Injectable Catalyst-Free Poly(Propylene Fumarate) System Cross-Linked by Strain Promoted Alkyne–Azide Cycloaddition Click Chemistry for Spine Defect Filling

A new PPF-BCN/hyPCL32-N₃ injectable system that can be cross-linked by catalyst-free, strain promoted alkyne–azide cycloaddition (SPAAC) click chemistry was developed for tissue engineering applications. The system consisted of two components: PPF-BCN, poly­(propylene fumarate) (PPF) functionalized with (1R,8S,9s)-bicyclo­[6.1.0]­non-4-yn-9-ylmethanol (BCN-OH), and hyPCL32-N₃, a hyper-branched 32-arm poly­(ε-caprolactone) (PCL) dendrimer functionalized with azide as the cross-linker core. Fast SPAAC click reaction allowed the desired gelation of the system without using any toxic initiator or catalyst. Compared to the conventional injectable formulation, e.g., poly­(methyl methacrylate) (PMMA), our PPF-BCN/hyPCL32-N₃ (abbreviated as PFCL-Click) injectable system showed enhanced biocompatibility and low heat generation during cross-linking. After reaction, the cross-linked PFCL-Click scaffolds supported excellent proliferation and differentiation of preosteoblast cells on the surface. The PFCL-Click system can be successfully injected into vertebral bodies of rabbit spine and can be monitored by X-ray imaging after incorporating zirconium dioxide (ZrO₂) powder. With these unique advantages, this injectable system has promising potential for bone defect repair and other tissue engineering and regenerative medicine applications.