Design of Porous Alginate Hydrogels by Sacrificial CaCO₃ Templates: Pore Formation Mechanism

Abstract

signifi cantly precise control over the scaffold architecture. Well-defi ned internal structure (porosity) determines both cellular infi ltration into the scaffold and its material properties. Pore size and distribution ensuring diffusion of nutrients into the scaffold and removal of metabolic products is of high importance. [ 4,11 ] Ionically crosslinked polymer gels such as alginate hydrogels have been extensively developed as scaffolds for tissue engineering. [12][13][14][15] The adjustable kinetics of the alginate gel degradation at neutral pH [ 1,16,17 ] gives an option to use the gels for multiple applications as wound dressings, anti-adhesive, and repair materials. [ 14,[18][19][20][21] Characteristics of alginate gels (hydration, softness, porosity, swelling in water, etc.) can be adjusted using a certain fabrication approach and by variation of interactions between charged polyanionic groups and crosslinking counterions; [ 13,17,[22][23][24][25] these interactions are known to be strongly affected by ionic strength, molecule length and structure, solvent pH, salt concentration, and temperature conditions. [26][27][28][29][30][31] This allows the fabrication of alginate scaffolds possessing desired properties corresponding to a certain tissue, for instance cartilage, [ 12 ] or dura mater. [ 21 ] Porous alginate gels can provide space and mechanical support to seed biological cells for tissue formation, [ 1,13,32 ] also allowing a controlled release of gel-laden drugs (peptides and proteins) trapped within the alginate network. [ 14,24,25,33,34 ] To achieve loading of both biological cells and bioactive molecules, the internal structure of hydrogels has to be controlled on the scale of nano-and micrometers. Adjustment of the gel geometry has been demonstrated on substrate surfaces using different micropatterning techniques including a light-addressable electrolytic system, [ 14 ] electrodeposition, [ 15 ] electrochemical patterning, [ 35 ] or the benchtop method using Nylon mesh. [ 11 ] The internal structure of alginate gels has been patterned with regular tube-like pores, [ 16,36 ] interconnected ordered honeycomb pores, [ 12 ] and sponge-like isotropic pores. [37][38][39] However, most of the approaches for alginate gel fabrication lack a precise control over the microstructure and require special equipment. Encapsulation of molecules of interest with controlled spatial distribution is rather complicated or even impossible. There is a need to develop a simple approach for design of a scaffold with welldefi ned internal structure providing both a space to culture cells and cavities to host/release encapsulated (bio)active molecules.Fabrication of porous alginate hydrogels with a well-controlled architecture useful for tissue engineering is still a challenge. Here, CaCO 3 -based templating is utilized to design stable alginate gels with controlled pore dimensions in the range of 5-50 µm. The mechanism of pore formation is studied considering two factors affecting the pore size: i) osmotic pressure generat...

The mechanism of catalase loading into porous vaterite CaCO3 crystals by co-synthesis

“…A high loading of proteins into the crystals will also ensure a high loading capacity for the carriers assembled using the crystal. We note that other applications of the crystals including sensors 67,68 or self-assembled tailor-made polymer macrostructures such as scaffolds [69][70][71] have been reported.…”

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…[41] Other salts can also be applied, with CaCO 3 attracting particular interest given its low solubility at high/neutral pH values but significantly higher solubility in acidic conditions. [34] On this basis, hydrogels can be formed in aqueous conditions that can maintain the size/structure of the salt porogen without requiring the use of an organic solvent.…”

3D-printed air-blast microfluidic nozzles for preparing calcium alginate microparticles

“…Gas ow distribution with a coaxial structure is more uniform than that of a symmetrical gas outlet. [34][35][36] 3D printing can print three-dimensional channels, so that the dispersed phase channel and the annular gas ow channel can be printed concentrically through structural optimization, achieving uniform distribution of gas around the droplets. Therefore, the prepared particles have a low CV value.…”

“…As for the silicon surface micromachining method, 7 its dimensional accuracy is favorable but the process needs a professional and has a high cost. For glass capillary 8 assembling, needles welding, 34 and tube 28,35 assembling methods, the materials are cheap but the processes are quite labor consuming. Most importantly, it's hard to guarantee accuracy within a range of tens of microns by conventional manual methods.…”

“…In the elds of genetic engineering, biology, and medicine, it is oen necessary to prepare sodium alginate functional granules containing CaCO 3 or similar insoluble drugs for special uses such as making porous materials. 34,35 The 3D printing microuidic nozzle in this paper has a 300 mm diameter outlet with length of only 3 mm, so it will not be blocked in the experiments. As shown in Fig.…”