker structure and degree of TzMS functionality are reported. Crosslinkers of different architecture, length and chemical nature (PEG versus peptide) are tested, and degree of TzMS functionality is modified by inclusion of RGD cell-adhesive ligand, all at concentration ranges typically used in cell culture. These studies corroborate that thiol/PEG-4TzMS hydrogels show gelation times and stiffnesses that are suitable for 3D cell encapsulation and tunable through changes in hydrogel composition. The results of this study guide formulation of encapsulating hydrogels for manual and automated 3D cell culture.
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    Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting
    (Amsterdam : Elsevier, 2021) Puertas-Bartolomé, María; Włodarczyk-Biegun, Małgorzata K.; del Campo, Aránzazu; Vázquez-Lasa, Blanca; San Román, Julio
    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.