Genipin-Crosslinked, Proteosaccharide Scaffolds for Potential Neural Tissue Engineering Applications
PUBLISHED IN: MDPI Pharmaceutics
ABSTRACT
Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited promise for the treatment and the reversibility of damage caused by TBIs. Injury beyond the critical size necessitates the implementation of scaffolds that function as surrogate extracellular matrices. Two scaffolds were synthesised utilising polysaccharides, chitosan and hyaluronic acid in conjunction with gelatin. Both scaffolds were chemically crosslinked using a naturally derived crosslinker, Genipin. The polysaccharides increased the mechanical strength of each scaffold, while gelatin provided the bioactive sequence, which promoted cellular interactions. The effect of crosslinking was investigated, and the crosslinked hydrogels showed higher thermal decomposition temperatures, increased resistance to degradation, and pore sizes ranging from 72.789 ± 16.85 µm for the full interpenetrating polymer networks (IPNs) and 84.289 ± 7.658 μm for the semi-IPN. The scaffolds were loaded with Dexamethasone-21-phosphate to investigate their efficacy as a drug delivery vehicle, and the full IPN showed a 100% release in 10 days, while the semi-IPN showed a burst release in 6 h. Both scaffolds stimulated the proliferation of rat pheochromocytoma (PC12) and human glioblastoma multiforme (A172) cell cultures and also provided signals for A172 cell migration. Both scaffolds can be used as potential drug delivery vehicles and as artificial extracellular matrices for potential neural regeneration.
Related Scientific Publications
Current treatments for glioblastoma (GBM) face challenges due to rapidly occurring tumor recurrences. In response, researchers have developed localized drug delivery systems, notably AT101-GlioMesh - an alginate-based mesh embedded with AT101-loaded PLGA microspheres. Fabricated for high encapsulation efficiency, this system ensures a sustained release of AT101, demonstrating a significant cytotoxic effect on GBM cell lines. This promising development could potentially revolutionize GBM therapy and prevent tumor recurrence.
Polysaccharide-based hydrogels offer great promise in 3D bioprinting due to their biocompatibility and cellular response, but their poor mechanical properties often require extensive crosslinking. The solution? Enter thermoresponsive bioinks. This study examines a triad of carboxymethyl cellulose, agarose, and gelatin as a potential thermoresponsive ink, demonstrating that specific blends can form stable hydrogels with desirable mechanical and physical properties. The bioinks' cytotoxicity was assessed on two cell lines according to ISO 10993-5 standards, and successful printing of complex 3D patterns confirmed their printability.
Dense collagen matrices, crafted through automated gel aspiration-ejection (GAE), offer exciting potential in the field of biofabrication. This study illuminates the crucial role fibrillization pH plays in both the real-time rheological changes during collagen hydrogel gelation and the properties of the resulting biofabricated matrices. Findings demonstrate a relative increase in hydrogel stiffness with higher gelation pH, with matrices demonstrating increased fibrillar density, alignment, and micro-compressive modulus at specific pH levels. Importantly, these matrices showed low cell mortality when seeded with fibroblasts. These findings may offer valuable insights applicable to other hydrogel systems and biofabrication techniques.
Understanding the biomechanical properties of arteries is complex due to their cylindrical shape and waveguide behavior. This study provides valuable insights by utilizing three-dimensional measurements on an artery-mimicking tube in water, categorizing the tube wall motion into transient and steady state responses. The study's approach enables a more accurate estimation of the motion and improves our understanding of wave propagation in arterial walls, presenting significant opportunities for enhanced measurement of arterial mechanical properties.
Researchers have devised a method called '3D wet writing' to create small-diameter arterial conduits. This technique uses ionic gelation for fabricating customizable constructs quickly and without a template. The constructs show mechanical properties similar to native blood vessels and demonstrate biocompatibility, indicating their potential use as vascular constructs.
User Cytocompatibility, biocompatibility, and biodegradability are amongst the most desirable qualities of wound dressings and can be tuned during the bioplatform fabrication steps to enhance wound healing capabilities. A three-stepped approach (partial-crosslinking, freeze-drying, and pulverisation) was employed in fabricating a particulate, partially crosslinked (PC), and transferulic acid (TFA)-loaded chitosan-alginate (CS-Alg) interpolymer complex (IPC) with enhanced wound healing capabilities.
