Enhanced tissue engineering properties of osteoinductive chitosan hydrogel

Abstract

[EMBARGOED UNTIL 6/1/2023] Lower back pain is a considerable medical problem that will impact 80 percent of the U.S. population at some point in their life. With the most severe cases, surgical repair is necessary and is associated with costs upwards of $10.2 billion annually in the United States. To allieviate back pain, spine fusions are a common treatment in which two or more vertebrae are biologically fused together often through the use of a graft material. Unfortunately, iliac crest bone autograft, the current gold standard graft material, can yield insufficient fusion and is associated with considerable donor site morbidity and pain as well as limited supply. Therefore, new materials need to be developed in order to better coordinate healing and new bone growth in the affected area to reduce unnecessary patient burden. In order to address this issue, the incorporation of allograft and one of two types of cellulose (i.e., 0CNCs and CNFs) into a dual-crosslinked chitosan hydrogel loaded with bioactive calcium phosphate was investigated. Hydrogels were then tested for both their material and biological properties. Specifically, hydrogel swelling ratio, mass loss, ion release profile, compressive strength, biocompatibility, and osteoinduction were determined. Cellulose and allograft incorporation significantly improved compressive strength and biocompatibility. CNFs were found to be a significantly more biocompatible form of cellulose when compared to 0CNCs. Additionally, through the controlled delivery of osteoinductive simple signaling molecules (i.e., calcium and phosphate ions), CNF/Chitosan hydrogels were able to induce osteoblast-like activity in murine mesenchymal stem cells. This research provides support for our novel material to be further investigated in vivo for its application in spine fusion procedures.