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Materials Today Bio

Elsevier BV

All preprints, ranked by how well they match Materials Today Bio's content profile, based on 18 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Luminescent ingestible electronic capsules for in vivo regulation of optogenetic engineered bacteria

Li, L.; Feng, Z.; Zhang, X.; Li, M.; Yang, H.; Sun, D.; Li, H.; Xue, H.; Wang, H.; Wang, Y.; Liu, L.; Shi, Y.; Liu, D.; Du, T.; Wang, H.

2024-05-24 synthetic biology 10.1101/2024.05.24.595681 medRxiv
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AbstractsThe ideal engineered microbial smart-drug should be capable of functioning on demand at specific sites in vivo. However, precise regulation of engineered microorganisms poses challenges in the convoluted and elongated intestines. Despite the promising application potential of optogenetic regulation strategies based on light signals, the poor tissue penetration of light signals limits their application in large experimental animals. Given the rapid development of ingestible electronic capsules in recent years, taking advantage of them as regulatory devices to deliver light signals in situ to engineered bacteria within the intestines has become feasible. In this study, we established an electronic-microorganism signaling system, realized by two Bluetooth-controlled luminescent electronic capsules were designed. The "Manager" capsule is equipped with a photosensor to monitor the distribution of engineered bacteria and to activate the optogenetic function of the bacteria by emitting green light. The other capsule, "Locator", can control the in situ photopolymerization of hydrogels in the intestines via ultraviolet light, aiding in the retention of engineered bacteria at specific sites. These two electronic capsules are expected to work synergistically to regulate the distribution and function of engineered bacteria in vivo, and their application in the treatment of colitis in pigs is currently being investigated, with relevant results to be updated subsequently.

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Decellularized Banana Leaves: Eco-Friendly Scaffolds for Cell-Based Seafood

Sarkarat, R.; Banavar, A.; Amirvaresi, A.; Li, X.; Nguyen, C.; Kaplan, D. L.; Nitin, N.; Ovissipour, R.

2023-11-03 synthetic biology 10.1101/2023.11.03.565310 medRxiv
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Cellular agriculture, as an emerging food production system, holds potential to address sustainability, food security, and agricultural resilience. Within the cell-based meat supply chain, one of the key steps is scaffolding. In this study, we assessed decellularized banana leaves, various coating materials, and different cell seeding strategies to determine their effects on cell viability, cell growth, cell alignment, and the response of the materials to thermal processing. The efficiency of decellularization was verified through DNA quantification, which decreased from 445 ng/mg in fresh banana leaves to non-detectable levels in the decellularized samples. This was further confirmed by FTIR and PCA modeling. Cell viability exceeded 98% on uncoated, soy-coated, and gelatin-coated samples of the decellularized banana leaves. Alignment of cells on gelatin-coated samples was the highest among the samples, with a dominant orientation of 65.8{degrees}, compared to soy-coated and uncoated samples with dominant orientations of 9.2{degrees} and -6.3{degrees}, respectively. In terms of quality attributes, the kinetics of shrinkage indicated that coating with soy and the presence of cells increased the activation energy due to the higher energy required for protein denaturation. Moreover, the kinetics of area changes in plain scaffolds without cells followed a first-order pattern, while with seeded cells a second-order pattern was followed. In summary, decellularized banana leaves present a sustainable and suitable biomaterial to support cells towards future needs related to meat production.

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Curcumin-Loaded Carboxymethyl Cellulose/Polyvinyl Alcohol Smart Wound Dressing: A Biosensor Approach for pH-Responsive Monitoring and Healing

Orangi, S.; Davaran, S.

2026-02-10 bioengineering 10.64898/2026.02.08.704648 medRxiv
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Developing wound dressings that support healing and allow real-time monitoring is a key priority in modern wound care. In this study, we designed a curcumin-loaded carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA) composite dressing with integrated pH-responsive colorimetric sensing. The films were made by solution blending and freeze-drying. They formed porous, absorbent structures that quickly absorbed fluid and managed wound exudates effectively. Curcumin served as both a therapeutic agent--delivering antioxidant, anti-inflammatory, and antibacterial effects--and a natural colorimetric indicator through its keto-enol tautomerism, enabling reversible pH-dependent transitions visible to the naked eye. UV-Vis spectroscopy confirmed absorbance shifts under acidic and alkaline conditions. It also showed that curcumin remained [~]80% stable after 14 days in the polymer matrix FTIR and SEM confirmed successful incorporation and uniform distribution of curcumin within the polymer network. Cytotoxicity assays demonstrated excellent biocompatibility, while disc diffusion and MIC assays revealed significant antibacterial activity of the curcumin-loaded films against Pseudomonas aeruginosa, confirming their potential to reduce bacterial growth. Smartphone-based RGB analysis showed a strong correlation with pH (R2 {approx} 0.99), highlighting the feasibility of low-cost digital wound monitoring. Mechanical testing indicated sufficient tensile strength and flexibility for practical wound application. Quantitative antibacterial data (inhibition zone diameter and MIC) supported strong antimicrobial performance. The primary objective of this study was to develop a multifunctional wound dressing capable of both protecting and monitoring wounds in real-time. The proposed system is specifically designed for chronic and infected wounds where pH imbalance delays healing. In addition to antimicrobial activity, the fabricated films demonstrated desirable swelling capacity and sustained curcumin release, further highlighting the practical applicability of the dressing in wound care. Cost- benefit analysis demonstrated clear economic advantages over commercial gauze-based and hydrocolloid dressings. The fabrication method is compatible with industrial scale-up, although process optimization is required. Overall, the curcumin-loaded CMC/PVA dressing provides a multifunctional platform that combines biocompatibility, antibacterial activity, pH-responsive biosensing, and cost-effectiveness for next-generation wound care. Future studies will investigate in vivo performance, long-term stability, and clinical translation potential to validate its effectiveness in real-world conditions. Overall, the curcumin-loaded CMC/PVA dressing provides a multifunctional platform that combines biocompatibility, antibacterial activity, pH-responsive biosensing, mechanical stability, and cost-effectiveness for next-generation wound care. Future studies will investigate in vivo performance, long-term stability, and clinical translation potential.

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Characterization of hybrid hydrogels combining natural polymers

Taylan, D.

2023-09-08 biochemistry 10.1101/2023.09.07.556716 medRxiv
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Hydrogels have emerged as an important field of study in biomedical engineering, biomaterials research and soft tissue modeling due to their versatility and customizable structures. They are three-dimensional networks capable of absorbing significant amounts of water and can be chemically or physically bonded, rendering them insoluble. The unique properties of hydrogels, such as excellent biocompatibility, degradation abilities, and ability to form chemical bonds between macromolecules, make them valuable in a variety of applications. One of the main applications of hydrogels is tissue engineering, where they are used in implantation, surgical procedures, targeted drug delivery and tissue regeneration. Hydrogels can act as scaffolds to mimic the properties of natural tissues, including mechanical strength, degradation properties, gel transformation, and swelling. Crosslinking hydrogels with other polymers, both natural and synthetic, allows their degradation rate to be controlled. Composite hydrogels or biohybrid gels offer advantages such as consistent properties between batches and a high degree of control in the manufacturing process. Using different types of polymers, researchers can fine-tune the chemical and physical properties of the resulting hydrogel, which is crucial for certain biomedical applications such as drug delivery, biocompatibility, and mechanical stability. In this study, our aim is to make hybrid hydrogel scaffolds more suitable for biomedical applications, which can show the healing effect of adding natural polymers to the scaffold structure. Our results revealed that the hybrid hydrogel obtained by chemically linking gelatin polymer chains to PEG polymers during crosslinking via UV light provides more advantageous properties in the final hydrogel structure, such as better durability and pore sizes for future cell placement in tissue engineering applications.

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Nanoparticles of bioactive natural collagen for wound healing: Experimental approach

Ghareeb, A.; Shalaby, M.

2023-02-21 synthetic biology 10.1101/2023.02.21.529363 medRxiv
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IntroductionBoth developing and developed nations have made the creation of innovative wound-healing nanomaterials based on natural extracts a top research goal. The objective of this research was to create a gel containing collagen nanoparticles and evaluate its therapeutic potential for skin lesions. MethodsCollagen nanoparticles from fish scales were produced for the first time using desolvation techniques. Using Fourier transform infrared spectroscopy (FTIR), the structure of the isolated collagen and its similarities to collagen type 1 were identified. The surface morphology of the isolated collagen and its reformulation into nanoparticles were examined using transmission and scanning electron microscopy. Human skin fibroblast cells were employed to examine the cytotoxicity of the nanomaterials, and an experimental model was used to evaluate the wound healing capability. ResultsCollagen nanoparticles formulation was confirmed using FTIR, SEM and TEM analysis. Cytotoxicity studies demomstrated that the manufactured nanoparticles have minor toxicity at high concentrations on human skin fibroblast. Histological investigation proved that the fabricated fish scale collagen nanoparticles promoted the healing process in comparison to the saline group. ConclusionThe fabricated product is a highly influential wound healing product that can be applicable for commercial use. The nanoscale size of collagen nanoparticles, make them interesting candidates for biological applications. Key Summary PointsO_LIThe goal of this research was to create natural, effective wound remedies that could lower health-care costs while also providing pain relief and, ultimately, effective scar repair. C_LIO_LICollagen nanoparticles can be synthesized from fish scale utilizing various nanotechnology-based approaches to stimulate skin cell proliferation and promote wound healing. C_LIO_LICollagen nanoparticles have a rough surface, have a negative potential, and can be used for drug delivery and wound healing. C_LIO_LIHistological and macroscopical analysis showed that the synthesized nanoparticles promoted faster wound healing. C_LI

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Advancing Therapeutic Solutions: Poloxamer-based Thermosensitive Injectable Hydrogels containing a Self-assembling Peptide for In situ Gelation in an Osteoarthritis Murine Model

Sayedipour, S.; Schomann, T.; van de Looij, S. M.; Rezaie, S.; Ramos, Y. F. M.; Vermonden, T.; van der Weerd, L.; Meulenbelt, I.; Cruz, L. J.

2025-05-03 biochemistry 10.1101/2025.04.30.651282 medRxiv
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This study presents the development and characterization of a novel thermosensitive injectable hydrogel designed to enhance the biomechanical properties of poloxamer 407 (P407) through the incorporation of a self-assembling peptide. The primary objective was to engineer a formulation that rapidly gels following intra-articular (i.a.) injection, exhibits improved mechanical strength, and enables sustained release of embedded therapeutic cargo. Gelation time assays demonstrated that the P407-peptide formulation solidified more quickly than P407 alone at equivalent concentrations. Rheological analysis revealed a 1.5 kPa increase in storage modulus in the hybrid hydrogel, confirming improved mechanical integrity. In vitro biocompatibility was assessed using human chondrocytes, with MTS assays and LIVE/DEAD staining indicating no cytotoxicity across tested concentrations. To evaluate in vivo applicability, a near-infrared fluorescent (NIRF) dye was incorporated into the hydrogel and injected intra-articularly into an osteoarthritis (OA) mouse model. The labeled formulation allowed for successful tracking and demonstrated localized gelation, supporting its suitability for site-specific, sustained delivery. Overall, the P407-peptide hydrogel offers a promising platform for i.a. therapeutic applications, combining injectability, rapid thermoresponsive gelation, mechanical reinforcement, and controlled release behavior, making it well-suited for regenerative medicine and OA treatment.

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Anti-fibrotic Effects of Atorvastatin Delivered via Keratin-based Hydrogels

Carroll, E. A.; Tarabokija, A. J.; Chaudhry, H.; Meer, A. S.; de Guzman, R. C.

2024-12-13 bioengineering 10.1101/2024.12.09.627550 medRxiv
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Implantations of degradable biomaterials for drug delivery or restoration and regenerative medicine cause fibrosis and acute inflammation which may lead to chronic side effects. Additionally, the fibrous encapsulation can itself inhibit the local cells from proliferating and forming new healthy tissue. Current drug delivery models require a new method to decrease the adverse effects following implantation of biomaterials in patients and inhibit the activation signaling sent to quiescent fibroblasts. This research details the novel chemical and physical properties of reduced keratin (KTN) hydrogels extracted from residual human hair with sheared cuticle layers, obtained from barbershops and beauty salons. KTN hydrogels with and without calcium ions conjugated with atorvastatin (Ator), which is thought to affect TGF-{beta} signaling pathways directly by competitively inhibiting key signal transmitters and cellular responses, were investigated via electron microscopy, absorbance spectroscopy, and computational modeling and simulation to observe the proliferative inhibition of fibroblastic cells in comparison to the alginate hydrogel controls. Hydrogel extracts were tested for non-cytotoxic effects via L929 adipose fibroblast cell culture following ISO 10993-5 standard for safety of medical device biomaterials. Two cell models were exposed to increasing serial concentrations of Ator to evaluate the half maximal effective concentration (EC50). For quiescent fibroblasts, Ators EC50 was observed at 368 M in PBS. For mesenchymal stem cells (MSCs), Ators EC50 was observed at 209 M in PBS. The mass of drug was normalized in all groups after calculating their timed absorption and release, and KTN hydrogels conjugated with calcium ions and Ator (ATCK) completely absorbed the drug < 0.5 h while KTN hydrogels with Ator alone (ATKR) completely absorbed the drug at 1h. After 7d in PBS, ATCK released Ator at 2.2 {+/-} 0.7% while Ator in calcium alginate spheres (ATLG) was released at 7.8 {+/-} 1.1% and ATKR released 11.2 {+/-} 4.3% of drug. On-going research focuses on other active fibroblastic cell types and in vivo experimentation to observe foreign body response in subcutaneous mouse tissue.

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Polysulfide Nanoparticles Ameliorate Ischaemia Reperfusion Injury in Renal Transplantation and Improve Kidney Function Post-Transplantation

Stone, J. P.; D'Arcy, R.; Geraghty, A.; Amin, K.; Montero-Fernandez, A.; Dabare, D.; Ghibaudi, M.; Francini, N.; Coradello, G.; Bramhall, J.; Galwey, N. W.; Ruseva, M.; Tirelli, N.; Fildes, J.

2023-06-22 synthetic biology 10.1101/2023.06.21.545864 medRxiv
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Ischemia-reperfusion injury (IRI) is a significant complication in kidney transplantation, often affecting the viability and function of organs. Normothermic machine perfusion (NMP) is a technique used to improve the condition of organs prior to transplantation. In this study, we show that incorporating antioxidant poly(propylene sulfide) nanoparticles (PPS-NPs) during cold-storage and NMP significantly enhances its efficacy in reducing IRI upon porcine kidney transplantation. We found that by scavenging reactive oxygen species, PPS-NPs reduced oxidative stress and inflammation that occurs during ischemia-reperfusion with oxidized DNA reduced 5.3x and both TNF- and complement activation approximately halved. Our studies show that this approach led to significantly improved hemodynamics, better renal function, and tissue health compared to NMP alone. The results suggest that incorporating PPS-NPs into transplantation protocols may expand the pool of kidneys suitable for transplantation and enhance overall transplantation success rates. The broader impact of this work could extend to other organ transplants, suggesting a wider application for nanoantioxidant technologies in organ preservation.

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Dual-Drug Loaded Biomimetic Chitosan-Collagen Hybrid Nanocomposite Scaffolds for Ameliorating Potential Tissue Regeneration in Diabetic Wounds

Tallapaneni, V.; Pamu, D.; Mude, L.; Karri, V. V. S. R.

2022-02-19 bioengineering 10.1101/2022.02.16.480700 medRxiv
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Diabetes Mellitus (DM) is one of the most concerning conditions, and its chronic complications are nearly synonymous with inflammation, oxidative stress, and infections. In the acute inflammatory phase of diabetic wound healing (DWH), reducing excessive reactive oxygen species (ROS) and inflammatory response of the wound is a necessary treatment. The current work used a mix of emulsification and lyophilization approaches to investigate the effects of resveratrol microparticles (RES-GMS) loaded chitosan-collagen (CS-CLG) scaffold with doxycycline (DOX) on DWH. Resveratrol (RES) is a powerful antioxidant that promotes cell proliferation in the dermis by improving fibroblast function and enhancing CLG production. DOX can potentially shift the balance away from the chronic wounds pro-inflammatory, proteolytic status toward an environment that promotes vascular ingrowth and, eventually, epithelial development. Cross-linked scaffolds had optimal porosity, reduced matrix degradation, and prolonged drug release when compared to non-cross-linked scaffolds, according to the results of composite scaffold characterization. Cell proliferation assay employing mouse fibroblasts was used to study the kinetics and bioactivity of growth factors produced from the scaffold. The RES-DOX-CS-CLG scaffold was biocompatible and promoted cell development compared to the control and CS-CLG scaffolds in in vitro experiments. DOX-loaded CS-CLG scaffold loaded with R-GMS delivers a prolonged release of RES, according to in vitro tests.

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Development of an automated high-content immuno-fluorescence assay of pSmads quantification: proof-of-concept with drugs inhibiting the BMP/TGFbeta pathways

KHODR, V.; CLAUZIER, L.; MACHILLOT, P.; SALES, A.; MIGLIORINI, E.; PICART, C.

2023-12-14 bioengineering 10.1101/2023.12.14.571626 medRxiv
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Bone morphogenetic proteins (BMPs) and transforming growth factors (TGF-{beta}) are members of the transforming growth factors superfamily, known for their role in several physiological and pathological processes. These factors are known to bind in vivo to BMP and TGF-{beta} receptors respectively, which induces the phosphorylation of the Smad (pSmad) transcription factors. This pathway is generally studied with western blot and luciferase bioluminescence assay, which present some limitations. In our work, we developed and optimized a high-content immunofluorescence assay to study the pSmad pathway on glass as well as on biomaterials by overcoming the technical challenges raised by image acquisition and analysis. Furthermore, with this assay, we present here a proof-of concept for drug testing on glass and on biomimetic films using drug inhibitors of the BMP receptor and of the TGF-{beta} receptors. Altogether, our results open perspectives for future drug testing on biomimetic films that present various growth factors and extracellular matrix proteins or peptides.

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Experimental Validation of an Organ-on-Chip for Mechanical Stimulation of Cell Cultures

Testa, M.; Tornabene, S.; Di Leonardo, S.; Burriesci, G.; La Carrubba, V.; Lopresti, F.

2023-12-15 bioengineering 10.1101/2023.12.15.571835 medRxiv
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This paper focuses on the design, fabrication, and characterization of a platform aiming to dynamically culture cells under mechanical stimulation. The platform, made of polymethylmethacrylate (PMMA), allows real-time mechanical stimuli, providing valuable insights for living tissue models. Through mechanical testing and dynamic microfluidic tests, the chip functionality was assessed. The experimental results validation showcases the potential of the device in mimicking physiological conditions, offering a promising avenue for pharmaceutical testing advancement.

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Fabrication of silver doped nano hydroxyapatite-carrageenan hydrogels for articular cartilage applications

Swain, S.; Kwon, T. Y.; Rautray, T. R.

2021-01-03 bioengineering 10.1101/2020.12.31.424664 medRxiv
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It can be found from the results that nano hydroxyapatite- silver -3.0 wt% carageenan (nHA-Ag-CG3.0) improved the mechanical properties of the as-formed hydrogel scaffold after incorporation of higher CG concentration. The Youngs modulus of hydroxyapatite- silver - 1.5wt% carageenan (nHA-Ag-CG1.5) was found to be 0.36 {+/-} 0.07 MPa that increased in case of nHA-Ag-CG3.0 demonstrating better interfacial compatibility of their matrix with respect to the reinforcement. This increase in reinforcement concentration resulted in higher stiffness that dissipated energy. The higher swelling ratio is envisaged to induce better cell adhesion and proliferation. The biodegradability test was performed in phosphate buffered saline at body temperature for 3 weeks. The biodegradability rate of nHA-Ag-CG1.5 was found to be equivalent to nHA-Ag-CG3.0 hydrogels at day 7 while it increased faster in nHA-Ag-CG3.0 on days 14 and 21 that may be ascribed to the possible interaction of nHA and Ag with their CG matrix. The bacterial cell viability of Staphylococcus aureus (S. aureus) was performed after 10 h, 20 h and 30 h of culture. The nHA-Ag-CG1.5 exhibited restrained growth of S. aureus as compared to nHA-Ag-CG3.0 and these results were validated by CLSM analysis. Hence, nHA-Ag-CG3.0 may be considered to have more cytocompatibility than nHA-Ag-CG 1.5.

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Nanofibrous Wound Dressing with a Smart Drug Delivery System: Poly(N-Isopropylacrylamide)-Conjugated Polycaprolactone Nanofibers Loaded with Curcumin

Khan, D.; Jyoti, M. A.; Aliaa, N.; Patel, K. D.; Tan, R.; Kim, H.-W.; Chau, D.; Nguyen, L.

2024-06-06 bioengineering 10.1101/2024.06.04.597437 medRxiv
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In response to clinical demands for advanced wound dressings, a "smart bandage" was developed by combining polycaprolactone (PCL) nanofibers and the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). This bandage incorporates curcumin, an anti-inflammatory and antioxidant agent, to enhance wound healing. The LCST of PNIPAAm (32{degrees}C) enables an "on-off" drug delivery system, transitioning from a hydrophilic coil to a hydrophobic state. The nanofiber matrix was characterized using FTIR spectroscopy, SEM, water contact angle, and dynamic mechanical analysis. Curcumin release was assessed both above and below the LCST. The bandage is comfortable, easy to apply and remove, and promotes rapid wound healing. In vitro studies confirmed its non-toxicity to human dermal fibroblast cells. This "smart bandage" represents a significant advancement in wound care, with the potential to meet clinical requirements and enhance patient compliance, offering controlled drug delivery combined with the therapeutic benefits of curcumin.

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On the biodegradation of micropatterned polymeric film

Guerriero, I.; Pesce, C.; Spano, R.; Sganga, S.; Tirelli, N.; Di Mascolo, D.; Palange, A. L.; Decuzzi, P.

2025-01-19 bioengineering 10.1101/2025.01.15.633178 medRxiv
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AO_SCPLOWBSTRACTC_SCPLOWPolymeric implants for local drug delivery offer significant advantages for treating various medical conditions by enabling the temporal and spatial control of drug release, improving efficacy, and reducing systemic side effects. In this context, {micro}MESH, a 20 m thin, dual-compartmentalized film comprising a poly(lactic-co-glycolic acid) (PLGA) micronetwork intercalated with a polyvinyl alcohol (PVA) microlayer, represents an interesting opportunity as its geometry can be systematically and accurately micropatterned during the fabrication process, enabling the systematic analysis of the effect of geometry on biodegradation rates mechanisms. In this study, four different {micro}MESH films were realized with different surface area-to-volume ratios (Sa/V), ranging from 0.67 to 1.7 {micro}m-1. After characterizing the {micro}MESH geometry via fluorescent and scanning electron microscopy, biodegradations studies were performed up to 60 days in different media to assess the mass loss of PLGA, the reduction in PLGA molecular weight, and the formation of macroscopic defects - pores, holes and crack - within the PLGA micronetwork. By comparing the four {micro}MESH films among themselves and to a flat, continuous PLGA slab (FLAT), it was confirmed the importance of the surface-to-volume ratio and demonstrated that {micro}MESH with higher Sa/V ratios exhibited slower degradation rates compared to FLAT. Scanning electron microscopy images of the PLGA micronetworks revealed morphological changes indicative of bulk erosion, including surface roughening and pore formation, in FLAT and {micro}MESH configurations with low Sa/V ratios. These findings confirm that film micropatterning significantly influences degradation kinetics.

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3D-bioprinted marine bacteria for the degradation of bioplastics

He, L.; Cai, H.; Gona, R. S.; Gangan, M. S.; Lai, T.; Silberstein, M. N.; Meyer, A. S.

2025-02-05 synthetic biology 10.1101/2025.02.05.636490 medRxiv
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The severe, long-lasting harm caused by plastic pollution to marine ecosystems and coastal economies has led to the development of biodegradable plastics; however, their limited decomposition in cold, dark marine environments remains a challenge. Here, we present our newly developed technologies for creating 3D-bioprinted living materials for bioplastic degradation with specific use in marine environments. Our approach integrates halotolerant bioplastic-degrading bacterium Bacillus sp. NRRL B-14911 into alginate-based bio-ink to print an engineered living material (ELM) termed a "bio-sticker." Quantification of bacteria viability reveals that bioprinted marine bacteria survive within bio-stickers for more than three weeks. The rate at which the bio-stickers degrade the bioplastic polyhydroxybutyrate (PHB) can be tuned by altering bio-sticker biomass concentration, bioplastic concentration, or incubation temperature. Bio-stickers that are transferred to a new PHB sample still retain high biodegradation activity, demonstrating their durability. Strain sweep oscillatory tests demonstrate viscoelastic behavior of the bio-stickers. Monotonic tensile tests indicate that the elastic modulus and the adhesion of the bio-stickers are not negatively impacted by bacteria growth or incubation temperature. Our work paves the way for development of ELMs to facilitate the inclusion of bioplastics within the blue economy, promoting the emergence of more sustainable and eco-friendly materials.

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Towards Biohybrid Lung Development? Inflammatory Conditions Disrupt Endothelial Layer Integrity on Gas Exchange Membranes

Cheremkhina, M.; Babendreyer, A.; Neullens, C. T.; Krapp, S.; Pabst, A.; Ohl, K.; Tenbrock, K.; Ruetten, S.; Ludwig, A.; Cornelissen, C. G.; Thiebes, A. L.; Jockenhoevel, S.

2023-11-02 bioengineering 10.1101/2023.10.31.564901 medRxiv
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Systemic inflammation presents a significant challenge to the long-term function of biohybrid implants. While endothelialisation of biohybrid implants has been shown to improve device hemocompatibility, its feasibility under the influence of patients inflammatory status remains largely unexplored. To investigate this, we developed a controlled in vitro model which allows to study endothelial dysfunction under inflammatory stress. Endothelial cells were cultured on polydimethylsiloxane under physiological shear stress and exposed to lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells (PBMCs), simulating inflammatory conditions. Endothelial morphology and confluence was assessed using immunohistochemistry and scanning electron microscopy. Leukocyte adhesion was evaluated directly as well as indirectly, using flow cytometry to analyse cell adhesion molecules. Quantitative PCR was used for gene expression analysis of inflammatory mediators. Notably, neither LPS nor PBMCs alone induced endothelial disruption, whereas their combination significantly impaired endothelial confluence: Inflammatory activation led to substantial loss of endothelial confluence, increased leukocyte adhesion, and elevated expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin. Gene expression analysis highlights the upregulation of inflammatory mediators, such as IL-6, IL-8, IL-10, and MCP-1. This study underscores the challenges of implementing endothelialisation in biohybrid devices, particularly in patients with systemic inflammation. By considering translational hurdles, this work contributes to the development of clinically viable biohybrid constructs and highlights the importance of considering inflammatory dynamics when designing next-generation implants.

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A New Bioink For Improved 3D Bioprinting Of Bone-Like Constructs

Marsh, A.; Apu, E. H.; Bunn, M.; Contag, C. H.; Ashammakhi, N.; Chatzistavrou, X.

2021-11-05 bioengineering 10.1101/2021.11.04.467312 medRxiv
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Bone tissue loss can occur due to disease, trauma or following surgery, in each case treatment involving the use of bone grafts or biomaterials is usually required. Recent development of three-dimensional (3D) bioprinting (3DBP) has enabled the printing of customized bone substitutes. Bioinks used for bone 3DBP employ various particulate phases such as ceramic and bioactive glass particles embedded in the bioink creating a composite. When composite bioinks are used for 3DBP based on extrusion, particles are heterogeneously distributed causing damage to cells due to stresses created during flow in the matrix of the composite. Therefore, the objective of this study was to develop cell-friendly osteopromotive bioink mitigating the risk of cell damage due to the flow of particles. Towards this end, we have linked organic and inorganic components, gelatin methacryloyl (GelMA) and Ag-doped bioactive glass (Ag-BaG), to produce a hybrid material, GelMA-Ag-BaG (GAB). The distribution of the elements present in the Ag-BaG in the resulting hybrid GAB structure was examined. Rheological properties of the resulting hydrogel and its printability, as well as the degree of swelling and degradation over time, were also evaluated. GAB was compared to GelMA alone and GelMA-Ag-BaG nanocomposites. Results showed the superiority of the hybrid GAB bioink in terms of homogenous distribution of the elements in the structure, rheological properties, printability, and degradation profiles. Accordingly, this new bioink represents a major advance for bone 3DBP.

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Deciphering dermal fibroblast behavior in 3D bioprinted dermis contructs

chastagnier, L.; essayan, L.; courtial, e. j.; Marquette, C.; thomann, c.; PETIOT, E.; el-Kholti, N.

2023-03-07 bioengineering 10.1101/2023.03.07.531460 medRxiv
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In recent years, numerous strategies have emerged to answer the growing demand for graftable tissues. Tissue engineering and in-vitro production are one of them. Among all the engineered tissues, skin is one of the most advanced. Nevertheless, biofabrication of graftable and fully functional skin substitutes is still far from being reached. Skin reconstruction, particularly dermis, necessitates cultivation and maturation for several weeks (> 3 weeks) to recover the tissues composition and functions, which prevent its transfer to clinical applications. Thus, several strategies, including 3D bioprinting, have been explored to accelerate these productions. In the present study, based on the successful application of 3D bioprinting achieved by our group for skin reconstruction in 21 days, we propose to detail the biological behaviors and maturation phases occurring in the bioprinted skin construct thanks to a descriptive approach transferred from the bioprocess field. The aim is to comprehensively characterize dermis construct maturation phases (cell proliferation and ECM secretion) to master later the interdependent and consecutive mechanisms involved in in-vitro production. Thus, standardized quantitative techniques were deployed to describe 3D bioprinted dermis proliferation and maturation phases. Then, in a second step, various parameters potentially impacting the dermis reconstruction phases were evaluated to challenge our methodology and reveal the biological behavior described (fibroblast proliferation and migration, cell death, ECM remodeling with MMP secretion). The parameters studied concern the bioprinting practice including various printed geometries, bioink formulations and cellular physiology in relation with their nutritional supplementation with selected medium additives.

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Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans

Yan, H.; Hjorth, M.; Winkeljann, B.; Dobryden, I.; Lieleg, O.; Crouzier, T.

2019-12-19 bioengineering 10.1101/2019.12.18.880757 medRxiv
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Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. Once assembled into hydrogels (Muc gels), mucins were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulation in vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar, then assembling the mucin variants into covalently crosslinked hydrogels with rheological and surface nanomechanical properties similar to non-modified Muc gels. Results with THP1 and human primary peripheral blood monocytes-derived macrophages were strikingly consistent and showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.

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Quaternary Ammonium Salt-Modified Isabgol (Psyllium) Scaffold as an Antibacterial Dressing for Improved Wound Healing

TK, V.; Patel, A. K.; Muthuvijayan, V.

2022-04-25 bioengineering 10.1101/2022.04.24.489269 medRxiv
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Chronic wounds require suitable treatment and management strategies for proper healing. Among other causes, infection delays the healing of wounds and increases the risk of wound-related complications. Healing of chronic wounds requires an ingenious biomaterial that is biocompatible and anti-infective to achieve effective wound management. In this study, a wound dressing with inherent antibacterial and biocompatible properties was developed to assist the healing process. Natural polysaccharide Isabgol was chemically modified with Epoxy propyl trimethyl ammonium chloride to render antibacterial activity to the material. This is the first report of such chemical modification of this polymer for biomedical applications. The modified material was freeze-dried to obtain scaffolds. 13C NMR and FTIR analysis confirmed the modification of the Isabgol polymer chains with EPTMAC. The scaffold exhibits an organized porous structure that allows the exchange of gases and nutrients through the matrix, as confirmed by SEM analysis. The material possesses excellent swelling properties up to 17 times its initial weight that allows it to absorb wound exudates and maintain a moist environment at the wound site. The scaffold is biodegradable, and thermally and mechanically stable. The material is anti-infective and can prevent infections at the wound site, which is one of the major causes of delayed wound healing. The developed scaffolds have been proven to be biocompatible and suitable for use in blood contact applications. Finally, since Isabgol is a low-cost raw material, the quaternary ammonium-modified Isabgol scaffold can be an affordable wound dressing material.