Biomechanical properties of calcium and barium alginate hydrogel scaffolds for bone tissue engineering applications

Design of bone tissue engineering scaffolds imposes a number of requirements for their physical properties, in particular porosity and mechanical behaviour. Alginates are known as a potential material for such purposes, usually deploying calcium as a cross-linker. Calcium over-expression was reported having proinflammatory effect, which is not always desirable. Contrary to this, barium has better immunomodulatory outcome but data for barium as a cross-linker are scarce. In this work the objective was to produce Ba-linked alginates and compare their viscoelastic properties with Ca-linked controls in vitro. Sodium alginate aqueous solution (1 wt%) with 0.03 wt.% CaCl 2 is gelled in dialysis tubing immersed in 27 mM CaCl 2 (controls) or BaCl 2 , for 48 h, followed by freeze-drying and rehydration (with 0.3 wt.% CaCl 2 and 0.8 wt.% NaCl). Hydrogel discs (diameter 8-10 mm, thickness 4-6 mm) were assessed in dry and wet (DMEM immersed) states by dynamic mechanical analysis (DMA) under compressive creep conditions with increased loads, frequency scans and strain-controlled sweeps in physiological range (0.1-20 Hz) at 25°C and 37°C. Resulting data were analysed by conventional methods and by a model-free BEST (Biomaterials Enhanced Simulation Testing) to extract invariant values and material functions. Significant differences were observed in properties of Ba-linked hydrogel scaffolds vs. Ca-linked controls. Specifically, for the similar porosity Ba-samples exhibited lower creep compliance, higher dynamical stiffness and lower loss factor in the whole studied range. Invariant modulus exhibited a non-linear decay vs. applied stress. These differences were observed in both dry and wet states and temperatures. Use of barium as a cross-linker for alginates allows further modification of biomechanical properties of the scaffolds for better compliancy to the tissues in the application. Barium release might have an immunomodulating effect but also promote ion exchange for osteogenesis due to additional Ca/Ba concentration gradient.