Effects of tissue processing on bioactivity of cartilage matrix-based hydrogels encapsulating osteoconductive particles

In the treatment of severe traumatic brain injury (TBI), decompressive craniectomy is commonly used to remove a large portion of calvarial bone to allow unimpeded brain swelling. Hydrogels have the potential to revolutionize TBI treatment by permitting a single-surgical intervention, remaining pliable during brain swelling, and tuned to regenerate bone after swelling has subsided. With this motivation, our goal is to present a pliable material capable of regenerating calvarial bone across a critical size defect. We therefore proposed the use of a methacrylated solubilized decellularized cartilage (MeSDCC) hydrogel encapsulating synthetic osteogenic particles of hydroxyapatite nanofibers, bioglass microparticles, or added rat bone marrow-derived mesenchymal stem cells (rMSCs) for bone regeneration in critical-size rat calvarial defects. Fibrin hydrogels were employed as a control material for the study. MeSDCC hydrogels exhibited sufficient rheological performance for material placement before crosslinking ( > 500 Pa), and sufficient compressive moduli post-crosslinking (E > 150 kPa). In vitro experiments suggested increased calcium deposition for cells seeded on the MeSDCC material; however, in vivo bone regeneration was minimal in both MeSDCC and fibrin groups, even with colloidal materials or added rMSCs. Minimal bone regeneration in the MeSDCC test groups may potentially be attributed to cartilage solubilization after decellularization, in which material signals may have degraded from enzymatic treatment. Looking to the future, an improvement in the bioactivity of the material will be crucial to the success of bone regeneration strategies for TBI treatment.