Tissue Eng Regen Med.  2022 Oct;19(5):987-1000. 10.1007/s13770-022-00462-4.

Lytic Bacteriophage as a Biomaterial to Prevent Biofilm Formation and Promote Neural Growth

• Liu ZH
• Chiang MT
• Lin HY

• KMID: 2533929
• DOI: http://doi.org/10.1007/s13770-022-00462-4

Abstract

BACKGROUND
Although non-lytic filamentous bacteriophages have been made into biomaterial to guide tissue growth, they had limited ability to prevent bacterial infection. In this work a lytic bacteriophage was used to make an antibacterial biomaterial for neural tissue repair.
METHODS
Lytic phages were chemically bound to the surface of a chitosan film through glutaraldehyde crosslinking. After the chemical reaction, the contact angle of the sample surface and the remaining lytic potential of the phages were measured. The numbers of bacteria on the samples were measured and examined under scanning electron microscopy. Transmission electron microscopy (TEM) was used to observe the phages and phage-infected bacteria. A neuroblast cell line was cultured on the samples to evaluate the sample’s biocompatibility.
RESULTS
The phages conjugated to the chitosan film preserved their lytic potential and reduced 68% of bacterial growth on the sample surface at 120 min (p < 0.001). The phage-linked surface had a significantly higher contact angle than that of the control chitosan (p < 0.05). After 120 min a bacterial biofilm appeared on the control chitosan, while the phagelinked sample effectively prevented biofilm formation. The TEM images demonstrated that the phage attached and lysed the bacteria on the phage-linked sample at 120 min. The phage-linked sample significantly promoted the neuroblast cell attachment (p < 0.05) and proliferation (p < 0.01). The neuroblast on the phage-linked sample demonstrated more cell extensions after day 1.
CONCLUSION
The purified lytic phages were proven to be a highly bioactive nanomaterial. The phage-chitosan composite material not only promoted neural cell proliferation but also effectively prevent bacterial growth, a major cause of implant failure and removal.

Keyword

Lytic bacteriophage; Antibacterial biomaterial; Chitosan biopolymer; Neural cell growth