Highly Concentrated Alginate-Gellan Gum Composites for 3D Plotting of Complex Tissue Engineering Scaffolds

Abstract

Abstract:In tissue engineering, additive manufacturing (AM) technologies have brought considerable progress as they allow the fabrication of three-dimensional (3D) structures with defined architecture. 3D plotting is a versatile, extrusion-based AM technology suitable for processing a wide range of biomaterials including hydrogels. In this study, composites of highly concentrated alginate and gellan gum were prepared in order to combine the excellent printing properties of alginate with the favorable gelling characteristics of gellan gum. Mixtures of 16.7 wt % alginate and 2 or 3 wt % gellan gum were found applicable for 3D plotting. Characterization of the resulting composite scaffolds revealed an increased stiffness in the wet state (15%-20% higher Young's modulus) and significantly lower volume swelling in cell culture medium compared to pure alginate scaffolds (~10% vs.~23%). Cytocompatibility experiments with human mesenchymal stem cells (hMSC) revealed that cell attachment was improved-the seeding efficiency was~2.5-3.5 times higher on the composites than on pure alginate. Additionally, the composites were shown to support hMSC proliferation and early osteogenic differentiation. In conclusion, print fidelity of highly concentrated alginate-gellan gum composites was comparable to those of pure alginate; after plotting and crosslinking, the scaffolds possessed improved qualities regarding shape fidelity, mechanical strength, and initial cell attachment making them attractive for tissue engineering applications.

3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo

“…Thus, the integration of AlgGG strands in CPC scaffolds was expected to not diminish the osteoconductivity of the scaffolds. Compatibility of bone forming cells with highly concentrated and therefore stiff hydrogels consisting of alginate and gellan gum was already demonstrated for MSC isolated from human bone marrow . Albeit, the setting regime of the scaffolds was found to impact adhesion and proliferation of rat MSC: cell attachment and growth was significantly higher on CPC samples set in humidity compared to water‐set CPC (groups A and B in Figure a and Figure S1 in the Supporting Information).…”

“…Another concept is the application of MP to fabricate a rigid grid from a stiff material for external stabilization of the soft alginate hydrogel which is printed inside the voids of the grid; however, such constructs lack an open‐porous structure beneficial for tissue ingrowth and vascularization. In our approach, the printability and high shape fidelity of the hydrogel component was realized by applying a highly concentrated (16.7 wt%) alginate suspension possessing appropriate rheological properties …”

“…Gellan gum is a natural anionic polysaccharide produced by the bacterium Sphingomonas paucimobilis which has favorable gelling properties, i.e., thermoreversible gelling at near body temperature and ionotropic gelling by low concentrations of mono‐ or multivalent cations, and has been therefore investigated for tissue engineering approaches including bioprinting . The combination of the highly concentrated alginate with gellan gum resulted in an improved shape fidelity and mechanical strength of the printed and crosslinked constructs . Moreover, the AlgGG component used for fabrication of the biphasic scaffolds has been shown to release more vascular endothelial growth factor (VEGF) compared to pure alginate equivalents, which was more effective for stimulation of endothelial cell proliferation …”

3D printing of hydrogel composite systems: Recent advances in technology for tissue engineering

“…Improved cell differentiation and self-organization Drug discovery [75] 3D plotting Alginate Gellan gum Improved swelling ratio and stiffness General [76] 3D plotting PCL PEG, HAc Improved storage modulus General [77] 3D plotting PEG P(HPMAm-lactate)…”

“…This printed hydrogel composite functions as an extracellular matrix that can offer an environment for cell growth and a platform for drug delivery in soft tissue engineering. The gellan gum, a versatile gelling agent, was introduced as compounding materials in 3D plotting method by Akkineni et al [76] They mixed high concentration of alginate and 2-3 wt % of gellan gum. The addition of gellan gum prevents rapid swelling and thus improves the shape fidelity of printed scaffolds.…”