Microfluidic Fabrication of Mineralized Alginate Hydrogel Fibers

Abstract

Alginates are a family of naturally occurring polysaccharides that form gels in the presence of Ca2+-ions at physiological conditions. Calcium phosphate mineralized alginates have previously been investigated as a synthetic extracellular matrix in bone tissue engineering. The isotropic nature of hydrogels fails to mimic the directional structure observed at different lengths scales in bone tissue. A composite structure of calcium phosphate mineralized alginate fibers embedded in a matrix of unmineralized alginate gel has been suggested as a method for imitating the structure of bone tissue. The fabrication of mineralized alginate fibers for bone tissue engineering applications using microfluidic devices has been investigated in this work. Fabrication of mineralized fibers was attempted using coaxial flow in microfluidic channels. A glass capillary microfluidic device was investigated to generate a coaxial flow of sodium alginate and phosphate ions surrounded by a flow of CaCl2. The device was prone to clogging caused by buildup of alginate and minerals at the device surfaces. A second microfluidic device was designed in an attempt to prevent clogging. A flow of DI water was flown between the sodium alginate and CaCl2 to act as a buffer delaying the onset of gelation until the flows cleared the device walls. Device geometries, flow rates and viscosities of the solutions were investigated to find parameters resulting in stable flow. Short lengths of calcium phosphate mineralized alginate fibers were successfully fabricated. Precipitation of CaP minerals and alginate buildup along device walls was decreased in the second device, but still resulted in device failure. Mineralized fibers were shown to have a inhomogeneous structure with CaP minerals concentrated around the perimeter. Calcium phosphate minerals were observed in SEM micrographs as nano-sized sheets within the gel network. Mineralized fibers were found to have a higher resistance to deformation compared to unmineralized. Further process development is required for stable fabrication of mineralized alginate fibers. A 3D microfluidic design has been proposed to further separate the sodium alginate flow from device walls in an attempt to prevent buildup of gel and minerals along device walls. In addition, an alternative mineralization process could be used where mineralization occurs outside the microchannels.