| 1. |
- Bajic, Andrej, et al.
(author)
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Physically and Chemically Crosslinked Hyaluronic Acid-Based Hydrogels Differentially Promote Axonal Outgrowth from Neural Tissue Cultures
- 2024
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In: Biomimetics. - : MDPI. - 2313-7673. ; 9:3
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Journal article (peer-reviewed)abstract
- Our aim was to investigate axonal outgrowth from different tissue models on soft biomaterials based on hyaluronic acid (HA). We hypothesized that HA-based hydrogels differentially promote axonal outgrowth from different neural tissues. Spinal cord sliced cultures (SCSCs) and dorsal root ganglion cultures (DRGCs) were maintained on a collagen gel, a physically crosslinked HA-based hydrogel (Healon 5®) and a novel chemically crosslinked HA-based hydrogel, with or without the presence of neurotrophic factors (NF). Time-lapse microscopy was performed after two, five and eight days, where axonal outgrowth was assessed by automated image analysis. Neuroprotection was investigated by PCR. Outgrowth was observed in all groups; however, in the collagen group, it was scarce. At the middle timepoint, outgrowth from SCSCs was superior in both HA-based groups compared to collagen, regardless of the presence of NF. In DRGCs, the outgrowth in Healon 5® with NF was significantly higher compared to the rest of the groups. PCR revealed upregulation of NeuN gene expression in the HA-based groups compared to controls after excitotoxic injury. The differences in neurite outgrowth from the two different tissue models suggest that axons differentially respond to the two types of biomaterials.
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| 2. |
- Ranamalla, Saketh Reddy, et al.
(author)
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A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels
- 2024
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In: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 339
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Journal article (peer-reviewed)abstract
- n this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.
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| 3. |
- Tavakoli, Shima, et al.
(author)
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Fine-tuning Dynamic Cross-linking for Enhanced 3D Bioprinting of Hyaluronic Acid Hydrogels
- 2024
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In: Advanced Functional Materials. - : Wiley-VCH Verlagsgesellschaft. - 1616-301X .- 1616-3028. ; 34:4
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Journal article (peer-reviewed)abstract
- 3D bioprinting of stem cells shows promise for medical applications, but the development of an efficient bioink remains a challenge. Recently, the emergence of dynamically cross-linked hydrogels has advanced this field to obtain self-healing materials. However, more advanced bioinks are needed that display optimum gelling kinetics, viscoelasticity, shear-thinning property, structural fidelity, and hold the printed structures sufficiently long enough that allow maturation of the new tissue. Here, a novel extracellular matrix-based bioink for human mesenchymal stem cells (hMSCs) is presented. Hyaluronic acid (HA) is modified with cysteine and aldehyde functional groups, creating hydrogels with dual cross-linking of disulfide and thiazolidine products. The investigation demonstrates that this cross-linking significantly improves hydrogel stability and biological properties. The bioink exhibits fast gelation kinetics, shear-thinning, shape-maintaining properties, high cell survival after printing with >2-fold increase in stemness marker (OCT3/4 and NANOG), and supports cell proliferation and migration. Disulfide cross-linking contributes to self-healing and cell migration, while thiazolidine cross-linking reduces gelation time, enhances long-term stability, and supports cell proliferation. Overall, the HA-based bioink fulfills the requirements for successful 3D printing of stem cells, providing a promising solution for cell therapy and regenerative medicine.
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