Use of the polycation polyethyleneimine to improve the physical properties of alginate–hyaluronic acid hydrogel during fabrication of tissue repair scaffolds

Recently alginate-based tissue repair scaffolds fabricated using 3D printing techniques have been extensively examined for use in tissue engineering applications. However, their physical and mechanical properties are unfavorable for many tissue engineering applications because these properties are poorly controlled during the fabrication process. Some improvement of alginate gel properties can be realized by addition of hyaluronic acid (HA), and this may also improve the ability of cells to interact with the gel. Here, we report improvement of the physical properties of alginate–HA gel scaffolds by the addition of the polycation polyethyleneimine (PEI) during the fabrication process in order to stabilize alginate molecular structure through the formation of a polyelectrolyte complex. We find that PEI has a significant beneficial influence on alginate–HA scaffold physical properties, including a reduction in the degree of gel swelling, a reduction in scaffold degradation rate, and an increase in the Young’s modulus of the gel. Further study shows that fabrication of alginate–HA gels with PEI increases the encapsulation efficiency of bovine serum albumin, a model protein, and reduces the subsequent initial protein release rate. However, it was also found that survival of Schwann cells or ATDC-5 chondrogenic cells encapsulated during the scaffold fabrication process was modestly reduced with increasing PEI concentration. This study illustrates that the use of PEI during scaffold fabrication by plotting can provide an effective means to control alginate-based scaffold properties for tissue engineering applications, but that the many effects of PEI must be balanced for optimal outcomes in different situations.