Sustained Release of Collagen-affinity SDF-1α from Book-shaped Acellular Fibrocartilage Scaffold Enhanced Bone-tendon Healing in a Rabbit Model

Rapid and functional bone-tendon (B-T) healing remains a difficulty in clinical practice. Tissue engineering has emerged as a promising strategy to address this problem. However, the majority of tissue engineering scaffolds are loaded with stem cells to enhance the regenerability in B-T healing, which is complicated and inconvenient for clinical application. Accordingly, developing a cell-free scaffold with chemotactic function and chondrogenic inducibility may be an effective approach. In this study, a collagen affinity peptide derived from the A3 domain of von Willebrand factor (a hemostasis factor) was fused into the C-terminal of a stromal cell-derived factor-1alpha (SDF-1alpha) to synthesize a recombinant SDF-1alpha capable of binding collagen and chemotactic activity. The recombinant SDF-1alpha was then tethered on the collagen fibers of a book-shaped acellular fibrocartilage scaffold (BAFS), thus fabricating a novel scaffold (C-SDF-1alpha/BAFS) with chemotactic function and chondrogenic inducibility. In vitro tests determined that this scaffold was noncytotoxic and biomimetic, could attract stem cells migrating to the scaffold using sustainably released C-SDF-1alpha, and inducedthe interacting stem cells down the chondrogenic lineage. In vivo, the C-SDF-1alpha/BAFS significantly enhanced the B-T healing in a rabbit partial patellectomy model, as shown by the larger cartilaginous metaplasia region, better fibrocartilage regeneration, additional bone formation, and improved biomechanical properties. Therefore, the findings of the study demonstrate that the C-SDF-1alpha/BAFS could potentially be applied for B-T healing.