Chitosan Hydrogels As an Alternative Injectable Treatment for Degenerative Bone Disorders

Trent Faulkner¹, Soheila Aliakbarighavimi¹, Allison Josselet², Ethan Lungren¹, Ying Wu², Yisheng Sun², Ferris Pfieffer^2,3, Christina Goldstein³, Caixia Wan^1,2, and Bret Ulery^1,2

¹Department of Chemical Engineering, University of Missouri, Columbia, MO 65211

²Department of Bioengineering, University of Missouri, Columbia, MO 65211

³Department of Orthopaedic Surgery, University of Missouri, Columbia, MO 65211

Osteoporosis is one of the most common orthopedic disorders, affecting approximately 10 million people in the United States alone. Osteoporosis of the spine is of particular concern as it increases the risk of vertebral compression fractures (VCFs). Vertebroplasty and kyphoplasty are minimally invasive methods commonly used to treat these fractures and consist of injecting poly(methyl methacrylate) (PMMA), a quickly solidifying bone cement, into the porous bone tissue. However, the high compressive strength of PMMA results in undue pressure being placed on the vertebrae adjacent to the treated area, increasing the chance that those vertebrae will experience a future VCF. Additionally, PMMA injections do not serve to aid in regeneration of the degraded bone, instead only providing mechanical support.

Aiming to develop a bioactive and mechanically supportive injectable treatment for degenerative bone disorders and fractures, we created a hydrogel composed of a polymeric chitosan backbone crosslinked with genipin and phosphate. Initial tests of the hydrogel found a maximum compressive strength of 50 kPa, considerably less than what is necessary to mechanically support bone. Looking to improve the compressive strength, we suspended negative, neutral, or positive cellulose nanocrystals (CNCs) in chitosan before gel fabrication and subsequent strength testing. The results of these trials showed minimal changes in compressive strength upon addition of positive or negative CNCs, but over a two-fold increase with the addition of neutral CNC. While still far from the strength of bone, we are currently investigating additional additives that may eventually lead to a mechanically competent and bioactive injectable alternative to PMMA.