Spinal fusion properties of mechanically-reinforced, osteomodulatory chitosan hydrogels

Lower back pain is a considerable medical problem that will impact 80% of the U.S. population at some point in their lifetime. For the most severe cases, surgical repair is necessary and is associated with annual costs upwards of $10 billion in the United States alone. To alleviate back pain, spinal fusions are a common treatment in which two or more vertebrae are biologically fused together often facilitated by 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 is in 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. To address this issue, we incorporated allograft (AG) and cellulose (i.e⁰CNCs 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,in vitrobiocompatibility and osteoinduction, andin vivobiocompatibility and effectiveness in a spine fusion model were assessed. Cellulose and AG incorporation significantly improved hydrogel compressive strength and biocompatibility and CNFs were found to be a significantly more biocompatible form of cellulose than⁰CNCs. Additionally, through the controlled delivery of osteoinductive simple signaling molecules (i.e. calcium and phosphate ions), dibasic calcium phosphate (DCF)-loaded CNF/chitosan hydrogels were able to induce osteoblast-like activity in murine mesenchymal stem cells. When evaluatedin vivo, these hydrogels were found to be non-toxic through the subacute phase (i.e. up to 14 d). A 6 week rabbit spine fusion study found these materials excitingly achieved near complete fusion when assessed radiographically. This research provides considerable support for the utility of our novel complex biomaterial for spine fusion procedures as well as potentially for other future bone applications.