Biomaterials Science

Journal: Biomaterials Science

Abbreviation

Biomater Sci

Publisher

Royal Society of Chemistry

ISSN

2047-4830
2047-4849

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Publications 1 - 10 of 26

Cellular fate and performance of group IV metal organic framework radioenhancers
Neuer, Anna Lena; Jessernig, Alexander; Gerken, Lukas R.H.; et al. (2022)
Biomaterials Science
Nano-sized metal organic frameworks (nanoMOFs) have gained increasing importance in biomedicine due to their tunable properties. In addition to their use as carriers in drug delivery, nanoMOFs containing hafnium have been successfully employed as radio-enhancers augmenting damage caused by X-ray irradiation in tumor tissue. While results are encouraging, there is little mechanistic understanding available, and the biological fate of these radio-enhancer nanoparticles remains largely unexplored. Here, we synthesized a selection of group IV metal-based (Hf, Ti, Ti/Zr) nanoMOFs and investigated their cell compatibility and radio-enhancement performance in direct comparison to the corresponding metal oxides. We report surprising radio-enhancement performance of Ti-containing nanoMOFs reaching dose modifying ratios of 3.84 in human sarcoma cells and no relevant dose modification in healthy human fibroblasts. These Ti-based nanoMOFs even outperformed previously reported Hf-based nanoMOFs as well as equimolar group IV metal oxides in direct benchmarking experiments. While group IV nanoMOFs were well-tolerated by cells in the absence of irradiation, the nanoMOFs partially dissolved in lysosomal buffer conditions showing distinctly different chemical stability compared to widely researched group IV oxides (TiO2, ZrO2, and HfO2). Taken together, this study illustrates the promising potential of Ti-based nanoMOFs for radio-enhancement and provides insight into the intracellular fate and stability of group IV nanoMOFs.
Patterning of supported lipid bilayers and proteins using material selective nitrodopamine-mPEG
Spycher, Philipp R.; Hall, Heike; Vogel, Viola; et al. (2015)
Biomaterials Science
Biomaterial-based treatments for the prevention of preterm birth after iatrogenic rupture of the fetal membranes
Avilla Royo, Eva; Ochsenbein-Kölble, Nicole; Vonzun, Ladina; et al. (2022)
Biomaterials Science
Minimally invasive interventions to ameliorate or correct fetal abnormalities are becoming a clinical reality. However, the iatrogenic preterm prelabor rupture of the fetal membranes (FMs) (iPPROM), which may result in preterm birth, remains a main complication. Despite the cause of iPPROM not being fully known, the puncture created by the fetoscope remains unhealed until the end of the pregnancy, which permits chorioamniotic separation and amniotic fluid leakage. Hence, there is an urgent need to develop strategies to treat the FMs after minimally invasive interventions. However, none of the previously tested strategies has been clinically translated. Here, we review the current knowledge about the FMs starting from their development and present the different models that have been developed both in vitro and ex vivo. We also systematically review and summarize the different approaches that have been investigated to plug, seal, heal or suture the FMs both in preclinical and clinical studies and discuss their limitations, outcomes, and future directions.
Isolation of extracellular vesicles from microalgae: Towards the production of sustainable and natural nanocarriers of bioactive compounds
Picciotto, Sabrina; Paganini, Carolina; Capasso Palmiero, Umberto; et al. (2021)
Biomaterials Science
Safe, efficient and specific nano-delivery systems are essential for current and emerging therapeutics, precision medicine and other biotechnology sectors. Novel bio-based nanotechnologies have recently arisen, which are based on the exploitation of extracellular vesicles (EVs). In this context, it has become essential to identify suitable organisms or cellular types to act as reliable sources of EVs and to develop their pilot- to large-scale production. The discovery of new biosources and the optimisation of related bioprocesses for the isolation and functionalisation of nano-delivery vehicles are fundamental to further develop therapeutic and biotechnological applications. Microalgae constitute sustainable sources of bioactive compounds with a range of sectorial applications including for example the formulation of health supplements, cosmetic products or food ingredients. In this study, we demonstrate that microalgae are promising producers of EVs. By analysing the nanosized extracellular nano-objects produced by eighteen microalgal species, we identified seven promising EV-producing strains belonging to distinct lineages, suggesting that the production of EVs in microalgae is an evolutionary conserved trait. Here we report the selection process and focus on one of this seven species, the glaucophyte Cyanophora paradoxa, which returned a protein yield in the small EV fraction of 1 μg of EV proteins per mg of dry weight of microalgal biomass (corresponding to 109 particles per mg of dried biomass) and EVs with a diameter of 130 nm (mode), as determined by the micro bicinchoninic acid assay, nanoparticle tracking and dynamic light scattering analyses. Moreover, the extracellular nanostructures isolated from the conditioned media of microalgae species returned positive immunoblot signals for some commonly used EV-biomarkers such as Alix, Enolase, HSP70, and β-actin. Overall, this work establishes a platform for the efficient production of EVs from a sustainable bioresource and highlights the potential of microalgal EVs as novel biogenic nanovehicles.
Porosity dominates over microgel stiffness for promoting chondrogenesis in zwitterionic granular hydrogels
Asadikorayem, Maryam; Brunel, Lucia G.; Weber, Patrick; et al. (2024)
Biomaterials Science
Granular hydrogels comprised of jammed, crosslinked microgels offer great potential as biomaterial scaffolds for cell-based therapies, including for cartilage tissue regeneration. As stiffness and porosity of hydrogels affect the phenotype of encapsulated cells and the extent of tissue regeneration, the design of tunable granular hydrogels to control and optimize these parameters is highly desirable. We hypothesized that chondrogenesis could be modulated using a granular hydrogel platform based on biocompatible, zwitterionic materials with independent intra- and inter-microgel crosslinking mechanisms. Microgels are made with mechanical fragmentation of photocrosslinked zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) hydrogels, and secondarily crosslinked in the presence of cells using horseradish peroxide (HRP) to produce cell-laden granular hydrogels. We varied the intra-microgel crosslinking density to produce microgels with varied stiffnesses (1-3 kPa) and swelling properties. These microgels, when resuspended at the same weight fraction and secondarily crosslinked, resulted in granular hydrogels with distinct porosities (5-40%) due to differing swelling properties. The greatest extent of chondrogenesis was achieved in scaffolds with the highest microgel stiffness and highest porosity. However, when scaffold porosity was kept constant and just microgel stiffness varied, cell phenotype and chondrogenesis were similar across scaffolds. These results indicate the dominant role of granular scaffold porosity on chondrogenesis, whereas microgel stiffness appears to play a relatively minor role. These observations are in contrast to cells encapsulated within conventional bulk hydrogels, where stiffness has been shown to significantly affect chondrocyte response. In summary, we introduce chemically-defined, zwitterionic biomaterials to fabricate versatile granular hydrogels allowing for tunable scaffold porosity and microgel stiffness to study and influence chondrogenesis.
Simultaneous drug delivery and cellular imaging using graphene oxide
Cheng, Sheng-Jen; Chiu, Hsien-Yi; Kumar, Priyank V.; et al. (2018)
Biomaterials Science
A self-assembling peptidic platform to boost the cellular uptake and nuclear delivery of oligonucleotides
Tarvirdipour, Shabnam; Skowicki, Michal; Schoenenberger, Cora-Ann; et al. (2022)
Biomaterials Science
The design of non-viral vectors that efficiently deliver genetic materials into cells, in particular to the nucleus, remains a major challenge in gene therapy and vaccine development. To tackle the problems associated with cellular uptake and nuclear targeting, here we introduce a delivery platform based on the self-assembly of an amphiphilic peptide carrying an N-terminal KRKR sequence that functions as a nuclear localization signal (NLS). By means of a single-step self-assembly process, the amphiphilic peptides afford the generation of NLS-functionalized multicompartment micellar nanostructures that can embed various oligonucleotides between their individual compartments. Detailed physicochemical, cellular and ultrastructural analyses demonstrated that integrating an NLS in the hydrophilic domain of the peptide along with tuning its hydrophobic domain led to self-assembled DNA-loaded multicompartment micelles (MCMs) with enhanced cellular uptake and nuclear translocation. We showed that the nuclear targeting ensued via the NLS interaction with the nuclear transport receptors of the karyopherin family. Importantly, we observed that the treatment of MCF-7 cells with NLS-MCMs loaded with anti-BCL2 antisense oligonucleotides resulted in up to 86% knockdown of BCL2, an inhibitor of apoptosis that is overexpressed in more than half of all human cancers. We envision that this platform can be used to efficiently entrap and deliver diverse genetic payloads to the nucleus and find applications in basic research and biomedicine.
Membrane deformation and layer-by-layer peeling of giant vesicles induced by the pore-forming toxin pneumolysin
Drücker, Patrick; Iacovache, Ioan; Bachler, Simon; et al. (2019)
Biomaterials Science
Protein–membrane interactions that modify the shape of membranes are important for generating curvature, membrane deformation by protein–protein crowding or trafficking of vesicles. Giant vesicles represent a simplified but versatile model for biological membranes and are commonly employed for the study of lipid domains and permeation across compartments. In this study, we investigated the interaction of pneumolysin (PLY), a pore-forming toxin secreted by Streptococcus pneumoniae, with multilamellar and unilamellar membranes. It reveals an enlargement of membrane area due to the insertion of pores into the bilayer and protein–membrane aggregations that induce membrane deformation and wrinkling. Moreover, we demonstrate that PLY peel-off layers from multilamellar giant vesicles in a hitherto unknown layer-by-layer peeling mechanism, which reveals the structure and number of membrane lamellae. We employed microfluidic methods to capture giant vesicles and confocal laser scanning microscopy, transmission microscopy, dynamic light scattering and cryo-electron microscopy to disclose the structure of multilamellar vesicles. Based on our findings we suggest how back-to-back pore arrangements stabilize large PLY–membrane entities and that pore-displaced lipids possibly remain in the membrane.
The role of poly(2-alkyl-2-oxazoline)s in hydrogels and biofabrication
Trachsel, Lucca; Zenobi-Wong, Marcy; Benetti, Edmondo M. (2021)
Biomaterials Science
Poly(2-alkyl-2-oxazoline)s (PAOXAs) have been rapidly emerging as starting materials in the design of tissue engineering supports and for the generation of platforms for cell cultures, especially in the form of hydrogels. Thanks to their biocompatibility, chemical versatility and robustness, PAOXAs now represent a valid alternative to poly(ethylene glycol)s (PEGs) and their derivatives in these applications, and in the formulation of bioinks for three-dimensional (3D) bioprinting. In this review, we summarize the recent literature where PAOXAs have been used as main components for hydrogels and biofabrication mixtures, especially highlighting how their easily tunable composition could be exploited to fabricate multifunctional biomaterials with an extremely broad spectrum of properties.
Interpenetrating network hydrogels for studying the role of matrix viscoelasticity in 3D osteocyte morphogenesis
Bernero, Margherita; Zauchner, Doris; Müller, Ralph; et al. (2024)
Biomaterials Science
During bone formation, osteoblasts are embedded in a collagen-rich osteoid tissue and differentiate into an extensive 3D osteocyte network throughout the mineralizing matrix. However, how these cells dynamically remodel the matrix and undergo 3D morphogenesis remains poorly understood. Although previous reports investigated the impact of matrix stiffness in osteocyte morphogenesis, the role of matrix viscoelasticity is often overlooked. Here, we report a viscoelastic alginate–collagen interpenetrating network (IPN) hydrogel for 3D culture of murine osteocyte-like IDG-SW3 cells. The IPN hydrogels consist of an ionically crosslinked alginate network to tune stress relaxation as well as a permissive collagen network to promote cell adhesion and matrix remodeling. Two IPN hydrogels were developed with comparable stiffnesses (4.4–4.7 kPa) but varying stress relaxation times (t_1/2, 1.5 s and 14.4 s). IDG-SW3 cells were pre-differentiated in 2D under osteogenic conditions for 14 days to drive osteoblast-to-osteocyte transition. Cellular mechanosensitivity to fluid shear stress (2 Pa) was confirmed by live-cell calcium imaging. After embedding in the IPN hydrogels, cells remained highly viable following 7 days of 3D culture. After 24 h, osteocytes in the fast-relaxing hydrogels showed the largest cell area and long dendritic processes. However, a significantly larger increase of some osteogenic markers (ALP, Dmp1, hydroxyapatite) as well as intercellular connections via gap junctions were observed in slow-relaxing hydrogels on day 14. Our results imply that fast-relaxing IPN hydrogels promote early cell spreading, whereas slow relaxation favors osteogenic differentiation. These findings may advance the development of 3D in vivo-like osteocyte models to better understand bone mechanobiology.

Publications 1 - 10 of 26

Journal: Biomaterials Science

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